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Diabetes and Vitamin DDiabetes and Vitamin D
Stefania Maggi
CNR Center on Aging
Padua Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
The primary function of calcitriol or 125 (OH)2D3 in the intestine is increased absorption of calcium and phosphorous Vitamin D is carried into the nucleus of the enterocyte where it binds to receptor proteins and acts as a steroid hormone resulting in the stimulation and synthesis of new messenger RNA moleculesThese messenger RNA molecules are then translated to produce a protein Calbindin a calcium binding protein in the intestinal mucosa that is synthesized in response to the action of calcitriol (active vit D) This calcium binding protein is needed for Ca transport across the cell membranes
Calcitriol and the BonePTH alone or with calcitriol directs the mobilization of Ca and P from the bones to help achieve a normal blood Ca concentration The bodyrsquos needs for calcium is regulated by the production of calcitriol by the kidneysldquoHypocalcemiardquo increases the secretion of parathyroid hormone which in turna) Stimulates the conversion of some of the circulating 25(OH)2D3 to 125(OH)2D3 (calcitriol) in the kidneysb) This active 125(OH)2D3 (calcitriol) then causeselevation of serum Ca and P by acting on kidney bone and GI Tract
Vitamin D metabolism and actions Vitamin D metabolism and actions
Maalouf NM Current opinion in Nephrology and hypertension 2008
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Suggested terminology to describe vitamin D status Suggested terminology to describe vitamin D status
according to circulating 25(OH)D concentrationsaccording to circulating 25(OH)D concentrations
Stages of vitamin D status
25(OH)D concentrations
(ngmL)
Deficiency 0ndash12
Insufficiency gt12ndash30
Adequacy gt30 to 100
Toxicity gt100
Souberbielle JC et al Autoimmune reviews 2010
Causes of hypovitaminosis DCauses of hypovitaminosis Dbull Reduced skin synthesis
ndash Sunscreen use skin pigment aging season latitude
bull Decreased bioavailabilityndash Malabsorption obesity
bull Increased catabolismndash Antconvulsants glucocorticoids (binding to the steroid receptor)
bull Breast feedingndash Poor vit D content in human milk
bull Decreased synthesis of 25(OH)Dndash Liver failure
bull Increased urinary loss of 25(OH)Dndash Nephrotic syndrome
bull Decreased synthesis of 125(OH)Dndash Chronic kidney failure
50-97
35-73
80 in aged 42 in adolescents
30-80
Hypovitaminosis D a global perspective
Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009
Van der Meer M et al Ospeop Int 2011
Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations
89 in adolescents
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
The primary function of calcitriol or 125 (OH)2D3 in the intestine is increased absorption of calcium and phosphorous Vitamin D is carried into the nucleus of the enterocyte where it binds to receptor proteins and acts as a steroid hormone resulting in the stimulation and synthesis of new messenger RNA moleculesThese messenger RNA molecules are then translated to produce a protein Calbindin a calcium binding protein in the intestinal mucosa that is synthesized in response to the action of calcitriol (active vit D) This calcium binding protein is needed for Ca transport across the cell membranes
Calcitriol and the BonePTH alone or with calcitriol directs the mobilization of Ca and P from the bones to help achieve a normal blood Ca concentration The bodyrsquos needs for calcium is regulated by the production of calcitriol by the kidneysldquoHypocalcemiardquo increases the secretion of parathyroid hormone which in turna) Stimulates the conversion of some of the circulating 25(OH)2D3 to 125(OH)2D3 (calcitriol) in the kidneysb) This active 125(OH)2D3 (calcitriol) then causeselevation of serum Ca and P by acting on kidney bone and GI Tract
Vitamin D metabolism and actions Vitamin D metabolism and actions
Maalouf NM Current opinion in Nephrology and hypertension 2008
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Suggested terminology to describe vitamin D status Suggested terminology to describe vitamin D status
according to circulating 25(OH)D concentrationsaccording to circulating 25(OH)D concentrations
Stages of vitamin D status
25(OH)D concentrations
(ngmL)
Deficiency 0ndash12
Insufficiency gt12ndash30
Adequacy gt30 to 100
Toxicity gt100
Souberbielle JC et al Autoimmune reviews 2010
Causes of hypovitaminosis DCauses of hypovitaminosis Dbull Reduced skin synthesis
ndash Sunscreen use skin pigment aging season latitude
bull Decreased bioavailabilityndash Malabsorption obesity
bull Increased catabolismndash Antconvulsants glucocorticoids (binding to the steroid receptor)
bull Breast feedingndash Poor vit D content in human milk
bull Decreased synthesis of 25(OH)Dndash Liver failure
bull Increased urinary loss of 25(OH)Dndash Nephrotic syndrome
bull Decreased synthesis of 125(OH)Dndash Chronic kidney failure
50-97
35-73
80 in aged 42 in adolescents
30-80
Hypovitaminosis D a global perspective
Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009
Van der Meer M et al Ospeop Int 2011
Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations
89 in adolescents
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
The primary function of calcitriol or 125 (OH)2D3 in the intestine is increased absorption of calcium and phosphorous Vitamin D is carried into the nucleus of the enterocyte where it binds to receptor proteins and acts as a steroid hormone resulting in the stimulation and synthesis of new messenger RNA moleculesThese messenger RNA molecules are then translated to produce a protein Calbindin a calcium binding protein in the intestinal mucosa that is synthesized in response to the action of calcitriol (active vit D) This calcium binding protein is needed for Ca transport across the cell membranes
Calcitriol and the BonePTH alone or with calcitriol directs the mobilization of Ca and P from the bones to help achieve a normal blood Ca concentration The bodyrsquos needs for calcium is regulated by the production of calcitriol by the kidneysldquoHypocalcemiardquo increases the secretion of parathyroid hormone which in turna) Stimulates the conversion of some of the circulating 25(OH)2D3 to 125(OH)2D3 (calcitriol) in the kidneysb) This active 125(OH)2D3 (calcitriol) then causeselevation of serum Ca and P by acting on kidney bone and GI Tract
Vitamin D metabolism and actions Vitamin D metabolism and actions
Maalouf NM Current opinion in Nephrology and hypertension 2008
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Suggested terminology to describe vitamin D status Suggested terminology to describe vitamin D status
according to circulating 25(OH)D concentrationsaccording to circulating 25(OH)D concentrations
Stages of vitamin D status
25(OH)D concentrations
(ngmL)
Deficiency 0ndash12
Insufficiency gt12ndash30
Adequacy gt30 to 100
Toxicity gt100
Souberbielle JC et al Autoimmune reviews 2010
Causes of hypovitaminosis DCauses of hypovitaminosis Dbull Reduced skin synthesis
ndash Sunscreen use skin pigment aging season latitude
bull Decreased bioavailabilityndash Malabsorption obesity
bull Increased catabolismndash Antconvulsants glucocorticoids (binding to the steroid receptor)
bull Breast feedingndash Poor vit D content in human milk
bull Decreased synthesis of 25(OH)Dndash Liver failure
bull Increased urinary loss of 25(OH)Dndash Nephrotic syndrome
bull Decreased synthesis of 125(OH)Dndash Chronic kidney failure
50-97
35-73
80 in aged 42 in adolescents
30-80
Hypovitaminosis D a global perspective
Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009
Van der Meer M et al Ospeop Int 2011
Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations
89 in adolescents
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Calcitriol and the BonePTH alone or with calcitriol directs the mobilization of Ca and P from the bones to help achieve a normal blood Ca concentration The bodyrsquos needs for calcium is regulated by the production of calcitriol by the kidneysldquoHypocalcemiardquo increases the secretion of parathyroid hormone which in turna) Stimulates the conversion of some of the circulating 25(OH)2D3 to 125(OH)2D3 (calcitriol) in the kidneysb) This active 125(OH)2D3 (calcitriol) then causeselevation of serum Ca and P by acting on kidney bone and GI Tract
Vitamin D metabolism and actions Vitamin D metabolism and actions
Maalouf NM Current opinion in Nephrology and hypertension 2008
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Suggested terminology to describe vitamin D status Suggested terminology to describe vitamin D status
according to circulating 25(OH)D concentrationsaccording to circulating 25(OH)D concentrations
Stages of vitamin D status
25(OH)D concentrations
(ngmL)
Deficiency 0ndash12
Insufficiency gt12ndash30
Adequacy gt30 to 100
Toxicity gt100
Souberbielle JC et al Autoimmune reviews 2010
Causes of hypovitaminosis DCauses of hypovitaminosis Dbull Reduced skin synthesis
ndash Sunscreen use skin pigment aging season latitude
bull Decreased bioavailabilityndash Malabsorption obesity
bull Increased catabolismndash Antconvulsants glucocorticoids (binding to the steroid receptor)
bull Breast feedingndash Poor vit D content in human milk
bull Decreased synthesis of 25(OH)Dndash Liver failure
bull Increased urinary loss of 25(OH)Dndash Nephrotic syndrome
bull Decreased synthesis of 125(OH)Dndash Chronic kidney failure
50-97
35-73
80 in aged 42 in adolescents
30-80
Hypovitaminosis D a global perspective
Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009
Van der Meer M et al Ospeop Int 2011
Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations
89 in adolescents
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Vitamin D metabolism and actions Vitamin D metabolism and actions
Maalouf NM Current opinion in Nephrology and hypertension 2008
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Suggested terminology to describe vitamin D status Suggested terminology to describe vitamin D status
according to circulating 25(OH)D concentrationsaccording to circulating 25(OH)D concentrations
Stages of vitamin D status
25(OH)D concentrations
(ngmL)
Deficiency 0ndash12
Insufficiency gt12ndash30
Adequacy gt30 to 100
Toxicity gt100
Souberbielle JC et al Autoimmune reviews 2010
Causes of hypovitaminosis DCauses of hypovitaminosis Dbull Reduced skin synthesis
ndash Sunscreen use skin pigment aging season latitude
bull Decreased bioavailabilityndash Malabsorption obesity
bull Increased catabolismndash Antconvulsants glucocorticoids (binding to the steroid receptor)
bull Breast feedingndash Poor vit D content in human milk
bull Decreased synthesis of 25(OH)Dndash Liver failure
bull Increased urinary loss of 25(OH)Dndash Nephrotic syndrome
bull Decreased synthesis of 125(OH)Dndash Chronic kidney failure
50-97
35-73
80 in aged 42 in adolescents
30-80
Hypovitaminosis D a global perspective
Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009
Van der Meer M et al Ospeop Int 2011
Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations
89 in adolescents
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Suggested terminology to describe vitamin D status Suggested terminology to describe vitamin D status
according to circulating 25(OH)D concentrationsaccording to circulating 25(OH)D concentrations
Stages of vitamin D status
25(OH)D concentrations
(ngmL)
Deficiency 0ndash12
Insufficiency gt12ndash30
Adequacy gt30 to 100
Toxicity gt100
Souberbielle JC et al Autoimmune reviews 2010
Causes of hypovitaminosis DCauses of hypovitaminosis Dbull Reduced skin synthesis
ndash Sunscreen use skin pigment aging season latitude
bull Decreased bioavailabilityndash Malabsorption obesity
bull Increased catabolismndash Antconvulsants glucocorticoids (binding to the steroid receptor)
bull Breast feedingndash Poor vit D content in human milk
bull Decreased synthesis of 25(OH)Dndash Liver failure
bull Increased urinary loss of 25(OH)Dndash Nephrotic syndrome
bull Decreased synthesis of 125(OH)Dndash Chronic kidney failure
50-97
35-73
80 in aged 42 in adolescents
30-80
Hypovitaminosis D a global perspective
Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009
Van der Meer M et al Ospeop Int 2011
Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations
89 in adolescents
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Suggested terminology to describe vitamin D status Suggested terminology to describe vitamin D status
according to circulating 25(OH)D concentrationsaccording to circulating 25(OH)D concentrations
Stages of vitamin D status
25(OH)D concentrations
(ngmL)
Deficiency 0ndash12
Insufficiency gt12ndash30
Adequacy gt30 to 100
Toxicity gt100
Souberbielle JC et al Autoimmune reviews 2010
Causes of hypovitaminosis DCauses of hypovitaminosis Dbull Reduced skin synthesis
ndash Sunscreen use skin pigment aging season latitude
bull Decreased bioavailabilityndash Malabsorption obesity
bull Increased catabolismndash Antconvulsants glucocorticoids (binding to the steroid receptor)
bull Breast feedingndash Poor vit D content in human milk
bull Decreased synthesis of 25(OH)Dndash Liver failure
bull Increased urinary loss of 25(OH)Dndash Nephrotic syndrome
bull Decreased synthesis of 125(OH)Dndash Chronic kidney failure
50-97
35-73
80 in aged 42 in adolescents
30-80
Hypovitaminosis D a global perspective
Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009
Van der Meer M et al Ospeop Int 2011
Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations
89 in adolescents
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Causes of hypovitaminosis DCauses of hypovitaminosis Dbull Reduced skin synthesis
ndash Sunscreen use skin pigment aging season latitude
bull Decreased bioavailabilityndash Malabsorption obesity
bull Increased catabolismndash Antconvulsants glucocorticoids (binding to the steroid receptor)
bull Breast feedingndash Poor vit D content in human milk
bull Decreased synthesis of 25(OH)Dndash Liver failure
bull Increased urinary loss of 25(OH)Dndash Nephrotic syndrome
bull Decreased synthesis of 125(OH)Dndash Chronic kidney failure
50-97
35-73
80 in aged 42 in adolescents
30-80
Hypovitaminosis D a global perspective
Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009
Van der Meer M et al Ospeop Int 2011
Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations
89 in adolescents
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
50-97
35-73
80 in aged 42 in adolescents
30-80
Hypovitaminosis D a global perspective
Bandeira et al Arq Bras Endocrinol Metab 50 2006 Mithal et al Osteop Int 2009
Van der Meer M et al Ospeop Int 2011
Midle East and Africa register the highest rates of hypovitaminosis D worldwide Turkish Moroccan Indian and Sub-Sahara African immigrants in Europe have higher level of hypovitaminosis D compared to indigenous European populations
89 in adolescents
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Copyright copy2001 The Endocrine Society
Lips P Endocr Rev 200122477-501
Serum 25(OH)D measured in elderly people in 16 European centers participating Serum 25(OH)D measured in elderly people in 16 European centers participating in the Euronut SENECA Studyin the Euronut SENECA Study
The lowest values were found in Greece Spain and Italy
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Vitamin D deficiencyVitamin D deficiency
1048707 Rickets--------------Children
1048707 Osteomalacia------ Adults
1048707 Osteoporosis-------Adults
helliphelliphellip And much more
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Vitamin D deficiencyVitamin D deficiency
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Independent Association of Low Serum 25-Hydroxyvitamin D Levels With All-Cause and Cardiovascular MortalityCause and Cardiovascular Mortality
Dobnig H H et al A et al Arch Intern Medrch Intern Med 2008168(12)1340-1349 2008168(12)1340-1349
Prospective cohort study of 3258 patients undergoingcoronary angiography
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Copyright restrictions may apply
Dobnig H et al Arch Intern Med 20081681340-1349
Cox proportional hazards regression model ratios (including 95 confidence intervals [CI]) for cardiovascular mortality are shown for 25-hydroxyvitamin D (A) and 125-dihydroxyvitamin D (B) quartiles (Q) for the following 3 different statistical models (M) (1) M1 (unadjusted) (2) M2 (adjusted for age sex body mass index and physical activity level) and (3) M3 (variables of M2 plus active smokers diabetes mellitus albumin level cystatin C level triglyceride level N-terminal pro-BNP level systolic and diastolic blood pressure low-density lipoprotein and high-density lipoprotein cholesterol levels and the use of statins aspirin -blockers bronchodilators and angiotensin-converting enzyme inhibitors)
Low 25-hydroxyvitamin D and 125-dihydroxyvitamin D levels are independently associated with all-cause and CVD mortality
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Copyright restrictions may apply
Martins D et al Arch Intern Med 20071671159-1165
Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Age- Sex- and Race-Adjusted Prevalence and ORs of Select Cardiovascular Disease Risk Factors Between the First and Fourth Quartiles of Serum 25(OH)D LevelsFactors Between the First and Fourth Quartiles of Serum 25(OH)D Levels
Data From the Third National Health and Nutrition Examination Survey(15088 participants gt20 yrs)
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Vit D and Metabolic SyndromeVit D and Metabolic Syndrome
Relation of 25-hydroxyvitamin D and PTH levels with metabolic syndrome among US adults
JP Reis D von Muhlen ER Miller
European Journal of Endocrinology 159 2008
We have strong evidences of hypovitaminosis D in MetS patients independent of Ca intake PTH BMI or renal function
The potential mechanisms to explain the protective effect of vitamin D against MetSis based on the effect on glucose homeostasis (insulin resistance β cell function)
Vit D increases insulin receptor capacity and responsiveness for glucose transport
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
bull Vitamin D metabolism and actions
bull Epidemiology of hypovitaminosis D
bull Association of low Vitamin D status and chronic diseases
bull Association of low vitamin D and diabetesndash epidemiological evidence ndash pathophysiological plausibilityndash efficacy of interventions
Diabetes and Vitamin DDiabetes and Vitamin D
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Association between type 1 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Association between type 2 diabetes mellitus and risk of hip fracture in case-control and cohort studies
Janghorbani M et al Am J Epidemiol 2007166495-505
American Journal of Epidemiology copy The Author 2007 Published by the Johns Hopkins Bloomberg School of Public Health All rights reserved For permissions please e-mail journalspermissionsoxfordjournalsorg
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Tuominen et al Diabetes Care 1999
0
01
02
03
04
05
06
07
08
09
1
Men Women
Type 1Type 2Controls
Plt005
Plt0005
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Bone Mineral Density (BMD) at the hip in subjects with Bone Mineral Density (BMD) at the hip in subjects with diabetes type 1 diabetes type 2 and without diabetes diabetes type 1 diabetes type 2 and without diabetes
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Diabetes is associated Diabetes is associated with a decrease in bone with a decrease in bone strength that is not strength that is not reflected in the reflected in the measurement of BMDmeasurement of BMD
Despite having a higher bone density on average patients with T2D have a higher risk of fractures Other factors associated with frailty and falls including age physical activity and BMI do not account for the association between T2D and fracture
Bone quality vs bone densityBone quality vs bone density
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Has Fat a Protective Role for the SkeletonHas Fat a Protective Role for the SkeletonldquoPros amp ConsrdquoldquoPros amp Consrdquo
Rosen CJ et al Nature 2006
Decreased Vit D bioavailability
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Role of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes MellitusRole of vitamin D in the pathogenesis of type 2 Diabetes Mellitus
Palomer et al Diabetes Obesity and Metabolism 2008
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Serum Vitamin D and Subsequent Serum Vitamin D and Subsequent Occurrence of Type 2 DiabetesOccurrence of Type 2 Diabetes
Study- and sex-specific and pooled age-adjusted relative odds of type 2 diabetes comparing highest and lowest quartiles of serum vitamin D The black squares and horizontal lines represent study- and sex-specific ORs and 95 CIs respectively The area of the black squares reflects the study- and sex-specific weight (inverse of the standard error) The diamond represents the pooled ORs and 95 CI The vertical dashed line represents the pooled relative risk
Knekt Epidemiology Volume 19(5)September 2008666-671
Two nested case-control studies collected by the Finnish Mobile Clinic in 1973ndash1980 During a follow-up period of 22 years 412 incident type 2 diabetes cases occurred and 986 controls were selected by individual matching
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Pittas AG et al Diabetes Care 33(9) 2010
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Levels of vitamin D and cardiometabolic disorders Systematic review and meta-analysis
Parker J et al Maturitas 2009
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Factors Contributing to Low Factors Contributing to Low Vitamin D Levels in DiabetesVitamin D Levels in Diabetes
Penckofer et al 2008
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Diabetes Care 33(10) 2010
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Vitamin D and diabetesVitamin D and diabetes
The metabolically active form of vitamin D 125(OH)2D3 and its analogues have been shown to have effects on the major players involved in the pathogenesis of type 1 and type 2 diabetes Beta cell function has been shown to be improved by 125(OH)2D3 in vitro and in vivo and the avoidance of vitamin D deficiency is essential for normal beta cell function In NOD mice 125(OH)2D3 protects against insulitis diabetes and disease recurrence after islet transplantation primarily through immunomodulatory effects
Review
Vitamin D and diabetesC Mathieu et al Diabetologia 2005
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Evidence of the efficacy of Vit D Evidence of the efficacy of Vit D supplementationsupplementation
Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low
vitamin D levelsJ A Sugden J I Davies M D Withamet al
DIABETIC Medicine 2007
Daily consumption of vitamin D-or vitamin D + calcium fortified yogurt drink improved glycemic control in patients with type 2
diabetes a randomized clinical trialNikooyeh B Neyestani TR Farvid M et al
AJCN 2011
Vitamin D as an analgesic for patients with T2Dand neuropathic pain
Lee P Chen R Arch Intern Med 2008
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Schematic representation of the multitude of other potential physiologicSchematic representation of the multitude of other potential physiologic action of vitamin D for cardiovascular health cancer prevention action of vitamin D for cardiovascular health cancer prevention
regulation of immune function and decreased risk of autoimmune diseasesregulation of immune function and decreased risk of autoimmune diseases
Holick Am J Clin Nutr 2004
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
November 2010
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Major challengesMajor challenges
bull Measuring 25(OH)Dndash Techniques available
ndash Clinical reporting of circulating 25(OH)D concentrations
bull Defining doses of Vitamin D supplements
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Recommendations for clinical practiceRecommendations for clinical practice
Souberbielle JC et al Autoimmunity reviews 2010
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
Copyright copy2011 The Endocrine Society
Heaney R P et al J Clin Endocrinol Metab 201196E447-E452
Vitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humansVitamin D3 is more potent than Vitamin D2 in humans
D2
D3
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective
ConclusionsConclusions
bull The role of Vitamin D in diabetes is not limited to the autoimmune form of diabetes
bull The relationship between vitamin D and diabetes is complicated involving various mechanisms not yet fully elucidated
bull Clinical trials are required to identify individuals with or at risk of T2D that will most benefit from Vitamin D supplementation and the dose and formulation which would be most effective