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Diabetes Mellitus
in the year2000
DiabetesMellitus
in the year2000
Report of the Expert Committee on
the Diagnosis and Classificationof
Diabetes Mellitus
DiabetesMellitus
in the year2000
Definition
Description
Classification
Diagnostic criteria
Testing for diabetes
DefinitionDiabetes Mellitus is a group of metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.
The chronic hyperglycemia of diabetes is associated with log-term damage, dysfunction, and failure of various organs, especially the eyes, Kidneys, nerves, heart, and blood vessels.
Description
Insulin deficiency
Blood glucose
Insulin resistance
Symptoms: Polyuria and polydipsia.Weight loss with polyphagia.Blurred vision.Infection susceptibility.DKA or NKHS.
Types&
Stages
Type 1
Type 2
Other SpecificTypes
Diabetes MellitusNot Insulin Insulin insulin requiring requiring
requiring for control for survival
Impaired Glucose Toleranceor
Impaired Fasting Glucose
Normalglucose
regulation
These patients can briefly return to normoglycemia
Type 1 diabetes presenting in pregnancy may require insulin for survival
HyperglycemiaNormal
Stages
Types
Gestational Diabetes
Vacor toxicity may require insulin for survival
Stage&
Aetiology
Islet cell destruction:AutoimmuneIdiopathic
Predominantly insulinresistancePredominantly insulin secretorydefects
Other specific disorders( eg MODY, Endocrinopathies )
Diabetes Mellitus
Not Insulin Insulin insulin requiring requiring
requiring for control for survival
Impaired Glucoseand / or fasting hyperglycemia
Normal glucosetolerance
( achieved without Pharmacological agents)
HyperglycemiaNormal
Aetiology
Gestational Diabetes
Type 2 diabetes
Other specific types of diabetes
Gestational diabetes
Type 1 diabetes
Etiologicclassification
of
diabetesmellitus
II- Type 2 diabetes.
III- Other specific types.
IV- Gestational diabetes mellitus.
I- Type 1 diabetes:
Etiologicclassification
of
diabetesmellitus
I- Type 1 diabetes:
A. Immune mediated:
Cellular-mediated autoimmunity.
Markers:Islet cell autoantibodies ( ICAs ).Autoantibodies to insulin ( IAAs ).Autoantibodies to glutamic acid decarboxylase ( GAD ).Autoantibodies to the tyrosine phosphatase IA-2 and IA-2B.
HLA:HLA-DR/DQ alleles can be eitherpredisposing or protective. Beta cell
B lymphocyte T lymphocyte
Etiologicclassification
of
diabetesmellitus
I- Type 1 diabetes:
Multiple genetic:
Graves’ diseaseHashimoto’s thyroiditisAddison’s diseaseVitiligoPernicious anemia
Autoimmune destruction
Environmental:
Viral infectionObesity
Etiologicclassification
of
diabetesmellitus
I- Type 1 diabetes:
Beta cell destruction:
Rapid infants and childrenSlow adults
Presentation:
DKA children and adolescentsHyperglycemia adultsHyperglycemia to DKA Adults
Presentation
Etiologicclassification
of
diabetesmellitus
I- Type 1 diabetes:
B. Idiopathic:
No autoimmunityDKAMinority of patientsStrongly inheritedNo HLA associationInsulin requirement may come and go
Etiologicclassification
of
diabetesmellitus
II- Type 2 diabetes.
Pathology:
•Relative insulin deficiency ( initially).
•No Autoimmune destruction of -cell.
•Obesity ( insulin resistance ).
•No DKA (some times with stress ie infection).
•Pass undiagnosed.
•Macro- & micro-vascular complications.
•Insulin is normal or high.
Etiologicclassification
of
diabetesmellitus
II- Type 2 diabetes.
Pathology:
•Relative insulin deficiency ( initially).
•No Autoimmune destruction of -cell.
•Obesity ( insulin resistance ).
•No DKA (some times with stress ie infection).
•Pass undiagnosed.
•Macro- & micro-vascular complications.
•Insulin is normal or high.
Etiologicclassification
of
diabetesmellitus
II- Type 2 diabetes.
Pathology:
•Relative insulin deficiency ( initially).
•No Autoimmune destruction of -cell.
•Obesity ( insulin resistance ).
•No DKA (some times with stress ie infection).
•Pass undiagnosed.
•Macro- & micro-vascular complications.
•Insulin is normal or high.
Etiologicclassification
of
diabetesmellitus
II- Type 2 diabetes.
Pathology:
•Relative insulin deficiency ( initially).
•No Autoimmune destruction of -cell.
•Obesity ( insulin resistance ).
•No DKA (some times with stress ie infection).
•Pass undiagnosed.
•Macro- & micro-vascular complications.
•Insulin is normal or high.
Etiologicclassification
of
diabetesmellitus
II- Type 2 diabetes.
Pathology:
•Relative insulin deficiency ( initially).
•No Autoimmune destruction of -cell.
•Obesity ( insulin resistance ).
•No DKA (some times with stress ie infection).
•Pass undiagnosed.
•Macro- & micro-vascular complications.
•Insulin is normal or high.
Etiologicclassification
of
diabetesmellitus
II- Type 2 diabetes.
Risk factors:
AgeObesityLack of physical activity
WomenH/O G.D.MHypertensionDyslipidemiaEthnic and racial subgroupsStrong genetic predisposition
Diabetes
Etiologicclassification
of
diabetesmellitus
III- Other specific types.
Genetic defects of -cell function:Chromosome 12, HNF-1 (MODY3)Chromosome 7, glucokinase (MODY2)Chromosome 20, HNF-4 (MODY1)Mitochondrial DNAOthers
Genetic defects in insulin action:Type A insulin resistanceLeprechaunismRabson-Mendenhall syndromeLipoatrophic diabetesOthers
Disease of the exocrine pancreas:PancreatitisTrauma/pancreatectomyNeoplasiaCystic fibrosisHemochromatosisFibrocalculous pancreatopathyOthers
Etiologicclassification
of
diabetesmellitus
III- Other specific types.
Endocrinopathies:AcromegalyCushing’s syndromeGlucagonomaPheochromocytomaHyperthyroidismSomatostatinomaAldosteronomaOthers
Drug or chemical-induced:VacorDilantinThiazidesDiazoxideNeoplasiaPentamidine - interferonNicotinic acidCystic fibrosisGlucocorticoidsThyroid hormoneHemochromatosis -adrenergic agonistsFibrocalculous pancreatopathyOthers
Etiologicclassification
of
diabetesmellitus
III- Other specific types.
Infections:Congenital rubellaCytomegalovirusOthers
Uncommon forms of immune-mediated diabetes:“ Stiff-man “ syndromeAnti-insulin receptor antibodiesOthers
Other genetic syndromes some times associated with diabetes:Down’s syndromeKlinefelter’sTurner’s syndromeWolfram’s syndromeFriedreich’s ataxiaHuntington’s choreaLaurence-Moon-Biedl syndromeMyotonic dystrophyPorphyria Prader-Willi syndrome Others
Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Definition:Any degree of glucose intolerance with onset or first recognition during pregnancy.
Prevalence:- 1 ~ 14% of the total pregnancies.- 90% of pregnancies complicated by diabetes.
Importance:- Perinatal morbidity and mortality- Maternal complications- Risk factor for glucose intolerance
Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Diagnostic criteria:
1964 O’Sullivan and Mahan
1979 NDDG (National Diabetes Data Group)
1997 American Diabetes Association’s Fourth International Workshop-Conference on Gestational Diabetes Mellitus.
Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Screening
American Diabetes Association’s (1997) fourth international workshop-conference on gestational diabetes recommendations
Screen all pregnant women( 24-28 weeks of gestation )
Excluding:Low risk group:
< 25 years of ageNormal body weight- ve family history- ve H/O abn. glucose metabolismH/O poor obstetric outcomeEthnic group of low diabetes risk
Including:High risk group:
Marked obesityH/O GDMGlycosuriaStrong FH
Including:Average risk group:
Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Screening
American Diabetes Association’s (1997) fourth international workshop-conference on gestational diabetes recommendations
Low risk group:
No screening
Average risk group:
Two step approach
High risk group:
One step approach
Glucose Challenge TestGCT
( 50 gm oral glucose load )Glucose after 1hr
Oral Glucose Tolerance Test
OGTT75 or 100
FBS, 1hr, & 2hrs
Glucose Challenge TestGCT
( 50 gm oral glucose load )Glucose after 1hr
Oral Glucose Tolerance Test
OGTT75 or 100
FBS, 1hr, & 2hrs
Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Screening
American Diabetes Association’s (1997) fourth international workshop-conference on gestational diabetes recommendations
Low risk group:
No screening
Average risk group:
Two step approach
High risk group:
One step approach
Oral Glucose Tolerance TestOGTT
75 or 100FBS, 1hr, & 2hrs
Oral Glucose Tolerance TestOGTT
75 or 100FBS, 1hr, & 2hrs
Etiologicclassification
of
diabetesmellitus
IV- Gestational diabetes mellitus.
Diagnostic criteria
mg/dl mmol/lFasting 95 5.31-h 180 10.02-h 155 8.63-h 140 7.8
mg/dl mmol/lFasting 95 5.31-h 180 10.02-h 155 8.6
100-g Glucose load
75-g Glucose load
Etiologicclassification
of
diabetesmellitus
Impaired glucose tolerance IGTImpaired fasting glucose IFG
IGT WHO criteria IGF FPG = 110 - 126 mg/dL
6.1 - 7.0 mmol/L
Normal DiabeticIGTIGF
Why
Etiologicclassification
of
diabetesmellitus
Impaired glucose tolerance IGTImpaired fasting glucose IFG
Prevalence of Retinopathy by DecilesNHANES III
0
5
1 0
1 5
FPG 90 93 96 98 101 104 109 1202h PG 86 94 102 112 120 133 154 195HbA1c 5.1 5.2 5.4 5.5 5.6 5.7 5.9 6.2
Diabetes Care 1997;20, 1183-1197
Re
tin
opa
thy
%Prevalence of Retinopathy by Deciles
Pima Indians
0
5
1 0
1 5
FPG 93 97 100 105 109 11 6 136 2262h PG 106 11 6 126 138 156 185 244 364HbA1c 5.0 5.2 5.3 5.5 5.7 6.0 6.7 9.5
Diabetes Care 1997;20, 11 83-11 97
Retin
op
ath
y %
Prevalence of Retinopathy by DecilesEgyptians
0
5
1 0
1 5
FPG 84 89 93 99 108 130 178 2582h PG 90 99 110 125 155 218 304 386HbA1c 4.9 5.1 5.4 5.6 6.0 6.9 8.5 10.3
Diabetes Care 1997;20, 1183-1197
Re
tin
opa
thy
%
Etiologicclassification
of
diabetesmellitus
Impaired glucose tolerance IGTImpaired fasting glucose IFG
• They are known risk factors for future diabetes and cardiovascular disease.
• Intermediate stage for all types of diabetes.
• Associated with insulin resistance syndrome or :
Syndrome X :Insulin resistanceHyperinsulinemiaObesityDyslipidemia ( high triglyceride and/or low HDL )
Hypertension
Etiologicclassification
of
diabetesmellitus
Diagnostic criteria for diabetes mellitusThe new criteria
1
2
3
Fasting plasma glucose ( FPG ) at least 8hours fast
= or > 126 mg/dL ( 7.0 mmol/L )
Two hours plasma glucose (2PG ) after 75 anhydrous glucose in water
= or > 200 mg/dL ( 11.1 mmol/L )
Symptoms of diabetes ( polyuria, polydepsia, and weight loss )
+Random Blood Sugar ( RBS )
casual plasma glucose
= or > 200 mg/dL ( 11.1 mmol/L )
Etiologicclassification
of
diabetesmellitus
Impaired fasting glucose IFG
For epidemiological studies FPG is:standardization
FacilitationCheep
Diagnosis New criteria WHO criteria
mg/dL mmol/L mg/dL mmol/L
Normal <110 <6.1 < 140 < 7.8
IFG / IGT 110 - <126 6.1- < 7.0 140 - < 200 7.8 - <11.1
? DM = or > 126 = or > 7.0 = or > 200 = or > 11.1
8 hours over night fast. 2 hours post 75 gm glucose load.
Etiologicclassification
of
diabetesmellitus
Old and new diagnostic criteria
The criteria New case Diabetes Discovered Prevalence
Known cases No 7.92%
WHO criteria 6.34% 14.26%
New criteria 4.35% 12.27%
Data from NHANES III for individuals 40-74 years old.
The new criteria will lead to 14% ( slightly ) lower estimates of diabetes prevalence.
- 1.99
14%
Etiologicclassification
of
diabetesmellitus
Testing healthy individuals
Type 1 diabetes:More than one antibodies ( ICA, IAA, GAD, IA-2 )No effective method can prevent or delay the disease
Screening is not cost-effective
Type 2 diabetes:50% of type 2 are undiagnosed Chronic complications precede diabetes ( Retinopathy 7 years )
Risk factors
Etiologicclassification
of
diabetesmellitus
HbA1c
Not recommended for diagnosis of diabetes,but valuable for glycemic control of diabetes.
Etiologicclassification
of
diabetesmellitus
Criteria for testing asymptomatic individuals
• All individual above 45 years of age every 3 years
• Any individual with:
Obese ( > 120% desirable weight or BMI > 27 ).
+ve F/H first degree relatives.
High risk ethnic population.
H/O GDM or big baby ( > 9 lb ).
Hypertension > 140/90
HDL < 35mg/dl ( 0.9 mmol/l ) ±
Triglyceride > 250mg/dl ( 2.82 mmol/l )
Known to have IGT or IFG