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Diabetes Mellitus
Diabetes Mellitus
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
A clinical case where there is relative or total absence of insulin, which reduces
glucose uptake and utilization by insulin-sensitive tissues and leads to serious
long term complications.
A clinical case where there is relative or total absence of insulin, which reduces
glucose uptake and utilization by insulin-sensitive tissues and leads to serious
long term complications.
Insulin release
Glucose is most potent stimulus for insulin release from cells. There is continuous basal secretions with peaks at feeding times.
Insulin release
Glucose is most potent stimulus for insulin release from cells. There is continuous basal secretions with peaks at feeding times.
What is diabetes ?What is diabetes ?
Types of Diabetes MellitusTypes of Diabetes Mellitus
Diabetes MellitusDiabetes Mellitus
Pathogenesis:Autoimmune disease or viral infection (e.g. mumps) or enviromental toxins β cell destruction plasma insulin level is low or even immeasurable
Sometimes type I appears late in adulthood latent autoimmune diabetes in adult (LADA) islet cell function and insulin antibodies tests should be performed in non-obese adult to exclude type 2 diabetes
Pathogenesis:Autoimmune disease or viral infection (e.g. mumps) or enviromental toxins β cell destruction plasma insulin level is low or even immeasurable
Sometimes type I appears late in adulthood latent autoimmune diabetes in adult (LADA) islet cell function and insulin antibodies tests should be performed in non-obese adult to exclude type 2 diabetes
Type I (IDDM) Insulin dependant DM
Age onset: juvenile (young age)
Diabetes MellitusDiabetes Mellitus
Type II (NIDDM) Non-insulin dependant DM
Age onset: maturity onset (after 40 years)
Pathogenesis:Insulin resistance ( peripheral glucose utilization hyperglycemia insulin secretion then after time β cell exhaustion defective insulin secretion
Type 2 diabetic patients are divided into:-obese individuals (insulin resistance predominates)-non-obese individuals (defective insulin secretion predominates)
Pathogenesis:Insulin resistance ( peripheral glucose utilization hyperglycemia insulin secretion then after time β cell exhaustion defective insulin secretion
Type 2 diabetic patients are divided into:-obese individuals (insulin resistance predominates)-non-obese individuals (defective insulin secretion predominates)
Types of Diabetes MellitusTypes of Diabetes Mellitus
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Other types of diabetes
- Gestational diabetes- 2ry diabetes (acromegaly, cushing, cystic fibrosis-related diabetes, drug related e.g. thiazide, phenytoin)
Other types of diabetes
- Gestational diabetes- 2ry diabetes (acromegaly, cushing, cystic fibrosis-related diabetes, drug related e.g. thiazide, phenytoin)
Insulin deficiency or resistance
Glucose uptake Glucose uptake
Hyperglycemia
Glucosuria
Osmotic diuresis
Dehydration
Polydipsia
Electrolyte imbalance
Hyperglycemia
Glucosuria
Osmotic diuresis
Dehydration
Polydipsia
Electrolyte imbalance
plasma a.a. & -ve nitrogen
balance
plasma a.a. & -ve nitrogen
balance
Protein catabolism Protein catabolism lipolysislipolysis
plasma FFA
ketogenesis
ketonuria
plasma FFA
ketogenesis
ketonuria
Dehydration & acidosisDehydration & acidosis
Coma & deathComa & death
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Diabetic Diabetic ketoacidosis (DKA)ketoacidosis (DKA)Insulin Insulin
DeficiencyDeficiencyIncreased Increased lipolysislipolysisFFA + GlycerolFFA + Glycerol
IncreaseIncreased Acetyl d Acetyl
CoACoAAcetoacetic Acetoacetic
acidacid-hydroxybutyric -hydroxybutyric acidacid
AcetoneAcetone
DKADKA
ReductioReductio
nn
Decarboxylatio
Decarboxylationn
The body responds to ketoacidosis by
hyperventilatin, why?Due to acidosis respiratory center to get rid of CO2 in blood stream which is an acidic moiety blood pH compensating for the case of metabolic acidosis.
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Symptoms Symptoms
Long Term ComplicationsLong Term Complications
Microvascular complication
Microvascular complication
Macrovascular complication
Macrovascular complication
Retina( diabetic retinopathy)
blindness
kidney( diabetic nephropathy)
Renal failure
-Numbness-Reduced sensation in the lower extremities-Erectile dysfunction (also from reduced blood flow to the penis)
nerves( diabetic neuropathy)
Microvascular complication Microvascular complication
thickening of capillary basement membrane thickening of capillary basement membrane
Macrovascular complication Macrovascular complication
•Accelerated atherosclerosis ( LDL).•Narrowing of artery lumen and reduce blood flow.•Plaque rupture ( risk of thrombosis).
•Accelerated atherosclerosis ( LDL).•Narrowing of artery lumen and reduce blood flow.•Plaque rupture ( risk of thrombosis).
Coronary arteries
coronary heart diseases heart attack, myocardial
infarction),
peripheral arteries
Ischemia and thrombosis
cerebral arteries
stroke
Diabetic feet careDiabetic feet careComplications of foot injury
Neuropathy (patients not aware of injuries to the feet). Poor blood circulation (micro- and macrovascular disease) slow wound healing. body immune system favors infection and anaerobic bacterial growth. The spread of gangrenous infection into blood stream can be life-threatening. Amputation of the limb may be done to prevent this possibility.
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
ComplicationsComplications
Diabetic Diabetic UlcerUlcer
Diabetic footDiabetic foot
Gum ulcersGum ulcers CataractCataract
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
DiagnosisDiagnosis
Laboratory test Specimen Normal values
Blood glucose (fasting) plasmaplasma 70-110 mg/dl70-110 mg/dl
Blood glucose (postprandial 2hrs) plasmaplasma 110-180 mg/dl110-180 mg/dl
Urine analysis for glucose & acetone Urine Urine ------------
Glycosylated haemoglobin(HbA1c)
Whole blood Whole blood 5-8%5-8%
Plasma C-peptide Whole blood Whole blood 0.5 - 2.0 ng/mL0.5 - 2.0 ng/mL
A.A. Physical ExaminationPhysical Examination
B.B. Laboratory tests Laboratory tests
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
DiagnosisDiagnosisGlycosylated haemoglobin (HbA1c)
• Non enzymatic binding of glucose to Hb ( diabetes due to blood glucose level) • It indicates diabetic control over the past three mouths (life span of RBCs).
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
DiagnosisDiagnosisC-peptide Measurement
Advantages1.1. More sensitive than HbMore sensitive than HbA1c.A1c.
2. Higher t2. Higher t½½ than insulin, so than insulin, so
more reliablemore reliable
3. Higher urinary concentration 3. Higher urinary concentration than insulin.than insulin.
Uses1.1. Monitor Monitor -cell function in NIDDM-cell function in NIDDM
2.2. Differentiate between IDDM & Differentiate between IDDM & NIDDMNIDDM
• This test indicates β cell function by determining level of endogenous insulin secretion equivalent to C- peptide level.• C-peptide level is low in type I diabetes and high but not always in type II diabetes or insulin resistance.
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
DiagnosisDiagnosisPrediabetic patients impaired glucose tolerance (IGT) glucose levels between normal and diabetic Weight loss and exercise may help these people and sometimes the use of insulin sensitizers such as metformin is necessary in early diabetic patient of type II
Prediabetic patients impaired glucose tolerance (IGT) glucose levels between normal and diabetic Weight loss and exercise may help these people and sometimes the use of insulin sensitizers such as metformin is necessary in early diabetic patient of type II
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Usually happens due to mismatching between insulin dose and diet or exerciseClinicallyCold clammy sweat.Coma.Management:100 cc glucose 50% slowly and monitor blood sugar or intramuscular glucagon injection. Glucagon causes the release of glucose from the liver (by promoting glycogenolysis and gluconeogenesis).
Hypoglycemic ComaHypoglycemic Coma
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Summary of some insulin preparationsSummary of some insulin preparations
Ultra-short-actingUltra-short-actingInsulin lispro (Humalog)Insulin lispro (Humalog)
Short acting insulinShort acting insulinRegular (Crystalline Zn)Regular (Crystalline Zn)
Intermediate actingIntermediate actingNeutral protamine Hagedorn (NPH) insulinNeutral protamine Hagedorn (NPH) insulin
Premixed (biphasic)Premixed (biphasic)%NPH, % regular%NPH, % regularHumulin 70/30Humulin 70/30
Long acting insulinLong acting insulinInsulin glargineInsulin glargineInsulin detemirInsulin detemir
TreatmentTreatment
Insulin Insulin regimensregimens
Basal-bolus regimen
Twice-daily regimen
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
SULPHONYLUREA COMPOUNDSSULPHONYLUREA COMPOUNDS (Long acting secretagogues)(Long acting secretagogues)11stst generation: generation: Tolbutamide, chlorpropamide.Tolbutamide, chlorpropamide.
22ndnd generation: generation: Glibenclamide (DaonilGlibenclamide (Daonil®®)) Gliclazide (DiamicronGliclazide (Diamicron®®)) Glimepiride (AmarylGlimepiride (Amaryl®®))
Oral Oral HypoglycemicsHypoglycemics
SULPHONYLUREA COMPOUNDSSULPHONYLUREA COMPOUNDS (Long acting secretagogues)(Long acting secretagogues)N.B. glipizide is the only SU that can be N.B. glipizide is the only SU that can be used in poor renal function.used in poor renal function.Adverse effects:Adverse effects:Common: Hypoglycemia, weight gain.Common: Hypoglycemia, weight gain.
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
BIGUANIDESBIGUANIDES Metformin (GlucophageMetformin (Glucophage®®))
MOA: reduces hepatic gluconeogenesis, reduces intestinal MOA: reduces hepatic gluconeogenesis, reduces intestinal absorption of glucose and has favourable effect on insulin absorption of glucose and has favourable effect on insulin senstivity. In addition to anorexic effect.senstivity. In addition to anorexic effect.S.Es. S.Es. Common: N/V, diarrhea and epigastric pain.Common: N/V, diarrhea and epigastric pain.Less common: lactic Less common: lactic acidosis acidosis metformin should not be recommended in patient with poor renal function so as to avoid lactic acidosis
Oral Oral HypoglycemicsHypoglycemics
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
MeglitinidesMeglitinides Repaglinide and nateglinideRepaglinide and nateglinide
MOA: Similar to that of sulphonylureas in increasing insulin MOA: Similar to that of sulphonylureas in increasing insulin secretion from the pancreas but with a very rapid onset and secretion from the pancreas but with a very rapid onset and shorter duration of activity.shorter duration of activity.S.Es. S.Es. Common: hypoglycemia and weight gainCommon: hypoglycemia and weight gain
Oral Oral HypoglycemicsHypoglycemics
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Thiazoldindiones (TZDs or glitazones)Thiazoldindiones (TZDs or glitazones) Pioglitazone and RosiglitazonePioglitazone and Rosiglitazone
MOA: PPARMOA: PPARagonist agonist →↑expression of genes →↑expression of genes responsible for glucose metabolism, resulting in responsible for glucose metabolism, resulting in improved insulin sensitivity.improved insulin sensitivity.In Semptember 2010, FDA initiated restriction access to In Semptember 2010, FDA initiated restriction access to Rosiglitazone concerned with cardiovascular safety.Rosiglitazone concerned with cardiovascular safety.Pioglitazone Pioglitazone may cause may cause fluid retention (resistant edema)fluid retention (resistant edema)
Oral Oral HypoglycemicsHypoglycemics
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Dipeptidyl peptidase-4 (DPP-4) inhibitorsDipeptidyl peptidase-4 (DPP-4) inhibitors Sitagliptin & SaxagliptinSitagliptin & Saxagliptin
MOA: inhibits the breakdown of glucagon-like peptide-1 MOA: inhibits the breakdown of glucagon-like peptide-1 (GLP-1) secreted during meals, which in turn increases (GLP-1) secreted during meals, which in turn increases pancreatic insulin secretion, limits glucagon secretion, slows pancreatic insulin secretion, limits glucagon secretion, slows gastric emptying, and promotes satietygastric emptying, and promotes satiety..
Oral Oral HypoglycemicsHypoglycemics
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Dipeptidyl peptidase-4 (DPP-4) inhibitorsDipeptidyl peptidase-4 (DPP-4) inhibitors Sitagliptin & SaxagliptinSitagliptin & Saxagliptin
MOA: inhibits the breakdown of glucagon-like peptide-1 MOA: inhibits the breakdown of glucagon-like peptide-1 (GLP-1) secreted during meals, which in turn increases (GLP-1) secreted during meals, which in turn increases pancreatic insulin secretion, limits glucagon secretion, slows pancreatic insulin secretion, limits glucagon secretion, slows gastric emptying, and promotes satietygastric emptying, and promotes satiety..
Oral Oral HypoglycemicsHypoglycemics
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
-GLUCOSIDASE INHIBITORS-GLUCOSIDASE INHIBITORS Miglitol (GlysetMiglitol (Glyset®®) - Acarbose (Glucobay) - Acarbose (Glucobay®®))Decreases intestinal absorption of glucoseDecreases intestinal absorption of glucose
Oral Oral HypoglycemicsHypoglycemics
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Diabetic ketoacidosisDiabetic ketoacidosis Results in significant hyperglycemia, dehydration Results in significant hyperglycemia, dehydration and ketoacidosis.and ketoacidosis.Signs/symptoms: polyuria, polydipsia, vomiting, Signs/symptoms: polyuria, polydipsia, vomiting, dehydration, altered mental status, coma.dehydration, altered mental status, coma.Treatment:Treatment:1.1.Fluid replacement: saline (0.9%).Fluid replacement: saline (0.9%).2.2.Insulin I.V. (Bolus or infusion).Insulin I.V. (Bolus or infusion).3.3.KCL (IV) in case of hypokalemia.KCL (IV) in case of hypokalemia.4.4.IV bicarbonate if serum pH less than 6.9.IV bicarbonate if serum pH less than 6.9.
Treatment of DMTreatment of DMcomplicationscomplications
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
NephropathyNephropathyACE inhibitors and ARBs are often used regardless of ACE inhibitors and ARBs are often used regardless of whether the patient has hypertension or not.whether the patient has hypertension or not.RetinopathyRetinopathyNo specific pharmacotherapy recommended except to No specific pharmacotherapy recommended except to adequate glucose control and BP.adequate glucose control and BP.
Treatment of DMTreatment of DMcomplicationscomplications
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
DM NeuropathiesDM NeuropathiesA-Neuropathic painA-Neuropathic pain1.1.TCAs ( amitriptyline, desipramine)TCAs ( amitriptyline, desipramine)2.2.Anticonvulsant (gabapentin, lamotrigine, pregabalin)Anticonvulsant (gabapentin, lamotrigine, pregabalin)Pregabalin is recommended in the treatment of DM Pregabalin is recommended in the treatment of DM neuropathyneuropathy3. SSRIs especially duloxetine or SNRIs .3. SSRIs especially duloxetine or SNRIs .B-GastroparesisB-GastroparesisAutonomic neuropathy causes considerable N/V after Autonomic neuropathy causes considerable N/V after meals because of delayed gastric emptying.meals because of delayed gastric emptying.ttt: prokinetics drugs such as metoclopramide, ttt: prokinetics drugs such as metoclopramide, domepridone or erythromycin.domepridone or erythromycin.
Treatment of DMTreatment of DMcomplicationscomplications
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Cardiovascular diseasesCardiovascular diseasesA-BP managementA-BP managementACE inhibitors or ARBsACE inhibitors or ARBsB-Lipid managementB-Lipid managementStaitnsStaitnsAntiplatelet as Aspirin or Clopidogrel may be added Antiplatelet as Aspirin or Clopidogrel may be added with existing cardiovascular diseases to prevent with existing cardiovascular diseases to prevent ischemic heart diseases.ischemic heart diseases.
Treatment of DMTreatment of DMcomplicationscomplications
Diabetes MellitusDiabetes MellitusDiabetes MellitusDiabetes Mellitus
Open QuestionsOpen Questions