Type 1 (IDDM) Type 2 (NIDDM) Diabetes Mellitus Type 1 (IDDM) Type 2 (NIDDM) 20-Apr-19 Diabetes Mellitus

Diabetes Mellitus Group of metabolic disorders Hyperglycaemia due to Sharing a common feature Hyperglycaemia Hyperglycaemia due to Relative or absolute lack of insulin Lack of insulin affect metabolism Carbohydrate Fats Proteins Water & electrolytes 20-Apr-19 Diabetes Mellitus

Diabetes Mellitus Hyperglycaemia in all cases is due A functional deficiency of insulin action Deficiency of insulin action ↓ in insulin secretion by B-cells ↓ response to insulin by target tissue Insulin resistance Or both ↑ in the counter regulatory hormones Oppose the effects of insulin 20-Apr-19 Diabetes Mellitus

Diagnostic criteria According to the National Diabetic Data group (NDDG) & WHO Fasting plasma glucose  126 mg/dL (>7.0 mmol/L) Symptoms of diabetes plus Random plasma glucose  200 mg/dL ( 11.1 mmol/L) Plasma glucose level  200 mg/dL ( 11.1 mmol/L) after Oral dose of 75g of glucose (OGTT) 20-Apr-19 Diabetes Mellitus

Classification The two types traditionally classified According to age at onset of DM Juvenile DM Maturity onset DM According to therapy Insulin dependent diabetes mellitus (IDDM) Non-insulin dependent diabetes mellitus (NIDDM) According to causation Immune dependent diabetes mellitus (IDDM) Non-immune dependent diabetes mellitus (NIDDM) 20-Apr-19 Diabetes Mellitus

Classification Type I diabetes mellitus Insulin dependent diabetes mellitus (IDDM) Caused by lack of Insulin Immuno-dependent diabetes mellitus 20-Apr-19 Diabetes Mellitus

Classification Type II diabetes mellitus Non Insulin dependent diabetes mellitus (NIDDM) Caused by Decreased sensitivity of target tissue to insulin Insulin resistance Non-immune dependent diabetes mellitus (NIDDM) 20-Apr-19 Diabetes Mellitus

Classification In both types of diabetes Metabolism of main food stuff is altered Efficient uptake and utilization of glucose In most cells is prevented ↑ Blood glucose concentration ↑ glucose output by liver ↓ Insulin ↑ Glucagon ↑ utilization of fat and protein 20-Apr-19 Diabetes Mellitus

Type 1 Diabetes Mellitus 20-Apr-19 Diabetes Mellitus

Pathogenesis of Type 1 DM Immuno-dependent diabetes mellitus Results from severe lack of insulin Due to destruction of B-cells Auto-immune mechanism 20-Apr-19 Diabetes Mellitus

Pathogenesis of Type 1 DM Factors that predispose to auto-immunity Genetic susceptibility Environmental factors Viral infections Measles, mumps, coxsackie virus B, rubella 20-Apr-19 Diabetes Mellitus

Pathogenesis of Type 1 DM Onset could be Early childhood (14 yrs) Juvenile diabetes mellitus May develop abruptly Over a period of few days or weeks Increase blood glucose concentration Increased fat utilization Depletion of protein 20-Apr-19 Diabetes Mellitus

Pathogenesis of Type 1 DM Blood glucose concentration ↑ to very high levels 300 to 1200 mg/dL 20-Apr-19 Diabetes Mellitus

Type I Diabetes Mellitus Consequences of elevated blood sugar levels Glucosuria Loss of glucose in urine When blood glucose > 180 mg/dL Cause osmotic diuresis Polyuria Na+ , K+ loss in urine 20-Apr-19 Diabetes Mellitus

Type I Diabetes Mellitus For every gm of glucose excreted 4.1 kCal is lost Hence there is ↑ in food intake Polyphagia Dehydration High blood glucose concentration in ECF ↑ osmotic pressure in ECF Cell dehydration 20-Apr-19 Diabetes Mellitus

Type I Diabetes Mellitus Osmotic diuresis Massive loss of fluid in urine Dehydration of ECF, ICF Excessive thirst Polydypsia Classic symptoms of diabetes Polyuria Polyphagia 20-Apr-19 Diabetes Mellitus

Type I Diabetes Mellitus Chronic high glucose concentration Cause tissue injury Damage to blood vessels leads to Inadequate blood supply to tissues Increased risks of heart attack, stroke Renal damage Retinal damage Ischaemia and gangrene of limbs 20-Apr-19 Diabetes Mellitus

Type I Diabetes Mellitus Hypertension Renal damage Artherosclerosis 20-Apr-19 Diabetes Mellitus

Type I Diabetes Mellitus Metabolic acidosis Due to ↑ utilization of fats ↑ fat catabolism ↑ formation of ketone bodies Acetoacetic acid, β-hydroxybutyric acid, acetone Patient develops severe metabolic acidosis Diabetic keto-acidosis (DKA) Diabetic coma 20-Apr-19 Diabetes Mellitus

Type I Diabetes Mellitus Protein metabolism in DM DM causes depletion of body protein Increase rate of protein breakdown Release large quantity of AA ↑ rate of AA catabolism to release energy AA converted into glucose Gluconeogenesis 20-Apr-19 Diabetes Mellitus

Type I Diabetes Mellitus Increased utilization of protein lead Negative protein balance Protein depletion Wasting Weight loss despite of Excess food intake 20-Apr-19 Diabetes Mellitus

Type 2 DM Adult onset DM NIDDM 20-Apr-19 Diabetes Mellitus

Type 2 Diabetes Mellitus Non-immune dependent diabetes mellitus Comprise a heterogeneous group Milder form of diabetes mellitus Occurs predominantly in adults Adult onset DM 20-Apr-19 Diabetes Mellitus

Type 2 DM More prevalent than type 1 DM Has much stronger genetic predisposition 35% of 1st degree relative have DM or IGT Interplay of genetic & environmental factors 20-Apr-19 Diabetes Mellitus

Type 2 DM Genetic factors Environmental factors More important than in type 1 DM However, autoimmune destruction of B-cells Not involved in type 2 DM Environmental factors Sedentary lifestyle Dietary habits 20-Apr-19 Diabetes Mellitus

Pathogenesis of Type 2 DM More complex Combination of Insulin resistance Relative insulin deficiency Type 2 DM associated Multiple metabolic abnormalities like type 2 DM High levels of ketoacids usually not present 20-Apr-19 Diabetes Mellitus

Pathogenesis of Type 2 DM Obesity, insulin resistance & metabolic syndrome Precede development of type 2 DM Insulin resistance appear to come first ↑ insulin secretion ↑ plasma insulin levels (hyperinsulinaemia) To maintain BG levels 20-Apr-19 Diabetes Mellitus

Pathogenesis of type 2 DM In susceptible individuals B-cells are unable to sustain increased demands for insulin There is ‘B-cell exhaustion’ BG rises to cause hyperglycaemia 20-Apr-19 Diabetes Mellitus

Pathogenesis of type 2 DM In many instances type 2 DM May be controlled (in early stages) by Dietary restrictions Weight reduction Drugs that increase insulin sensitivity Metformins Drugs that increase insulin release from B-cells Sulfonylureas 20-Apr-19 Diabetes Mellitus

Insulin Resistance Insulin resistance and impaired glucose tolerance (IGT) Develop gradually Begin with weight gain and obesity Insulin resistance in obesity due to ? Few receptors in obese individuals 20-Apr-19 Diabetes Mellitus

Insulin Resistance Resistance appear to be caused by Abnormality in the signaling pathway linking Receptor activation Metabolic effects of insulin Impaired signaling related Toxic effects of lipid accumulation 20-Apr-19 Diabetes Mellitus

Insulin Resistance Adipocytes (fat cells) Adipokines (adipose cytokines) Leptin, adiponectin, resistin Biologically active substances May contribute in the development of insulin resistance 20-Apr-19 Diabetes Mellitus

Insulin Resistance Other factors that can cause IR Genetic abnormalities Impair signaling pathway Polycystic Ovary syndrome (PCOS) ↑ secretion of ovarian androgens Insulin resistance Excess formation of glucocorticoids Cushing's syndrome ↓ sensitivity to metabolic effects of insulin 20-Apr-19 Diabetes Mellitus

Metabolic Syndrome Insulin resistance is part of cluster of metabolic derangements Metabolic syndrome Syndrome X Insulin resistance Feature of metabolic syndrome Hyperinsulinaemia 20-Apr-19 Diabetes Mellitus

Metabolic syndrome Features Obesity Fasting hyperglycaemia Central or visceral obesity Fasting hyperglycaemia Lipid abnormalities (dyslipidaemia) ↑ blood TG, ↓HDL cholesterol Hypertension 20-Apr-19 Diabetes Mellitus

Diagnosis Based on chemical tests of blood and urine Urinary glucose Estimation of quantity of glucose lost in urine Fasting blood glucose (FBG) FBG in the morning 80 to 90 mg/dL FBG > 110 mg/dL indicates diabetes 20-Apr-19 Diabetes Mellitus

Diagnosis Estimation of insulin levels Type 1 DM Insulin levels very low or undetected Type 2 DM High levels of insulin Oral glucose tolerance test (OGTT Unrestricted carbohydrate diet for 3 days Fasted overnight (at least 8 hrs) Rest before test Plasma glucose measured 2 hrs after 75 g glucose load 20-Apr-19 Diabetes Mellitus

Glucose Tolerance Test (GTT) Response to oral test doses of glucose 75 mg of glucose in 300 ml of water In a normal individual Resting fasting venous BG < 115mg/dL 20-Apr-19 Diabetes Mellitus

Glucose Tolerance Test (GTT) The 2 hrs values <140 mg/dL No values >200mg/dL Diabetes mellitus is present 2 hr value and one other value >200 mg/dL 20-Apr-19 Diabetes Mellitus

Glucose Tolerance Test (GTT) Impaired GTT Values are above limits of normal Below the diagnostic values for diabetes Impaired GTT is due to Reduced entry of glucose into cells ↓peripheral utilization 20-Apr-19 Diabetes Mellitus

Glucose Tolerance Test (GTT) Glucose uptake by Liver is also reduced GIT is unaffected Brain, RBCs normal Renal absorption of glucose Unaffected Increased glucose output from liver 20-Apr-19 Diabetes Mellitus