3. Diabetes and its complication 22.pptx

DM

1. Diabetes mellitus Medical Biochemistry and Molecular Biology Department Faculty of Medicine – Menoufia University

2. ILOs Interpret symptoms, signs of diabetes mellitus. Interpret biochemical and laboratory findings of some metabolic disorders with special emphasis on diabetes mellitus.

3. Diabetes Mellitus Diabetes mellitus (DM) is as a state of diminished insulin action due to its decreased availability (secretion) or effectiveness. It is a chronic condition characterized by raised blood glucose levels (Hyperglycemia).

4. Classifications of DM Primary diabetes mellitus: It is divided into types I and II. Type I (Insulin-dependent DM), (juvenile- early onset DM): There is defective insulin secretion. It usually presents in young (under 30 years) non-obese subjects. The serum of these patients contains islet cell antibodies that react with the beta cell of the pancreas. Insulin is required for treatment.

5. Type II (Non-insulin dependent DM), (adult- late onset DM): This condition usually presents in older (over 40 years) patients, who are obese. Insulin levels may be normal, decreased or increased and the metabolic defect may be defective insulin secretion or insulin resistance.

6. Insulin resistance (IR) Insulin resistance (IR) is a pathological condition in which cells either fail to respond normally to insulin hormone or down regulate their insulin receptors in response to hyperinsulinemia . It is a condition that is closely associated with obesity especially central obesity. Obesity predisposes to insulin resistance due to the following causes : Obesity causes a state of low-grade chronic inflammation with increased production of pro inflammatory cytokines and glucocorticoids. Visceral adipose tissue is not simply an energy storage organ, but also a secretory organ. Adipocytes produce regulatory substances as leptin and adiponectin . Hyperlipidemia with elevated free fatty acid levels.

7. These factors collectively interfere with insulin signaling pathways and also lead to chronic hyperinsulinemia with internalization of insulin receptors predisposing to type II DM.

8. Secondary diabetes This occurs as a consequence of other diseases or drugs. Causes include: Endocrine disorders: Acromegaly, Cushing`s syndrome, pheochromocytoma and thyrotoxicosis. Insulin receptor abnormalities: as in autoimmune insulin receptor antibodies. Pancreatic diseases: as in chronic pancreatitis. Drugs: as estrogen-containing oral contraceptives and thiazide diuretics.

9. Symptoms of DM Polyuria (Glucose acts as osmotic diuretic) Polydipsia (exaggerated water intake and thirst from increased plasma osmolarity and also dehydration caused by polyuria) Polyphagia (hunger since cell can’t utilize glucose and glucose can’t enter cells of satiety center which is insulin dependent) Weight loss (Lipolysis and protein breakdown to restore energy sources) Malaise and fatigue (Decrease body energy) Glucosuria (Renal threshold for glucose: 180 mg/ dL )

10. Diagnosis of DM Symptoms of DM. Diabetic Profile: Group of tests used to diagnose diabetes mellitus and to measure response to treatment. They include: Colorimetric determination of serum / plasma glucose level: Fasting blood glucose, post prandial, random blood glucose & oral glucose tolerance test. Glycated hemoglobin (HbA1c): It is derived from the reaction of hemoglobin with glucose. Its value reflects the average level of blood glucose over the previous 1-2 months (life span of erythrocytes). Measurement of HbA1c therefore provides valuable information of management of diabetes mellitus. Normal value: 4.5%- 5.7%.

11. C- peptide: It differentiates between type I and type II diabetes mellitus. A person with type I diabetes has a low level of insulin and C peptide, while a person with type II diabetes has a normal level of C peptide. Insulin levels and HOMA-IR for insulin resistance. Islet cell antibodies.

12. Metabolic changes in DM Hyperglycemia Hypertriglyceridemia with increased levels of plasma chylomicrons and VLDL due to decreased activity of lipoprotein lipase enzyme (LPL) in response to defective insulin action. Hyperlipidemia with elevated plasma free fatty acid levels due to increased lipolysis (defective insulin action as insulin inhibits hormone sensitive lipase). Ketoacidosis

13. Complications of DM Acute complications: Diabetic coma is a state of unconsciousness due to diabetes. It is a life threating complication. Chronic complications: These occur with long standing diabetes due to direct glucose-mediated endothelial damage caused by formation of advanced glycation end-products ( AGES ) and increased expression of AGEs receptor and their activating ligands.

14. Chronic complications They include: Microvascular complications: a. Diabetic Retinopathy b. Diabetic Nephropathy c. Diabetic Neuropathy They occur predominantly in tissues where glucose uptake is independent of insulin activity (kidney, retina, neurons and vascular endothelium) because these tissues are exposed to glucose levels that correlate very closely with blood glucose levels.

15. Macrovascular complications: a. Coronary heart disease (CHD) and myocardial infarction (MI). b. Cerebral ischemia and stroke. c. Diabetic foot and gangrene. Chronic hyperglycemia induces reactive oxygen species (ROS) production with inflammatory changes in vascular endothelium. The increased production of inflammatory mediators leads to monocytes adhesion, extravasation and formation of foam cells contributing to the development of atherosclerosis.