Diabetes Mellitus

Overview A heterogeneous group of syndromes characterized by an elevation of fasting blood glucose caused by absolute or relative deficiency of insulin Two types of DM: Type 1 (insulin-dependent DM) Type 2 (noninsulin dependent DM) Prevalence of type 2 is increasing as: Aging (increase in rate of life-age of population) Increasing prevalence of obesity

Comparison between type 1 & type 2 DM

Type 1 Diabetes Mellitus about 10% of diabetics (in USA) Onset: usually during childhood Caused by absolute deficiency of insulin caused by autoimmune attack of b-cells of the pancreas Destruction is enhanced by environmental factors as viral infection & a genetic element (that allows b-cells to be recognized as nonself) (in identical twins if one sibling has type 1 DM, the other twin has only 30-50% chance of developing DM) Rapid symptoms appear when 80-90% of the b-cells have been destroyed Commonly complicated by DKA treated only by insulin

Diagnosis of type 1 DM Clinically: Age: during childhood or puberty (< 20 years of age) Abrupt appearance of : polyuria (frequent urination) polydepsia (excessive thirst) polyphagia (excessive hunger) fatigue weight loss complicated by ketoacidosis (common, may be the cause of diagnosis) Laboratory diagnosis: fasting blood glucose: > or equal 126 mg/dl 100 – 125 mg/dl impaired fasting blood glucose testing of circulating islet-cell antibodies

Metabolic changes of type 1 DM 1- Hyperglycemia decreased glucose uptake by muscles & adipose tissues (by GLUT-4) & increased hepatic gluconeogenesis 2- Ketoacidosis (in untreated or uncontrolled cases) in 25 – 40% of newly diagnosed type 1 DM in stress states demanding more insulin (as during infection, illness or during surgery) no comply with therapy (intake of meals with no insulin medication) Biochemical causes of diabetic ketoacidosis (DKA) no insulin ------ increased mobilization of FFA from adipose tissues in the liver, FFA --- b-oxidation ----- acetyl CoA ----- KETONE BODIES

Metabolic changes of type 1 DM (cont.) 3- Hypertriacylglyceridemia Released fatty acids from adipose tissues are converted to triacylglycerol Triacylglycerol is secreted from the liver in VLDL Chylomicrons accumulates (low lipoprotein lipase in DM) Increased VLDL & chylomicrons results in hypertriacylglyceridemia

Treatment of type 1 DM Standard treatment: Exogenous insulin by sc injection to control hyperglycemia & ketoacidosis Standard treatment: by one or two injections of insulin / day AIM: Mean blood glucose level 225-275 mg/dl (normal: 110 mg/dl) HbA1c level: 8-9 % of total Hb (normal: 6% of total HB) HbA1c: is proportional to average blood concentration over the previous several months So, it provides a measure of how well treatment normalized blood glucose in diabetic over several months

Treatment of type 1 DM (cont.) Intensive treatment more closely normalize blood glucose to prevent complications of existence of hyperglycemia for a long period by more frequent monitoring & subsequent injection of insulin (3 or more times / day) AIM: Mean blood glucose levels of 150 mg/dl HbA1c : approximately 7% of total Hb Advantage: reduction in chances of occurrence of complications of DM: retinopathy, nephropathy & neuropathy (about 60%)

Hypoglycemia in type 1 DM is a complication of insulin treatment (in more than 90% of patients) Common with intensive treatment regimens Diabetics cannot depend on glucagon or epinephrine to avoid hypoglycemia ?? No glucagon (early in the disease) No epinephrine ( with progression of the disease diabetic autonomic neuropathy with inability to secrete epinephrine) So, patients with long-standing type 1 DM are particularly vulnerable to hypoglycemia

Contraindications of tight control Children: risk of episodes of hypoglycemia may affect the brain development Elderly people: as hypoglycemia can cause strokes & heart attacks in older people