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Diabetes Mellitus

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)

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Diabetes Mellitus

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  1. Diabetes Mellitus

  2. 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

  3. Comparison between type 1 & type 2 DM

  4. 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

  5. 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

  6. 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

  7. 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 & chylomicronsresults in hypertriacylglyceridemia

  8. Treatment of type 1 DM • 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

  9. 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%)

  10. 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

  11. 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

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