DIABETES MELLITUS

1. DIABETES MELLITUS By: Dr. Hala M. Al-Khalidi Faculty of Pharmacy King Abdulaziz University 2008 - 1429

2. Overview • New diagnostic criteria and a new classification system, treatment for diabetes mellitus • Now many new data available, more etiological information has appeared • Updates many sources- Journals, WHO reports • ADA -American Diabetes Association • ACE -American College of Endocrinology • AACE -American Association of Clinical Endocrinology • DCCT -Diabetes Control and Complications Trial (UK)

3. Definition • Diabetes mellitus (DM) is a group of metabolic disorders • Characterized by hyperglycemia • Poor control due Insufficient insulin • associated with abnormalities in CHO, fat, & protein metabolism • Resulting in chronic complications; microvascular, macrovascular, and neuropathic disorders.

4. Definition • Leading cause of blindness in adults age 20- 74 • End-stage renal disease. • 82,000 lower extremity amputations annually. • Finally, a cardiovascular event is responsible for 75% of deaths in individuals with type 2 DM • Interventions to prevent disease in high-risk populations have been reported for type 1 and type 2

5. Epidemic Concerns • World wide epidemic of DM is alarming • CDC centers predict that incidence of DM will rise by 37.5% in the USA, developing countries 170% over the next 30 years • Type 2 DM is increasing in both adult & children • New methods of control need to be developed by health care providers

6. Epidemic Concerns • Cost ~ $132 billion 2002, indirect costs to disability and mortality • DM lead cause of blindness, end-stage renal disease • Annual ~82,000 lower extremity amputations • Finally, a cardiovascular event in 75% of deaths with type-2 DM

7. Pathogenesis Hyperglycemia

8. Pathogenesis of Type 2 DM ENVIRONMENT GENETIC PREDISPOSITION Obesity Multiple genetic defects PERIPHERAL TISSUE INSULIN RESISTANCE PRIMARY BETA-CELL DEFECT Inadequate glucose utilization Deranged insulin secretion HYPERGLYCEMIA Beta-cell exhaustion TYPE 2 DIABETES

9. CLASSIFICATION OF DIABETES TYPE 1 DIABETES TYPE 2 DIABETES • Autoimmune • 10% • Children & adolescents, or any age • Rapid/complete β-cell destruction with ketoacidosis • Insulin requiring for survival • C-peptide deficient • Obesity • 90% • β-cell dysfunction; may range from insulin resistance with relative insulin deficiency to a secretory defect with or without insulin resistance, or Genetic defects

10. Metabolic Syndrome/ (IR) Individuals Having at Least Three Components meet the Criteria for Diagnosis; The National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III Guidelines

11. Risk factors for Type 2-DM • FH (i.e., parents or siblings) • Obesity ( ≥20% over IBW, or [BMI] ≥25 kg/m2 • Physical inactivity • Race or ethnicity • Hypertension (≥140/90 mm Hg in adults) • HDL ≤35 mg/dl and/or a TG level ≥250 mg/dL • Hx. Gestational diabetes mellitus/ delivery baby weighing >9pd’s • Hx. vascular disease • polycystic ovary disease. • Age • Common women > men

12. Other Specific Types of Diabetes Genetic defects in insulin action • Type A insulin resistance • Leprechaunism • Rabson-Mendenhall syndrome • Lipoatrophic diabetes Exocrine pancreas • Fibrocalculous pancreatopathy • Pancreatitis • Trauma / pancreatectomy

13. Other Specific Types of Diabetes • Neoplasia • Cystic fibrosis • Haemochromatosis Endocrinopathies Cushing's syndrome • Acromegaly • Phaeochromocytoma • Glucagonoma • Hyperthyroidism • Somatostatinoma • Infections • Congenital rubella • Cytomegalovirus • Drug- or chemical-induced

14. Drug- or Chemical-induced Diabetes • Nicotinic acid • Glucocorticoids • Thyroid hormone • Alpha-adrenergic agonists • Beta-adrenergic agonists • Thiazides • Dilantin • Pentamidine • Vacor • Interferon-alpha therapy

15. GESTATIONAL HYPERGLYCAEMIA AND DIABETES • Gestational diabetes is CHO intolerance resulting in hyperglycaemia of variable severity with onset/ first recognition during pregnancy • Definition applies irrespective of whether or not insulin is used for treatment or the condition persists after pregnancy

16. Criteria for Diagnosis of DM • Symptoms of diabetes - Polyuria - Polydipsia - Unexplained weight loss - & Casual Plasma glucose conc. ≥ 200mg/dl (11.1mmol/L) OR • Fasting Plasma Glucose ≥ 126mg/dl (7.0mmol/L) OR • 2-hr postload glucose ≥ 200mg/dl (11.1mmol/L) OGTT*(only in pregnancy) *WHO 75g anhydrous glucose in water 8hr fasting

17. Impaired Glucose Tolerance (IGT) Impaired Fasting Glycaemia (IFG) • A metabolic state intermediate between normal glucose homeostasis and diabetes • Not interchangeable and represent different abnormalities of glucose regulation

18. Acute Complications • Hypoglycemia (Insulin Shock). • Diabetic ketoacidosis (DKA). • Hyperglycemic hyperosmolar non-ketotic coma (HHNK). 14

19. Chronic Complications Microvasculare • Diabetic Retinopathy. • Diabetic Nephropathy. • Diabetic Neuropathy. • Infection Macrovascularischmia • Periphry Diabetic gangrene • Heart CAD • Brain CVA or TIA’s 15

20. DESIRED OUTCOME Near-normal glycemia will reduce the risk for microvascular and macrovascular disease complications Ameliorate symptoms, to reduce mortality, and to improve quality of life. Current evidence targets aggressive control Avoid hypoglycemia and excess weight

21. TREATMENT

22. Key Aspect The pancrease in a non-diabetic’s secretes small amount Insulin (basal secretion). After meals a large amount of insulin is secreted (bouls secretion). The goal of insulin therapy is to mimic this pattern of 24-hr glycaemic coverage. Type-1 DM basal-bolus insulin therapy or pump therapy is successful. Basal-bolus therapy in Type-2 DM is increasing. Multiple oral agents, or oral agents with insulin to obtain goals.