DIABETES MELLITUS By Dr Hala M AlKhalidi Faculty

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

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)

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.

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

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

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

Pathogenesis Hyperglycemia

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

CLASSIFICATION OF DIABETES TYPE 1 DIABETES Autoimmune 10% Children & adolescents, or any age Rapid/complete β-cell destruction with ketoacidosis Insulin requiring for survival C-peptide deficient TYPE 2 DIABETES 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

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

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

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

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

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

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

Criteria for Diagnosis of DM Symptoms of diabetes - Polyuria - Polydipsia - Unexplained weight loss - & Casual Plasma glucose conc. ≥ 200 mg/dl (11. 1 mmol/L) OR Fasting Plasma Glucose ≥ 126 mg/dl (7. 0 mmol/L) 8 hr fasting OR 2 -hr postload glucose ≥ 200 mg/dl (11. 1 mmol/L) OGTT*(only in pregnancy) *WHO 75 g anhydrous glucose in

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 TEST mg/dl NORMAL FASTING PLASMA GLUC. < 110 2 HR AFTER GLUC. LOAD < 140 RANDOM IMPAIRED FASTING GLUCOSE IMPAIRED GLUCOSE TOLERANCE > 110 but< 126 DIABETES MELLITUS ≥ 126 >140 but< 200 ≥ 200 with symptoms

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

Microvasculare Diabetic Retinopathy. Diabetic Nephropathy. Diabetic Neuropathy. Infection Macrovascular ischmia Periphry Diabetic gangrene Heart CAD Brain CVA or TIA’s 15

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

TREATMENT

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.