By: Dr. Hala M. Al-Khalidi Faculty of Pharmacy King Abdulaziz University

 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 r eports  ADA - American Diabetes Association  ACE - American College of Endocrinology  AACE - American Association of Clinical Endocrinology  DCCT - Diabetes Control and Complications Trial (UK)

 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.

 Leading cause of blindness in adults age  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

 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

 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

Hyperglycemia

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

TYPE 1 DIABETESTYPE 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

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

 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

Genetic defects in insulin action  Type A insulin resistance  Leprechaunism  Rabson-Mendenhall syndrome  Lipoatrophic diabetes Exocrine pancreas  Fibrocalculous pancreatopathy  Pancreatitis  Trauma / pancreatectomy

 Neoplasia  Cystic fibrosis  Haemochromatosis Endocrinopathies Cushing's syndrome  Acromegaly  Phaeochromocytoma  Glucagonoma  Hyperthyroidism  Somatostatinoma  Infections  Congenital rubella  Cytomegalovirus  Drug- or chemical- induced

 Nicotinic acid  Glucocorticoids  Thyroid hormone  Alpha-adrenergic agonists  Beta-adrenergic agonists  Thiazides  Dilantin  Pentamidine  Vacor  Interferon-alpha therapy

 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

 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

 A metabolic state intermediate between normal glucose homeostasis and diabetes  Not interchangeable and represent different abnormalities of glucose regulation DIABETES MELLITUS IMPAIRED GLUCOSE TOLERANCE IMPAIRED FASTING GLUCOSE NORMALTEST mg/dl ≥ 126> 110 but< 126< 110 FASTING PLASMA GLUC. ≥200>140 but< 200< 140 2HR AFTER GLUC. LOAD ≥200 with symptoms RANDOM

 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

 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

 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.