Chapter 36 Drugs Used to Treat Diabetes Mellitus Diabetes Mellitus - group of diseases characterized by: o hyperglycemia (fasting blood

glucose > 100 mg/dL) o abnormalities fat carbohydrate protein metabolism leads to: 1. microvascular 2. macrovascular 3. neuropathic complications o impairment of insulin secretion and o defects in insulin action > hyperglycemia o Predisposing Factors 1. Relatives with diabetes (2.5 times greater) 2. Obese 3. Older o Classifies diabetes by the underlying Pathology causing hyperglycemia 1. NDDG National Diabetes Data Group of the national institute of the health 2. World Health Organization - Type 1 Diabetes Mellitus (Insulin-dependent diabetes mellitus) o Immune mediated o idipathic 1. Caused by an autoimmune destruction of the beta cells in the pancreas 2. Juveniles 3. can be symptomatic at any age 4. onset has rapid progression of symptoms 1. polydipsia 2. polyuria 3. polyphagia 5. increased frequency of infections

6. loss of weight and strength 7. irritability 8. ketoacidosis o require administration of exogenous insulin o easily influenced by inconsistent patterns of physical activity and dietary irregularities o honeymoon period little or no exogenous insulin Type 2 DM (Non insulin dependent DM NIDDM) o Decrease in : 1. Beta cell activity 2. Insulin resistance o Increase in glucose production by the liver o Beta cells fail and exogenous insulin may bre required o Metabolic syndrome 1. insulin resistance syndrome 2. syndrome x o onset is more insidious than type 1 diabetes o pancreas 1. still maintains some capability to produce and secrete insulin Third Subclass o Genetic defects of beta-cell function o Genetic defects in insulin action o Disease of the exocrine pancreas o Endocrinopathies o Drug- or chemical- induced o Infections o Uncommon forms of immune mediated diabetes o Diseases that have a diabetic component: 1. pheochromocytoa 2. acromegaly 3. cushings syndrome GDM Gestational Diabetes o Does not include diabetic women who become pregnant o Reclassified 6 weeks after delivery: 1. diabetes mellitus 2. impaired fasting glucose

3. impaired glucose tolerance 4. normoglycemia Impaired glucose tolerance (IGT) or Impaired fasting glucose (IFG) o Patients euglycemic o Hyperglycemia when challenged with oral glucose tolerance test o Prediabetes 1. glucose tolerance returns to normal or 2. persists in the intermediate range for years 3. intermediate stage between normal and diabetes

Periodontal disease with loss of teeth Neuropathies o First observed as numbness o Tingling of extremities (paresthesoa) o Loss of sensation o Orthostatic hypotension o Impotence o Difficulty in controlling urination (neurogenic bladder) Nonhealing ulcers of lower extremities >chronic vascular disease

Categories of Fasting Plasma Glucose - < 100 mg/dl = normal - 126 > 100 = mg/dl = IFG - 2 hour plasma glucose at 140 or greater but less than 199 mg/dl = IGT Complications of Diabetes Mellitus - Microvascular o Destruction of capillaries in eyes, kidneys, peripheral tissues - Macrovascular o Atherosclerosis of middle to large arteries such as those in the heart nad brain Hypertension Cardiocascular disease (atherosclerosis) > MI and stroke Retinopathy > blindness Renal disease > End stage renal disease (ESRD) and need for dialysis Peripheral arterial disease > nonhealing ulcers, infections ,lower extremity amputations Neuropathies with sexual dysfunction, bladder incontinence, paresthesias, gastroparesis

Treatment of DM Purpose of treatment - prevent ketoacidosis - sumptoms resulting from hyperglycemia Determinants to success - balanced diet - Insulin or oral antidiabetic therapy - Routine exercise - Good hygiene Type 1 - always require exogenous insulin - dietary control - pancreas lost the capacity to produce and secrete insulin - aims of dietary control o prevention of excessive postprandial hyperglycemia o prevention of hypoglycemia (blood glucose less than 60 mg/dL) in patients treated with antidiabetic agents or insulin o achievement and maintenance of an ideal body weight o reduction of lipids and cholesterol o return to normal weight is often accompanied by reduction in hyperglycemia

o diet adjusted to reduce elevated cholesterol and triglyceride levels in an attempt to retard the progression of atherosclerosis o diet should be planned acoording to American Diabetes Association o relation to patients food preferences, economic status, occupation and physical activit o Treated with Comorbid diseases Smoking cessation Treatment of dyslipidemia Bp control Antiplatelet therapy Influenza Pneumococcal vaccination o American Association of Clinical Endocrinologists ACCE Developed System of Intensive Diabetes SelfManagement Concepts of care Responsibilities of patient and physician Appropriate intervals for laboratory testing and follow-up Key components o Patient education o Understanding o Direct participation by the patient Intensive therapy o Program o Includes self monitoring of blood glucose four or more times daily o