Diabetes Mellitus : Definition, Pathophysiology, Diagnosis, and Treatment
Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism. It results from defects in insulin secretion, insulin sensitivity, or both. Chronic microvascular, macrovascular, and neuropathic complications may ensue.
Pathophysiology of Diabetes Mellitus :
- Type 1 DM accounts for up to 10% of all diabetes cases. It generally develops in childhood or early adulthood and results from immune-mediated destruction of pancreatic Î² cells, resulting in an absolute deficiency of insulin. There is a long preclinical period (up to 9 to 13 years) marked by the presence of immune markers when Î²-cell destruction is thought to occur. Hyperglycemia occurs when 80% to 90% of Î² cells are destroyed. There is a transient remission (â€œhoneymoonâ€ phase) followed by established disease with associated risks for complications and death. The factors that initiate the autoimmune process are unknown, but the process is mediated by macrophages and T lymphocytes with circulating autoantibodies to various Î²-cell antigens (e.g., islet cell antibody, insulin antibodies).
- Type 2 DM accounts for as many as 90% of DM cases and is usually characterized by the presence of both insulin resistance and relative insulin deficiency. Insulin resistance is manifested by increased lipolysis and free fatty acid production, increased hepatic glucose production, and decreased skeletal muscle uptake of glucose. Î²-Cell dysfunction is progressive and contributes to worsening blood glucose control over time. Type 2 DM occurs when a diabetogenic lifestyle (excessive calories, inadequate exercise, and obesity) is superimposed upon a susceptible genotype.
- Uncommon causes of diabetes (1% to 2% of cases) include endocrine disorders (e.g., acromegaly, Cushing’s syndrome), gestational diabetes mellitus (GDM), diseases of the exocrine pancreas (e.g., pancreatitis), and medications (e.g., glucocorticoids, pentamidine, niacin, and Î±-interferon).
- Impaired fasting glucose and impaired glucose tolerance are terms used to describe patients whose plasma glucose levels are higher than normal but not diagnostic of DM (see DIAGNOSIS). These disorders are risk factors for developing DM and cardiovascular disease and are associated with the insulin-resistance syndrome.
- Microvascular complications include retinopathy, neuropathy, and nephropathy. Macrovascular complications include coronary heart disease, stroke, and peripheral vascular disease.
Diagnosis of Diabetes Mellitus :
- The recommended screening test is a fasting plasma glucose (FPG). Normal FPG is less than 100 mg/dL.
- Impaired fasting glucose (IFG) is defined as FPG of at least 110 mg/dL but less than 126 mg/dL.
- Impaired glucose tolerance (IGT) is diagnosed when the 2-hour postload sample of the oral glucose tolerance test (OGTT) is 140 mg/dL or greater but less than 200 mg/dL.
- Pregnant women should undergo risk assessment for GDM at their first prenatal visit and proceed with glucose testing if at high risk (e.g., marked obesity, personal history of GDM, glycosuria, or a strong family history of DM).
Treatment of Diabetes Mellitus :
- Medical nutrition therapy is recommended for all patients. For individuals with type 1 DM, the focus is on regulating insulin administration with a balanced diet to achieve and maintain a healthy body weight. Most patients require a meal plan that is moderate in carbohydrates and low in saturated fat, with a focus on balanced meals. In addition, patients with type 2 DM often require caloric restriction to promote weight loss. Bedtime and between-meal snacks are not usually needed if pharmacologic management is appropriate.
- Regular insulin has a relatively slow onset of action when given subcutaneously, requiring injection 30 minutes prior to meals to achieve optimal postprandial glucose control and to prevent delayed postmeal hypoglycemia.
- Sulfonylureas exert a hypoglycemic action by stimulating pancreatic secretion of insulin. All sulfonylureas are equally effective in lowering blood glucose when administered in equipotent doses. On average, the HbA1c will fall by 1.5% to 2% with FPG reductions of 60 to 70 mg/dL.
- Metformin is the only biguanide available in the United States. It enhances insulin sensitivity of both hepatic and peripheral (muscle) tissues. This allows for increased uptake of glucose into these insulin-sensitive tissues. Metformin consistently reduces HbA1c levels by 1.5% to 2%, FPG levels by 60 to 80mg/dL, and retains the ability to reduce FPG levels when they are very high (greater than 300 mg/dL). It reduces plasma triglycerides and low-density lipoprotein (LDL) cholesterol by 8% to 15% and modestly increases high-density lipoprotein (HDL) cholesterol (2%). It does not induce hypoglycemia when used alone.