Diabetes Mellitus

DIABETES MELLITUS

Diabetes Mellitus-

Is a multisystem disease related to abnormal insulin production, impaired insulin utilization, or both. Diabetes Mellitus is a serious health problem throughout the world. It is the 5th leading cause of death in the U.S. It is the leading cause of heart disease, stroke, adult blindness, and nontraumatic lower limb amputations.

Etiology and Pathophysiology

Current theories link the cause of diabetes, singly or in combination, to genetic, autoimmune, viral, and environmental factors (obesity, stress). Regardless of its cause, diabetes is primarily a disorder of glucose metabolism related to absent or insufficient insulin supplies and/or poor utilization of the insulin that is available. The two most common types of diabetes are classified as type I or type II diabetes mellitus. Gestational diabetes and secondary diabetes are other classifications of diabetes commonly seen in clinical practice

Normal Insulin Metabolism

Insulin is a hormone produced by the B cells in the islets of Langerhans of the pancreas. Under normal conditions, insulin is continuously released into the bloodstream in small pulsatile increments (a basal rate), with increased release (bolus) when food is ingested. The activity of released insulin lowers blood glucose and facilitates a stable, normal glucose range of approximately 70 to 120 mg/dl. The average amount of insulin secreted daily by and adult is approx. 40 to 50 U, or 0.6 U/kg of body weight.

Other hormones (glucagons, epinephrine, growth hormone, and cortisol) work to oppose the effects of insulin and are often referred to as counterregulatory hormones. These hormones work to increase blood glucose levels by stimulating glucose production and output by the liver and by decreasing the movement of glucose into the cells. Insulin and the these counterregulatory hormones provide a sustained but regulated release of glucose for energy during food intake and periods of fasting and usually maintain blood glucose levels within the normal range. An abnormal production of any or all of these hormones may be present in diabetes.

Insulin is released from the pancreatic B cells as its precursor, proinsulin, and is then routed through the liver. Proinsulin is composed of two polypeptide chains, chain A and chain B, which are linked by the C-peptide chain. The presence of C peptide in serum and urine is a useful indicator of B cell function.

Insulin promotes glucose transport from the bloodstream across the cell membrane to the cytoplasm of the cell. The rise in plasma insulin after a meal stimulates storage of glucose as glycogen in liver and muscle, inhibits gluconeogenesis, enhances fat deposition in adipose tissue, and increases protein synthesis. The fall in insulin level during normal overnight fasting facilitates the release of stored glucose from the liver, protein form muscle, and fat from adipose tissue. For this reason insulin is known as the anabolic or storage hormone.

Skeletal muscle and adipose tissue have specific receptors for insulin and are considered insulin-dependent tissues. Other tissues (brain, liver, blood cells) do not directly depend on insulin for glucose transport but require an adequate glucose supply for normal function. Although liver cells are not considered insulin-dependent tissue, insulin receptor sites on the liver facilitate the hepatic uptake of glucose and its conversion to glycogen.

Type I Diabetes Mellitus

Formally known as "juvenile onset" or "insulin dependent" diabetes, type I diabetes mellitus most often occur in people who are under 30 years of age, with a peak onset between ages 11 and 13. The rate of type I diabetes is 1.5 to 2 times higher in whites than nonwhites, with a similar incidence among males and females. Typically, it is seen in people with a lean body type, although it can occur in people who are overweight.

Etiology and Pathophysiology

Type I diabetes results from progressive destruction of pancreatic B cells due to an autoimmune process in susceptible individuals. Autoantibodies to the islet cells cause a reduction of 80% to 90% of normal B cell function before hyperglycemia and other manifestations occur. A genetic predisposition and exposure to a virus are factors that may contribute to the pathogenesis of type I diabetes.

Predisposition to type I diabetes is believed to be related to human leukocyte antigens (HLAs). When an individual with certain HLA types is exposed to viral infections, the B cells of the pancreas are destroyed, either directly or through an autoimmune process. The HLA types associated with an increased risk of type I diabetes include HLA-DR3 and HLA-DR4.

Onset of Disease

Type I diabetes is associated with a long preclinical period. The islet cell autoantibodies responsible for B cell destruction are present for months to years before the onset of symptoms. Manifestations of type I diabetes develop when the person's pancreas can no longer produce insulin. Once this occurs, the onset of symptoms is usually rapid, and the patient comes to the emergency department with impending or actual ketoacidosis. The cpatient usually has a history of recent and sudden weight loss, as well as the classic symptoms of polydipsia (excessive thirst), polyuria (frequent urination), and polyphagia (excessive hunger).

The individual with type I diabetes requires a supply of insulin from an outside source (exogenous insulin), such as an injection, in order to sustain life. Without insulin, the patient will develop diabetic ketoacidosis (DKA), a life-threatening condition resulting in metabolic acidosis. During this time, the patient requires very little injected insulin because B cell mass remains sufficient for glucose control as the progressive destruction continues to occur. Eventually, as more B cells are destroyed, blood glucose levels increase, more insulin is needed, and the honeymoon period ends. This usually lasts 3 to 12 months, after which the person will require insulin on a permanent basis.

Type II Diabetes Mellitus

Type II diabetes mellitus is, by far, the most prevalent type of diabetes, accounting for over 90% of patients with diabetes. Type II usually occurs in people over 40 years of age, and 80% to 90% of patients are overweight at the time of diagnosis. It has a tendency to run in families and probably has a genetic basis. Prevalence of this type of diabetes