Diabetes mellitus (diabetes) is not one disease but rather is a heterogeneous group of multifactorial, primarily polygenic syndromes characterized by an elevated fasting blood glucose (FBG) caused by a relative or absolute deficiency in insulin. Over 29 million people in the United States (~9% of the population) have diabetes. Of this number, ~8 million are as yet undiagnosed. Diabetes is the leading cause of adult blindness and amputation and a major cause of renal failure, nerve damage, heart attacks, and strokes. Most cases of diabetes mellitus can be separated into two groups (Fig. 25.1), type 1 ([T1D] formerly called insulin-dependent diabetes mellitus) and type 2 ([T2D] formerly called non– insulin-dependent diabetes mellitus). The incidence and prevalence of T2D is increasing because of the aging of the U.S. population and the increasing prevalence of obesity and sedentary lifestyles (see p. 349). The increase in children with T2D is particularly disturbing.
II. TYPE 1
T1D constitutes <10% of the ~21 million known cases of diabetes in the United States. The disease is characterized by an absolute deficiency of insulin caused by an autoimmune attack on the islet β cells of the pancreas. In T1D, the islets of Langerhans become infiltrated with activated T lymphocytes, leading to a condition called insulitis. Over a period of years, this autoimmune attack on the β cells leads to gradual depletion of the β-cell population (Fig. 25.2). However, symptoms appear abruptly when 80%–90% of the β cells have been destroyed. At this point, the pancreas fails to respond adequately to ingestion of glucose, and insulin therapy is required to restore metabolic control and prevent life-threatening ketoacidosis. β-Cell destruction requires both a stimulus from the environment (such as a viral infection) and a genetic determinant that causes the β cells to be mistakenly identified as “nonself.” [Note: Among monozygotic (identical) twins, if one sibling develops T1D, the other twin has only a 30%– 50% chance of developing the disease. This contrasts with T2D (see p. 341), in which the genetic influence is stronger and, in virtually all monozygotic twinships, the disease eventually develops in both individuals.]
A. Diagnosis
The onset of T1D is typically during childhood or puberty, and symptoms develop suddenly. Individuals with T1D can usually be recognized by the abrupt appearance of polyuria (frequent urination), polydipsia (excessive thirst), and polyphagia (excessive hunger), often triggered by physiologic stress such as an infection. These symptoms are usually accompanied by fatigue and weight loss. The diagnosis is confirmed by a FBG ≥126 mg/dl (normal is 70–99). [Note: Fasting is defined as no caloric intake for at least 8 hours.] A FBG of 100–125 mg/dl is categorized as an impaired FBG. Individuals with impaired FBG are considered prediabetic and are at increased risk for developing T2D. Diagnosis can also be made on the basis of a nonfasting (random) blood glucose level >200 mg/dl or a glycated hemoglobin (see p. 340) concentration ≥6.5 mg/dl (normal is <5.7) in an individual with symptoms of hyperglycemia. [Note: The oral glucose tolerance test, in which blood glucose is measured 2 hours after ingestion of a solution containing 75 g of glucose, also is used but is less convenient. It is most typically used to screen pregnant women for gestational diabetes (see p. 342).]