DIABETES MELLITUS

Diabetes mellitus (see Chapter 27 ) is the most common endocrine disease and is characterized by long-term complications involving the eyes, kidneys, nerves, and

TABLE 46-16 -- Classification of diabetes

Class	Causes and Characteristics
Primary	Insulin-dependent diabetes mellitus (IDDM, type 1: without insulin the patient will develop ketoacidosis and die)
	Non-insulin-dependent diabetes mellitus (NIDDM, type 2: the patient will not necessarily develop ketoacidosis without insulin)
	Nonobese NIDDM (type 1 IDDM in evolution?)
	Obese NIDDM
	Maturity-onset diabetes of the young
Secondary	Pancreatic disease, hormonal abnormalities, drug or chemical induced, insulin receptor abnormalities, genetic syndrome, other
Adapted from Foster DW: Diabetes mellitus. In Isselbacher KJ, Braunwald E, Wilson JD, et al (eds): Harrison's Principles of Internal Medicine, 13th ed. New York, McGraw-Hill, 1995, p 1980.

blood vessels. Diabetes is a major risk factor for heart disease, stroke, kidney disease, blindness, and nontraumatic amputations. The cause of diabetic complications is multifactorial, including glycosylation of proteins and glucose reduction to sorbitol, which functions as a tissue toxin. This pathophysiologic process is associated with a decrease in myoinositol content and metabolism and with a decrease in sodium-potassium-adenosine triphosphatase activity. Hyperglycemia has been recognized as a major factor in the development of complications associated with diabetes. The patient population is not homogeneous, and several diabetic syndromes have been delineated. There are almost 8 million diagnosed diabetics in the United States and another 8 million who are unaware of their diabetes. These numbers approach 10% of the overall population in this country^[69] ( Table 46-16 ).

Pathology

Hyperglycemia of diabetes is the consequence of relative or absolute deficiency of insulin and a relative or absolute excess of glucagon. In type 1 diabetes, there is an absolute deficiency in insulin production, and without insulin, patients die. These patients eventually become dependent on exogenous insulin to prevent lipolysis and eventually ketoacidosis. The onset of type 1 diabetes usually occurs by adolescence, although it may occur at any age and is thought to result from autoimmune destruction of islet cells in the pancreas.

Type 2 diabetes is characterized by a relative deficiency in insulin, typically caused by insulin resistance. The onset of this type of diabetes is usually in adulthood, although evidence suggests that the mean age of onset of type 2 diabetes is decreasing.^[70] Type 2 diabetes almost certainly has a heterogeneous group of etiologic factors. However, commonly associated findings in type 2 diabetes are obesity, abnormal insulin levels, and a strong genetic component ^[71] ( Table 46-17 ).

A third type of diabetes mellitus is gestational diabetes. Gestational diabetes is defined as any degree of glucose intolerance with the onset first recognized during pregnancy. Gestational diabetes complicates approximately 4% of all pregnancies in the United States, resulting in about 135,000 cases annually.^[72] Clinical recognition of gestational diabetes is important because therapy and

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During the past decade, a new disorder known as syndrome X has been described. As the name implies, it is a syndrome rather than a specific disease state. The hallmark of syndrome X is insulin resistance with hyperinsulinemia. The underlying pathology is similar to type 2 diabetes; however, syndrome X patients do not exhibit hyperglycemia. Syndrome X patients may never develop type 2 diabetes. The clinical significance of this condition stems from its association with multiple metabolic abnormalities, including low levels of high-density lipoprotein (HDL), increased blood pressure, and increased plasminogen activator inhibitor-1 levels. All these abnormalities have definite or possible association with coronary artery disease. Whether syndrome X and type 2 diabetes are on a spectrum of disease with insulin resistance as a common denominator or are totally separate entities has yet to be clarified.