Sean F. Dinneen and Robert A. Rizza

Definition

The term diabetes mellitus does not represent a single disease entity but rather a set of disease states that share certain characteristics. Foremost among these is the presence of elevated plasma glucose levels. As is discussed below, the presence of hyperglycemia in a patient is used both to diagnose diabetes and to guide management decisions, which are directed largely toward avoiding hyperglycemia. The hyperglycemia itself results from a combination of defects in insulin secretion, insulin action, or both.¹ An important characteristic of the various disease states that are labeled as diabetes is the development of end-organ damage in vital organs of the body, including the retina, the renal glomerulus, and peripheral nerves. Damage results, at least in part, from the long-term effects of hyperglycemia and are mediated through glycation of tissue proteins, increased activity of the polyol pathway, or other, as yet unrecognized, mechanisms.² Individual patients vary in their predisposition to develop these so-called microvascular complications. Because of this and because of the length of time they take to develop (frequently decades), the complications of diabetes cannot be used to classify or diagnose the disease. People with diabetes are at considerably greater risk for developing atherosclerotic disease affecting the coronary, cerebrovascular, peripheral arterial, or other parts of the circulation. A cause-and-effect relationship between chronic hyperglycemia and these so-called macrovascular complications of diabetes has not been as clearly established, although evidence linking the two is accumulating.³ Any definition of diabetes that refers only to carbohydrate metabolism is incomplete. Oskar Minkowski is reputed to have first made the association between the insulin-deficient pancreatectomized state of his laboratory dogs and the sweet taste of their urine. It has been suggested that if Minkowski had lacked a sense of taste but possessed a keen sense of smell, he might have smelled the ketones on the breath of his animals and thereby directed diabetes research toward the study of fat metabolism.⁴ Disordered fat and protein metabolism must be included in a complete definition of the disease, although an emphasis on the pathogenesis of hyperglycemia continues to this day. To define a disease purely in biochemical terms is to diminish the component of the disease that leads to much physical, mental, and psychosocial distress for the many millions of people around the world who live with it every day. Chronic rheumatic diseases such as rheumatoid arthritis are not associated with any biochemical hallmark, and their definition is based largely on patient-derived symptoms and signs. Therefore, it is important to try to include the patient’s perspective in any definition of the chronic disease referred to as diabetes.

Classification

Before 1979, a classification system for diabetes was not well established, and many different terms were used to describe essentially the same clinical entity. Following publication that year of the report of the National Diabetes Data Group (NDDG),⁵ some order was brought to bear in this area. The recommendations of the NDDG were subsequently endorsed by the World Health Organization (WHO) in a publication in 1980, and minor modifications were later made in a document published in 1985.⁶ This classification in large part was based on pharmacologic treatment of the disease. Insulin-dependent diabetes mellitus (IDDM) and non–insulin-dependent diabetes mellitus (NIDDM) were the two major forms of diabetes that had been identified. The term insulin-dependent diabetes mellitus was used to describe patients who typically were lean at presentation, were prone to ketosis, and required insulin for survival. The term non–insulin-dependent diabetes mellitus was used to describe patients who typically were overweight or obese at presentation, were not prone to ketosis, and did not require insulin for survival. The NDDG also had categories for gestational diabetes, malnutrition-related diabetes mellitus (MRDM), and a category labeled “other types,” which included certain forms of diabetes for which a cause had been suggested at that time. As the terms IDDM and NIDDM became widely used during the 1980s and 1990s, several problems became apparent. The main problem arose from the fact that many patients with NIDDM ended up at some point in the course of their disease being treated with insulin and being misclassified as IDDM or having the rather confusing term insulin-requiring NIDDM applied to them. In addition, as more information became available on the causes of the various forms of diabetes, it became apparent that a classification based on therapy was not always consistent with new insights into the pathogenesis of the various forms of diabetes. For this reason, the American Diabetes Association (ADA) convened an expert panel in 1995 to address the issue of classification. This panel published its recommendations in 1997,⁷ and these were subsequently endorsed by a WHO consultation group in a 1998 report.⁸ The main thrust of this proposal was to move away from a classification based on therapy and toward one based on pathogenesis. Four major categories were proposed: type 1 diabetes, type 2 diabetes, other specific types of diabetes (including categories for which a cause has been established), and gestational diabetes. The details of this system, which are outlined in Table 13-1, are discussed in the following sections.