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Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the phenotype of hyperglycemia. Several distinct types of DM are caused by a complex interaction of genetics and environmental factors. Depending on the etiology of the DM, factors contributing to hyperglycemia include reduced insulin secretion, decreased glucose utilization, and increased glucose production. The metabolic dysregulation associated with DM causes secondary pathophysiologic changes in multiple organ systems that impose a tremendous burden on the individual with diabetes and on the health care system. In the United States, DM is the leading cause of end-stage renal disease (ESRD), nontraumatic lower extremity amputations, and adult blindness. It also predisposes to cardiovascular diseases. With an increasing incidence worldwide, DM is likely to continue to be a leading cause of morbidity and mortality in the future.


DM is classified on the basis of the pathogenic process leading to hyperglycemia, as opposed to earlier criteria such as age of onset or type of therapy (Fig. 396-1). There are two broad categories of DM, designated as either type 1 or type 2 DM (Table 396-1). However, there is increasing recognition of other forms of diabetes in which the molecular pathogenesis is better understood and may be associated with a single gene defect. These alternative forms may share features of type 1 and/or type 2 DM. Type 1 DM develops as a result of autoimmunity against the insulin-producing beta cells, resulting in complete or near-total insulin deficiency. Type 2 DM is a heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion, and increased hepatic glucose production. Distinct genetic and metabolic defects in insulin action and/or secretion give rise to the common phenotype of hyperglycemia in type 2 DM and have important therapeutic implications now that pharmacologic agents are available to target specific metabolic derangements. Both type 1 and type 2 diabetes are preceded by a period of progressive worsening of glucose homeostasis, followed by the development of hyperglycemia that exceeds the threshold for clinical diagnosis. In terms of type 2 diabetes, this phase is referred to as prediabetes and are more specifically classified as impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (Fig. 396-1). Recently, three distinct stages of type 1 DM have been defined based on the development of autoantibodies against pancreatic beta cell antigens or the development of worsening dysglycemia (discussed below).

FIGURE 396-1

Spectrum of glucose homeostasis and diabetes mellitus (DM). The spectrum from normal glucose tolerance to diabetes in type 1 DM, type 2 DM, specific types of diabetes, and gestational DM is shown from left to right. In most types of DM, the individual traverses from normal glucose tolerance to impaired glucose tolerance to overt diabetes (these should be viewed not as abrupt categories but as a spectrum). Arrows indicate that changes in glucose tolerance may be bidirectional in some types ...

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