Diabetes mellitus refers to a spectrum of metabolic diseases characterized by hyperglycemia that results from defects in insulin secretion, insulin action, or both. The American Diabetes Association (ADA) recognizes four categories of diabetes with different underlying pathophysiologic mechanisms, as shown in Table 24-1. There is frequent overlap between the various types, and many patients do not easily fit into a single class. It is therefore less important to label the particular type of diabetes than it is to understand the pathogenesis of the hyperglycemia and to treat it effectively.

The ADA Expert Committee recognizes an intermediate group of people whose glucose levels, although not meeting criteria
for diabetes, are too high to be considered normal (5) (Fig. 24-1). These individuals have been categorized as having impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). IFG and IGT are often referred to as “prediabetes,” indicating the high risk for future development of T2DM. The annual rate of progression from prediabetes to T2DM is approximately 5% to 10% (6). Although this term may be useful in that it stresses the increased risk of diabetes associated with these conditions, it potentially excludes many people who are also at increased risk. Other important risk factors for diabetes include advanced age, excess adiposity, sedentary lifestyle, family history of diabetes, high-risk ethnic group, history of gestational diabetes, hypertension, dyslipidemia, polycystic ovarian syndrome, and history of vascular disease (7). Most individuals with prediabetes are euglycemic in their daily lives. They may experience transient elevation of the blood glucose during an acute illness, especially if amplified by certain drugs or intravenous glucose. This transient hyperglycemia, which likely indicates reduced insulin sensitivity or secretory capacity, is sometimes the first clue to incipient diabetes. Although the hyperglycemia may resolve immediately following resolution of the illness, it is important to recognize these patients as being at increased risk for T2DM. Regular screening for diabetes should be incorporated into their subsequent medical care.

Although there is increasing evidence that prediabetes increases risk for CVD and CVD mortality independent of traditional cardiovascular risk factors (8), there is no clear evidence that lowering glucose at this stage will reduce diabetes complications. On the other hand, because prediabetes is frequently associated with the metabolic syndrome (see following), components of the syndrome should be sought out and treated.

To date, trials aimed at preventing T1DM have not been successful. Treatments with parenteral insulin (21), oral insulin (22), and oral nicotinamide (23) have not been effective in preventing T1DM among relatives of patients with T1DM. Nevertheless, this remains an area of intense investigation. Multiple trials aimed to prevent T1DM or to delay the progressive loss of β-cell function in newly diagnosed patients are currently in progress.

It has been estimated that 20% to 60% of people with newly diagnosed T2DM already have a complication at the time of diagnosis (24,25). Consequently, there is intense interest in preventing diabetes, and many trials have studied whether the onset of T2DM can be avoided or delayed (6,26). The hope is that forestalling the development of T2DM would likewise reduce diabetic complications. However, the impact of diabetes prevention on diabetes complications is currently unknown. It is likely that diabetes prevention would reduce microvascular complications (retinopathy, nephropathy, and neuropathy), which are strongly associated with hyperglycemia (25). However, because people with prediabetes and metabolic syndrome have an increased risk for CVD even in the absence of overt hyperglycemia, preventing T2DM in these individuals may not significantly reduce cardiovascular risk.

The major diabetes prevention trials are outlined in Table 24-3. Lifestyle changes (27,28) and treatment with metformin (28), troglitazone (29,30), and acarbose (31) have all been shown to reduce rates of progression to T2DM among high-risk patients. It is still not known whether these interventions truly prevent diabetes or simply delay its inevitable diagnosis.

Post-trial testing after discontinuation of metformin (32) and troglitazone (30) suggest persistent reductions in progression to diabetes, but further studies will be needed to establish that these treatments significantly alter the natural history of disease.

At this point in time, lifestyle modification remains the preferred approach to diabetes prevention. Weight loss and increased physical activity have beneficial effects on the entire cardiovascular risk profile (33,34,35) in addition to potential benefits in delaying the onset of diabetes. Unfortunately, lifestyle modification is difficult to achieve and maintain. Pharmacologic therapy to prevent T2DM may become an important therapeutic modality when lifestyle interventions are not sufficiently potent or are not feasible. Currently, there is insufficient evidence that pharmacologic therapy can produce sustained effects. Furthermore, its safety and cost-effectiveness are unknown.