Review
Role of Lifestyle and Oral Anti-Diabetic Agents to Prevent Type 2 Diabetes Mellitus and Cardiovascular Disease

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Patients with type 2 diabetes mellitus (DM) and those with impaired glucose tolerance are at increased risk for the development of cardiovascular disease. With an increasing global incidence and prevalence of type 2 DM, and with the 2003 lowering of the glucose threshold required for the diagnosis of impaired glucose tolerance to 100 mg/dl (5.6 mmol/L), the concept of DM prevention, and presumed reduction of cardiovascular risk, is attractive. However, there is little evidence to guide the choice of DM prevention strategy and no certainty that DM prevention will result in reduced cardiovascular events or an overall favorable balance of benefit to risk. In conclusion, this review examines previous reports on DM prevention, with special attention to evidence for cardiovascular event reduction in association with specific interventions to prevent DM.

Section snippets

Prediabetes and Cardiovascular Risk

Because the average interval between the onset of β-cell dysfunction and the development of overt DM is 10 years,2 there exists a window of opportunity for DM prevention. This interval has been termed “prediabetes” and is defined by an abnormal response to oral glucose tolerance testing, in the form of IGT and/or IFG (Figure 1).3 Epidemiologic evidence suggests that this long period of glucose dysregulation, characterized first by postprandial hyperglycemia alone and progressing to fasting

Lifestyle modification

Epidemiologic studies suggest an association between a favorable lifestyle and improved metabolic parameters. The Insulin Resistance Atherosclerosis Study (IRAS) demonstrated that increasing participation in vigorous and nonvigorous exercise, as assessed by recall of physical activities on a weekly and yearly basis, was correlated with improved insulin sensitivity as measured by an intravenous glucose tolerance test in a group of subjects with normal glucose tolerance, IGT, and early type 2 DM.9

Discussion

Despite the increased risk for cardiovascular morbidity and mortality in patients also at risk for the development of DM, little evidence is available to guide the choice of glycemic therapy for these patients. Although a growing body of evidence indicates that it is possible to improve metabolic parameters (such as hemoglobin A1c and lipid levels) through the use of lifestyle modification or oral antidiabetic agents, and that a delay in DM onset is achievable, the effect of these modifications

Acknowledgment

We wish to acknowledge the NAVIGATOR Trial Executive Committee, Stephen Haffner, MD, Rury Holman, MD, and John McMurray, MD, for their support.

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  • Cited by (10)

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    Drs. Bethel and Califf received grant support from Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

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