Does diabetes prevention translate into reduced long-term vascular complications of diabetes?

Abstract

The global epidemic of type 2 diabetes has prompted numerous studies and public health efforts to reduce its development. A variety of interventions, including lifestyle modifications and pharmacological agents directed at ameliorating the major risk factors for type 2 diabetes, are of proven efficacy in reducing the development of type 2 diabetes in people with impaired glucose tolerance. While prevention of the hyperglycaemia characteristic of diabetes is arguably an important, clinically relevant outcome, a more compelling outcome with greater clinical significance is the prevention or reduction of the relatively diabetes-specific microvascular and less-specific cardiovascular disease (CVD) complications associated with diabetes. These complications cause the majority of morbidity and excess mortality associated with diabetes. Any reduction in diabetes should, logically, also reduce the occurrence of its long-term complications; however, most diabetes prevention trials have not been of sufficient duration to allow such an evaluation. The limited long-term data, largely from the Da Qing Diabetes Prevention Study (DQDPS) and the Diabetes Prevention Program (DPP) and their respective follow-up studies (DQDPOS and DPPOS), suggest a reduction in microvascular complications and amelioration of CVD risk factors. Only the DQDPOS and Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) studies have shown a reduction in CVD events and only DQDPOS has demonstrated a decrease in CVD and overall mortality. While these limited data are promising, whether diabetes prevention directly reduces complication-related morbidity and mortality remains unclear. Longer follow-up of prevention studies is needed to supplement the limited current clinical trial data, to help differentiate the effects of diabetes prevention itself from the means used to reduce diabetes development and to understand the balance among benefits, risks and costs of prevention.

Keywords: Cardiovascular disease; Cardiovascular disease risk factors; Diabetes prevention; Long-term diabetes complications; Microvascular disease; Review.

Fig. 1

HbA_1c levels and 95% confidence interval bands, measured annually over time in DPP/DPPOS in all participants based on original intention-to-treat assignments (red, placebo; green, intensive lifestyle intervention; blue, metformin). The colored area surrounding each line represents the 95% CI. The differences in the mean HbA_1c over time for intensive lifestyle intervention vs placebo, and metformin vs placebo, were significant (p<0.001). The dashed lines reflect the HbA_1c levels currently used by the American Diabetes Association to define ‘prediabetes’ (5.7–6.4% [39–46 mmol/mol]) and diabetes (≥6.5% [48 mmol/mol]). Values in mmol/mol on the right-hand y-axis are converted from the % values on the left and rounded up or down. This figure is available as a downloadable slide.