HbA1c as a predictor of diabetes and as an outcome in the diabetes prevention program: A randomized clinical trial

OBJECTIVE : Glycated hemoglobin (HbA_1c), a standard measure of chronic glycemia for managing diabetes, has been proposed to diagnose diabetes and identify people at risk. The Diabetes Prevention Program (DPP) was a 3.2-year randomized clinical trial of preventing type 2 diabetes with a 10-year follow-up study, the DPP Outcomes Study (DPPOS).We evaluated baseline HbA_1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA_1c <6.5% (48 mmol/mol).

RESEARCH DESIGN AND METHODS: We randomized 3,234 nondiabetic adults at high risk of diabetes to placebo, metformin, or intensive lifestyle intervention and followed them for the development of diabetes as diagnosed by fasting plasma glucose (FPG) and 2-h postload glucose (2hPG) concentrations (1997 American Diabetes Association [ADA] criteria). HbA_1c was measured but not used for study eligibility or outcomes. We now evaluate treatment effects in the 2,765 participants who did not have diabetes at baseline according to FPG, 2hPG, or HbA_1c (2010 ADA criteria).

RESULTS : Baseline HbA_1c predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA_1c &Dagger;6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% bymetformin and 29% by lifestyle throughout follow-up. Unlike the primary DPP and DPPOS findings based on glucose criteria, metformin and lifestyle were similarly effective in preventing diabetes defined by HbA_1c.

CONCLUSIONS : HbA1c predicted incident diabetes. In contrast to the superiority of the lifestyle intervention on glucose-defined diabetes, metformin and lifestyle interventions had similar effects in preventing HbA_1c-defined diabetes. The long-term implications for other health outcomes remain to be determined.