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

Abstract

Objective: Glycated hemoglobin (HbA1c), 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 HbA1c as a predictor of diabetes and determined the effects of treatments on diabetes defined by an HbA1c ≥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). HbA1c 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 HbA1c (2010 ADA criteria).

Results: Baseline HbA1c predicted incident diabetes in all treatment groups. Diabetes incidence defined by HbA1c ≥6.5% was reduced by 44% by metformin and 49% by lifestyle during the DPP and by 38% by metformin 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 HbA1c.

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 HbA1c-defined diabetes. The long-term implications for other health outcomes remain to be determined.

Trial registration: ClinicalTrials.gov NCT00004992 NCT00038727.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1

Incidence of diabetes (new cases/100 person-years) by baseline HbA1c, where diabetes was determined by 1997 ADA criteria using FPG and 2hPG concentrations or by HbA1c ≥6.5% (48 mmol/mol). Results are shown for the original masked treatment phase (DPP with mean follow-up of 3.0 years) (A and C) and for the DPP plus long-term follow-up (total follow-up with median follow-up of 9.9 years) (B and D). Met, metformin; Plac, placebo.

Figure 2

Comparison of treatment effects on the incidence of diabetes diagnosed by glucose criteria or by HbA1c ≥6.5% (48 mmol/mol). Results are shown for the original masked treatment phase (DPP) (A) and for the total follow-up period (B). Met, metformin; Plac, placebo.

Figure 3

Incidence of diabetes diagnosed by glucose criteria or by HbA1c ≥6.5% (48 mmol/mol) by baseline age and treatment assignment in men (A–D) and women (E–H). Results are shown for the original masked treatment phase (DPP) and for the total follow-up period. Met, metformin; Plac, placebo.