Regression to Normal Glucose Regulation in American Indians and Alaska Natives of a Diabetes Prevention Program

OBJECTIVE This study evaluated whether regression from impaired glucose regulation (IGR) to normal glucose regulation (NGR) after 1 year of a lifestyle intervention reduces diabetes risk in American Indians and Alaska Natives (AI/ANs). In addition, we sought to identify predictors for regression to NGR and understand possible mechanisms for the association between NGR and future diabetes risk. RESEARCH DESIGN AND METHODS Data from participants enrolled from 2006 to 2009 in the Special Diabetes Program for Indians Diabetes Prevention Program with IGR at baseline and an oral glucose tolerance test at year 1 were analyzed (N = 1,443). Cox regression models were used to estimate the subsequent diabetes risk (year 1 to year 3) by year 1 glucose status. Mediation analysis was used to estimate the proportions of the association between year 1 glycemic status and diabetes risk explained by specific factors. RESULTS Those who reverted to NGR at year 1 (38%) had lower diabetes risk than those with sustained IGR (adjusted hazard ratio 0.28, 95% CI 0.12–0.67). The lower risk associated with regression to NGR was explained by both baseline risk factors and differences in weight loss. Metformin use, weight loss, and an increase in exercise were modifiable risk factors associated with higher odds of regression to NGR. CONCLUSIONS Patients with prediabetes who reverted to NGR had a reduced risk of developing type 2 diabetes over the next 2 years. Both baseline and modifiable risk factors explained the risk reduction associated with NGR.