Objectives: To evaluate whether regression from impaired glucose regulation (IGR) to normal glucose regulation (NGR) after one year of a lifestyle intervention reduces diabetes risk in American Indians and Alaska Natives (AI/ANs). Additionally, 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 (OGTT) at year 1 were analyzed (N = 1443). Based on OGTT results, participants were classified into four categories: NGR; isolated IFG (iIFG); isolated IGT (iIGT); or both IFG and IGT (IFG/IGT). Cox regression models were used to estimate the subsequent diabetes risk (year 1 to year 3) by year 1 glucose status. Mediation analysis was employed 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 (HR) = 0.28, 95% CI: 0.12-0.67). Compared to the NGR group at year 1, IFG/IGT carried the highest risk of developing diabetes with an adjusted HR of 4.72 (95% CI: 1.84-12.07), followed by the iIGT group (HR=3.26, 95% CI: 0.96-11.12; p-value=0.059) and the iIFG group (HR=3.13, 95% CI: 1.27-7.31). 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 increase in exercise were modifiable risk factors associated with a higher odds of regression to NGR.

Conclusions: AI/AN patients with prediabetes who reverted to NGR had a reduced risk of developing type 2 diabetes over the next two years; modifiable risk factors explained a major proportion of risk reduction associated with NGR.


K.A. Pratte: None. A. Johnson: None. J. Beals: None. A. Bullock: None. S.M. Manson: None. L. Jiang: None.


Indian Health Service (HHSI242200400049C to S.M.M.); National Institute of Diabetes and Digestive and Kidney Diseases (1P30DK092923 to S.M.M), (R21DK108187 to L.J.)

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