Abstract

Objective: Participants in the Diabetes Prevention Program (DPP) randomized to intensive lifestyle modification (ILS) or metformin had a significantly reduced incidence of diabetes compared to those randomized to placebo, yet most were still at risk because they had pre-diabetes. We explored the effect of baseline characteristics, weight change, ILS and metformin on regression from pre-diabetes to the lowest risk state of normal glucose regulation (NGR) defined by ADA criteria.

Research Design And Methods: DPP was a prospective randomized trial. Cox proportional hazards modeling was used to identify predictors of regression from pre-diabetes to NGR over 3 years of follow-up.

Results: Lower baseline fasting (HR 1.52, p<0.01) and 2-hour (HR 1.23, p<0.01) glucose predicted regression to NGR, as did younger age (HR 1.06, p<0.01) and greater insulin secretion (HR 1.09, p=0.04). ILS (HR 2.05, p<0.01) and weight loss (HR 1.35, p<0.01) had significant and independent effects on regression. A non-significant trend for regression was also observed for metformin (HR 1.25, p=0.06), male sex (HR 1.18, p=0.08), and insulin sensitivity (HR 1.07, p=0.09). In those entering the study with both IFG and IGT, ILS, male sex, and insulin sensitivity predicted regression to isolated impaired fasting glucose (IFG), whereas metformin, female sex and greater insulin secretion predicted regression to isolated impaired glucose tolerance (IGT).

Conclusions: Insulin secretion, and other biologic processes retained with younger age, are key in restoring NGR in people with pre-diabetes. However, NGR may also be attained through weight loss and additional aspects of ILS.