Changes in Weight and Glucose Can Protect Against Progression in Early Diabetes Independent of Improvements in β-Cell Function

Context: Evidence-based strategies to prevent progression of dysglycemia in newly diagnosed type 2 diabetes are needed. Objective: To undertake a secondary analysis of the Early Diabetes Intervention Program (EDIP) in order to understand the features that were protective against worsening glycemia. Design: EDIP was a randomized, placebo-controlled trial. Setting: Two university diabetes centers. Patients: A total of 219 overweight individuals with fasting glucose < 7.8 mmol/L and 2-hour oral glucose tolerance test (OGTT) glucose > 11.1 mmol/L. Interventions: Acarbose versus placebo, on a background of dietary recommendations, with quarterly visits to assess glycemia and intervention adherence for up to 5 years. Main Outcome Measures: Progression of fasting glucose ≥ 7.8 mmol/L on two consecutive quarterly visits. Cox proportional hazards modeling and ANOVA were performed to evaluate determinants of progression. Results: Progression-free status was associated with reductions in weight, fasting glucose, 2-hour OGTT glucose, and increases in the high-density lipoprotein/triglyceride ratio. The reduction in fasting glucose was the only effect that remained significantly associated with progression-free status in multivariable Cox modeling. The reduction in fasting glucose was in turn primarily associated with reductions in weight and in 2-hour OGTT glucose. Acarbose treatment did not explain these changes. Conclusions: In early diabetes, reductions in glucose, driven by reductions in weight, can delay progressive metabolic worsening. These observations underscore the importance of lifestyle management including weight loss as a tool to mitigate worsening of glycemia in newly diagnosed diabetes. Reductions in fasting glucose, via reductions in weight, provided protection from progressive dysglycemia in EDIP. Lifestyle change can contribute importantly to glycemic control in early diabetes.