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

J Clin Endocrinol Metab. 2016 Nov;101(11):4076-4084. doi: 10.1210/jc.2016-2056. Epub 2016 Aug 17.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01470937.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acarbose / administration & dosage
  • Acarbose / pharmacology*
  • Adult
  • Aged
  • Blood Glucose / metabolism*
  • Combined Modality Therapy
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / therapy*
  • Diet, Carbohydrate-Restricted / methods*
  • Diet, Reducing / methods*
  • Disease Progression*
  • Female
  • Glycoside Hydrolase Inhibitors / administration & dosage
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Humans
  • Insulin-Secreting Cells / metabolism
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Overweight / blood*
  • Overweight / therapy*
  • Weight Loss*

Substances

  • Blood Glucose
  • Glycoside Hydrolase Inhibitors
  • Acarbose

Associated data

  • ClinicalTrials.gov/NCT01470937