The Risks of Cardiovascular Disease and Mortality Following Weight Change in Adults with Diabetes: Results from ADVANCE

J Clin Endocrinol Metab. 2020 Jan 1;105(1):152-162. doi: 10.1210/clinem/dgz045.

Abstract

Context: Weight loss is strongly recommended for overweight and obese adults with type 2 diabetes. Unintentional weight loss is associated with increased risk of all-cause mortality, but few studies have examined its association with cardiovascular outcomes in patients with diabetes.

Objective: To evaluate 2-year weight change and subsequent risk of cardiovascular events and mortality in established type 2 diabetes.

Design and setting: The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation was an international, multisite 2×2 factorial trial of intensive glucose control and blood pressure control. We examined 5 categories of 2-year weight change: >10% loss, 4% to 10% loss, stable (±<4%), 4% to 10% gain, and >10% gain. We used Cox regression with follow-up time starting at 2 years, adjusting for intervention arm, demographics, cardiovascular risk factors, and diabetes medication use from the 2-year visit.

Results: Among 10 081 participants with valid weight measurements, average age was 66 years. By the 2-year examination, 4.3% had >10% weight loss, 18.4% had 4% to 10% weight loss, and 5.3% had >10% weight gain. Over the following 3 years of the trial, >10% weight loss was strongly associated with major macrovascular events (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.26-2.44), cardiovascular mortality (HR, 2.76; 95% CI, 1.87-4.09), all-cause mortality (HR, 2.79; 95% CI, 2.10-3.71), but not major microvascular events (HR, 0.91; 95% CI, 0.61-1.36), compared with stable weight. There was no evidence of effect modification by baseline body mass index, age, or type of diabetes medication.

Conclusions: In the absence of substantial lifestyle changes, weight loss may be a warning sign of poor health meriting further workup in patients with type 2 diabetes.

Publication types

  • Multicenter Study
  • Observational Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Body-Weight Trajectory*
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / prevention & control
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetes Mellitus, Type 2 / physiopathology
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Gliclazide / therapeutic use*
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / mortality
  • Indapamide / therapeutic use*
  • Life Style
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy
  • Obesity / mortality
  • Overweight / complications
  • Overweight / drug therapy
  • Overweight / mortality
  • Perindopril / therapeutic use*
  • Risk Factors
  • Weight Gain / physiology
  • Weight Loss / physiology

Substances

  • Drug Combinations
  • indapamide, perindopril drug combination
  • Indapamide
  • Gliclazide
  • Perindopril