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

• Published in: The journal of clinical endocrinology and metabolism 2020-01, Vol.105 (1), p.152-162
• Main Authors: Lee, Alexandra K, Woodward, Mark, Wang, Dan, Ohkuma, Toshiaki, Warren, Bethany, Sharrett, A Richey, Williams, Bryan, Marre, Michel, Hamet, Pavel, Harrap, Stephen, Mcevoy, John W, Chalmers, John, Selvin, Elizabeth
• Format: Article
• Language: English
• Subjects: Adult; Aged; Blood pressure; Body mass index; Body weight; Body weight gain; Body weight loss; Body-Weight Trajectory; Cardiovascular diseases; Cardiovascular Diseases - etiology; Cardiovascular Diseases - mortality; Cardiovascular Diseases - prevention & control; Clinical s; Complications and side effects; Demography; Diabetes; Diabetes mellitus (non-insulin dependent); 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; Health aspects; Humans; Hypertension - complications; Hypertension - drug therapy; Hypertension - mortality; Indapamide - therapeutic use; Life Style; Male; Microvasculature; Middle Aged; Mortality; Obesity - complications; Obesity - drug therapy; Obesity - mortality; Overweight; Overweight - complications; Overweight - drug therapy; Overweight - mortality; Patient outcomes; Perindopril - therapeutic use; Prognosis; Risk Factors; Type 2 diabetes; Vascular diseases; Weight Gain - physiology; Weight loss; Weight Loss - physiology
• ISSN: 0021-972X; 1945-7197; 1945-7197
• 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 (±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.