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

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.

Nutrition Management in Older Adults with Diabetes: A Review on the Importance of Shifting Prevention Strategies from Metabolic Syndrome to Frailty

“…Unintentional body weight loss is another potential risk factor for cardiovascular diseases and mortality. In a secondary analysis of the ADVANCE study, an interventional trial of patients with diabetes, the risk for cardiovascular diseases and mortality doubled in those with unintentional body weight loss of > 10% compared to those without apparent body weight change (between −4% and 4%); the finding was independent of age [112]. Unintentional weight loss is a diagnostic criterion for frailty based on the CHS; therefore, body weight should be regularly monitored for early detection of even a slight weight reduction.…”

Weight change and risk of cardiovascular disease among adults with type 2 diabetes: more than 14 years of follow-up in the Tehran Lipid and Glucose Study

“…Model 2: Model 1 + further adjusted for BMI, educational level, current smoking (at first follow-up), GLD use (at baseline or first follow-up), family history of premature CVD, hypertension, hypercholesterolemia, CKD, and FPG CHD coronary heart disease, BMI body mass index, GLD glucose-lowering drugs, CVD cardiovascular disease, CKD chronic kidney disease, FPG fasting plasma glucose [13]. Based on results from the ADVANCE trial, compared to a stable weight, 2-year weight loss > 10% was associated significantly with increased risk of major cardiovascular events and CVD mortality; in contrast, weight gain did not contain a significant effect on CVD [16]. Recently, among about 20,000 White British UK biobank participants with T2DM, it was shown that the minimum mortality risk was seen in those with a BMI of 32 kg/m 2 ; moreover, using Mendelian randomization, the researchers did not find a significant impact of obesity on mortality in this population [27].…”

“…In a meta-analysis of prospective studies, despite a high heterogeneity, weight loss increased the risk of CVD mortality by 15% among overweight or obese patients with diabetes; moreover, weight gain had a HR of 0.97 [0.93–1.01] [ 13 ]. Based on results from the ADVANCE trial, compared to a stable weight, 2-year weight loss > 10% was associated significantly with increased risk of major cardiovascular events and CVD mortality; in contrast, weight gain did not contain a significant effect on CVD [ 16 ]. Recently, among about 20,000 White British UK biobank participants with T2DM, it was shown that the minimum mortality risk was seen in those with a BMI of 32 kg/m 2 ; moreover, using Mendelian randomization, the researchers did not find a significant impact of obesity on mortality in this population [ 27 ].…”

“…Results of the recent studies on this issue also remained inconsistent. Data from the ORIGIN trial and the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Cambridge trial showed significant protection for weight loss among participants with T2DM [14,15]; however, the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) trial showed a significantly increased risk of CVD among participants with weight loss [16]. Moreover, results from other studies were not statistically significant for the association of weight loss with CVD [17][18][19].…”

“…Moreover, results from other studies were not statistically significant for the association of weight loss with CVD [ 17 – 19 ]. Similar to weight loss, findings for the effect of weight gain on CVD events were inconclusive among populations with T2DM, in which adverse [ 16 , 20 ], protective [ 15 ], and neutral [ 18 , 19 ] effects have been reported for weight gain all together.…”