Body Weight Fluctuations May Be Linked to Adverse Outcomes in Patients with T2D

Justin B. Echouffo-Tcheugui, MD, PhD

New data suggest that in a cohort of individuals with type 2 diabetes (T2D), higher variability of adiposity indices was linked to significantly increased risk of cardiovascular disease (CVD) outcomes or death in a control group, but not those in an intensive lifestyle intervention (ILI) group.

Study investigators conducted a cohort analysis of the Look AHEAD trial to evaluate the associations of long-term variability in 2 adiposity indices, including body mass index (BMI) and waist circumference (WC) with incident cardiovascular outcomes and mortality.

“Among participants assigned to the ILI group, we found no association of the variability in adiposity indices with outcomes, while a positive and consistent association was found between the variability in adiposity indices and CVD outcomes and deaths in the diabetes support and education [DSE] groups,” wrote study author Justin B. Echouffo-Tcheugui, MD, PhD, Division of Endocrinology, Diabetes & Metabolism, Johns Hopkins University School of Medicine.

A total of 5145 participants aged 45 - 76 years were enrolled from August 2001 - April 2004 in 16 locations, with trial termination in September 2012. The intervention aimed to achieve a 7% weight loss or greater via increased physical activity and decreased caloric intake.

The analysis was restricted to patients with complete data on BMI and waist circumference at baseline, 12-, 24-, and 36-month visits. For each adiposity measure, long-term variability was defined using the coefficient of variation, the intra-individual standard deviation, and the variability independent of the mean (VIM).

Investigators evaluated outcomes including all-cause mortality, cardiovascular death, and CVD events, a composite of myocardial infarction, stroke, and death from cardiovascular causes. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and associated 95% CIs for each outcome.

A total of 3604 participants were included, with a mean age of 58.4 years and consisting of 2240 women (62.3%). Over a median of 6.7 years, there were 216 CVD events, 33 CVD deaths, and 166 deaths.

In participants in DSE, the HRs for each 3% increment in the coefficient of variation of BMI were:

• 1.47 (95% CI, 1.24-1.74) for all-cause mortality
• 1.78 (95% CI, 1.26-2.53) for CVD mortality
• 1.19 (95% CI, 0.97-1.45) for CVD events

Then, when analyzed as quartiles, participants in quartile 4 had increased hazards for all-cause mortality (HR, 4.06; 95% CI, 2.17 - 7.57), CVD-related mortality (HR, 15.28; 95% CI, 2.89 - 80.90), and CVD events (HR, 2.16; 95% CI, 1.21 - 3.87).

In the ILI, investigators observed the HRs per 1-SD increase in the coefficient of variation of BMI were

• 1.23 (95% CI, 1.01 - 1.50) for all-cause mortality
• 1.54 (95% CI, 1.05 - 2.25) for CVD mortality
• 1.06 (95% CI, 0.86 - 1.31) for CVD events

Through quartile analysis, the corresponding HRs were 0.99 (95% CI, 0.45 - 2.16) for all-cause mortality, 1.14 (95% CI, 0.12 - 10.53) for CVD-related mortality, and 0.77 (95% CI, 0.40 - 1.49) for CVD events.

Further, regarding waist circumference, the control group HRs for quartile 4 were 1.84 (95% CI, 1.01 - 3.35) for all-cause mortality, 6.46 (95% CI, 1.16 - 36.01), and 1.28 (95% CI, 0.72 - 2.29). In the ILI group, the respective HRs were 1.23 (95% CI, 0.61 - 2.46), 0.55 (95% CI, 0.15 - 2.11), and 0.70 (95% CI, 0.39 - 1.25) for quartile 4.

"Our findings imply that weight fluctuations during weight loss attempts among individuals with type 2 diabetes may lead to deleterious health outcomes," investigators concluded.

The study, “Body Weight Variability and Risk of Cardiovascular Outcomes and Death in the Context of Weight Loss Intervention Among Patients With Type 2 Diabetes,” was published in JAMA Network Open.