Association of weight status with mortality in adults with incident diabetes

Abstract

Context: Type 2 diabetes in normal-weight adults (body mass index [BMI] <25) is a representation of the metabolically obese normal-weight phenotype with unknown mortality consequences.

Objective: To test the association of weight status with mortality in adults with new-onset diabetes in order to minimize the influence of diabetes duration and voluntary weight loss on mortality.

Design, setting, and participants: Pooled analysis of 5 longitudinal cohort studies: Atherosclerosis Risk in Communities study, 1990-2006; Cardiovascular Health Study, 1992-2008; Coronary Artery Risk Development in Young Adults, 1987-2011; Framingham Offspring Study, 1979-2007; and Multi-Ethnic Study of Atherosclerosis, 2002-2011. A total of 2625 participants with incident diabetes contributed 27,125 person-years of follow-up. Included were men and women (age >40 years) who developed incident diabetes based on fasting glucose 126 mg/dL or greater or newly initiated diabetes medication and who had concurrent measurements of BMI. Participants were classified as normal weight if their BMI was 18.5 to 24.99 or overweight/obese if BMI was 25 or greater.

Main outcome measures: Total, cardiovascular, and noncardiovascular mortality.

Results: The proportion of adults who were normal weight at the time of incident diabetes ranged from 9% to 21% (overall 12%). During follow-up, 449 participants died: 178 from cardiovascular causes and 253 from noncardiovascular causes (18 were not classified). The rates of total, cardiovascular, and noncardiovascular mortality were higher in normal-weight participants (284.8, 99.8, and 198.1 per 10,000 person-years, respectively) than in overweight/obese participants (152.1, 67.8, and 87.9 per 10,000 person-years, respectively). After adjustment for demographic characteristics and blood pressure, lipid levels, waist circumference, and smoking status, hazard ratios comparing normal-weight participants with overweight/obese participants for total, cardiovascular, and noncardiovascular mortality were 2.08 (95% CI, 1.52-2.85), 1.52 (95% CI, 0.89-2.58), and 2.32 (95% CI, 1.55-3.48), respectively.

Conclusion: Adults who were normal weight at the time of incident diabetes had higher mortality than adults who are overweight or obese.

Figure 1. Kaplain-Meier Survial Estimates Comparing Mortality in Participants Stratified by Weight Status at the Time of Incident Diabetes

Red Line = Normal Weight (BMI 18.5 – 24.9 kg/²) Blue Line=Overweight/Obese (BMI > 25 kg/m²)

Figure 2. Adjusted hazard ratios (95% confidence intervals) of mortality by weight status (normal weight vs. overweight/obese), stratified by subgroup

Adjusted for age, race, gender, education, waist circumference, total cholesterol, HDL-cholesterol, systolic blood pressure, smoking status (ever. vs. never). Statistical significance (P-value) for interaction term based on the maximum likelihood χ² from a proportional hazards model that included a multiplicative interaction term. PAR= Population at Risk. Normal weight = BMI 18.5 – 24.99 kg/m²; Overweight/Obese = BMI >= 25 kg/m².