Adiposity and Mortality in Type 1 Diabetes

BACKGROUND: In the general population, adiposity exhibits a J- or U-shaped relationship with mortality; however, in catabolic states this relationship is often inversely linear. We have recently documented an age-independent increase in overweight/obesity in the Pittsburgh Epidemiology of Diabetes Complications study (EDC) of type 1 diabetes (T1D). As intensified insulin therapy (IIT) may promote weight gain, the impact of weight gain in T1D is of importance. We therefore assessed the association of adiposity with mortality in 655 EDC participants during twenty years of follow-up. METHODS: Individuals were categorized as underweight (BMI <20), normal (20≤BMI<25), overweight (25≤BMI<30), or obese (BMI≥30). Cox models were constructed using BMI and covariates at baseline, updated means during follow-up, time-varying (reflecting most recent status), and change during adulthood as predictors of mortality. RESULTS: The prevalence of IIT (3+ insulin shots daily and/or pump) increased from 7% to 82%. Overweight increased 47%; obesity increased 7-fold. There were 146 deaths. In unadjusted models BMI (modeled continuously) demonstrated a quadratic relationship with mortality (p=0.002, <0.0001, <0.0001 for baseline, updated mean, and time-varying models, respectively). However, only in the time-varying model were the obese significantly different from the normal weight. while the baseline model revealed no differences by BMI category, in both the updated mean and time varying models, the underweight were at greater risk than the normal weight (p<0.0001 both models). The nonlinear relationship of adiposity with mortality remained after adjustment for diabetes complications, biological, or socioeconomic/lifestyle risk factors, with the exception of baseline socioeconomic/lifestyle risk factors where a linear association emerged. Adjustment for waist circumference eliminated the risk in the obese. Finally, weight gain during follow-up was protective. CONCLUSION: The relationship of adiposity with mortality in T1D now appears to resemble that of the general population, albeit with a marked increased risk in those underweight.