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 20 years of follow-up. Methods: Individuals were categorized as underweight (body mass index (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 variation (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 by 47% and obesity increased sevenfold. There were 146 deaths. In unadjusted models, BMI (modeled continuously) showed 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, whereas the baseline model showed no differences by BMI category. In both the updated mean and time-varying models, the underweight were at greater risk than were the normal weight (P<0.0001 both models). The nonlinear relationship of adiposity with mortality remained after adjustment for diabetes complications and for biological or socioeconomic/lifestyle risk factors, with the exception of baseline socioeconomic/lifestyle risk factors, in which a linear association emerged. Adjustment for waist circumference eliminated risk in the obese. Finally, weight gain during follow-up was protective. Conclusion: The relationship of adiposity with mortality in T1D now seems to resemble that of the general population, albeit with a marked increased risk in those who are underweight. International Journal of Obesity (2009) 33, 796-805; doi:10.1038/ijo.2009.75; published online 19 May 2009