Journal
NEW ENGLAND JOURNAL OF MEDICINE
Volume 370, Issue 3, Pages 233-244Publisher
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa1304501
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Funding
- National Institutes of Health [UM1 CA167552, UM1 CA176726, P01 CA87969, R01 HL034594, P01CA055075, DK58845, CA55075, CA87969, HL34594, P30 DK46200, 1U54CA155626-01]
- American Diabetes Association [7-12-MN-34]
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BackgroundThe relation between body weight and mortality among persons with type 2 diabetes remains unresolved, with some studies suggesting decreased mortality among overweight or obese persons as compared with normal-weight persons (an obesity paradox). MethodsWe studied participants with incident diabetes from the Nurses' Health Study (8970 participants) and Health Professionals Follow-up Study (2457 participants) who were free of cardiovascular disease and cancer at the time of a diagnosis of diabetes. Body weight shortly before diagnosis and height were used to calculate the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters). Multivariable Cox models were used to estimate the hazard ratios and 95% confidence intervals for mortality across BMI categories. ResultsThere were 3083 deaths during a mean period of 15.8 years of follow-up. A J-shaped association was observed across BMI categories (18.5 to 22.4, 22.5 to 24.9 [reference], 25.0 to 27.4, 27.5 to 29.9, 30.0 to 34.9, and 35.0) for all-cause mortality (hazard ratio, 1.29 [95% confidence interval {CI}, 1.05 to 1.59]; 1.00; 1.12 [95% CI, 0.98 to 1.29]; 1.09 [95% CI, 0.94 to 1.26]; 1.24 [95% CI, 1.08 to 1.42]; and 1.33 [95% CI, 1.14 to 1.55], respectively). This relationship was linear among participants who had never smoked (hazard ratios across BMI categories: 1.12, 1.00, 1.16, 1.21, 1.36, and 1.56, respectively) but was nonlinear among participants who had ever smoked (hazard ratios across BMI categories: 1.32, 1.00, 1.09, 1.04, 1.14, and 1.21) (P=0.04 for interaction). A direct linear trend was observed among participants younger than 65 years of age at the time of a diabetes diagnosis but not among those 65 years of age or older at the time of diagnosis (P<0.001 for interaction). ConclusionsWe observed a J-shaped association between BMI and mortality among all participants and among those who had ever smoked and a direct linear relationship among those who had never smoked. We found no evidence of lower mortality among patients with diabetes who were overweight or obese at diagnosis, as compared with their normal-weight counterparts, or of an obesity paradox. (Funded by the National Institutes of Health and the American Diabetes Association.) Some studies suggest lower mortality among patients with type 2 diabetes who were overweight or obese at diagnosis. In this study, there was a direct linear relation between BMI and mortality among participants who had never smoked but a nonlinear relation among those who had smoked. Excess adiposity is a well-established risk factor for premature death in the general population, including death due to cardiovascular disease or cancer.(1)-(4) However, a so-called obesity paradox (i.e., an association between obesity, as compared with normal weight, and reduced mortality) has been reported among patients with heart failure, end-stage renal disease, or hypertension, and, recently, among those with type 2 diabetes.(5)-(12) Most of these studies, however, have been limited by small samples and suboptimal control for smoking status and preexisting chronic conditions. Smoking is a concern in analyses of body weight and mortality because it is associated with ...
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