Body-mass index and mortality among adults with incident type 2 diabetes

Abstract

Background: The 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").

Methods: We 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.

Results: There 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).

Conclusions: We 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.).

Figure 1. Hazard Ratios for All-Cause Mortality among Participants with Incident Type 2 Diabetes, According to Body-Mass Index (BMI) Shortly before Diagnosis of Type 2 Diabetes

The results from the two cohorts (Nurses’ Health Study [NHS] and Health Professionals Follow-up Study) were combined with the use of a fixed-effect meta-analysis. Panel A shows the results for the total study population (3083 deaths; 179,081 person-years). Panel B shows the results of the analysis that excluded deaths occurring in the first 4 years of follow-up (2856 deaths; 177,906 person-years). Panel C shows the results for participants who had never smoked (1167 deaths; 79,946 person-years). Panel D shows the results for participants who had never smoked, with the exclusion of deaths occurring in the first 4 years of follow-up (1089 deaths; 79,546 person-years). Panel E shows the results for participants who had ever smoked (1892 deaths; 97,762 person-years). Panel F shows the results for participants who had ever smoked, with the exclusion of deaths occurring in the first 4 years of follow-up (1743 deaths; 96,999 person-years). All estimates have been adjusted for age, race, marital status, menopausal status (for the NHS cohort only), presence or absence of a family history of diabetes, smoking status (in Panels A, B, E, and F), alcohol intake, and Alternate Healthy Eating Index score. A total of 20 women (7 deaths) and 79 men (17 deaths) with missing data on smoking status were excluded from the stratified analyses. The bars represent 95% confidence intervals.

Figure 2. Hazard Ratios for Cause-Specific Mortality among Participants with Incident Type 2 Diabetes, According to BMI Shortly before Diagnosis of Type 2 Diabetes

The results from the two cohorts (NHS and Health Professionals Follow-up Study) were combined with the use of a fixed-effect meta-analysis. The numbers of person-years were 179,081 for all participants, 79,546 for those who had never smoked, and 97,762 for those who had ever smoked. Panel A shows cardiovascular mortality in the total study population (941 deaths), among participants who had never smoked (340 deaths), and among those who had ever smoked (592 deaths). Panel B shows cancer mortality in the total study population (784 deaths), among participants who had never smoked (266 deaths), and among those who had ever smoked (514 deaths). Panel G shows mortality from other causes in the total study population (1358 deaths), among participants who had never smoked (561 deaths), and among those who had ever smoked (786 deaths). All estimates have been adjusted for age, race, marital status, menopausal status (for the NHS cohort only), presence or absence of a family history of diabetes, smoking status (among all participants and those who had ever smoked), alcohol intake, and Alternate Healthy Eating Index score. A total of 20 women and 79 men with missing data on smoking status were excluded from the stratified analyses (24 total deaths, including 9 from cardiovascular causes, 4 from cancer, and 11 from other causes). The bars represent 95% confidence intervals.