Relationship of Obesity to Adverse Events Among Patients With Mean 10-Year History of Type 2 Diabetes Mellitus: Results of the ACCORD Study

Zhenhua Xing, Junyu Pei, Jiabing Huang, Xiaofan Peng, Pengfei Chen, Xinqun Hu, Zhenhua Xing, Junyu Pei, Jiabing Huang, Xiaofan Peng, Pengfei Chen, Xinqun Hu

Abstract

Background Recent evidence from cohort studies and meta-analyses suggests that the obesity paradox phenomenon may exist in patients with diabetes mellitus. The goal of this study was to assess the association between adverse events and obesity by using 2 different measures of obesity, body mass index (BMI; kg/m2) and waist circumference, in patients with a mean 10-year history of type 2 diabetes mellitus. Methods and Results We used data from the ACCORD (the Action to Control Cardiovascular Risk in Diabetes) study to evaluate the relationship between obesity and adverse events in patients with a mean 10-year history of type 2 diabetes mellitus. The primary outcome of this study was all-cause mortality. Secondary outcomes were cardiac death, nonfatal myocardial infarction, and stroke. Patients who were class III obese with BMI ≥40 had the highest risk of all-cause mortality, followed by patients with class II obesity, whereas overweight patients had the lowest risk. We found significant correlations between BMI and waist circumference ( r=0.802). We observed that the relationships between waist circumference and primary and second end points were much like the relationships between BMI and primary and second end points (J-shaped relationship for all-cause mortality, V-shaped relationship for cardiac death, U-shaped relationship for nonfatal myocardial infarction, and reverse linear relationship for noncardiac death). Conclusions No evidence of the obesity paradox was observed in patients with a 10-year history of diabetes mellitus. Class III obese patients showed the highest risk of adverse events (all-cause mortality, cardiac death, nonfatal myocardial infarction, and noncardiac death). BMI and waist circumference showed similar relationships with adverse events. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00000620.

Trial registration: ClinicalTrials.gov NCT00000620.

Keywords: all‐cause death; body mass index; diabetes mellitus; obesity paradox; waist circumference.

Figures

Figure 1
Figure 1
Primary and secondary end points by body mass index category. A, All‐cause mortality. B, Cardiac death. C, Nonfatal MI. D, Noncardiac death. All models were adjusted for sex, age, race, hypertension, smoking, hyperlipidemia, previous cardiovascular events, previous heart failure, proteinuria, depression, heart rate, systolic blood pressure, diastolic blood pressure, total cholesterol, low‐density lipoprotein, high‐density lipoprotein, glycated hemoglobin, and glomerular filtration rate. CI indicates confidence interval; HR, hazard ratio; MI, myocardial infarction.
Figure 2
Figure 2
Survival curves for primary and secondary end points for 5 predefined body mass index categories after adjusting multivariate rates. A, All‐cause mortality. B, Cardiac death. C, Nonfatal MI. D, Noncardiac death. All models were adjusted for cofounders in Figure 1. MI indicates myocardial infarction.
Figure 3
Figure 3
Smooth spline curves of BMI for the estimation of risk of primary and second end points after adjusting multivariate rates. A, All‐cause mortality. B, Cardiac death. C, Nonfatal MI. D, Noncardiac death. Red line denotes fitted curves, and blue line represents 95% confidence intervals for the association between BMI and adverse events. All models were adjusted for cofounders in Figure 1. BMI indicates body mass index; MI, myocardial infarction.
Figure 4
Figure 4
Correlation and agreement between body mass index (BMI) and waist circumference.
Figure 5
Figure 5
Smooth spline curves of waist circumference for the estimation of risk of primary and second end points after adjusting the confounding factors. A, All‐cause mortality. B, Cardiac death. C, Nonfatal MI. D, Noncardiac death. Red line denotes fitted curves, and blue line represents 95% confidence intervals for the association between waist circumference and adverse events. All models were adjusted for cofounders in Figure 1. MI indicates myocardial infarction.

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