Association between insulin resistance and cardiovascular disease risk varies according to glucose tolerance status: a nationwide prospective cohort study
Authors: Wang Tiange , Li Mian , Zeng Tianshu , Hu Ruying , Xu Yu , Xu Min , Zhao Zhiyun , Chen Yuhong , Wang Shuangyuan , Lin Hong , Yu Xuefeng , Chen Gang , Su Qing , Mu Yiming , Chen Lulu , Tang Xulei , Yan Li , Qin Guijun , Wan Qin , Gao Zhengnan , Wang Guixia , Shen Feixia , Luo Zuojie , Qin Yingfen , Chen Li , Huo Yanan , Li Qiang , Ye Zhen , Zhang Yinfei , Liu Chao , Wang Youmin , Wu Shengli , Yang Tao , Deng Huacong , Zhao Jiajun , Shi Lixin , Ning Guang , Bi Yufang , Wang Weiqing , Lu Jieli 
Published: June 2022

<p><strong>Objective: </strong>To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status.</p>
<p><strong>Research Design and Methods: </strong>We analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific homeostasis model assessment of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1-standard deviation (SD) of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and to evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality.</p>
<p><strong>Results:</strong> In participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (HRs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (95% confidence interval [CI]: 0.82-1.30), 1.23 (1.07-1.42), and 1.61 (1.30-2.00), respectively; the corresponding HRs (95% CIs) for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92-1.18), 1.12 (1.06-1.18), and 1.15 (1.09-1.21), respectively (P[interaction]=0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI: 2%-34%) higher risks of CVD; while the combination of the lowest two HOMA-IR quartiles and non-obesity showed 15%-17% lower risks of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44%-77% higher risks of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters.</p>
<p><strong>Conclusions: </strong>Glucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risks related to insulin resistance remained regardless of obesity.<br>
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