OBJECTIVE To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status. RESEARCH DESIGN AND METHODS 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 HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 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 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. RESULTS In participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82–1.30), 1.23 (1.07–1.42), and 1.61 (1.30–2.00), respectively; the corresponding values 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 for 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 risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15–17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44–77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters. CONCLUSIONS 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 risk related to insulin resistance remained, regardless of obesity.

中文翻译：

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胰岛素抵抗与心血管疾病风险之间的关联因葡萄糖耐量状态而异：一项全国性前瞻性队列研究

目的 研究胰岛素抵抗和心血管疾病 (CVD) 之间的关联是否因葡萄糖耐量状态而异。研究设 对于葡萄糖耐量正常、前驱糖尿病或糖尿病的参与者，分别通过胰岛素抵抗的性别特异性 HOMA (HOMA-IR) 四分位数来估计胰岛素抵抗，而对于整个研究参与者，则采用 1 SD 的 HOMA-IR。我们使用 Cox 比例风险模型根据葡萄糖耐量状态检查胰岛素抵抗与心血管疾病事件之间的关联，并评估与前驱糖尿病和糖尿病中胰岛素抵抗和肥胖的组合类别相关的 CVD 风险，与正常的糖耐量相比。模型根据年龄、性别、教育程度、饮酒、吸烟、体力活动和饮食质量进行了调整。结果 在具有正常葡萄糖耐量、糖尿病前期和由三个葡萄糖参数定义的糖尿病的参与者中，与 HOMA-IR 最高四分位数与最低四分位数相关的 CVD 的多变量调整风险比 (95% CI) 为 1.03 (0.82–1.30) , 1.23 (1.07–1.42), 和 1.61 (1.30–2.00), 分别; HOMA-IR 中每增加 1-SD 对应的 CVD 值分别为 1.04 (0.92-1.18)、1.12 (1.06-1.18) 和 1.15 (1.09-1.21)（相互作用的 P = 0.011）。与糖耐量正常的参与者相比，在糖尿病前期参与者中，最高 HOMA-IR 四分位数和肥胖的组合显示 CVD 风险高 17% (95% CI 2–34%)，而最低的两个 HOMA-IR 四分位数和非肥胖者的组合显示 CVD 风险降低了 15-17%。在患有糖尿病的参与者中，无论肥胖状况如何，HOMA-IR 上两个四分位数的 CVD 风险都高出 44-77%。对于由血糖参数的不同组合定义的葡萄糖耐量状态，观察到一致的结果。结论 葡萄糖不耐受状态加剧了胰岛素抵抗与心血管疾病风险之间的关联。与糖耐量正常的成年人相比，同时存在胰岛素抵抗和肥胖的前驱糖尿病成年人患心血管疾病的风险更高，而在患有糖尿病的成年人中，无论是否肥胖，与胰岛素抵抗相关的心血管疾病风险仍然存在。无论肥胖状况如何，上两个 HOMA-IR 四分位数的 CVD 风险高出 44-77%。对于由血糖参数的不同组合定义的葡萄糖耐量状态，观察到一致的结果。结论 葡萄糖不耐受状态加剧了胰岛素抵抗与心血管疾病风险之间的关联。与糖耐量正常的成年人相比，同时存在胰岛素抵抗和肥胖的前驱糖尿病成年人患心血管疾病的风险更高，而在患有糖尿病的成年人中，无论是否肥胖，与胰岛素抵抗相关的心血管疾病风险仍然存在。无论肥胖状况如何，上两个 HOMA-IR 四分位数的 CVD 风险高出 44-77%。对于由血糖参数的不同组合定义的葡萄糖耐量状态，观察到一致的结果。结论 葡萄糖不耐受状态加剧了胰岛素抵抗与心血管疾病风险之间的关联。与糖耐量正常的成年人相比，同时存在胰岛素抵抗和肥胖的前驱糖尿病成年人患心血管疾病的风险更高，而在患有糖尿病的成年人中，无论是否肥胖，与胰岛素抵抗相关的心血管疾病风险仍然存在。结论 葡萄糖不耐受状态加剧了胰岛素抵抗与心血管疾病风险之间的关联。与糖耐量正常的成年人相比，同时存在胰岛素抵抗和肥胖的前驱糖尿病成年人患心血管疾病的风险更高，而在患有糖尿病的成年人中，无论是否肥胖，与胰岛素抵抗相关的心血管疾病风险仍然存在。结论 葡萄糖不耐受状态加剧了胰岛素抵抗与心血管疾病风险之间的关联。与糖耐量正常的成年人相比，同时存在胰岛素抵抗和肥胖的前驱糖尿病成年人患心血管疾病的风险更高，而在患有糖尿病的成年人中，无论是否肥胖，与胰岛素抵抗相关的心血管疾病风险仍然存在。