Association Between Insulin Resistance and Cardiovascular Disease Risk Varies According to Glucose Tolerance Status: A Nationwide Prospective Cohort Study.
Association Between Insulin Resistance and Cardiovascular Disease Risk Varies According to Glucose Tolerance Status: A Nationwide Prospective Cohort Study.
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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：一项全国前瞻性队列研究
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调查胰岛素抵抗与心血管疾病 (CVD) 之间的关联是否因糖耐量状态而异。我们使用中国心血管代谢疾病和癌症队列研究的数据，分析了全国范围内 111,576 名基线时无 CVD 成年人的样本。对于正常糖耐量、糖尿病前期或糖尿病的参与者，胰岛素抵抗分别通过胰岛素抵抗的性别特异性 HOMA (HOMA-IR) 四分位数进行估计，对于整个研究参与者，胰岛素抵抗则通过 HOMA-IR 的 1 SD 进行估计。我们使用 Cox 比例风险模型根据糖耐量状态检查胰岛素抵抗与 CVD 事件之间的关联，并与正常糖耐量相比，评估糖尿病前期和糖尿病中与胰岛素抵抗和肥胖组合相关的 CVD 风险。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。在由三个葡萄糖参数定义的糖耐量正常、糖尿病前期和糖尿病的参与者中，与 HOMA-IR 最高和最低四分位数相关的 CVD 事件的多变量调整风险比 (95% CI) 分别为 1.03 (0.82–1.30)、1.23 (1.07–1.42) 和 1.61 (1.30–2.00)； HOMA-IR 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)（交互作用 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%)，而最低两个 HOMA-IR 四分位数和非肥胖的组合显示 CVD 风险低 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 风险要高出 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。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，同时患有胰岛素抵抗和肥胖的糖尿病前期成人表现出更高的 CVD 风险，而在糖尿病成人中，无论是否肥胖，与胰岛素抵抗相关的 CVD 风险仍然存在。
To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status. 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. 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. 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.