Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai National Clinical Research Center for Endocrine and Metabolic Diseases, State Key Laboratory for Endocrine and Metabolic Diseases, State Key Laboratory for Endocrine Tumor, State Key Laboratory for Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Diabetes Care. 2022 Aug 1;45(8):1863-1872. doi: 10.2337/dc22-0202.
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.
探讨胰岛素抵抗与心血管疾病（CVD）的相关性是否因葡萄糖耐量状态而异。
我们分析了一项来自中国心血管代谢性疾病和癌症队列研究的全国性样本，共纳入 111576 名基线时无 CVD 的成年人。分别根据正常葡萄糖耐量、糖尿病前期和糖尿病患者的性别特异性胰岛素抵抗 HOMA 指数（HOMA-IR）四分位数，以及所有研究参与者的 HOMA-IR 标准差，对胰岛素抵抗进行评估。我们使用 Cox 比例风险模型，根据葡萄糖耐量状态，评估胰岛素抵抗与新发 CVD 之间的关联，并评估与糖尿病前期和糖尿病中胰岛素抵抗和肥胖相结合的 CVD 风险，与正常葡萄糖耐量相比。模型调整了年龄、性别、教育程度、饮酒、吸烟、体力活动和饮食质量。
在根据三种血糖参数定义的正常葡萄糖耐量、糖尿病前期和糖尿病患者中，与 HOMA-IR 最低四分位相比，HOMA-IR 最高四分位与新发 CVD 的多变量调整后 HR（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 个标准差对应的 CVD 发生率分别为 1.04（0.92-1.18）、1.12（1.06-1.18）和 1.15（1.09-1.21）（P 交互=0.011）。与正常葡萄糖耐量患者相比，在糖尿病前期患者中，HOMA-IR 最高四分位数和肥胖的组合患 CVD 的风险增加 17%（95%CI 2-34%），而 HOMA-IR 最低两个四分位数和非肥胖的组合患 CVD 的风险降低 15-17%。在糖尿病患者中，无论肥胖状态如何，HOMA-IR 上两个四分位数的 CVD 风险增加 44-77%。对于不同血糖参数组合定义的葡萄糖耐量状态，也观察到了一致的结果。
葡萄糖耐量状态加重了胰岛素抵抗与 CVD 风险之间的关联。与正常葡萄糖耐量的成年人相比，糖尿病前期且胰岛素抵抗和肥胖的成年人 CVD 风险更高，而在糖尿病患者中，无论肥胖与否，与胰岛素抵抗相关的 CVD 风险仍然存在。
