State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing, China.
Diabetes. 2016 Jun;65(6):1731-40. doi: 10.2337/db15-1533. Epub 2016 Mar 7.
We aimed to explore the causal association between type 2 diabetes (T2D) and increased arterial stiffness. We performed a Mendelian randomization (MR) analysis in 11,385 participants from a well-defined community study in Shanghai during 2011-2013. We genotyped 34 T2D-associated common variants identified in East Asians and created a genetic risk score (GRS). We assessed arterial stiffness noninvasively with the measurement of brachial-ankle pulse wave velocity (baPWV). We used the instrumental variable (IV) estimator to qualify the causal relationship between T2D and increased arterial stiffness. We found each 1-SD increase in T2D_GRS was associated with 6% higher risk in increased arterial stiffness (95% CI 1.01, 1.12), after adjustment of other metabolic confounders. Using T2D_GRS as the IV, we demonstrated a causal relationship between T2D and arterial stiffening (odds ratio 1.24, 95% CI 1.06, 1.47; P = 0.008). When categorizing the genetic loci according to their effect on insulin secretion or resistance, we found genetically determined decrease in insulin secretion was associated with increase in baPWV (βIV = 122.3 cm/s, 95% CI 41.9, 204.6; P = 0.0005). In conclusion, our results provide evidence supporting a causal association between T2D and increased arterial stiffness in a Chinese population.
我们旨在探索 2 型糖尿病（T2D）与动脉僵硬度增加之间的因果关系。我们在 2011 年至 2013 年期间对来自上海一个明确社区研究的 11385 名参与者进行了孟德尔随机化（MR）分析。我们对东亚人群中确定的 34 个与 T2D 相关的常见变体进行了基因分型，并创建了一个遗传风险评分（GRS）。我们使用无创的肱踝脉搏波速度（baPWV）测量来评估动脉僵硬度。我们使用工具变量（IV）估计器来确定 T2D 和动脉僵硬度增加之间的因果关系。我们发现，T2D_GRS 每增加 1 个标准差，动脉僵硬度增加的风险就增加 6%（95%CI 1.01，1.12），在调整了其他代谢混杂因素后。使用 T2D_GRS 作为 IV，我们证明了 T2D 和动脉僵硬度之间存在因果关系（比值比 1.24，95%CI 1.06，1.47；P = 0.008）。当根据其对胰岛素分泌或抵抗的影响对遗传位点进行分类时，我们发现胰岛素分泌的遗传决定减少与 baPWV 的增加有关（IVβ = 122.3 cm/s，95%CI 41.9，204.6；P = 0.0005）。总之，我们的结果提供了证据，支持在中国人群中 T2D 与动脉僵硬度增加之间存在因果关系。
