Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Institute for Metabolic Disease, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, China.
Obesity (Silver Spring). 2018 May;26(5):934-942. doi: 10.1002/oby.22167. Epub 2018 Apr 6.
This study aimed to compare the causal effect of overall obesity and abdominal obesity on type 2 diabetes among Chinese Han individuals.
The causal relationship of BMI and waist-to-hip ratio (WHR) with the risk of glucose deterioration and glycemic traits was compared using two different genetic instruments based on 30 BMI loci and 6 WHR loci with Mendelian randomization (MR) in three prospective cohorts (n = 6,476).
Each 1-SD genetically instrumented higher WHR was associated with a 65.7% higher risk of glucose deterioration (95% CI = 1.069-2.569, P = 0.024), whereas no significant association of BMI with glucose deterioration was observed. Furthermore, a causal relationship was found only between BMI and homeostatic model assessment β-cell function (HOMA-B) (β = 0.143, P = 0.001), and there was a nominal association with Stumvoll second-phase insulin secretion traits (β = 0.074, P = 0.022). The significance level did not persist in sensitivity analyses, except in the causal estimate of WHR on the Gutt index in MR-Egger (β = -0.379, P = 0.022) and the causal estimate of BMI on homeostatic model assessment β-cell function in weighted median MR (β = 0.128, P = 0.017).
The data from this study support the potential causal relationship between abdominal obesity and hyperglycemia, which may be driven by aggravated insulin resistance, in contrast with the potential causal relationship between overall obesity and insulin secretion.
本研究旨在比较整体肥胖和腹型肥胖对中国汉族个体 2 型糖尿病的因果影响。
使用基于 30 个 BMI 位点和 6 个 WHR 位点的两种不同遗传工具，通过孟德尔随机化（MR）在三个前瞻性队列（n=6476）中比较 BMI 和腰臀比（WHR）与葡萄糖恶化风险和血糖特征的因果关系。
每 1 个 SD 遗传上较高的 WHR 与葡萄糖恶化风险增加 65.7%相关（95%CI=1.069-2.569，P=0.024），而 BMI 与葡萄糖恶化无显著关联。此外，仅发现 BMI 与稳态模型评估β细胞功能（HOMA-B）之间存在因果关系（β=0.143，P=0.001），并且与 Stumvoll 二期胰岛素分泌特征存在名义关联（β=0.074，P=0.022）。除了在 MR-Egger 中 WHR 对 Gutt 指数的因果估计（β=-0.379，P=0.022）和 BMI 对稳态模型评估β细胞功能的因果估计在加权中位数 MR 中具有统计学意义（β=0.128，P=0.017）外，其他敏感性分析的显著性水平均未持续。
本研究数据支持腹型肥胖与高血糖之间存在潜在的因果关系，这可能是由胰岛素抵抗加重引起的，而与整体肥胖和胰岛素分泌之间潜在的因果关系相反。
