Pancreatic beta-cell function and type 2 diabetes risk: quantify the causal effect using a Mendelian randomization approach based on meta-analyses.
Pancreatic beta-cell function and type 2 diabetes risk: quantify the causal effect using a Mendelian randomization approach based on meta-analyses.
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DOI：
10.1093/hmg/dds339
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发表时间：
2012-11
影响因子：
3.5
通讯作者：
Yiqing Song;E. Yeung;Aiyi Liu;T. VanderWeele;Liwei Chen;Chen Lu;Chunling Liu;E. Schisterman;Y. Ning;Cuilin Zhang
中科院分区：
文献类型：
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作者：
Yiqing Song;E. Yeung;Aiyi Liu;T. VanderWeele;Liwei Chen;Chen Lu;Chunling Liu;E. Schisterman;Y. Ning;Cuilin Zhang
该研究的目的是通过最大限度地减少残留混杂因素和反向因果关系来量化 β 细胞功能对 2 型糖尿病的因果影响。我们采用孟德尔随机化 (MR) 方法，使用 TCF7L2 变体 rs7903146 作为终生水平 β 细胞功能的工具。我们首先进行了两组荟萃分析，通过计算汇总比值比 (OR) 来量化 66 项研究中 55 436 例病例和 106 020 名对照者中 TCF7L2 变异与 2 型糖尿病风险的关联，并通过计算汇总平均差来量化 31 项研究中 35 052 名非糖尿病个体中 35 052 名非糖尿病个体中 β 细胞功能的多个直接或间接测量值之间的关联。我们进一步应用 MR 方法，根据荟萃分析的结果，获得 β 细胞功能对 2 型糖尿病风险影响的因果估计。胰岛素分泌稳态模型评估 (HOMA-%B) 每增加 5 个单位，OR [95% 置信区间 (CI)] 为 0.87 (0.81-0.93) (P = 3.0 × 10(-5))。此外，对于基于静脉葡萄糖耐量试验的测量，胰岛素敏感性指数和处置指数每增加 1 个标准差，与 2 型糖尿病风险相关的 OR (95% CI) 分别为 0.24 (0.08-0.74) (P = 0.01) 和 0.14 (0.04-0.48) (P = 0.002)。本研究的结果支持胰腺 β 细胞功能本身在 2 型糖尿病病因学中的因果作用。
The objective of the study is to quantify the causal effect of β-cell function on type 2 diabetes by minimizing residual confounding and reverse causation. We employed a Mendelian randomization (MR) approach using TCF7L2 variant rs7903146 as an instrument for lifelong levels of β-cell function. We first conducted two sets of meta-analyses to quantify the association of the TCF7L2 variant with the risk of type 2 diabetes among 55 436 cases and 106 020 controls from 66 studies by calculating pooled odds ratio (OR) and to quantify the associations with multiple direct or indirect measures of β-cell function among 35 052 non-diabetic individuals from 31 studies by calculating pooled mean difference. We further applied the method of MR to obtain the causal estimates for the effect of β-cell function on type 2 diabetes risk based on findings from the meta-analyses. The OR [95% confidence interval (CI)] was 0.87 (0.81-0.93) for each five unit increment in homeostasis model assessment of insulin secretion (HOMA-%B) (P = 3.0 × 10(-5)). In addition, for measures based on intravenous glucose tolerance test, ORs (95% CI) associated with type 2 diabetes risk were 0.24 (0.08-0.74) (P = 0.01) and 0.14 (0.04-0.48) (P = 0.002) for per 1 standard deviation increment in insulin sensitivity index and disposition index, respectively. Findings from the present study lend support to a causal role of pancreatic β-cell function itself in the etiology of type 2 diabetes.