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Causal Graph Between Serum Lipids and Glycemic Traits: a Mendelian Randomization Study
Diabetes ( IF 6.2 ) Pub Date : 2022-05-27 , DOI: 10.2337/db21-0734
Ziwei Zhu 1 , Kai Wang 1 , Xingjie Hao 1 , Liangkai Chen 2 , Zhonghua Liu 3 , Chaolong Wang 1
Affiliation  

We systematically investigated the bidirectional causality between high-densitylipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), triglycerides (TG), fasting insulin (FI), and glycated hemoglobin A1c (HbA1c) based on genome-wide association summary statistics of Europeans (sample size n = 1,320,016 for lipids, 151,013 for FI, and 344,182 for HbA1c). We applied multivariable Mendelian randomization (MR) to account for the correlation between different traits, and constructed a causal graph with 13 significant causal effects after adjusting for multiple testing (P < 0.05/20). Remarkably, we found the effects of lipids on glycemic traits were through FI from TG (β = 0.06 [95% CI: 0.03, 0.08] in unit of 1-SD for each trait) and HDL-C (β = -0.02 [-0.03, -0.01]). On the other hand, FI had strong a negative effect on HDL-C (β = -0.15 [-0.21, -0.09]) and positive effects on TG (β = 0.22 [0.14, 0.31]) and HbA1c (β = 0.15 [0.12, 0.19]), while HbA1c could raise LDL-C (β = 0.06 [0.03, 0.08]) and TG (β = 0.08 [0.06, 0.10]). These estimates derived from the inversevariance weighting method were robust when using different MR methods. Our results suggested that elevated FI was a strong causal factor of high TG and low HDL-C, which in turn would further increase FI. Therefore, early control of insulin resistance is critical to reduce the risk of type 2 diabetes, dyslipidemia, and cardiovascular complications.

中文翻译:

血清脂质和血糖特征之间的因果图:孟德尔随机化研究

我们基于基因组系统研究了高密度脂蛋白胆固醇 (HDL-C)、低密度脂蛋白胆固醇 (LDL-C)、甘油三酯 (TG)、空腹胰岛素 (FI) 和糖化血红蛋白 A1c (HbA1c) 之间的双向因果关系欧洲人的全协会汇总统计数据(样本量 n = 1,320,016 的脂质,151,013 的 FI,344,182 的 HbA1c)。我们应用多变量孟德尔随机化(MR)来解释不同性状之间的相关性,并在调整多重检验后构建了具有 13 个显着因果效应的因果图(P < 0.05/20)。值得注意的是,我们发现脂质对血糖特性的影响是通过来自 TG 的 FI(β = 0.06 [95% CI: 0.03, 0.08],每个性状的单位为 1-SD)和 HDL-C(β = -0.02 [- 0.03,-0.01])。另一方面,FI 对 HDL-C (β = -0.15 [-0.21, -0.09]) 和 TG (β = 0.22 [0.14, 0.31]) 和 HbA1c (β = 0.15 [0.12, 0.19]) 有强烈的负面影响,而 HbA1c 可以提高 LDL-C (β = 0.06 [0.03, 0.08]) 和 TG (β = 0.08 [0.06, 0.10])。当使用不同的 MR 方法时,从逆方差加权方法得出的这些估计是稳健的。我们的研究结果表明,FI 升高是高 TG 和低 HDL-C 的重要原因,这反过来又会进一步增加 FI。因此,早期控制胰岛素抵抗对于降低 2 型糖尿病、血脂异常和心血管并发症的风险至关重要。当使用不同的 MR 方法时,从逆方差加权方法得出的这些估计是稳健的。我们的研究结果表明,FI 升高是高 TG 和低 HDL-C 的重要原因,这反过来又会进一步增加 FI。因此,早期控制胰岛素抵抗对于降低 2 型糖尿病、血脂异常和心血管并发症的风险至关重要。当使用不同的 MR 方法时,从逆方差加权方法得出的这些估计是稳健的。我们的研究结果表明,FI 升高是高 TG 和低 HDL-C 的重要原因,这反过来又会进一步增加 FI。因此,早期控制胰岛素抵抗对于降低 2 型糖尿病、血脂异常和心血管并发症的风险至关重要。
更新日期:2022-05-27
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