Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study

作者：Sizhi Ai, Xiaoyu Wang, Shanshan Wang, Yilin Zhao, Shuxun Guo, Guohua Li, Zhigang Chen, Fei Lin, Sheng Guo, Li Y, Jihui Zhang, Guoan Zhao · 发表于：Cardiovascular Diabetology · 年份：2022 · DOI：10.1186/s12933-022-01540-6 · 被引用次数：18 · 研究领域：Genetic Associations and Epidemiology、Cardiovascular Function and Risk Factors、Diabetes, Cardiovascular Risks, and Lipoproteins

Abstract Background Adverse ventricular structure and function is a key pathogenic mechanism of heart failure. Observational studies have shown that both insulin resistance (IR) and glycemic level are associated with adverse ventricular structure and function. However, whether IR and glycemic level are causally associated with cardiac structure and function remains unclear. Methods Genetic variants for IR, fasting insulin, HbA1c, and fasting glucose were selected based on published genome-wide association studies, which included 188,577, 108,557, 123,665, and 133,010 individuals of European ancestry, respectively. Outcome datasets for left ventricular (LV) parameters were obtained from UK Biobank Cardiovascular Magnetic Resonance sub-study (n = 16,923). Mendelian randomization (MR) analyses with the inverse-variance weighted (IVW) method were used for the primary analyses, while weighted median, MR-Egger, and MR-PRESSO were used for sensitivity analyses. Multivariable MR analyses were also conducted to examine the independent effects of glycemic traits on LV parameters. Results In the primary IVW MR analyses, per 1-standard deviation (SD) higher IR was significantly associated with lower LV end-diastolic volume (β = − 0.31 ml, 95% confidence interval [CI] − 0.48 to − 0.14 ml; P = 4.20 × 10 −4 ), lower LV end-systolic volume (β = − 0.34 ml, 95% CI − 0.51 to − 0.16 ml; P = 1.43 × 10 −4 ), and higher LV mass to end-diastolic volume ratio (β = 0.50 g/ml, 95% CI 0.32 to 0.67 g/ml;...