Wang Xiao-Hong, Wan Qin
Department of Endocrinology and Metabolism, Wenjiang District People's Hospital, Chengdu, China.
Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, China.
Medicine (Baltimore). 2025 Jun 20;104(25):e42912. doi: 10.1097/MD.0000000000042912.
Several observational investigations have documented correlations between circulating metabolic biomarkers and hyperthyroidism; nevertheless, the implications of blood lipids, amino acids, and blood glucose in hyperthyroidism remain elusive. Employing summary-level data from the most recent large-scale genome-wide association study(N = 136,016) for 233 circulating metabolic biomarkers, along with data on hyperthyroidism from the R10 dataset released by the FinnGen consortium(N = 412,181), we performed a bidirectional two-sample Mendelian randomization (MR) analysis. We computed the impacts of both utilizing the inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode techniques, and evaluated the dependability of the findings utilizing Cochran Q test, MR-Egger intercept regression analysis, and MR-PRESSO. Subsequently, a reverse MR analysis was conducted on the circulating metabolic biomarkers identified to exhibit an association with hyperthyroidism in the forward MR analysis. The inverse variance-weighted analysis revealed that for each 1-standard deviation increase in alanine levels, glucose levels, and the cholesteryl esters to total lipids ratio in large very low-density lipoprotein particles, the risk of hyperthyroidism decreased by 14%, 19%, and 15%, respectively. The reverse MR analysis did not identify any significant effect of hyperthyroidism on circulating metabolic biomarkers. Alanine levels, glucose levels, cholesteryl esters to total lipids ratio in large very low-density lipoprotein levels, and the free cholesterol to total lipids ratio in large low-density lipoprotein levels were differentially associated with the risk of hyperthyroidism, and have the potential to be used as biomarkers of hyperthyroidism. The findings of this study may offer novel insights into the prevention and management of hyperthyroidism.
多项观察性研究记录了循环代谢生物标志物与甲状腺功能亢进之间的相关性；然而，血脂、氨基酸和血糖在甲状腺功能亢进中的影响仍不明确。我们利用来自最近一项针对233种循环代谢生物标志物的大规模全基因组关联研究（N = 136,016）的汇总水平数据，以及芬兰基因联盟发布的R10数据集中关于甲状腺功能亢进的数据（N = 412,181），进行了双向双样本孟德尔随机化（MR）分析。我们计算了使用逆方差加权、MR Egger、加权中位数、简单模式和加权模式技术的影响，并利用 Cochr an Q检验、MR-Egger截距回归分析和MR-PRESSO评估了研究结果的可靠性。随后，对在前向MR分析中确定与甲状腺功能亢进相关的循环代谢生物标志物进行了反向MR分析。逆方差加权分析显示，丙氨酸水平、葡萄糖水平以及大的极低密度脂蛋白颗粒中胆固醇酯与总脂质的比率每增加1个标准差，甲状腺功能亢进的风险分别降低14%、19%和15%。反向MR分析未发现甲状腺功能亢进对循环代谢生物标志物有任何显著影响。丙氨酸水平、葡萄糖水平、大的极低密度脂蛋白水平中胆固醇酯与总脂质的比率以及大的低密度脂蛋白水平中游离胆固醇与总脂质的比率与甲状腺功能亢进的风险存在差异关联，并且有可能用作甲状腺功能亢进的生物标志物。本研究结果可能为甲状腺功能亢进的预防和管理提供新的见解。
