Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, 2300RC Leiden, the Netherlands.
J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2502-e2511. doi: 10.1210/clinem/dgab277.
Thyroid status is hypothesized to be causally related with the risk of diabetes mellitus (DM), but previous results were conflicting possibly because of a complex interaction between thyrotropin (TSH), body mass index (BMI) and DM.
This work aims to investigate the causal association between thyroid status with DM and glucose homeostasis and to what extent this association is dependent on BMI.
A mendelian randomization study was conducted of European-ancestry participants from the UK Biobank population. The present study involved 408 895 individuals (mean age 57.4 years [SD 8.0], 45.9% men), of whom 19 773 had DM. Genetic variants for circulatory TSH, free thyroxine (fT4) concentrations and BMI to calculate weighted genetic risk scores. The main outcome measures included self-reported DM-stratified analyses by BMI. Analyses were repeated for nonfasting glucose and glycated hemoglobin A1c (HbA1c) among individuals without DM.
Genetically determined TSH and fT4 levels were not associated with risk of DM in the total UK Biobank population. However, in analyses stratified on genetically determined BMI, genetically determined higher TSH, and not fT4, was associated with a lower risk for DM only in the low BMI group (odds ratio 0.91; 95% CI, 0.85-0.98 in low BMI; P value for interaction = .06). Similar results were observed for glucose and HbA1c among individuals without DM.
TSH, but not fT4, is a potential causal risk factor for DM in individuals with genetically determined low BMI highlighting potential protective effects of TSH only in low-risk populations.
甲状腺功能状态被假设与糖尿病（DM）的风险有关，但之前的结果存在冲突，可能是由于促甲状腺激素（TSH）、体重指数（BMI）和 DM 之间的复杂相互作用。
本研究旨在探讨甲状腺功能与 DM 和葡萄糖稳态之间的因果关系，并确定这种关联在多大程度上依赖于 BMI。
本研究为英国生物库人群的欧洲血统参与者进行了孟德尔随机化研究。本研究共纳入 408895 名参与者（平均年龄 57.4 岁[SD 8.0]，45.9%为男性），其中 19773 人患有 DM。循环 TSH、游离甲状腺素（fT4）浓度和 BMI 的遗传变异用于计算加权遗传风险评分。主要观察指标包括按 BMI 分层的 DM 报告分析。在没有 DM 的个体中，重复进行非禁食血糖和糖化血红蛋白 A1c（HbA1c）分析。
在整个英国生物库人群中，遗传决定的 TSH 和 fT4 水平与 DM 风险无关。然而，在根据遗传决定的 BMI 进行分层分析时，遗传决定的较高 TSH 而不是 fT4 仅与低 BMI 组的 DM 风险降低相关（低 BMI 组的比值比为 0.91[95%CI，0.85-0.98]；P 值用于交互作用=0.06）。在没有 DM 的个体中，也观察到了类似的葡萄糖和 HbA1c 结果。
TSH 而不是 fT4 是低 BMI 个体中 DM 的潜在因果风险因素，这突出了 TSH 仅在低风险人群中具有潜在的保护作用。
