Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria.
Agency for Preventive and Social Medicine, Bregenz, Austria.
JAMA Netw Open. 2021 Mar 1;4(3):e212612. doi: 10.1001/jamanetworkopen.2021.2612.
It is unknown whether the triglyceride-glucose (TyG) index as a measure of insulin resistance is associated with the risk of developing end-stage kidney disease (ESKD). Because individuals who are overweight or obese often develop insulin resistance, mediation of the association between body mass index (BMI) and ESKD risk through the TyG index seems plausible but has not been investigated.
To evaluate whether the TyG index is associated with ESKD risk and, if so, to what extent the TyG index mediates the association between BMI and ESKD.
DESIGN, SETTING, AND PARTICIPANTS: A total of 176 420 individuals were recruited during routine health examinations to participate in the Austrian Vorarlberg Health Monitoring and Promotion Program (VHM&PP), a prospective, population-based cohort study with participant enrollment between January 1, 1988, and June 30, 2005, and a mean follow-up of 22.7 years. Data analysis was conducted from March 1, 2020, to September 30, 2020.
Body mass index and the logarithmized product of fasting triglyceride and glucose concentrations (TyG index), as determined during the baseline health examination.
End-stage kidney disease, as indicated by initiation of kidney replacement therapy, either dialysis or kidney transplantation.
Of the 176 420 participants, 94 885 were women (53.8%); mean (SD) age was 42.5 (15.4) years. During a mean (SD) follow-up of 22.7 (6.9) years, 454 (0.3%) participants developed ESKD and 35 234 (20.0%) died. In multivariable-adjusted Cox proportional hazards models, the TyG index was significantly associated with the risk of ESKD, both with (hazard ratio [HR] per 1-SD increase, 1.68; 95% CI, 1.56-1.82) and without (HR per 1-SD increase, 1.79; 95% CI, 1.66-1.93) the inclusion of BMI as a covariate. Mediation analysis using a newly proposed 2-stage regression method for survival data showed that a 5-point increase in BMI increased the risk of ESKD by 58% (HR [total association], 1.58; 95% CI, 1.43-1.75), and that 41.7% of the total association (95% CI, 31.6%-51.8%) was mediated through the TyG index (HR [indirect association], 1.21; 95% CI, 1.18-1.25).
This study found that the TyG index appeared to be associated with ESKD risk and mediates nearly half of the total association between BMI and ESKD in the general population. Public health efforts aiming at the reduction of body weight might decrease the kidney sequelae of insulin resistance and the burden of ESKD.
重要性：尚不清楚三酰甘油-葡萄糖（TyG）指数作为胰岛素抵抗的衡量标准是否与终末期肾病（ESKD）的发病风险相关。由于超重或肥胖的个体通常会出现胰岛素抵抗，因此通过 TyG 指数来调解 BMI 与 ESKD 风险之间的关联似乎是合理的，但尚未得到证实。
目的：评估 TyG 指数是否与 ESKD 风险相关，如果相关，TyG 指数在多大程度上调解了 BMI 与 ESKD 之间的关联。
设计、环境和参与者：总共招募了 176420 名个体在常规健康检查期间参加奥地利福拉尔贝格健康监测和促进计划（VHM&PP），这是一项前瞻性、基于人群的队列研究，参与者登记时间为 1988 年 1 月 1 日至 2005 年 6 月 30 日，平均随访时间为 22.7 年。数据分析于 2020 年 3 月 1 日至 2020 年 9 月 30 日进行。
暴露：在基线健康检查期间确定的 BMI 和空腹三酰甘油和葡萄糖浓度的对数值的乘积（TyG 指数）。
主要结果和措施：ESKD 的发生，由肾脏替代治疗（透析或肾移植）启动来指示。
结果：在 176420 名参与者中，有 94885 名女性（53.8%）；平均（标准差）年龄为 42.5（15.4）岁。在平均（标准差）22.7（6.9）年的随访中，有 454 名（0.3%）参与者发展为 ESKD，35234 名（20.0%）死亡。在多变量调整的 Cox 比例风险模型中，TyG 指数与 ESKD 风险显著相关，无论是否包含 BMI 作为协变量（每增加 1-SD，风险比 [HR]，1.68；95%CI，1.56-1.82）和（每增加 1-SD，HR，1.79；95%CI，1.66-1.93）。使用新提出的用于生存数据的 2 阶段回归方法进行的中介分析表明，BMI 增加 5 分，ESKD 的风险增加 58%（总关联 HR，1.58；95%CI，1.43-1.75），总关联的 41.7%（95%CI，31.6%-51.8%）通过 TyG 指数介导（间接关联 HR，1.21；95%CI，1.18-1.25）。
结论和相关性：本研究发现，TyG 指数似乎与 ESKD 风险相关，并在一般人群中调解了 BMI 与 ESKD 之间总关联的近一半。旨在降低体重的公共卫生努力可能会降低胰岛素抵抗的肾脏后果和 ESKD 的负担。
