甘油三酯-葡萄糖指数及其变异性对2型糖尿病肾脏病的影响

Effects of triglyceride-glucose index and its variability on diabetic kidney disease in patients with type 2 diabetes mellitus

目的探讨2型糖尿病(T2DM)患者甘油三酯-葡萄糖(TyG)指数及其变异性对糖尿病肾脏病(DKD)的影响。方法为前瞻性队列研究。选取2002年1月1日至2018年12月31日在台湾地区李氏联合诊所6个中心定期就诊且基线时无DKD的1986例T2DM患者作为研究对象,并对其进行前瞻性随访。收集患者的年龄、性别、血肌酐、甘油三酯(TG)、空腹血糖(FPG)、尿微量白蛋白和尿肌酐,并计算TyG指数、估算的肾小球滤过率(eGFR)和尿白蛋白/肌酐比值(UACR),依据基线和随访年每年1次的TyG指数,计算TyG指数的均值和TyG指数变异性。根据《中国糖尿病肾脏病防治指南(2021年版)》的诊断标准诊断DKD。根据随访结束时患者是否发生DKD将其分为DKD组和无糖尿病肾脏病(NDKD)组,按照TyG指数的均值将患者分为T_(1)组(TyG指数均值<8.67)、T_(2)组(8.67≤TyG指数均值<9.09)和T_(3)组(TyG指数均值≥9.09),根据TyG指数的变异性将患者分为T′_(1)组(TyG指数变异性<0.29)、T′_(2)组(0.29≤TyG指数变异性<0.43)和T′_(3)组(TyG指数变异性≥0.43)。采用两独立样本t检验比较DKD组和NDKD组患者相关指标的差异,采用Cox比例风险回归模型研究TyG指数及其变异性与DKD之间的关系,采用广义线性混合模型探讨TyG指数等因素对DKD的影响。结果随访时间为(7.27±3.48)年。随访结束时,1986例T2DM患者中,DKD组676例,NDKD组1310例。与NDKD组相比,DKD组T2DM患者的UACR、TyG指数均值及TyG指数变异性均更高,而eGFR更低(均P<0.05)。Cox比例风险回归模型结果显示,校正混杂变量后,相较于T_(1)组,T_(3)组T2DM患者发生DKD的风险最高,较T 1组升高68.9%(HR=1.689,95%CI 1.376~2.073,P<0.001);相较于T′1组,T′3组T2DM患者发生DKD的风险最高,较T′_(1)组升高74.2%(HR=1.742,95%CI 1.421~2.135,P<0.001)。广义线性混合模型结果显示,随访过程中每年的TyG指数对DKD的发生有明显影响(β=0.244,95%CI 0.111~0.376,P<0.001)。结论TyG指数及其变异性的升高都会增加T2DM患者的DKD发病风险,TyG指数及其变异性均是DKD发生的独立危险因素。

Objective To investigate the effects of triglyceride-glucose(TyG)index and its variability on diabetic kidney disease(DKD)in patients with type 2 diabetes mellitus(T2DM).Methods This study was a prospective cohort study.A total of 1986 patients with T2DM who had regular visits at 6 centers of the Lee′s United Clinics in Taiwan,China from January 1,2002 to December 31,2018 and no DKD at baseline were selected as the study subjects,and prospective follow-up was performed.Age,sex,serum creatinine,triglycerides(TG),fasting plasma glucose(FPG),urine microalbumin and urine creatinine were collected,and the TyG index,estimated glomerular filtration rate(eGFR)and urinary albumin-to-creatinine ratio(UACR)were calculated,and the mean value of TyG index and the variability of TyG index were calculated according to the TyG index once a year at baseline and follow-up years.DKD was diagnosed according to the diagnostic criteria of the Clinical guideline for the prevention and treatment of diabetic kidney disease in China(2021 Edition).According to whether the patients had DKD at the end of the follow-up,they were divided into DKD group and non-diabetic kidney disease(NDKD)group,and according to the mean value of TyG index,the patients were divided into T_(1) group(mean TyG index<8.67),T_(2) group(8.67≤mean TyG index<9.09)and T_(3) group(mean TyG index≥9.09),and according to the variability of TyG index,the patients were divided into T′_(1) group(TyG index variability<0.29)and T′_(2) group(0.29≤TyG index variability<0.43)and T′_(3) group(TyG index variability≥0.43).The t-test of two independent samples was used to compare the differences in the relevant indexes between the DKD group and the NDKD group,the Cox proportional hazards regression model was used to study the relationship between TyG index and DKD,and between TyG index variability and DKD,and the generalized linear mixed model was used to explore the effects of factors including TyG index on DKD.Results The follow-up period was(7.27±3.48)years.At the end of follow-up,of the 1986 patients with T2DM,676 were in the DKD group and 1310 were in the NDKD group.Compared with the NDKD group,the UACR,mean TyG index and TyG index variability in patients with T2DM in the DKD group were higher,while the eGFR was lower(all P<0.05).The results of Cox proportional hazards regression model showed that after adjusting for confounding variables,the risk of DKD in patients with T2DM in the T_(3) group was the highest compared with that in the T_(1) group,which was 68.9%higher than that in the T_(1) group(HR=1.689,95%CI 1.376-2.073,P<0.001);compared with the T′_(1) group,the risk of DKD was highest in the T′_(3) group,which was 74.2%higher than that in the T′_(1) group(HR=1.742,95%CI 1.421-2.135,P<0.001).The results of the generalized linear mixed model show that the TyG index of each year during the follow-up process has a significant effect on the occurrence of DKD(β=0.244,95%CI 0.111-0.376,P<0.001).Conclusion Elevated TyG index and its variability both increase the risk of DKD in patients with T2DM,and the TyG index and its variability are independent risk factors for the DKD.