Abstract
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. 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.
Highlights
Chronic kidney disease (CKD) affects approximately 10% to 15% of the adult general population worldwide
In multivariable-adjusted Cox proportional hazards models, the TyG index was significantly associated with the risk of end-stage kidney disease (ESKD), both with and without (HR per 1-SD increase, 1.79; 95% CI, 1.66-1.93) the inclusion of body mass index (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 was mediated through the TyG index (HR [indirect association], 1.21; 95% CI, 1.18-1.25)
Summary
Chronic kidney disease (CKD) affects approximately 10% to 15% of the adult general population worldwide. The numbers are increasing owing to the growing aging population and lifestyle changes associated with an increased prevalence of obesity, hypertension, and diabetes.[1,2,3] The increase in obesity prevalence is reported worldwide and is estimated to further increase by 40% by 2027.4 Globally, obesity is associated with a 36% increased risk of CKD in the general population.[5,6] Individuals who are obese have a more than 3-fold higher risk of developing end-stage kidney disease (ESKD) than those with normal body weight.[7,8,9] End-stage kidney disease and the subsequent kidney replacement therapy represent a major burden for individuals and health care systems.[10,11]. In addition to and independent of the later development of diabetes, insulin resistance per se is associated with glomerular hyperfiltration, sodium retention, defective tubular reabsorption, tissue inflammation, and fibrosis.[14,15,16]
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