Impact of Triglyceride-to-High-Density Lipoprotein Cholesterol Ratio as a Hyperinsulinemia Marker of Kidney Function Decline

Background: The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is known as a surrogate marker for hyperinsulinemia, which underlies obesity, and is also an excellent predictor of progression to type 2 diabetes. This study aims to investigate whether hyperinsulinemia can predict renal function decline in the absence of diabetes and obesity using the proxy marker TG/HDL-C ratio. Methods: This single-institutional observational study in Japan targeted individuals who had annual health check-ups measuring creatinine, TG, HDL-C, and body mass index (BMI) from 2012 to 2022. Exclusion criteria included individuals under 18, those with an initial estimated glomerular filtration rate (eGFR) below 45, blood test results for less than one year, and initial hemoglobin A1c (HbA1c) levels of 6.5% or higher. Participants were divided into two groups based on their baseline TG/HDL-C ratio and BMI. The TG/HDL-C threshold was set at 2.1, based on the previous report, and the BMI threshold was set at 23, according to Asian overweight criteria. The primary endpoint was the time to an eGFR decline below 45, analyzed using time-to-event analysis. Results: A total of 3,914 individuals met the criteria (mean age: 50.0 years, 44.5% male, mean BMI: 23.0, mean eGFR: 75.1). During the observation period, 135 individuals (3.5%) developed diabetes, with the incidence rate being 2.51 times higher in the high TG/HDL-C group compared to the low group. Univariate analysis showed that the high TG/HDL-C group had significantly worse renal function (Log-rank p<0.01, hazard ratio 2.2 [1.3-4.0])(Figure). Further analysis of 2,022 non-obese individuals (BMI<23) showed similar results (Log-rank p<0.01). Conclusion: The TG/HDL-C ratio, a surrogate marker for hyperinsulinemia, was associated with renal function decline in non-diabetic individuals. This association persisted even in non-obese individuals.