Glycemic Status, Insulin Resistance, and the Risk of Nephrolithiasis: A Cohort Study.

Rationale & Objective The effect of glycemic status on nephrolithiasis risk remains controversial. This study sought to examine the association of glycemic status and insulin resistance with incident nephrolithiasis. Study Design A retrospective cohort study. Setting & Participants 278,628 Korean adults without nephrolithiasis who underwent a comprehensive health examination between 2011 and 2017. Exposures Glucose level, glycated hemoglobin level, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Outcome Nephrolithiasis ascertained using abdominal ultrasound. Analytical Approach A parametric proportional hazard model was used to estimate adjusted HRs and 95% CIs. We explored prespecified potential sex differences in the association of glycemic status and incident nephrolithiasis. Results During a median follow-up of 4.2 years, 6,904 participants developed nephrolithiasis. Associations between levels of glycemic status and incident nephrolithiasis were examined separately in men and women (P for interaction = 0.003). Among men, multivariable-adjusted HRs for incident nephrolithiasis comparing glucose levels of 90-99, 100-125, and 126- Limitations Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available. Conclusions Glycemic status, even within the nondiabetic range, and HOMA-IR were positively associated with increased risk for nephrolithiasis, associations that were only observed among men. Insulin resistance and hyperglycemia may contribute to the development of nephrolithiasis, particularly among men.