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 mg/dL were 1.10 (95% CI, 1.01-1.19), 1.11 (95% CI, 1.02-1.21), and 1.27 (95% CI, 1.10-1.46), respectively, while HRs for incident nephrolithiasis comparing glycated hemoglobin levels of 5.7%-5.9%, 6.0%-6.4%, and 6.5%-<5.7% were 1.03 (95% CI, 0.96-1.10), 1.18 (95% CI, 1.07-1.31), and 1.20 (95% CI, 1.06-1.37), respectively. The HR for incident nephrolithiasis comparing the highest HOMA-IR quintile to the lowest quintile was 1.18 (95% CI, 1.06-1.31). Among women, no apparent association was found between glycemic status and nephrolithiasis risk. Limitations: Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available. Conclusions: Higher glycemic values, even within the normoglycemic 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.