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. 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. A retrospective cohort study. 278,628 Korean adults without nephrolithiasis who underwent a comprehensive health examination between 2011 and 2017. Glucose level, glycated hemoglobin level, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Nephrolithiasis ascertained using abdominal ultrasound. 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. 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. Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available. 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.