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

Abstract

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.

Keywords: Cohort study; abdominal ultrasonography; glycemic status; hemoglobin A(1c) (HbA(1c)); hyperglycemia; insulin resistance; kidney stone; modifiable risk factor; nephrolithiasis; prediabetes; sex differences.