Impact of Glucose Tolerance and Its Change on Incident Proteinuria: Analysis of a Nationwide Population-Based Dataset

Abstract

Introduction: Although diabetes mellitus (DM) increases the risk of proteinuria, the relationship between prediabetes and proteinuria remains not fully understood. Further, whether the change in glucose is associated with the risk for proteinuria is unknown. Methods: This was a retrospective cohort study that included 1,849,074 participants (median age, 45 years; 59.3% men). No participants were taking glucose-lowering medications, and none had positive proteinuria at the initial health check-up. Each participant was categorized into three groups: normal (hemoglobin A1c [HbA1c] of <5.7%, n = 1,563,121), prediabetes (HbA1c of 5.7-6.4%, n = 253,490), and DM (HbA1c of ≥6.5%, n = 32,463) groups. We investigated the association between each HbA1c category and incident proteinuria using Cox proportional hazards models. We analyzed the association between the annual change in HbA1c and the risk for proteinuria. Results: A total of 65,954 participants developed proteinuria during the observation period. Not only DM (hazard ratio [HR]: 2.15, 95% confidence interval [CI]: 2.07-2.24) but also prediabetes (HR: 1.14, 95% CI: 1.12-1.17) was associated with a greater risk for proteinuria. The relative risk reduction for proteinuria that was associated with prediabetes and DM was 12.3% and 53.5%, respectively. An annual increase in HbA1c was associated with a greater risk for proteinuria. This association was more pronounced in participants having prediabetes. Conclusion: Not only DM but also prediabetes increased the risk for proteinuria. The influence of change in HbA1c on incident proteinuria was pronounced in people with prediabetes. Optimizing glucose would provide more benefit to individuals having prediabetes for proteinuria prevention.