The effect of HbA1C variability on the development and progression of diabetic nephropathy.

Objective: Diabetes mellitus (DM) is a prevalent chronic disease that can lead to severe microvascular complications. Among these, diabetic nephropathy (DN) remains a leading cause of end-stage renal disease worldwide. Glycemic variability, reflecting fluctuations in blood glucose, has been suggested as a potential predictor of DM complications. This study aimed to investigate whether visit-to-visit HbA1c variability contributes to the development and progression of DN in patients with DM. Methods: In this retrospective cohort study, 228 patients were selected from 2,000 individuals diagnosed with DM between January 2007 and December 2017. A total of 80 patients without DN at baseline (ODN) and 148 patients with DN at baseline (WDN) were included in the study. HbA1c was measured 2-4 times per year over 3-5 years. Mean, standard deviation (SD), and coefficient of variation (CV) of HbA1c were calculated. Annual urea, creatinine, and albumin/protein levels were recorded. Logistic regression identified independent risk factors. Results: DN developed in 47 (58.8%) patients in the ODN group, whereas progression occurred in 44 (29.7%) patients in the WDN group. In the ODN group, higher HbA1c mean, SD, CV, hypertension, and albuminuria were significantly associated with DN onset (p<0.05). Logistic regression analysis confirmed HbA1c variability and hypertension as independent predictors. No significant association was found between HbA1c variability and DN progression. Conclusions: Variability in HbA1c is linked to the onset of DN but not its progression. These findings highlight the need for strategies targeting glycemic stability in DM management. Larger, multicenter prospective studies are warranted to confirm these results.