Frontiers in Endocrinology · Oct 30, 2026
A Retrospective Cohort Study on the Dynamic Changes of Different Prediabetes Subtypes to Early Kidney Function Impairment
By Rui Yu, Wei Chuan Yuan, Yan Jiang et al.
Objective: Based on a previously established prediabetes subtype classification, this retrospective cohort study aimed to investigate the differential risks of dynamic changes to early glomerular filtration function impairment across PD subtypes and to explore potential underlying mechanisms. Methods: The study employed a retrospective cohort design, enrolling 3,819 patients with prediabetes identified from health examinations at the Health Management Center of the First Affiliated Hospital of Xinjiang Medical University between 2023 and 2025. Baseline data comprised age, sex, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose , triglycerides , high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase, and cystatin C , from which the eGFRcys, TyG index, and TG/HDL-C ratio were derived. Subtypes were classified using the clara clustering algorithm. The outcome was defined as at least one annual eGFRcys measurement <90ml·min⁻¹·(1.73 m²)⁻¹ during the 2023–2025 period. A mixed-effects interaction model was applied to evaluate the interaction between subtype grouping and follow-up time on eGFRcys positivity rates. Results: The cohort (mean age 49.91±11.87 years; 67.2% male) was classified into three subtypes: age-related (n=1,489), relatively healthy (n=1,113), and severe metabolic disturbance (n=1,217). Over the three-year follow-up, eGFRcys positivity rates exhibited a V-shaped trend across all subtypes. The age-related group consistently showed the highest rates, the relatively healthy group the lowest, and the severe metabolic disturbance group intermediate, with the absolute risk gradient between groups remaining stable.. Mixed-effects modeling revealed that, compared with the age-related subtype, the relatively healthy (OR=0.0795%CI 0.06–0.10) and severe metabolic disturbance (OR=0.33,95%CI 0.26–0.43) subtypes had significantly lower eGFRcys positivity rates (both P<0.001). Time effects showed gradual increases in positivity rates in 2024 and 2025 versus 2023 (both P<0.001). Significant positive interactions with the year 2025 were observed for both the relatively healthy (OR=2.17, 95%CI 1.59–2.97, P<0.001) and severe metabolic disturbance (OR=1.38,95%CI 1.04–1.84, P=0.027) subtypes.. Conclusion: Three distinct heterogeneous subtypes exist among patients with prediabetes, differing in their risk of transient eGFRcys decline, which may serve as an early marker of renal impairment.. Despite dynamic fluctuations in eGFRcys positivity rates during follow-up, the stable risk gradient among subtypes supports the utility of subtype classification for risk stratification in this population.