Risk Evaluation of Progression of Proteinuria and Renal Decline Based on a Novel Subgroup Classification in Chinese Patients with Type 2 Diabetes

Introduction: Type 2 diabetes mellitus (T2DM) is a highly heterogeneous disease with a varying risk of complications. The recent novel subgroup classification using cluster analysis contributed to the risk evaluation of diabetic complications. However, whether the subgroup classification strategy could be adopted to predict the risk of onset and progression of diabetic kidney disease (DKD) in Chinese individuals with T2DM remains to be elucidated.

Methods: In this retrospective study, 612 Chinese patients with T2DM were enrolled, and the median follow-up time was 3.5 years. The T2DM subgroups were categorized by a two-step cluster analysis based on five parameters, including age at onset of diabetes, body mass index (BMI), glycosylated hemoglobin (HbA1c), homeostasis model assessment 2 of insulin resistance (HOMA2-IR), and homeostasis model assessment 2 of β-cell function (HOMA2-β). Clinical characteristics across subgroups were compared using t-tests and chi-square tests. Furthermore, multivariate logistic regression models were adopted to assess the risk of albuminuria progression and renal function decline among different subgroups.

Results: The cohort was categorized into four groups: severe insulin-deficient diabetes (SIDD), with 146 patients (23.9%); mild insulin resistance (MIRD), with 81 patients (13.2%); moderate glycemic control diabetes (MGCD), with 211 patients (34.5%); and moderate weight insulin deficiency diabetes (MWIDD), with 174 patients (28.4%). The MIRD group exhibited an increased risk of progression from non-albuminuria to albuminuria as compared with the MWIDD group, with an adjusted odds ratio (OR) and 95% confidence interval (CI) of 2.92 (1.06, 8.04). The SIDD group had a higher risk of progression from micro-albuminuria to macro-albuminuria as compared with the MGCD group, with an adjusted OR and 95% CI of 3.39 (1.01, 11.41). There was no significant difference in the glomerular filtration rate (GFR) decline among all groups.

Conclusion: The present study offered the first evidence for risk evaluation of the development of DKD in the novel cluster-based T2DM Chinese subgroups. It suggested that the MIRD subgroup had a higher risk of DKD onset than the MWIDD subgroup. Meanwhile, the SIDD subgroup showed a higher risk of progression of albuminuria than the MGCD subgroup. This novel classification system could be effective in predicting the risk of DKD in Chinese patients with T2DM, which could facilitate the implementation of personalized therapeutic strategies.

Trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2300077183).