Identification of two novel subgroups in patients with diabetes mellitus and their association with clinical outcomes: A two-step cluster analysis

Aims/introduction: The aim of this study was to determine whether distinct subphenotypes of patients with type 2 diabetes in the European classification exist in Chinese populations, and to further establish novel subphenotypes more suitable for Chinese populations.

Material and methods: The research retrospectively analyzed 5414 patients with type 2 diabetes from the National Clinical Research Center for Metabolic Diseases Diabetes Center in China, and a two-step cluster analysis was carried out. First, we confirmed the European classification in Chinese populations by six parameters, including age at disease onset, body mass index, glycosylated hemoglobin, homeostatic model assessment 2 to estimate β-cell function and insulin resistance, and glutamate decarboxylase antibodies. Furthermore, triglycerides and uric acid were added to refine the cluster analysis, and Cox regression was used to evaluate the risk of diabetic complications.

Results: Just three clusters were replicated in our cohort according to Emma Ahlqvist's European classification. When other variables were added to the cluster analysis, seven subgroups were identified, including five clusters of the European classification and two novel subgroups, namely, uric acid-related diabetes and inheritance-related diabetes. Compared with patients with inheritance-related diabetes, patients with severe insulin-resistant diabetes showed a higher risk of diabetic peripheral neuropathy, hypertension and chronic kidney disease, and the uric acid-related diabetes subgroup showed a higher risk of coronary heart disease, cerebral vascular disease and end-stage renal disease. Patients with severe insulin-deficient diabetes showed a higher risk of diabetic retinopathy and diabetic foot than those with inheritance-related diabetes. Furthermore, there were sex-specific associations between subgroups and clinical outcomes. No significant difference was observed in the prevalence of cancer in each subgroup.

Conclusions: Seven subgroups of type 2 diabetes were identified in Chinese populations, with distinct characteristics and disparate clinical outcomes. This etiology-based stratification might contribute to the diagnosis and management of type 2 diabetes.