Novel Subgroups and Chronic Complications of Diabetes in Middle-Aged and Elderly Chinese:A Prospective Cohort Study

BACKGROUND: Diabetes mellitus, especially type 2 diabetes mellitus (T2DM), is regarded as highly heterogeneous. Novel diabetes phenotypes by cluster analysis have been proposed in Europeans but may show different cluster features in Asians. The applicability of cluster analysis in middle-aged and elderly Chinese community T2DM patients needs further investigation. METHODS: Participants were recruited from Jiading community in Shanghai, China. We adopted k-means cluster analysis in 1130 patients (aged ≥ 40 years) with newly-diagnosed T2DM at baseline. Cluster analysis was performed based on seven variables, including fasting plasma glucose, 2 hours postprandial blood glucose, age at diagnosis, body mass index, hemoglobin A1c, homoeostatic model assessment estimates of β-cell function and insulin resistance. All subjects were re-examined at 4.4 years later. Metabolic associated fatty liver disease was diagnosed using B-ultrasound, hepatic fibrosis by non-invasive scores, renal and cardiovascular status by subclinical biomarkers. Multivariable logistic regression models were used to compare the risks of complications between clusters. RESULTS: Patients were classified into 4 clusters. 381 (33.7%), 456 (40.4%), 87 (7.7%), and 206 (18.2%) patients were separately assigned to mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), severe insulin-deficient and insulin-resistant diabetes (SIDRD), or severe obesity-related and insulin-resistant diabetes (SOIRD), respectively. Participants in MARD, SOIRD, and SIDRD clusters were associated with significantly increased risks of different complications. SOIRD and SIDRD showed novel features in Chinese T2DM patients that were different from those in Europeans. CONCLUSIONS: The refined diabetes phenotypic approach was applicable to Chinese middle-aged and elderly T2DM patients. Patients in different clusters presented significantly different characteristics, progression of metabolic features, and risks of diabetic complications.