Association of glucose metabolism with advanced cardiovascular-kidney-metabolic syndrome and prediction model development in type 2 diabetes mellitus

Cardiovascular-Kidney-Metabolic (CKM) syndrome, characterized by progressive dysfunction of the cardiovascular, renal, and metabolic systems, has gained increasing recognition in recent years. However, the relationship between glucose metabolism and advanced CKM stages in type 2 diabetes mellitus (T2DM) remains insufficiently explored. To investigate the association between glucose metabolism and advanced CKM stages, and to develop and validate a prediction model for advanced CKM syndrome in Chinese adults with T2DM. This cross-sectional study enrolled 3,410 patients with T2DM, who were classified into CKM stages 1–4. Glucose metabolism was evaluated using fasting and post-load insulin, C-peptide, HOMA-β, disposition index (DI), HOMA-IR, QUICKI, Matsuda index, and ISI. Associations between glucose metabolic indices and advanced CKM stages (stages 3–4) were examined using logistic regression and restricted cubic spline (RCS) models. A prediction model for advanced CKM syndrome was subsequently developed and validated by assessing the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis. Among the participants, CKM stages 1–4 accounted for 18.6%, 50.8%, 28.8%, and 1.9%, respectively. Advanced CKM stages (3–4) were more prevalent among older and male patients. As CKM stages progressed, markers of insulin resistance (HOMA-IR, fasting insulin, C-peptide, HOMA-β) significantly increased, while β-cell function and insulin sensitivity indices (QUICKI, Matsuda index, ISI) decreased (all p < 0.001). Higher quartiles of fasting insulin, C-peptide, HOMA-IR, and HOMA-β were positively associated with advanced CKM syndrome, while better insulin sensitivity and preserved β-cell function exhibited protective effects. The developed prediction model demonstrated excellent discrimination (AUC = 0.935), strong calibration, and favorable clinical utility. Advanced CKM syndrome is strongly associated with impaired glucose metabolism in Chinese adults with T2DM. The validated prediction model based on glucose metabolism may facilitate early identification and targeted management of individuals with a high likelihood of advanced CKM syndrome.