Diabetes Research and Clinical Practice · Nov 14, 2026

Cumulative exposure and longitudinal changes in KDM age Acceleration-Integrated insulin resistance indices in relation to incident cardiometabolic multimorbidity among individuals with Cardiovascular-Kidney-Metabolic syndrome stages 0–3: A prospective cohort study

By Tan MY, Jiang ZN, Huang SJ

Background Insulin resistance (IR) and biological aging may jointly contribute to cardiovascular-kidney-metabolic (CKM) syndrome progression, but longitudinal evidence for cardiometabolic multimorbidity (CMM) is limited. Methods Using the China Health and Retirement Longitudinal Study, we included participants with CKM stages 0–3 who were free of CMM. KDM age acceleration was integrated with TyG and related IR indices. Cox models assessed baseline and Wave 3 levels, cumulative exposure, annualized change, and longitudinal exposure profiles in relation to incident CMM. Predictive performance was evaluated using the C-index, time-dependent AUC, Brier score, and reclassification metrics. Results Higher baseline and Wave 3 levels of all KDM age acceleration-integrated IR indices were associated with higher CMM risk when modeled continuously, whereas associations with cumulative exposure were less consistent. Per 1-SD increase, the adjusted HRs were 1.28, 1.24, and 1.21 for baseline, Wave 3, and cumulative KDM age acceleration × TyG, respectively. In exploratory longitudinal exposure-profile analyses, higher-level profiles were associated with increased CMM risk for several indices, although these profiles mainly reflected relative exposure levels across the two assessments rather than distinct temporal trajectories. The cumulative KDM age acceleration × TyG model achieved an optimism-corrected C-index of 0.762 and a 5-year AUC of 0.770. Conclusions Higher single-time-point levels of KDM age acceleration-integrated IR indices were associated with incident CMM, whereas associations with cumulative exposure were less consistent and annualized changes were not significantly associated with risk. Incremental predictive performance was modest.

doi.org/10.1016/j.diabres.2026.113665PubMed 43034020Biomarkers