The association of combined metabolic score for insulin resistance and frailty index with incident cardiometabolic multimorbidity.

Abstract

Cardiometabolic multimorbidity (CMM), defined as the coexistence of two or more cardiometabolic diseases, poses a growing global health burden. However, few studies have jointly evaluated the risk of CMM using indicators of both insulin resistance and frailty. Using data from the China Health and Retirement Longitudinal Study (CHARLS), we constructed a composite index integrating the metabolic score for insulin resistance (METS-IR) and the frailty index (FI) and investigated its association with incident CMM among 2,968 middle-aged and older Chinese adults. During the follow-up period, 230 participants (7.75%) developed CMM. In fully adjusted Cox regression models, each 1-SD increase in baseline and cumulative METSIR-FI was associated with a 35% (HR = 1.35, 95%CI: 1.22-1.49) and 45% (HR = 1.45, 95%CI: 1.31-1.61) higher risk of CMM, respectively. Participants in the highest tertile of baseline METSIR-FI had a significantly higher risk of CMM (HR = 2.78, 95%CI: 1.79-4.30), with even stronger associations observed for cumulative METSIR-FI (HR = 4.29, 95%CI: 2.63-6.98) and the highest-risk cluster (HR = 3.69, 95%CI: 2.46-5.55). Restricted cubic spline analyses revealed significant nonlinear dose-response relationships with threshold effects. Incorporating METSIR-FI into conventional risk models improved the C-statistic from 71.32% to 77.47%, with significant net reclassification improvement and integrated discrimination improvement. These findings suggest that a joint metabolic-frailty burden indicator provides incremental prognostic value beyond conventional risk factors and may serve as a practical composite indicator for CMM risk stratification among middle-aged and older adults.