Predictive value of an integrated insulin resistance and lipometabolic score for cardiometabolic multimorbidity in older adults: a UK cohort study

BACKGROUND: Markers of insulin resistance, such as the triglyceride-glucose (TyG) index and estimated glucose disposal rate (eGDR), have been extensively linked to cardiometabolic multimorbidity (CMM). However, the roles of lipid metabolism indicators, including the atherogenic index of plasma (AIP) and remnant cholesterol (RC), remain less clearly defined. This study aimed to evaluate both the individual and combined effects of insulin resistance and dyslipidemia on the risk of CMM. METHODS: Data were derived from the English Longitudinal Study of Ageing. A composite metabolic index integrating the TyG, eGDR, AIP, and RC was developed using principal component analysis. The associations of individual and composite indices with incident CMM were examined using multivariable Cox proportional hazards models, while their predictive performance was assessed via receiver operating characteristic (ROC) and net reclassification improvement (NRI) analysis. RESULTS: Over a 6.8-year follow-up period, 552 cases of CMM occurred among 4232 participants. After multivariable adjustment, each standard deviation (SD) increase in TyG, AIP, and RC was linked to a higher risk of CMM by 30.8% (HR = 1.308; 95% CI: 1.202-1.422), 22.2% (HR = 1.222; 95% CI: 1.117-1.338), and 7.6% (HR = 1.076; 95% CI: 1.025-1.129), respectively. In contrast, eGDR and the composite metabolic index were linked to 35.0% (HR = 0.650; 95% CI: 0.565-0.747) and 37.4% (HR = 0.626; 95% CI: 0.554-0.707) lower risks of CMM. The eGDR and CompositeIndex showed high Population attributable fraction (PAF) of 56.3% (95% CI: 47.3-63.4) and 38.3% (95% CI: 29.8-47.8), respectively. Dose-response analyses showed near-linear relationships for all indices. ROC and NRI analysis further indicated that the CompositeIndex offered highest discrimination with a modest improvement for CMM (AUC = 0.754, 95% CI: 0.737-0.778; NRI = 0.066 (0.027-0.106). The associations were more pronounced among participants younger than 65 years and consistent across sex. CONCLUSIONS: The integrated index combining insulin resistance and lipid dysregulation was associated with incident CMM and provided modest improvements in risk discrimination and reclassification beyond traditional risk factors.