Combined effects of insulin resistance and dyslipidaemia on cardiometabolic multimorbidity in Chinese middle-age and older adults: a longitudinal cohort study

Cardiometabolic multimorbidity (CMM), defined as the coexistence of ≥ 2 cardiometabolic diseases, is a significant public health burden. Insulin resistance and dyslipidaemia are key risk factors for CMM; however, their combined effects remain unexplored. As such, the present study investigated the individual and combined associations of the estimated glucose disposal rate (eGDR, a marker of insulin resistance) and remnant cholesterol (RC [reflecting dyslipidaemia]) with the incidence of CMM. A longitudinal cohort of 7094 participants ≥ 45 years of age from the China Health and Retirement Longitudinal Study was analysed. Participants were divided into four groups based on the optimal cut-off values for eGDR (9.13 mg/kg/min) and RC (13.53 mg/dL). Cox regression models were used to evaluate associations, whereas cross-lagged and mediation analyses were used to explore temporal and mechanistic relationships. The stability of the results was examined through various subgroup analyses (age, sex, smoking, alcohol consumption, body mass index, residential area, and hypertension) and three sensitivity analyses (excluding participants with missing covariate data, follow-up duration < 2 years, or non-fasting blood samples at baseline). In total, 856 CMM cases were reported over a nine-year period. Compared with the high-eGDR/low-RC group, the low-eGDR/high-RC group had a 3.42-fold higher risk (hazard ratio [HR] 3.42 [95% confidence interval (CI) 2.68-4.37]). Independently, low eGDR and high RC increased the risk for CMM by 153% (HR 2.53 [95% CI 2.18-2.94]) and 53% (HR 1.53 [95% CI 1.31-1.80]), respectively. No synergistic interaction was observed between eGDR and RC (P > 0.05). Cross-lagged analysis revealed bidirectional effects between eGDR and RC, with baseline eGDR exerting a stronger influence on subsequent RC. Mediation analysis revealed that 44.3% of the effect of RC on CMM was mediated by a reduced eGDR. Concurrent low eGDR and high RC were associated with the highest risk for CMM, highlighting the importance of dual assessment for early prevention. These findings underscore insulin resistance and dyslipidaemia as key targets for mitigating the burden of CMM.