Cumulative estimated glucose disposal rate, atherogenic index of plasma, and incident cardiometabolic multimorbidity: a prospective cohort study

Insulin resistance and atherogenic dyslipidemia are key interrelated processes in the development of cardiometabolic multimorbidity (CMM). Although estimated glucose disposal rate (eGDR) and atherogenic index of plasma (AIP) have been linked to CMM, whether they provide complementary information when evaluated simultaneously remains unclear. This prospective cohort study included 4,215 participants from the China Health and Retirement Longitudinal Study. Cumulative eGDR and cumulative AIP were calculated using repeated measurements from Wave 1 and Wave 3. Participants were followed from Wave 3 to Wave 5 for incident CMM. Cox regression models, restricted cubic splines, interaction analyses, and prognostic performance analyses were performed. During a median follow-up of 5.0 years, 452 participants developed incident CMM. In the mutually adjusted model, each 1-SD increase in cumulative eGDR was associated with a lower risk of incident CMM (HR, 0.57; 95% CI, 0.52–0.63), whereas each 1-SD increase in cumulative AIP was associated with a higher risk (HR, 1.17; 95% CI, 1.06–1.28). Joint analysis further differentiated risk. Compared with participants with high cumulative eGDR and low cumulative AIP, the fully adjusted HRs were 1.50 (95% CI, 1.05–2.14), 2.19 (95% CI, 1.58–3.02), and 3.83 (95% CI, 2.89–5.06) for those with high eGDR and high AIP, low eGDR and low AIP, and low eGDR and high AIP, respectively. Positive additive interaction was observed, whereas multiplicative interaction was not statistically significant. The prognostic contributions of the two indices were unequal. Adding cumulative AIP to a model containing cumulative eGDR resulted in statistically significant but modest improvements in reclassification, whereas adding cumulative eGDR to cumulative AIP produced larger improvements. The model incorporating cumulative eGDR and cumulative AIP also showed better prognostic performance than the corresponding cumulative triglyceride-glucose index (TyG)–AIP model, as reflected by improvements in continuous net reclassification improvement and integrated discrimination improvement. Findings were consistent across subgroup and sensitivity analyses. Cumulative eGDR and cumulative AIP were both associated with incident CMM after mutual adjustment and provided complementary risk information. Participants with low cumulative eGDR and high cumulative AIP had the highest CMM risk, with evidence of positive additive interaction. Not applicable.