Key result
Combined low eGDR and depression linked to ~3-fold higher incident CVD risk.
Why the study?
Depression and insulin resistance measured by eGDR are both linked to cardiovascular disease, but whether eGDR mediates this relationship remains unclear.
Does the combination of insulin resistance (low eGDR) and depressive symptoms synergistically increase the risk of incident cardiovascular disease in adults without prior CVD?
Cohort (n=6,311)
Yes
Does the combination of insulin resistance (low eGDR) and depressive symptoms synergistically increase the risk of incident cardiovascular disease in adults without prior CVD?
Hazard Ratio: 3.01 (95% CI 2.35–3.85)
Absolute Event Rate: 45.7% vs 18.2%
p-value: p=<0.001
Low estimated glucose disposal rate (a proxy for insulin resistance) and depressive symptoms synergistically elevate incident CVD risk, suggesting the clinical utility of combined metabolic and psychological screening.
May inform combined metabolic-mental health assessment in primary prevention; leaves open whether targeting either reduces incident CVD.
Background Depression and insulin resistance—measured by the estimated glucose disposal rate (eGDR)—are both linked to cardiovascular disease (CVD), but whether eGDR mediates this relationship remains unclear. We examined the mediating role of eGDR and its joint and interactive effects with depression on incident CVD. Methods Data were derived from the China Health and Retirement Longitudinal Study (2011–2020). Participants without baseline CVD and with complete eGDR and CESD-10 data were included. eGDR was calculated as 21.158 − (0.09 × waist circumference) − (3.407 × hypertension) − (0.551 × HbA1c). Depressive symptoms were defined as CESD-10 ≥ 12. Cox models adjusted for demographic and lifestyle factors assessed CVD risk across four groups defined by eGDR and depression status. Results During a median 9-years follow-up, 1643 CVD events occurred. Participants with low eGDR and depression had the highest CVD risk (HR = 1.87, 95% CI: 1.40–2.49, p < 0.001). Additive interaction analysis indicated biological synergy (relative excess risk = 1.37; attributable proportion = 0.32). eGDR mediated 9.82% of the depression–CVD association. Interactions were stronger in older adults. Conclusion Low eGDR and depressive symptoms synergistically elevate CVD risk, highlighting the importance of integrating metabolic and psychological assessments in CVD prevention.
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Chen et al. (2026) conducted a cohort in Incident cardiovascular disease (n=6,311). Co-occurrence of low estimated glucose disposal rate (eGDR) and depressive symptoms vs. High eGDR and no depressive symptoms was evaluated on Incident cardiovascular disease (occurrence of stroke or physician-diagnosed cardiac disease) (HR 3.01, 95% CI 2.35-3.85, p=<0.001). The co-occurrence of low estimated glucose disposal rate and depressive symptoms synergistically elevated the risk of incident cardiovascular disease by 3-fold (HR 3.01) compared to individuals with neither condition.
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