L-shaped association between fasting blood glucose and comorbid anxiety in Chinese patients with first-episode untreated major depressive disorder

BACKGROUND Major depressive disorder (MDD) frequently presents with comorbid anxiety, complicating treatment outcomes. While glucose metabolism dysfunction has been linked to both depression and anxiety, the specific relationship between fasting blood glucose (FBG) levels and comorbid anxiety in MDD remains inadequately characterized. AIM To investigate the relationship between FBG and comorbid anxiety in individuals with first-episode untreated MDD. METHODS This cross-sectional study included 1718 participants with first-episode untreated MDD. Demographic, anthropometric, and biochemical parameters, including FBG, were collected. Depressive and anxiety symptoms were assessed using the 17-item Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale, respectively. Potential non-linear relationships were examined using smoothing curves and two-piecewise logistic regression analysis. RESULTS The betweengroup comparison indicated that patients comorbid with anxiety have significantly higher FBG levels than those without comorbid anxiety (P < 0.001). Smoothing curve analysis identified a non-linear (L-shaped) association, with a threshold of 4.8 mmol/L. Below this threshold, FBG was inversely associated with comorbid anxiety (OR = 0.20, 95%CI: 0.06-0.67, P = 0.009), whereas no significant association was observed above this threshold (OR = 1.22, 95%CI: 0.91-1.63, P = 0.188). CONCLUSION Our results suggest an L-shaped non-linear association: Lower FBG correlates with elevated comorbid anxiety risk in Chinese Han first-episode untreated MDD patients, particularly when FBG is below 4.8 mmol/L.