Lower insulin resistance in Chinese patients with severe major depressive disorder: associations with the inflammatory response

BACKGROUND: Major depressive disorder (MDD) is widely acknowledged as stemming from the dysregulation of neuroimmune, metabolic, and oxidative stress (NIMETOX) pathways. The objective of this study was to examine insulin metabolism in Chinese patients with MDD and to examine the relationship between insulin resistance and the acute-phase protein (APP) response, as indicated by lower albumin and transferrin. METHODS: This investigation utilized a cross-sectional case-control approach, enrolling 125 inpatients with MDD and 40 healthy controls. RESULTS: Compared with controls, patients with MDD showed lower fasting plasma glucose, insulin, and insulin resistance, together with higher insulin sensitivity. These differences remained significant after adjustment for metabolic syndrome (MetS), body mass index (BMI), and age, but disappeared after adjustment for the negative APP response. Elevated BMI, albumin, transferrin, and age explained 41.4% of the variance in insulin resistance. Insulin resistance was inversely associated with weight loss. In addition, 27.7% of the variance in overall depression severity was explained by adverse childhood experiences (positive association) and insulin resistance (negative association). CONCLUSIONS: These findings indicate that, in this Chinese cohort with a relatively low prevalence of comorbid MetS and obesity, severe MDD is associated with lower insulin resistance and higher insulin sensitivity in relation to inflammatory APPs. Therefore, MDD does not appear to be intrinsically associated with increased insulin resistance. Rather, it may be accompanied by a compensatory, hormesis-like response that enhances insulin sensitivity, thereby optimizing glucose utilization to support normal organ function.