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

Abstract 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 clarify the relationship between insulin resistance and the acute phase protein (APP) response, as shown by the negative APPs albumin and transferrin. Methods This investigation utilized a cross-sectional case-control approach, enrolling 125 inpatients with MDD and 40 healthy controls. Results Patients with MDD exhibited markedly reduced levels of fasting plasma glucose, insulin, and insulin resistance, and heightened insulin sensitivity, in comparison to healthy controls. The significance of these alterations persisted after controlling for metabolic syndrome, body mass index (BMI), and age, but was nullified with adjustment for both negative APPs. We determined that 41.4% of the variance in insulin resistance was accounted for by elevated levels of BMI, albumin, transferrin, and age. Insulin resistance was significantly and inversely associated with weight loss. We found that 27.7% of the variance in overall depression severity was accounted for by adverse childhood experiences (positive correlation) and insulin resistance (negative correlation). Conclusions This work demonstrates that Chinese MDD patients display increased insulin sensitivity and reduced insulin resistance, with these alterations being associated with a modest smoldering inflammatory response. MDD is characterized by a hormetic response that enhances insulin efficacy, hence optimizing glucose consumption to sustain normal organ function. It is incorrect to claim that MDD is intrinsically associated with increased insulin resistance.