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Rationale and objective Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. Methods We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. Results Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients’ BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. Conclusion Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.

Background: Previous research has indicated that there are significant sex differences in serum BDNF levels and metabolic indicators in patients with schizophrenia. Studies have found that BDNF is involved in blood sugar regulation. Homeostasis model assessment of insulin resistance (HOMA-IR) is currently a sensitive indicator for measuring insulin resistance. Our study aims to explore the sex differences in the relationship between serum BDNF levels and HOMA-IR in patients with chronic schizophrenia (CS).Methods: A total of 332 patients with CS were enrolled in this study. General information of all participants was collected. Haematological indicators were collected, and the Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychiatric symptoms. Sex differences in serum BDNF levels, HOMA-IR index and other metabolic indexes were investigated. Then, linear regression analysis was used to analyse the relationship between the HOMA-IR index and BDNF levels in male and female patients.Results: The HOMA-IR index of female patients was significantly higher than that of males, but there was no significant difference in serum BDNF levels between male patients and female patients. There was a positive correlation between BDNF level and HOMA-IR index, and this relationship only existed in female patients.Conclusion: The results show that there are significant sex differences in HOMA-IR in patients with CS. In addition, only in female patients was there a positive correlation between the HOMA-IR index and BDNF level, which suggests that sex factors should be taken into account in evaluating the relationship between BDNF and blood glucose in patients with CS.