Proinflammatory biomarkers are associated with prediabetes in patients with schizophrenia

Objective: Treatment with antipsychotics is associated with an increased risk of type 2 diabetes mellitus (T2D), and increased levels of inflammatory biomarkers are present in patients with T2D. We previously demonstrated that the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. This study aims to assess the involvement of cytokines in the therapeutic effects of liraglutide. 35 Methods: Serum concentrations of 10 cytokines (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13) from fasting prediabetic and normal glucose tolerant (NGT) patients with schizophrenia-spectrum disorders were measured using multiplexed immunoassays. Prediabetic patients were randomized to 16 weeks of treatment with liraglutide or placebo 39 and cytokines were measured again at the end of the treatment. Results: IFN-γ (1.98 vs. 1.17 pg/ml, P = 0.001), IL-4 (0.02 vs. 0.01 pg/ml, P < 0.001) and IL-6 (0.73 vs. 0.46 pg/ml, P < 0.001) were significantly higher in prediabetic (n=77) vs. NGT patients (n=31). No significant changes in cytokine levels following treatment with 4liraglutide (n=37) vs. placebo (n=40) were found. 44 Conclusion: Prediabetic vs. NGT patients with schizophrenia treated with clozapine or 4olanzapine had increased serum levels of several proinflammatory cytokines, further 4substantiating the link between inflammation and T2D. Treatment with liraglutide did not 47 affect the investigated cytokines. Further testing of these findings in larger numbers of 4individuals is needed.