Psychiatric Centre Copenhagen, Rigshospitalet, Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark.
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
CNS Spectr. 2022 Jun;27(3):347-354. doi: 10.1017/S1092852920002217. Epub 2020 Dec 14.
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 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.
Serum concentrations of 10 cytokines (interferon-γ [IFN-γ], tumor necrosis factor-α, interleukin 1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and 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, and cytokines were measured again at the end of the treatment.
IFN-γ (1.98 vs 1.17 pg/ml, P = .001), IL-4 (0.02 vs 0.01 pg/ml, P < .001), and IL-6 (0.73 vs 0.46 pg/ml, P < .001) were significantly higher in prediabetic (n = 77) vs NGT patients (n = 31). No significant changes in cytokine levels following treatment with liraglutide (n = 37) vs placebo (n = 40) were found.
Prediabetic vs NGT patients with schizophrenia treated with clozapine or olanzapine had increased serum levels of several proinflammatory cytokines, further substantiating the link between inflammation and T2D. Treatment with liraglutide did not affect the investigated cytokines. Further testing of these findings in larger numbers of individuals is needed.
抗精神病药物治疗与 2 型糖尿病（T2D）风险增加相关，而 T2D 患者体内存在炎症生物标志物水平升高的情况。我们之前的研究表明，胰高血糖素样肽-1 受体激动剂利拉鲁肽可显著改善接受氯氮平或奥氮平治疗的、处于糖尿病前期的超重/肥胖精神分裂症谱系障碍患者的糖代谢紊乱和体重。本研究旨在评估细胞因子在利拉鲁肽治疗效果中的作用。
使用多重免疫分析法测量了 77 例处于糖尿病前期的精神分裂症谱系障碍患者和 31 例血糖正常的糖耐量患者（NGT）的空腹血清中 10 种细胞因子（干扰素-γ[IFN-γ]、肿瘤坏死因子-α、白细胞介素 1β[IL-1β]、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12p70 和 IL-13）的浓度。将糖尿病前期患者随机分为接受利拉鲁肽或安慰剂治疗 16 周，治疗结束时再次测量细胞因子。
与 NGT 患者（n=31）相比，处于糖尿病前期（n=77）的患者血清中 IFN-γ（1.98 vs 1.17 pg/ml，P=0.001）、IL-4（0.02 vs 0.01 pg/ml，P<0.001）和 IL-6（0.73 vs 0.46 pg/ml，P<0.001）的水平显著更高。与接受安慰剂治疗的患者（n=40）相比，接受利拉鲁肽治疗的患者（n=37）的细胞因子水平无显著变化。
与接受氯氮平或奥氮平治疗的 NGT 患者相比，处于糖尿病前期的精神分裂症患者的几种促炎细胞因子血清水平升高，进一步证实了炎症与 T2D 之间的联系。利拉鲁肽治疗并未影响所研究的细胞因子。需要在更多个体中进一步测试这些发现。
