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Proinflammatory biomarkers are associated with prediabetes in patients with schizophrenia

Published online by Cambridge University Press:  14 December 2020

Marco Møller Open the ORCID record for Marco Møller [Opens in a new window] ,
Simon Fredholm ,
Mathias E. Jensen ,
Gitta Wörtwein Open the ORCID record for Gitta Wörtwein [Opens in a new window] ,
Julie R. Larsen Open the ORCID record for Julie R. Larsen [Opens in a new window] ,
Tina Vilsbøll Open the ORCID record for Tina Vilsbøll [Opens in a new window] ,
Niels Ødum Open the ORCID record for Niels Ødum [Opens in a new window]  and
Anders Fink-Jensen Open the ORCID record for Anders Fink-Jensen [Opens in a new window]
Marco Møller
Affiliation:
Psychiatric Centre Copenhagen, Rigshospitalet, Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark
Simon Fredholm
Affiliation:
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
Mathias E. Jensen
Affiliation:
Psychiatric Centre Copenhagen, Rigshospitalet, Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark
Gitta Wörtwein
Affiliation:
Psychiatric Centre Copenhagen, Rigshospitalet, Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
Julie R. Larsen
Affiliation:
Psychiatric Centre Copenhagen, Rigshospitalet, Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark
Tina Vilsbøll
Affiliation:
Steno Diabetes Center Copenhagen, Gentofte, Denmark Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Niels Ødum
Affiliation:
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
Anders Fink-Jensen*
Affiliation:
Psychiatric Centre Copenhagen, Rigshospitalet, Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
*
*Author for correspondence: Anders Fink-Jensen, Email: anders.fink-jensen@regionh.dk
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords

AntipsychoticsGLP-1inflammationliraglutideprediabetesschizophrenia
Type
Original Research
Information
CNS Spectrums , Volume 27 , Issue 3 , June 2022 , pp. 347 - 354
Copyright
© The Author(s), 2020. Published by Cambridge University Press

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