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Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus

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Abstract

Aims/hypothesis

Glucagon-like peptide 1 (GLP-1) is a gut hormone used in the treatment of type 2 diabetes mellitus. There is emerging evidence that GLP-1 has anti-inflammatory activity in humans, with murine studies suggesting an effect on macrophage polarisation. We hypothesised that GLP-1 analogue therapy in individuals with type 2 diabetes mellitus would affect the inflammatory macrophage molecule soluble CD163 (sCD163) and adipocytokine profile.

Methods

We studied ten obese type 2 diabetes mellitus patients starting GLP-1 analogue therapy at a hospital-based diabetes service. We investigated levels of sCD163, TNF-α, IL-1β, IL-6, adiponectin and leptin by ELISA, before and after 8 weeks of GLP-1 analogue therapy.

Results

GLP-1 analogue therapy reduced levels of the inflammatory macrophage activation molecule sCD163 (220 ng/ml vs 171 ng/ml, p < 0.001). This occurred independent of changes in body weight, fructosamine and HbA1c. GLP-1 analogue therapy was associated with a decrease in levels of the inflammatory cytokines TNF-α (264 vs 149 pg/ml, p < 0.05), IL-1β (2,919 vs 748 pg/ml, p < 0.05) and IL-6 (1,379 vs 461 pg/ml p < 0.05) and an increase in levels of the anti-inflammatory adipokine adiponectin (4,480 vs 6,290 pg/ml, p < 0.002).

Conclusions/interpretation

In individuals with type 2 diabetes mellitus, GLP-1 analogue therapy reduces the frequency of inflammatory macrophages. This effect is not dependent on the glycaemic or body weight effects of GLP-1.

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Fig. 1

Abbreviations

GLP-1:

Glucagon-like peptide 1

iNKT:

Invariant natural killer T

PBMC:

Peripheral blood mononuclear cell

sCD163:

Soluble CD163

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Funding

AEH is supported by a fellowship from the National Children’s Research Centre.

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

AEH, LL, GG, CW, MAC, JOC and DOS designed the study, analysed clinical and scientific data and wrote the manuscript. GG and CW recruited the patients and controls, collated the clinical data for the manuscript. AEH and MAC performed the experiments and prepared the figures for the manuscript. AEH and DOS revised the manuscript. All authors approved final manuscript.

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Author notes

  1. Lydia Lynch

    Present address: Rheumatology, Allergy and Immunology, Brigham and Women’s Hospital, Boston, MA, USA

Authors and Affiliations

  1. Obesity Immunology, Education and Research Centre, St Vincent’s University Hospital, University College Dublin, Dublin, Ireland

    Andrew E. Hogan, Gadintshware Gaoatswe, Michelle A. Corrigan, Conor Woods, Jean O’Connell & Donal O’Shea

  2. National Children’s Research Centre, Our Lady’s Children’s Hospital, Dublin, Ireland

    Andrew E. Hogan

  3. Haematology and Oncology, BIMDC, Harvard Medical School, Boston, MA, USA

    Lydia Lynch

  4. Department of Endocrinology, St Columcille’s Hospital, Health Service Executive, Loughlinstown, Ireland

    Donal O’Shea

  5. Department of Endocrinology, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland

    Donal O’Shea

Authors
  1. Andrew E. Hogan
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  2. Gadintshware Gaoatswe
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  3. Lydia Lynch
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  4. Michelle A. Corrigan
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  5. Conor Woods
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  6. Jean O’Connell
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  7. Donal O’Shea
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Corresponding author

Correspondence to Donal O’Shea.

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Hogan, A.E., Gaoatswe, G., Lynch, L. et al. Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus. Diabetologia 57, 781–784 (2014). https://doi.org/10.1007/s00125-013-3145-0

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  • DOI: https://doi.org/10.1007/s00125-013-3145-0

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