, Volume 57, Issue 4, pp 781–784 | Cite as

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

  • Andrew E. Hogan
  • Gadintshware Gaoatswe
  • Lydia Lynch
  • Michelle A. Corrigan
  • Conor Woods
  • Jean O’Connell
  • Donal O’Shea
Short Communication



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.


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.


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).


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.


GLP-1 Inflammation Macrophage Obesity 

Abbreviations used


Glucagon-like peptide 1


Invariant natural killer T


Peripheral blood mononuclear cell


Soluble CD163



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.


  1. 1.
    Dalmas E, Clément K, Guerre-Millo M (2011) Defining macrophage phenotype and function in adipose tissue. Trends Immunol 32:307–314PubMedCrossRefGoogle Scholar
  2. 2.
    Fujisaka S, Usui I, Bukhari A et al (2009) Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58:2574–2582PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Parkner T, Sørensen LP, Nielsen AR et al (2012) Soluble CD163: a biomarker linking macrophages and insulin resistance. Diabetologia 55:1856–1862PubMedCrossRefGoogle Scholar
  4. 4.
    Ridaura VK, Faith JJ, Rey FE et al (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341:1241214PubMedCrossRefGoogle Scholar
  5. 5.
    Wu JD, Xu XH, Zhu J et al (2011) Effect of exenatide on inflammatory and oxidative stress markers in patients with type 2 diabetes mellitus. Diabetes Technol Ther 13:143–148PubMedCrossRefGoogle Scholar
  6. 6.
    Hattori Y, Jojima T, Tomizawa A et al (2010) A glucagon-like peptide-1 (GLP-1) analogue, liraglutide, upregulates nitric oxide production and exerts anti-inflammatory action in endothelial cells. Diabetologia 53:2256–2263PubMedCrossRefGoogle Scholar
  7. 7.
    Lee YS, Park MS, Choung JS et al (2012) Glucagon-like peptide-1 inhibits adipose tissue macrophage infiltration and inflammation in an obese mouse model of diabetes. Diabetologia 55:2456–2468PubMedCrossRefGoogle Scholar
  8. 8.
    Chaudhuri A, Ghanim H, Vora M et al (2012) Exenatide exerts a potent antiinflammatory effect. J Clin Endocrinol Metab 97:198–207PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Hogan AE, Tobin AM, Ahern T et al (2011) Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis. Diabetologia 54:2745–2754PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Lynch L, Nowak M, Varghese B et al (2012) Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37:574–587PubMedCrossRefGoogle Scholar
  11. 11.
    Feingold KR, Soued M, Adi S et al (1991) Effect of interleukin-1 on lipid metabolism in the rat. Similarities to and differences from tumor necrosis factor. Arterioscler Thromb 11:495–500PubMedCrossRefGoogle Scholar
  12. 12.
    Wisse BE (2004) The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 15:2792–2800PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Andrew E. Hogan
    • 1
    • 2
  • Gadintshware Gaoatswe
    • 1
  • Lydia Lynch
    • 3
  • Michelle A. Corrigan
    • 1
  • Conor Woods
    • 1
  • Jean O’Connell
    • 1
  • Donal O’Shea
    • 1
    • 4
    • 5
  1. 1.Obesity Immunology, Education and Research Centre, St Vincent’s University HospitalUniversity College DublinDublinIreland
  2. 2.National Children’s Research CentreOur Lady’s Children’s HospitalDublinIreland
  3. 3.Haematology and Oncology, BIMDCHarvard Medical SchoolBostonUSA
  4. 4.Department of Endocrinology, St Columcille’s HospitalHealth Service ExecutiveLoughlinstownIreland
  5. 5.Department of EndocrinologySt Vincent’s University HospitalDublin 4Ireland

Personalised recommendations