title: Glucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Obesity Immunology, Education and Research Centre, St Vincent's University Hospital, University College Dublin, Dublin, Ireland.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Hogan
authors.forename: Gadintshware
authors.initials: G
authors.lastname: Gaoatswe
authors.forename: Lydia
authors.initials: L
authors.lastname: Lynch
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Corrigan
authors.forename: Conor
authors.initials: C
authors.lastname: Woods
authors.forename: Jean
authors.initials: J
authors.lastname: O'Connell
authors.forename: Donal
authors.initials: D
authors.lastname: O'Shea
mesh_terms: D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D018836:Inflammation Mediators; D052216:Glucagon-Like Peptide 1