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

AbstractAIMS/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.
AuthorsAndrew E Hogan, Gadintshware Gaoatswe, Lydia Lynch, Michelle A Corrigan, Conor Woods, Jean O'Connell, Donal O'Shea
JournalDiabetologia (Diabetologia) Vol. 57 Issue 4 Pg. 781-4 (Apr 2014) ISSN: 1432-0428 [Electronic] Germany
PMID24362727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Inflammation Mediators
  • Glucagon-Like Peptide 1
Topics
  • Body Weight (drug effects)
  • Diabetes Mellitus, Type 2 (drug therapy, immunology)
  • Female
  • Glucagon-Like Peptide 1 (analogs & derivatives, therapeutic use)
  • Humans
  • Immunity, Innate (drug effects)
  • Inflammation (drug therapy)
  • Inflammation Mediators (therapeutic use)
  • Male
  • Middle Aged

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