Peroxisome proliferator-activated receptor gamma (PPAR) agonism reduces the insulin-stimulated increase in circulating interleukin-6 in GH replaced GH-deficient adults.

Author(s): Krag MB, Rasmussen LM, Hansen TK, Frystyk J, Flyvbjerg A, Moller N, Jorgensen JO

Affiliation(s): Medical Department M (Endocrinology and Diabetes), Medical Research Laboratories, Clinical Institute, Aarhus C., Denmark.

Publication date & source: 2009-09, Clin Endocrinol (Oxf)., 71(3):363-8. Epub 2008 Dec 3.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

CONTEXT: Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists modify cardiovascular risk factors and inflammatory markers in patients with type 2 diabetes. GH treatment in GH-deficient (GHD) patients may cause insulin resistance and exerts ambiguous effects on inflammatory markers. OBJECTIVE: To investigate circulating markers of inflammation and endothelial function in GH replaced GHD patients before and after 12 weeks administration of either pioglitazone 30 mg/day (N = 10) or placebo (N = 10) in a randomized double-blind parallel design. METHODS: Circulating levels of interleukins (ILs)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, high sensitivity C-reactive protein, vascular cell adhesion molecule-I, and osteoprotegerin (OPG) were measured in the basal state and after a 2.5 h hyperinsulinaemic euglycaemic clamp. RESULTS: Insulin sensitivity improved in the group receiving PPARgamma agonist (P = 0.03). Serum IL-6 levels increased by 114 +/- 31% (mean +/- SE) in the entire group (N = 20) following the hyperinsulinaemic euglycaemic clamp (P = 0.01) performed at study start. Twelve weeks of PPARgamma agonist treatment significantly abrogated this insulin-stimulated increment in IL-6 levels compared to placebo (P = 0.01). Furthermore PPARgamma agonist treatment significantly lowered basal IL-4 levels (P < 0.05). CONCLUSIONS: (i) IL-6 levels increase during a hyperinsulinaemic clamp in GH replaced patients (ii) This increase in IL-6 is abrogated by PPARgamma agonist treatment (iii) we hypothesize that PPARgamma agonist-induced improvement of insulin sensitivity may obviate a compensatory rise in IL-6.