title: Peroxisome proliferator-activated receptor gamma (PPAR) agonism reduces the insulin-stimulated increase in circulating interleukin-6 in GH replaced GH-deficient adults.
abstract: BACKGROUND
  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.
authors.affiliation: Medical Department M (Endocrinology and Diabetes), Medical Research Laboratories, Clinical Institute, Aarhus C., Denmark.
authors.forename: Morten B
authors.initials: MB
authors.lastname: Krag
authors.forename: Lars M
authors.initials: LM
authors.lastname: Rasmussen
authors.forename: Troels K
authors.initials: TK
authors.lastname: Hansen
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.forename: Jens O L
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D000328:Adult; D000368:Aged; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007328:Insulin; D015850:Interleukin-6; D047495:PPAR gamma; D045162:Thiazolidinediones; D019382:Human Growth Hormone; D000077205:Pioglitazone