Peroxisome proliferator-activated receptor gamma (PPAR) agonism reduces the insulin-stimulated increase in circulating interleukin-6 in GH replaced GH-deficient adults.
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.
Krag
Morten B
MB
Medical Department M (Endocrinology and Diabetes), Medical Research Laboratories, Clinical Institute, Aarhus C., Denmark.
Rasmussen
Lars M
LM
Hansen
Troels K
TK
Frystyk
Jan
J
Flyvbjerg
Allan
A
Møller
Niels
N
Jørgensen
Jens O L
JO
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*
D007328:Insulin; D015850:Interleukin-6; D047495:PPAR gamma; D045162:Thiazolidinediones; D019382:Human Growth Hormone; D000077205:Pioglitazone