Total and high molecular weight (HMW) adiponectin levels and measures of glucose and lipid metabolism following pioglitazone treatment in a randomized placebo-controlled study in polycystic ovary syndrome.
OBJECTIVE
Recent studies suggested that the effect of adiponectin on insulin-stimulated glucose metabolism is mediated primarily by the high molecular weight (HMW) form of adiponectin. In the present study we evaluated total and HMW adiponectin in polycystic ovary syndrome (PCOS) patients and controls and examined possible mechanisms for increased insulin sensitivity during pioglitazone treatment.


METHODS
Thirty PCOS patients randomized to pioglitazone, 30 mg/day, or placebo for 16 weeks and 14 weight-matched healthy females were studied.


METHODS
Total and HMW adiponectin levels were measured, and euglycaemic hyperinsulinaemic clamps and indirect calorimetry were performed. Delta-values denoted changes during pioglitazone treatment (16 weeks--basal).


RESULTS
Pretreatment adiponectin levels were decreased in PCOS patients vs. controls (P < 0.05), whereas no significant differences were found in HMW adiponectin levels. Following pioglitazone treatment, total and HMW adiponectin increased (all P < 0.05), whereas no significant changes were observed with placebo. Delta-total adiponectin levels correlated positively with the rate of Delta-insulin-stimulated glucose disposal (R(d)) (r = 0.89) and Delta-oxidative glucose metabolism (r = 0.71) and inversely with Delta-fasting free fatty acid (FFA) levels (r = -0.69) and Delta-lipid oxidation (r = -0.73) during insulin stimulation (all P < 0.01). Weaker correlations were found between Delta-HMW adiponectin levels and Delta-measures of glucose and lipid metabolism during insulin stimulation than with Delta-total adiponectin.


CONCLUSIONS
A close correlation between increased total adiponectin levels and increased insulin-stimulated glucose metabolism during pioglitzone treatment supports the hypothesis that the insulin-sensitizing effect of pioglitazone in PCOS is, at least in part, mediated by adiponectin. Measures of changes in HMW adiponectin did not add further information to this relationship.
Glintborg
Dorte
D
Department of Endocrinology and Metabolism, Odense University Hospital, Odense C, Denmark. dorte.glintborg@dadlnet.dk
Frystyk
Jan
J
Højlund
Kurt
K
Andersen
Kristian Kjaer
KK
Henriksen
Jan Erik
JE
Hermann
Anne Pernille
AP
Hagen
Claus
C
Flyvbjerg
Allan
A
Andersen
Marianne
M
D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D000077205:Pioglitazone; D010919:Placebos; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D045162:Thiazolidinediones / Q000627:therapeutic use*