Circulatory changes of the novel adipokine adipolin/<scp>CTRP</scp>12 in response to metformin treatment and an oral glucose challenge in humans

Abstract

OBJECTIVE: Adipolin/CTRP12 is a novel adipokine with anti-inflammatory and glucose-lowering properties in rodents. We sought to investigate the effects of metformin treatment (850 mg twice daily for 6 months) and a 2 h 75 g oral glucose tolerance test (OGTT) on serum adipolin concentrations in humans. DESIGN: Cross-sectional study [PCOS (n = 83) and control (n = 39) subjects]. Serum adipolin was measured by ELISA. Metformin treatment (850 mg twice daily for 6 months) was offered to all women with PCOS, 34 women participated but 21 women completed 6 months of metformin therapy. Reasons for subjects not completing the study were nausea and gastrointestinal side effects (n = 4), pregnancies (n = 5), noncompliance (n = 2) and loss of contact (n = 2). RESULTS: Metformin treatment (850 mg twice daily for 6 months) substantially increased serum adipolin concentrations (P < 0·05) in women with polycystic ovary syndrome (PCOS), a pro-inflammatory state associated with obesity, diabetes, dyslipidaemia and atherosclerosis. Furthermore, changes in waist-hip ratio, glucose, triglycerides, CRP and carotid intima media thickness showed significant negative associations with changes in adipolin levels (P < 0·05, P < 0·01); in multiple regression analyses, only changes in glucose were predictive of changes in adipolin levels (β = -0·570, P = 0·009). Serum adipolin decreased significantly in response to the OGTT in PCOS and control subjects at 90 min (P < 0·05) and 120 min (P < 0·01). CONCLUSIONS: Adipolin and/or novel pharmacologic agents that increase adipolin's circulating concentrations might constitute a novel approach in the treatment of insulin resistant states.