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

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
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DOI:
10.1111/j.1365-2265.2007.03015.x
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发表时间:
2008-02-01
影响因子:
3.2
通讯作者:
Andersen, Marianne
Andersen, Marianne
中科院分区:
医学3区
文献类型:
--
作者:
Glintborg, Dorte;Frystyk, Jan;Andersen, Marianne

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目的脂联素对胰岛素刺激的葡萄糖代谢的影响主要是由脂联素的高分子量形式介导的。在本研究中,我们评估了多囊卵巢综合征(PCOS)患者和对照组的总脂联素和高分子量脂联素水平,并研究了吡格列酮治疗期间胰岛素敏感性增加的可能机制。并进行正常血高胰岛素钳夹和间接量热法。结果PCOS患者治疗前脂联素水平较对照组明显降低(P < 0.05),而高分子量脂联素水平无明显差异。吡格列酮治疗后,总脂联素和高分子量脂联素增加(均P < 0.05),而安慰剂组未观察到显著变化。胰岛素刺激期间,Delta总脂联素水平与Delta胰岛素刺激的葡萄糖处置率(R-d)(r = 0.89)和Delta氧化葡萄糖代谢(r = 0.71)呈正相关,与Delta空腹游离脂肪酸(FFA)水平(r = -0.69)和Delta脂质氧化(r = -0.73)呈负相关(均P < 0.01)。较弱的相关性被发现之间的Δ-HMW脂联素水平和Δ-措施的葡萄糖和脂质代谢在胰岛素stimulation.Conclusion总脂联素水平的增加和胰岛素刺激的葡萄糖代谢增加吡格列酮治疗期间的密切相关性支持的假设,吡格列酮在PCOS的胰岛素增敏作用,至少在部分,介导的脂联素。高分子量脂联素变化的测量没有为这种关系提供更多信息。
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.Study subjects Thirty PCOS patients randomized to pioglitazone, 30 mg/day, or placebo for 16 weeks and 14 weight-matched healthy females were studied.Design 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.Conclusion 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.