可溶性瘦素受体（sOB-R）在多囊卵巢综合征合并胰岛素抵抗中的临床研究及机制的初步探讨
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摘要
研究目的了解多囊卵巢综合征(PCOS)合并胰岛素抵抗(IR)患者血清可溶性瘦素受体(sOB-R)水平,解析高胰岛素血症(HI)及IR对瘦素系统的影响,探索HI及IR与PCOS发病的关系,探讨其在PCOS发病中的作用。
方法将97例诊断为PCOS的患者,年龄13～38岁,平均(25±5)岁,分为高胰岛素血症组(HI组,n=60)和非高胰岛素血症组(NHI组,n=37)；对其中55例PCOS合并IR患者,根据(BMI)分为非肥胖(BMI<23 kg/m2,n=34)和超重或肥胖(BMI>_25kg/m2,n=21),用二甲双胍进行为期6个月的治疗；另外选择同期31例BMI正常,月经规律,排卵正常的妇女作为对照。检测以上各组年龄、体重、身高、臀围、腰围、Ferriman-Gallwey (F-G)多毛评分、痤疮评分及体重指数(BMI),放射免疫法测定血清促黄体生成素(LH)、促卵泡生成素(FSH)、睾酮(T)、泌乳素(PRL)、脱氢表雄酮(DHEA)、雄烯二酮(A)、空腹血糖(FPG)和胰岛素(FINS)、口服糖耐量试验(OGTT)和胰岛素释放实验(IRT),计算腰臀比(WHR)、LH/FSH比值、葡萄糖及胰岛素曲线下面积(AUC)、胰岛素敏感指数(ISI)、稳态模型指数(HOMA), ISI和HOMA-IR评估胰岛素抵抗(IR)的程度,HOMA-IS评价胰岛β细胞功能和胰岛素及sOB-R水平。
结果发现PCOS患者雄激素水平,多毛评分,30、60、120和180min血糖、IRT各时点胰岛素值、AUC、HOMA-IR均明显高于对照组。相关分析结果显不,HOMA-IR与腰围、臀围、BMI、FPG、FIN、GAUC、IAUC、HOMA-IS均成正相关(P值<0.01)。血清sOB-R水平均明显低于对照组。PCOS组血清sOB-R水平与体重指数,腰围和臀围,T, A, DHEA, LH及多毛平分均无明显相关性,但与(HOMA-IR)呈负相关。治疗后PCOS患者血清sOB-R水平较治疗前明显增高(P值<0.01)。
结论HI可促进PCOS患者肥胖尤其腹型肥胖的发生,并与PCOS糖代谢紊乱密切相关。早期干预HI对预防PCOS远期并发症的具有积极意义。PCOS患者低水平的sOB-R是廋素抵抗的代偿机制。二甲双胍降低HI的同时可有效的提升sOB-R水平,改善PCOS患者的廋素抵抗。sOB-R水平降低和廋素浓度增高是PCOS合并胰岛素抵抗患者的临床指征之一。
OBJECTIVE The aim of this study was to investigate the levels of Soluble Leptin Receptor (sOB-R) in patients with Polycystic ovary syndrome (PCOS) and insulin resistance (IR), the effects of insulin resistance and chronic hyperinsulinemia(HI) on the leptin system, the relationship between HI/IR and PCOS and explore their role in the pathogenesis of PCOS.
METHODS 97 patients with PCOS, aged 13～38 (25±5, on average), divided into two groups:hyperinsulinemia group (HI Group, n=60) and non-hyperinsulinemia group (NHI Group, n=37), to investigate the relationship between hyperinsulinemia (HI), insulin resistance (IR) and polycystic ovary syndrome (PCOS). And In order to investigate the levels of Soluble Leptin Receptor (sOB-R) in women with PCOS, from the 97 patients we chose 55 with insulin resistance treated with Metformin for six months. According to body mass index (BMI), they were divided into two subgroups:lean PCOS (BMI＜23 kg/m2, n=34) and overweight or obese PCOS (BMI>25 kg/m2,n=21). Other 31 body mass index (BMI)-matched ovulatory women wee as controls. Both Patients and controls were measured of Age, standing height, weight, waist circumference, hip circumference, Ferriman-Gallwey score(F-G), Rosenfield acne score, body mass index(BMI), luteinizing hormone(LH), follicle stimulating hormone(FSH), prolactin(PRL), testosterone(T), dehydroepiandrosterone (DHEA), androstenedione(A), fasting plasma glucose(FPG), fasting insulin(FINS), oral glucose tolerance test(OGTT), insulin releasing test(IRT), Insulin resistance andβ-cell function were defined by the homeostasis model assessment (HOMA-IR), insulin and sOB-R levels were determined.
RESULTS PCOS patients were found to have high indices of androgen levels, hirsutism scores, blood glucose level after OGTT for 30min,60min and 120min and 180 min, FINS, the insulin level after IRT, AUC for glucose and insulin as well as insulin resistance (HOMA-IR). Furthermore, HOMA-IR was positively correlated with waist circumference, hip circumference, BMI, FPG, FIN, GAUC, IAUC and HOMA-IS (every P<0.01). In PCOS pateints sOB-R levels were lawer than controls. No correlation was found between sOB-R and BMI, waist and hip circumference, total testosterone, androstendione, DHEAS, LH or hirsutism scores. However, a significant negative correlation was found between sOB-R and HOMA-IR. After treatment, the sOB-R levels in women with PCOS increased significantly.
CONCLUSION HI and IR can promote the development of the obesity in PCOS; they have a close relationship with the disorder of glucose metabolism, which shows a positive significance for its early intervention as well as the prevention of its late complications. Low sOB-R levels in PCOS women as a possible mechanism to compensate for leptin resistance. It is likely that reduction of hyperinsulinemia that is produce by metformin effectively improves the sOB-R levels and improves leptin resistance in PCOS. Decreased sOB-R levels and increased leptin concentrations can be one of the elements of PCOS clinical picture.
方法将97例诊断为PCOS的患者,年龄13～38岁,平均(25±5)岁,分为高胰岛素血症组(HI组,n=60)和非高胰岛素血症组(NHI组,n=37)；对其中55例PCOS合并IR患者,根据(BMI)分为非肥胖(BMI<23 kg/m2,n=34)和超重或肥胖(BMI>_25kg/m2,n=21),用二甲双胍进行为期6个月的治疗；另外选择同期31例BMI正常,月经规律,排卵正常的妇女作为对照。检测以上各组年龄、体重、身高、臀围、腰围、Ferriman-Gallwey (F-G)多毛评分、痤疮评分及体重指数(BMI),放射免疫法测定血清促黄体生成素(LH)、促卵泡生成素(FSH)、睾酮(T)、泌乳素(PRL)、脱氢表雄酮(DHEA)、雄烯二酮(A)、空腹血糖(FPG)和胰岛素(FINS)、口服糖耐量试验(OGTT)和胰岛素释放实验(IRT),计算腰臀比(WHR)、LH/FSH比值、葡萄糖及胰岛素曲线下面积(AUC)、胰岛素敏感指数(ISI)、稳态模型指数(HOMA), ISI和HOMA-IR评估胰岛素抵抗(IR)的程度,HOMA-IS评价胰岛β细胞功能和胰岛素及sOB-R水平。
结果发现PCOS患者雄激素水平,多毛评分,30、60、120和180min血糖、IRT各时点胰岛素值、AUC、HOMA-IR均明显高于对照组。相关分析结果显不,HOMA-IR与腰围、臀围、BMI、FPG、FIN、GAUC、IAUC、HOMA-IS均成正相关(P值<0.01)。血清sOB-R水平均明显低于对照组。PCOS组血清sOB-R水平与体重指数,腰围和臀围,T, A, DHEA, LH及多毛平分均无明显相关性,但与(HOMA-IR)呈负相关。治疗后PCOS患者血清sOB-R水平较治疗前明显增高(P值<0.01)。
结论HI可促进PCOS患者肥胖尤其腹型肥胖的发生,并与PCOS糖代谢紊乱密切相关。早期干预HI对预防PCOS远期并发症的具有积极意义。PCOS患者低水平的sOB-R是廋素抵抗的代偿机制。二甲双胍降低HI的同时可有效的提升sOB-R水平,改善PCOS患者的廋素抵抗。sOB-R水平降低和廋素浓度增高是PCOS合并胰岛素抵抗患者的临床指征之一。
OBJECTIVE The aim of this study was to investigate the levels of Soluble Leptin Receptor (sOB-R) in patients with Polycystic ovary syndrome (PCOS) and insulin resistance (IR), the effects of insulin resistance and chronic hyperinsulinemia(HI) on the leptin system, the relationship between HI/IR and PCOS and explore their role in the pathogenesis of PCOS.
METHODS 97 patients with PCOS, aged 13～38 (25±5, on average), divided into two groups:hyperinsulinemia group (HI Group, n=60) and non-hyperinsulinemia group (NHI Group, n=37), to investigate the relationship between hyperinsulinemia (HI), insulin resistance (IR) and polycystic ovary syndrome (PCOS). And In order to investigate the levels of Soluble Leptin Receptor (sOB-R) in women with PCOS, from the 97 patients we chose 55 with insulin resistance treated with Metformin for six months. According to body mass index (BMI), they were divided into two subgroups:lean PCOS (BMI＜23 kg/m2, n=34) and overweight or obese PCOS (BMI>25 kg/m2,n=21). Other 31 body mass index (BMI)-matched ovulatory women wee as controls. Both Patients and controls were measured of Age, standing height, weight, waist circumference, hip circumference, Ferriman-Gallwey score(F-G), Rosenfield acne score, body mass index(BMI), luteinizing hormone(LH), follicle stimulating hormone(FSH), prolactin(PRL), testosterone(T), dehydroepiandrosterone (DHEA), androstenedione(A), fasting plasma glucose(FPG), fasting insulin(FINS), oral glucose tolerance test(OGTT), insulin releasing test(IRT), Insulin resistance andβ-cell function were defined by the homeostasis model assessment (HOMA-IR), insulin and sOB-R levels were determined.
RESULTS PCOS patients were found to have high indices of androgen levels, hirsutism scores, blood glucose level after OGTT for 30min,60min and 120min and 180 min, FINS, the insulin level after IRT, AUC for glucose and insulin as well as insulin resistance (HOMA-IR). Furthermore, HOMA-IR was positively correlated with waist circumference, hip circumference, BMI, FPG, FIN, GAUC, IAUC and HOMA-IS (every P<0.01). In PCOS pateints sOB-R levels were lawer than controls. No correlation was found between sOB-R and BMI, waist and hip circumference, total testosterone, androstendione, DHEAS, LH or hirsutism scores. However, a significant negative correlation was found between sOB-R and HOMA-IR. After treatment, the sOB-R levels in women with PCOS increased significantly.
CONCLUSION HI and IR can promote the development of the obesity in PCOS; they have a close relationship with the disorder of glucose metabolism, which shows a positive significance for its early intervention as well as the prevention of its late complications. Low sOB-R levels in PCOS women as a possible mechanism to compensate for leptin resistance. It is likely that reduction of hyperinsulinemia that is produce by metformin effectively improves the sOB-R levels and improves leptin resistance in PCOS. Decreased sOB-R levels and increased leptin concentrations can be one of the elements of PCOS clinical picture.
引文
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[1]2009, Vol.14, No.2, Pages 153-159 (doi:10.1080/13625180802549962) Prof.Blagovest Pehlivanov1+and Mitko Mitkov2'Department of Obstetrics and Gynaecology 2Department of Endocrinology, Medical University, Plovdiv, Bulgaria +Correspondence:Prof.Blagovest Pehlivanov,110 Bulgaria Bul,4003-Plovdiv, Bulgaria
[2]G. A. LAUGHLIN, A. J. MORALES, AND S. S. C. YEN+ Department of Reproductive Medicine, School of Medicine 0633, University of California, San Diego, La Jolla, California 92093-0633
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[5]Susanne Hahn, Uwe Haselhorst2, Beate Quadbeck, Susanne Tan, Rainer Kimmig1, Klaus Mann and Onno E Janssen Division of Endocrinology, Department of Medicine and 1 Department of Obstetrics and Gynecology, University of Duisburg-Essen, Hufelandstr.55,45122 Essen, Germany and 2 Biofocus, Recklinghausen, Germany
[6]Aleksandra Marciniak, Jolanta Nawrocka-Rutkowska, Agnieszka Brodowska, Robert Sienkiewicz, Iwona Szyd3owska, Andrzej Starczewski. Department of Reproduction and Gynecology, Pomeranian Medical University, Szczecin, Poland
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[1]2009, Vol.14, No.2, Pages 153-159 (doi:10.1080/13625180802549962) Prof.Blagovest Pehlivanov1+and Mitko Mitkov2'Department of Obstetrics and Gynaecology 2Department of Endocrinology, Medical University, Plovdiv, Bulgaria +Correspondence:Prof.Blagovest Pehlivanov,110 Bulgaria Bul,4003-Plovdiv, Bulgaria
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