初诊多囊卵巢综合征患者血清betatrophin水平及其影响因素
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摘要
目的探讨初诊多囊卵巢综合症征(PCOS)患者血清betatrophin水平及其影响因素。方法收集2016年8月至2017年3月就诊于安徽医科大学第一附属医院的初诊PCOS患者81例作为PCOS组,同期选择安徽医科大学第一附属医院体检中心就诊的30名月经周期规律的健康女性作为对照组。测量两组受试者基本临床及生化指标,采用酶联免疫吸附法测定空腹血清中betatrophin水平,比较两组上述指标变化;使用Pearson相关性分析betatrophin水平与代谢指标之间的关系,根据相关分析结果确定可能影响betatrophin的因素,进一步多元逐步回归分析betatrophin的独立因素。结果 PCOS组患者血清betatrophin水平(95.52±58.59)pg/mL高于对照组(148.57±110.91)pg/mL,差异有统计学意义(P<0.05),Pearson相关分析显示,PCOS组患者血清betatrophin水平与空腹血糖(FBG)、三酰甘油(TG)、体质指数(BMI)、腰臀比(WHR)呈正相关(P<0.01),与空腹胰岛素(FINS)、稳态模式胰岛素抵抗指数(HOMA-IR)无相关性(P>0.05);多元逐步回归分析提示,TG是血清betatrophin的独立影响因素;NC组无上述相关性。结论 PCOS患者血清betatrophin水平水平高于健康人群,TG是其独立影响因素,betartophin可能与PCOS患者体内的糖、脂代谢紊乱有关。
Objective To investigate the serum levels of betatrophin in those patients with newly-diagnosed polycystic ovary syndrome( PCOS) and its influential factors. Methods From Aug 2016 to Mar 2017,81 cases of patients with newly-diagnosed PCOS ever treated in our hospital were enrolled as the PCOS group,and other 30 healthy women with regular menstrual cycles were collected simultaneously as controls from our physical examination center. The routine clinical or biochemical indexes of all subjects,together with their fasting serum levels of betatrophin by means of enzyme-linked immunosorbent assay( ELISA),were detected and compared between the PCOS group and healthy controls. The relationship between betatrophin and metabolic indexes was analyzed by Pearson correlation analysis,and those factors influencing betatrophin levels were determined according to the analysis results,with further multiple stepwise regression analysis for those independent factors. Results Serum betatrophin levels in the PCOS group were higher than those in the control group( 95. 52 ± 58.59) pg/mL vs( 148. 57 ± 110. 91) pg/mL,with significant difference between them( P < 0. 05). Pearson correlation analysis showed that serum betatrophin levels in the PCOS group were positively correlated with their fasting blood glucose( FBG),triglyceride( TG),body mass index( BMI) andwaist-to-hip ratio( WHR)( P < 0. 01),but were uncorrelated with the fasting insulin( FINS) and homeostasis model assessment of insulin resistance( HOMA-IR)( P > 0. 05). Multiple stepwise regression analysis showed that TG level was an independent influential factor for the serum betatrophin level. Nevertheless,correlations mentioned above were not found in the control group. Conclusion Serum betatrophin levels in those PCOS women are usually higher than those in healthy controls,and TG level would be an independent influencing factor for it. Changes of betatrophin in those patients with PCOS might be associated with metabolic disorders ofcarbohydrates and lipids.
Objective To investigate the serum levels of betatrophin in those patients with newly-diagnosed polycystic ovary syndrome( PCOS) and its influential factors. Methods From Aug 2016 to Mar 2017,81 cases of patients with newly-diagnosed PCOS ever treated in our hospital were enrolled as the PCOS group,and other 30 healthy women with regular menstrual cycles were collected simultaneously as controls from our physical examination center. The routine clinical or biochemical indexes of all subjects,together with their fasting serum levels of betatrophin by means of enzyme-linked immunosorbent assay( ELISA),were detected and compared between the PCOS group and healthy controls. The relationship between betatrophin and metabolic indexes was analyzed by Pearson correlation analysis,and those factors influencing betatrophin levels were determined according to the analysis results,with further multiple stepwise regression analysis for those independent factors. Results Serum betatrophin levels in the PCOS group were higher than those in the control group( 95. 52 ± 58.59) pg/mL vs( 148. 57 ± 110. 91) pg/mL,with significant difference between them( P < 0. 05). Pearson correlation analysis showed that serum betatrophin levels in the PCOS group were positively correlated with their fasting blood glucose( FBG),triglyceride( TG),body mass index( BMI) andwaist-to-hip ratio( WHR)( P < 0. 01),but were uncorrelated with the fasting insulin( FINS) and homeostasis model assessment of insulin resistance( HOMA-IR)( P > 0. 05). Multiple stepwise regression analysis showed that TG level was an independent influential factor for the serum betatrophin level. Nevertheless,correlations mentioned above were not found in the control group. Conclusion Serum betatrophin levels in those PCOS women are usually higher than those in healthy controls,and TG level would be an independent influencing factor for it. Changes of betatrophin in those patients with PCOS might be associated with metabolic disorders ofcarbohydrates and lipids.
引文
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[4]YI P,PARK J S,MELTON D A.betatrophin:a hormone that controls pancreaticβcell proliferation[J].Cell,2013,153(4):747-758.
[5]FU Z,BERHANE F,FITE A,et al.Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity[J].Sci Rep,2014,4:5013.
[6]YAMADA H,SAITO T,AOKI A,et al.Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes[J].Endocr,2015,62(5):417-421.
[7]EBERT T,KRALISCH S,WURST U,et al.betatrophin levels are increased in women with gestational diabetes mellitus compared to healthy pregnant controls[J].Eur J Endocrinol,2015,173(1):1-7.
[8]Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group.Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome(PCOS)[J].Hum Reprod,2004,19(1):41-47.
[9]ESPES D,LAU J,CARLSSON P O.Increased circulating levels of betatrophin in individuals with long-standing type 1diabetes[J].Diabetologia,2014,57(1):50-53.
[10]HU H,SUN W,YU S,et al.Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients[J].Diabetes care,2014,37(10):2718-2722.
[11]GOMEZ-AMBROSI J,PASCUAL E,CATALAN V,et al.Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes[J].J Clin Endocr Metab,2014,99(10):2004-2009.
[12]ABU-FARHA M,ABUBAKER J,AL-KHAIRI I,et al.Higher plasma betatrophin/ANGPTL8 level in Type 2 Diabetes subjects does not correlate with blood glucose or insulin resistance[J].Sci Rep,2015,5:10949.
[13]QU Q,ZHAO D,ZHANG F,et al.Serum betatrophin levels are increased and associated with insulin resistance in patients with polycystic ovary syndrome[J].J Int Med Res,2017,45(1):193-202.
[14]CALAN M,YILMAZ O,KUME T,et al.Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome[J].Endocr,2016,53(1):271-279.
[15]DUAN Y,LIU D,QU H,et al.Decreased circulating levels of betatrophin in Chinese women with polycystic ovary syndrome[J].Int J Cli Exp Med,2017,10(3):5196-5202.
[16]ZHANG R.Lipasin,a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels[J].Biochem Bioph Res Co,2012,424(4):786-792.
[17]QUAGLIARINI F,WANG Y,KOZLITINA J,et al.Atypical angiopoietin-like protein that regulates ANGPTL3[J].P Natl Sci USA,2012,109(48):19751-19756.
[18]WANG Y,QUAGLIARINI F,GUSAROVA V,et al.Mice lacking ANGPTL8(betatrophin)manifest disrupted triglyceride metabolism without impaired glucose homeostasis[J].P Natl Sci USA,2013,110(40):16109-16114.
[19]ZHANG R,ABOU-SAMRA A B.Emerging roles of Lipasin as a critical lipid regulator[J].Biochem Bioph Res Co,2013,432(3):401-405.
[20]REN G,KIM J Y,SMAS C M.Identification of RIFL,a novel adipocyte-enriched insulin target gene with a role in lipid metabolism[J].Am J Physiol Endocrinol Metab,2012,303(3):E334-E351.
[2]NORMAN R J,DEWAILLY D,LEGRO R S,et al.Polycystic ovary syndrome[J].Lancet,2007,370(9588):685-697.
[3]OVALLE F,AZZIZ R.Insulin resistance,polycystic ovary syndrome,and type 2 diabetes mellitus[J].Fertil Steri,2002,77(6):1095-1105.
[4]YI P,PARK J S,MELTON D A.betatrophin:a hormone that controls pancreaticβcell proliferation[J].Cell,2013,153(4):747-758.
[5]FU Z,BERHANE F,FITE A,et al.Elevated circulating lipasin/betatrophin in human type 2 diabetes and obesity[J].Sci Rep,2014,4:5013.
[6]YAMADA H,SAITO T,AOKI A,et al.Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes[J].Endocr,2015,62(5):417-421.
[7]EBERT T,KRALISCH S,WURST U,et al.betatrophin levels are increased in women with gestational diabetes mellitus compared to healthy pregnant controls[J].Eur J Endocrinol,2015,173(1):1-7.
[8]Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group.Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome(PCOS)[J].Hum Reprod,2004,19(1):41-47.
[9]ESPES D,LAU J,CARLSSON P O.Increased circulating levels of betatrophin in individuals with long-standing type 1diabetes[J].Diabetologia,2014,57(1):50-53.
[10]HU H,SUN W,YU S,et al.Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients[J].Diabetes care,2014,37(10):2718-2722.
[11]GOMEZ-AMBROSI J,PASCUAL E,CATALAN V,et al.Circulating betatrophin concentrations are decreased in human obesity and type 2 diabetes[J].J Clin Endocr Metab,2014,99(10):2004-2009.
[12]ABU-FARHA M,ABUBAKER J,AL-KHAIRI I,et al.Higher plasma betatrophin/ANGPTL8 level in Type 2 Diabetes subjects does not correlate with blood glucose or insulin resistance[J].Sci Rep,2015,5:10949.
[13]QU Q,ZHAO D,ZHANG F,et al.Serum betatrophin levels are increased and associated with insulin resistance in patients with polycystic ovary syndrome[J].J Int Med Res,2017,45(1):193-202.
[14]CALAN M,YILMAZ O,KUME T,et al.Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome[J].Endocr,2016,53(1):271-279.
[15]DUAN Y,LIU D,QU H,et al.Decreased circulating levels of betatrophin in Chinese women with polycystic ovary syndrome[J].Int J Cli Exp Med,2017,10(3):5196-5202.
[16]ZHANG R.Lipasin,a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels[J].Biochem Bioph Res Co,2012,424(4):786-792.
[17]QUAGLIARINI F,WANG Y,KOZLITINA J,et al.Atypical angiopoietin-like protein that regulates ANGPTL3[J].P Natl Sci USA,2012,109(48):19751-19756.
[18]WANG Y,QUAGLIARINI F,GUSAROVA V,et al.Mice lacking ANGPTL8(betatrophin)manifest disrupted triglyceride metabolism without impaired glucose homeostasis[J].P Natl Sci USA,2013,110(40):16109-16114.
[19]ZHANG R,ABOU-SAMRA A B.Emerging roles of Lipasin as a critical lipid regulator[J].Biochem Bioph Res Co,2013,432(3):401-405.
[20]REN G,KIM J Y,SMAS C M.Identification of RIFL,a novel adipocyte-enriched insulin target gene with a role in lipid metabolism[J].Am J Physiol Endocrinol Metab,2012,303(3):E334-E351.