二甲双胍马来酸罗格列酮对PCOS患者IR、高雄激素血症及超长链脂肪酸的影响
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摘要
目的：探讨二甲双胍马来酸罗格列酮对多囊卵巢综合征(PCOS)患者胰岛素抵抗(IR)、高雄激素血症及血浆超长链脂肪酸(VLCFAs)等的影响。
方法：选取符合2003年鹿特丹诊断标准的PCOS患者70例(年龄18-40岁),根据体重指数(BMI)分为肥胖组(BMI≧ 25 kg/m2,34例)和非肥胖组(BMI<25 kg/m2,36例),选择同期因输卵管或男方因素不孕患者35例为对照组。两组PCOS患者口服二甲双胍马来酸罗格列酮片(每日2片)3个月。治疗前后检测：身高、体重、腰围、臀围、肝功能、血脂,葡萄糖氧化酶法检测空腹血糖(FPG)；化学发光法检测空腹胰岛素(FINS)、黄体生成素(LH)、卵泡刺激素(FSH)、总睾酮(T)；酶联免疫吸附法(ELISA)测定游离睾酮(FT),并检查卵巢面积及卵泡数目。计算体重指数(BMI)、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)。气相色谱质谱联用仪(GC-MS)检测血浆VLCFAs,包括超长链饱和脂肪酸(VLCSFAs)、超长链单不饱和脂肪酸(n-9VLCMUFAs)、n-3和n-6系超长链多不饱和脂肪酸(n-3VLCPUFAs,n-6VLCPUFAs)。
结果：①与对照组相比,治疗前两组PCOS患者LH、LH/FSH、T、FT、FINS、HOMA-IR明显增高,FSH、ISI明显下降(P均<0.05)。PCOS患者肥胖组与非肥胖组相比,HOMA-IR及卵泡数目增高,ISI下降(P均<0.05),但LH、LH/FSH、T、FT及卵巢面积差异无统计学意义。②治疗后两组PCOS患者体重、BMI、腰围、臀围、FPG、FINS、HOMA-IR明显下降(P均<0.05),ISI明显上升(P<0.05)；肥胖组LH、LH/FSH、FT及非肥胖组FT明显下降(P均<0.05),且肥胖组FT下降的差值大于非肥胖组(P<0.05)；两组卵巢面积、卵泡数目均减少(P<0.05); T、FSH无明显变化。③治疗前两组PCOS患者VLCSFAs,肥胖组n-3VLCPUFAs、n-9VLCMUFAs明显均高于对照组,肥胖组n-9VLCMUFAs也明显高于非肥胖组(P均<0.05)。n-6VLCPUFAs三组无差异。治疗后两组PCOS患者的n-3VLCPUFAs均明显升高,肥胖组VLCSFAs下降,非肥胖组n-9VLCMUFAs升高(P均<0.05)。④治疗过程中胃肠道不良反应发生率非肥胖组为9.3%,肥胖组为6.3%,无肝毒性、水肿及低血糖等不良反应。
结论：①肥胖较非肥胖的PCOS患者IR及卵巢多囊样改变更明显,但T、FT差异无显著性。②二甲双胍马来酸罗格列酮能降低PCOS患者的BMI和FT,改善IR及卵巢多囊样改变,对肥胖PCOS患者作用更显著,无明显不良反应。③肥胖和非肥胖的PCOS患者均存在超长链脂肪酸代谢的紊乱,二甲双胍马来酸罗格列酮能升高PCOS患者的n-3VLCPUFAs,降低肥胖PCOS患者的VLCSFAs,升高非肥胖PCOS患者的n-9VLCMUFAs。
OBJECTIVE:The aim of the study is to evaluate the therapeutic effects of metformin hydrochloride and rosiglitazone maleate tablets on insulin resistance(IR), androgen concentration and plasma very long chain fatty acids(VLCFAs) levels in women with polycystic ovarian syndrome (PCOS).
METHOD:Seventy women(aged 18 to 40 years) with PCOS were enrolled into this study according to the diagnostic criteria of Rotterdam conference(2003).The women with PCOS were divided into the obese group(BMI= 25 kg/m2, n=34) and the nonobese group(BMI< 25 kg/m2,n=36) according to BMI. In the corresponding period,35 infertile women due to the problems of uterine tube or spouses was taken as the control group.All women with PCOS had metformin hydrochloride and rosiglitazone maleate tablets twice daily for 3 months. There were some tests as the following before and after the treatment:height (Ht),weight(Wt),waist circumference(WC), liver function, lipids were tested; the fasting plasma glucose (FPG) was detected by glucose oxidase;the luteinizint hormone(LH),follicle stimulating hormone (FSH),total testosterone(T) and fasting plasma insulin (FINS) were examined by chemiluminescence method;the follicular number and ovarian area were checked in follicle period or amenorrhoea period; the plasma free testosterone was examined by enzyme-linked immunosorbentassay (ELISA);the BMI, waist to hip ratio (WHR),and homeostasis model assessment for insulin resistance (HOMA-IR), insulin sensitivity index(ISI) were calculated;the plasma VLCFAs were analysed by gas chromatography-mass spectrometry (GC-MS),including very long chain saturated fatty acids (VLCSFAs),n-9 very long chain monounsaturated fatty acids (n-9VLCMUFAs),n-3 very long chain polyunsaturated fatty acids (n-3VLCPUFAs) and n-6 very long chain polyunsaturated fatty acids (n-6VLCPUFAs).
RESULT:①Compared with the control group, LH, LH/FSH, T,FT, FINS, HOMA-IR were significantly higher and FSH, ISI were obviously lower in women with PCOS(P<0.05). Compared with the nonobese group, dramatic increases in HOMA-IR and follicle number were observed in obese group(P<0.05), while LH, LH/FSH, T, FT had no significant difference between two gruops.②After the treatment with metformin hydrochloride and rosiglitazone maleate tablets, Wt, BMI, WC, hip circumference, FPG, FINS, HOMA-IR significantly decreased and ISI rised apparently in two groups(P<0.05). There were also significant declines of LH, LH/FSH, FT,ovarian area, follicular number,especially in the obese women with PCOS(P<0.05),while T and FSH did not change significantly.③Compared with the control,the levels of VLCSFAs in both groups, and the levels of n-3VLCPUFAs and n-9VLCMUFAs in obese group were significant higher(P<0.05),while n-6VLCPUFAs had no significant difference among these groups. Compared with the nonobese group, there was an increase of n-9VLCMUFAs in obese group(P<0.05).Clinically significant increases of n-3VLCPUFAs in both groups,n-9VLCMUFAs in nonobese group and significant reduction in VLCSFAs of obese group were observed after the treatment with metformin hydrochloride and rosiglitazone maleate tablets(P<0.05), while n-6 VLCPUFAs did not change significantly in either group after the treatment.④The incidence of gastrointestinal adverse reactions happened in nonobese and obese group was 9.3% and 6.3% respectively, and no liver toxicity, edema, hypoglycemia and other adverse reactions was observed in the treatment.
CONCLUSION:①Compared with the nonobese group, there were severer insulin resistance and polycystic ovary in obese women with PCOS, while T and FT had no significant difference between two gruops.②Metformin hydrochloride and rosiglitazone maleate tablets can ameliorate insulin resistance and polycystic ovary,and also reduce BMI and FT in women with PCOS particularly in the obese,which may have no significant adverse reaction.③The metabolic disorders of plasma very long chain fatty acids existed in women with PCOS. After the treatment with metformin hydrochloride and rosiglitazone maleate tablets for three months, the concentration of n-3VLCPUFAs in both groups and n-9VLCMUFAs in nonobese group was significantly increased, while the concentration of VLCSFAs in obese group decreased.
方法：选取符合2003年鹿特丹诊断标准的PCOS患者70例(年龄18-40岁),根据体重指数(BMI)分为肥胖组(BMI≧ 25 kg/m2,34例)和非肥胖组(BMI<25 kg/m2,36例),选择同期因输卵管或男方因素不孕患者35例为对照组。两组PCOS患者口服二甲双胍马来酸罗格列酮片(每日2片)3个月。治疗前后检测：身高、体重、腰围、臀围、肝功能、血脂,葡萄糖氧化酶法检测空腹血糖(FPG)；化学发光法检测空腹胰岛素(FINS)、黄体生成素(LH)、卵泡刺激素(FSH)、总睾酮(T)；酶联免疫吸附法(ELISA)测定游离睾酮(FT),并检查卵巢面积及卵泡数目。计算体重指数(BMI)、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)。气相色谱质谱联用仪(GC-MS)检测血浆VLCFAs,包括超长链饱和脂肪酸(VLCSFAs)、超长链单不饱和脂肪酸(n-9VLCMUFAs)、n-3和n-6系超长链多不饱和脂肪酸(n-3VLCPUFAs,n-6VLCPUFAs)。
结果：①与对照组相比,治疗前两组PCOS患者LH、LH/FSH、T、FT、FINS、HOMA-IR明显增高,FSH、ISI明显下降(P均<0.05)。PCOS患者肥胖组与非肥胖组相比,HOMA-IR及卵泡数目增高,ISI下降(P均<0.05),但LH、LH/FSH、T、FT及卵巢面积差异无统计学意义。②治疗后两组PCOS患者体重、BMI、腰围、臀围、FPG、FINS、HOMA-IR明显下降(P均<0.05),ISI明显上升(P<0.05)；肥胖组LH、LH/FSH、FT及非肥胖组FT明显下降(P均<0.05),且肥胖组FT下降的差值大于非肥胖组(P<0.05)；两组卵巢面积、卵泡数目均减少(P<0.05); T、FSH无明显变化。③治疗前两组PCOS患者VLCSFAs,肥胖组n-3VLCPUFAs、n-9VLCMUFAs明显均高于对照组,肥胖组n-9VLCMUFAs也明显高于非肥胖组(P均<0.05)。n-6VLCPUFAs三组无差异。治疗后两组PCOS患者的n-3VLCPUFAs均明显升高,肥胖组VLCSFAs下降,非肥胖组n-9VLCMUFAs升高(P均<0.05)。④治疗过程中胃肠道不良反应发生率非肥胖组为9.3%,肥胖组为6.3%,无肝毒性、水肿及低血糖等不良反应。
结论：①肥胖较非肥胖的PCOS患者IR及卵巢多囊样改变更明显,但T、FT差异无显著性。②二甲双胍马来酸罗格列酮能降低PCOS患者的BMI和FT,改善IR及卵巢多囊样改变,对肥胖PCOS患者作用更显著,无明显不良反应。③肥胖和非肥胖的PCOS患者均存在超长链脂肪酸代谢的紊乱,二甲双胍马来酸罗格列酮能升高PCOS患者的n-3VLCPUFAs,降低肥胖PCOS患者的VLCSFAs,升高非肥胖PCOS患者的n-9VLCMUFAs。
OBJECTIVE:The aim of the study is to evaluate the therapeutic effects of metformin hydrochloride and rosiglitazone maleate tablets on insulin resistance(IR), androgen concentration and plasma very long chain fatty acids(VLCFAs) levels in women with polycystic ovarian syndrome (PCOS).
METHOD:Seventy women(aged 18 to 40 years) with PCOS were enrolled into this study according to the diagnostic criteria of Rotterdam conference(2003).The women with PCOS were divided into the obese group(BMI= 25 kg/m2, n=34) and the nonobese group(BMI< 25 kg/m2,n=36) according to BMI. In the corresponding period,35 infertile women due to the problems of uterine tube or spouses was taken as the control group.All women with PCOS had metformin hydrochloride and rosiglitazone maleate tablets twice daily for 3 months. There were some tests as the following before and after the treatment:height (Ht),weight(Wt),waist circumference(WC), liver function, lipids were tested; the fasting plasma glucose (FPG) was detected by glucose oxidase;the luteinizint hormone(LH),follicle stimulating hormone (FSH),total testosterone(T) and fasting plasma insulin (FINS) were examined by chemiluminescence method;the follicular number and ovarian area were checked in follicle period or amenorrhoea period; the plasma free testosterone was examined by enzyme-linked immunosorbentassay (ELISA);the BMI, waist to hip ratio (WHR),and homeostasis model assessment for insulin resistance (HOMA-IR), insulin sensitivity index(ISI) were calculated;the plasma VLCFAs were analysed by gas chromatography-mass spectrometry (GC-MS),including very long chain saturated fatty acids (VLCSFAs),n-9 very long chain monounsaturated fatty acids (n-9VLCMUFAs),n-3 very long chain polyunsaturated fatty acids (n-3VLCPUFAs) and n-6 very long chain polyunsaturated fatty acids (n-6VLCPUFAs).
RESULT:①Compared with the control group, LH, LH/FSH, T,FT, FINS, HOMA-IR were significantly higher and FSH, ISI were obviously lower in women with PCOS(P<0.05). Compared with the nonobese group, dramatic increases in HOMA-IR and follicle number were observed in obese group(P<0.05), while LH, LH/FSH, T, FT had no significant difference between two gruops.②After the treatment with metformin hydrochloride and rosiglitazone maleate tablets, Wt, BMI, WC, hip circumference, FPG, FINS, HOMA-IR significantly decreased and ISI rised apparently in two groups(P<0.05). There were also significant declines of LH, LH/FSH, FT,ovarian area, follicular number,especially in the obese women with PCOS(P<0.05),while T and FSH did not change significantly.③Compared with the control,the levels of VLCSFAs in both groups, and the levels of n-3VLCPUFAs and n-9VLCMUFAs in obese group were significant higher(P<0.05),while n-6VLCPUFAs had no significant difference among these groups. Compared with the nonobese group, there was an increase of n-9VLCMUFAs in obese group(P<0.05).Clinically significant increases of n-3VLCPUFAs in both groups,n-9VLCMUFAs in nonobese group and significant reduction in VLCSFAs of obese group were observed after the treatment with metformin hydrochloride and rosiglitazone maleate tablets(P<0.05), while n-6 VLCPUFAs did not change significantly in either group after the treatment.④The incidence of gastrointestinal adverse reactions happened in nonobese and obese group was 9.3% and 6.3% respectively, and no liver toxicity, edema, hypoglycemia and other adverse reactions was observed in the treatment.
CONCLUSION:①Compared with the nonobese group, there were severer insulin resistance and polycystic ovary in obese women with PCOS, while T and FT had no significant difference between two gruops.②Metformin hydrochloride and rosiglitazone maleate tablets can ameliorate insulin resistance and polycystic ovary,and also reduce BMI and FT in women with PCOS particularly in the obese,which may have no significant adverse reaction.③The metabolic disorders of plasma very long chain fatty acids existed in women with PCOS. After the treatment with metformin hydrochloride and rosiglitazone maleate tablets for three months, the concentration of n-3VLCPUFAs in both groups and n-9VLCMUFAs in nonobese group was significantly increased, while the concentration of VLCSFAs in obese group decreased.
引文
[1]Asuncion M, Calvo RM, San Millan JL. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian womenfrom Spsan[J] J Clin Endoerinol Metab,2000,85:2434-2438.
[2]Hoeger K. Obesity and weight loss in polycystic ovary syndrome [J]. Obstect Gynecol Clin North Am,2001,28(1):85.
[3]Strowitzki T, Hlser B, Demant T.Body fat distribution,insulin sensitivity, ovarian dysfunction and serum lipoproteins in patients with polycystic ovary syndrome [J]. Gynecol Endocrinol,2002,16 (1):52-51.
[4]王继波.侯丽辉.吴效科.肥胖与多囊卵巢综合征关系[J].医学研究杂志2009(4)：127-128
[5]Ovalle F, Azziz R. Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus [J]. Fertil Steril,2002,77:1095-1105.
[6]Davison RM. New approaches to insulin resistance in polycystic ovary syndrome [J]. Curr Opin Obstet Gynecol,1998,10:193.
[7]范乐平,朱杰.多囊卵巢综合征的胰岛索抵抗机制研究进展[J].医学综述,2009,5(15)：1381-1383.
[8]Nestler JE. Role of hyperimulinemia in the pathologenesis of polycystic ovary syndrome and its clinic alimplication [J].Semia Reprod Endoerinol,1997, 15(2):111-122.
[9]Pasquali R,Gambineri A. Insulin-sensitizing agents in polycystic ovary syndrome [J]. Eur J Endocrinol,2006,154(6):763-775.
[10]Nestler JE, Jakubowiez DJ, Evans WS, et al. Effects of metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia,and systolic blood pressure,while facilitateing normal menses pregnancy [J]. polycystic ovary syndrome metabolism,1994(43):647-654
[11]夏丹岚,华凯.二甲双胍在PCOS中的作用[J].国外医学妇产科学分册,2004,31(2)：73-76.
[12]陶建英,徐惠民.罗格列酮治疗多囊卵巢综合征胰岛素抵抗临床研究[J].中国现代医药杂志,2008, 10(3)：45-47.
[13]Shobokshi A Shaarawy M. Correction of insulin resistance and hyperandrogenism in polycystic ovary syndrome by combined rosigitazone and clomiphene citrate therapy[J]. J Soc Gynecol Invesfig,2003(2):99-104.
[14]Rosenstock J, Rood J, Cobitz A, et al. Initial treatment with Rosiglitazone /metformin fixed-dose combination therapy compared with monotherapy with either rosiglitazone or metformin in patients with uncontrolled type 2 diabetes [J]. Diabetes Obes Metab,2007,9(6):914.
[15]Vessby B, Unsitupa M, Hermansen K. Substituting dietary saturated fat for monounsaturated fat impairs insulin sensitivity in healthy men and women [J], The KANWU Study,2001(03):312-319.
[16]Takayoshi S, Kanami TK, Junko N, et al. Role of the toll-like receptor 4/NF-κB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages changes in both adipocytes and macrophages through NF-κB activation [J]. Arterioscler Thromb Vasc Biol,2007,27:84-91.
[17]Anette D,Thomas ML, Kjeld H, et al.Comparison of the effects on insulin resistance and glucose tolerance of 6-mo high-monounsaturated-fat, low-fat, and control diets[J]. Am J Clin Nutr,2008,87:855-862.
[18]Baer DJ, Judd JT, Clevidence BA, Tracey RP. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets:randomised crossover study [J]. Am J Clin Nutr,2004,79:969-973.
[19]Ailhaud G, Massicra F, Weill P, et al.Temporal changes in dietary fats:role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity [J]. Prog Lipid Res,2006,45(3):203-236.
[20]Taouis M, Dagou C, Ster C, et al. N-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle [J].Physiol Endocrinol Metab,2002, 282(3):664-671.
[21]史继虹,史虹莉,方京冲,等.脂肪酸对糖尿病模型大鼠血磷脂脂肪谱的影响[J]. 中国公共卫生,2004,20(5)：542-544.
[22]Niamh P, Annalouise O, Tommy KT, et al. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial[J]. Am J Clin Nutr,2011,93(3):652-662.
[23]Diamanti-Kandarakis E, Alezandraki K, Piperi C, et al. Inflammatory and endothelial markers in women with polycystic ovary syndrome [J].Eur J Clin Invest, 2006 (36):691-697.
[24]Harris WS, Muzio F. Fish oil reduces postprandial triglyceride concentrations without accelerating lipidemulsion removal rates [J].Am J Clin Nutr,1993,58: 68-74.
[25]Aitken RJ, Baker HW, Irvine DS, et al. On the nature of semen quality and infertility [J].Hum Reprod,1995,10:248-249.
[26]Gasperikova D, Demcakova E, Ukropec J, et al. Insulin resistance in the here ditary hypertriglyceridemic rat is associated with an im pairment of delta-6 desaturase expression in liver [J]. Ann NYAcad Sci,2002,967:336-453.
[27]Flegal KM, Graubard BI, Williamson DF, et al. Excess deaths associated with underweight, overweight, and obesity [J]. J AMA,2005.293(15):1861-7.
[28]Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome [J]. Fertil Steril,2004,81(1):19-25.
[29]Wendy Y, Chang MD, Eric S, et al. Phenotypic spectrum of polycystic ovary syndrome:cliniczl and biochemical characterization of the three major clinical subgroups [J]. Fertility and Sterility,2005,83(6):1717-1723.
[30]Codner E, Soto N, Lopez P, et al. Diagnostic Criteria for Polycystic Ovary Syndrome and Ovarian Morphology in Women with Type 1 Diabetes Mellitns [J]. J Clin Endocrinol Metab,2006,91(6):2250--6.
[31]Hatch R, Rosenfield RL, Kim MH, et al. Hirsutism:implications,etiology,and management [J].Am J Obstet Gynecol,1981,140:815-830.
[32]Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome(PCOS) [J].The Rotterdam ESHRE/ASRM Sponsored PCOS consensus workshop group.Hum. Reprod,2004,19(1):41-47
[33]Sobhonslidsuk A.Jongjirasiri S.Thakkinstian A.etal.Visceral fat and insulin resistanc-e as predictors of non-alcoholic steato hepatitis [J]. World J Gastro-enterol. 2007.13 (26):3614-8
[34]李光伟,潘孝仁,Lillioja S,等.检测人群胰岛素敏感性的一项新指数[J].中华内科杂志,1993,32：656-660.
[35]Swanson M, Sauerbrei EE, Cooperberg PL. Medical implications of ultrasonically detected polycystic ovaries [J].J Clin Ultrasound,1981,9:219-222.
[36]LZ Yi, J He, YZ Liang, et al. Plasma fatty acid metabolic profiling and biomarkers of type 2 diabetes mellitus based on GC/MS and PLS-LDA [J]. FEBS Letters, 2006,580:6837-6845.
[37]Cetinkalp, SM, Karadeniz, et al. The effects of rosiglitazone, metformin, and estradiol-cyproterone acetate on lean patients with polycystic ovary syndrome [J]. Endocrinologist,2009,19(3):94-97.
[38]Trolle BA. Flyvbjerg, et al. Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome:a randomized, double-blinded, placebo-controlled cross-over trial [J]. Hum Reprod,2007,22(1):2967-73.
[39]Con JJ, Jacobs HS,Conway CS. The prevalence of polycystic ovades in women with 2 type diabetes mellitus [J]. Clin Eudocrinol(Oxf),2000,52(1):81-86.
[40]Strowitzki T, Halser B. Demant body fat distribution, insulin sensitivity, ovarian dysfunction and serum lipoproteins in patients with polycystic ovary syndrome [J]. Gynecol Endocrinnol,2002,16(1):45-51.
[41]Livingstone C, Collison M. Sex steroids and insulin resistance [J]. Clin Sci (Lond), 2002(2):151-166.
[42]A Yilmaz M, Bifi A, Karakoq A, et al. The effects of rosiglitazone and mefformin on insulin resistance and serum androgen levels in obese and lean patients with polycystie ovary syndrome [J].Endocrinol Invest,2005,28(11):1003·1008
[43]Baillargeon JP, Jakubowicz DJ, Iuorno MJ, et al. Effect of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity [J]. Fertil Steril.2004,82: 893-902
[44]李光伟.当前胰岛素敏感性评估及胰岛素抵抗研究中的某些误区[J].中华内科杂志,1998,,37(2)：81-83
[45]林金芳,李听,苏椿淋.多囊卵巢综合征患者胰岛素抵抗的诊断方法及治疗策略.中国实用妇科与产科杂志,2007,23(9)：663-667.
[46]Mather KJ, Hunt AJ, Steinberg HO, et al. Repeatability character ristics of simple indices of insulin resistance:implications for research applications [J]. J Clin Endoerinol Mctab,2001,86(11):5457-5464.
[47]李光伟,Bennett PH糖尿病流行病学研究中应用OGTT资料评估胰岛β细胞功能的可能性—468例非糖尿病Pima印第安人葡萄糖钳研究资料分析[J].中华内分泌代谢杂志,2003,(01)：8-12.
[48]Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17a activity and serum free testosterone after reduction of insuline secretion in polycystic ovary system [J].N Engl J Med,1996,335:617-623.
[49]Genazzani AD, Battaglia C, Malavasi B, et al. Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome [J].2004, (08):114-119.
[50]Mu YM, Yanase T, Nishi Y, et al. Insulin sensitizer,troglitazone,directly inhibits aromatase activity in human ovarian granulosa cells [J].Biochen Biophys Res Commun,2000,271(3):710-713.
[51]Attila GR, Rainey WE, Cart BR, et al. Mefformin directly inhibits androgen production in human thecal cells [J],2001,76(3):517-524.
[52]Arlt W, Auchus RJ, Miller WL. Thiazolidinediones but not metformin directly inhibit the steroidogenic enzymes P450c17 and beta-hydroxysteroid dehydrogenase [J].J Biol Chem,2001,20:16767-16771.
[53]Storlien LH,Baur LA, Kriketos AD, et al. Dietary fats and insulin action [J]. Diabetologia,1996,39:621-631.
[54]Sidika EK, Rogelio UA, Laura G, et al. Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome [J].J Clin Endocrinol Metab,2004(02):1019-1027
[55]Kalgaonkar S, Almario RU, Gurusinghe D, et al. Differential effects of walnuts vs almonds on improving metabolic and endocrine parameters in PCOS [J]. European J Clinical Nutrition,2011,65:386-393.
[56]Matsuzaka T, Shimano H, Yahagi N, et al. Dual regulation of mouse Delta5- and Delta6-desaturase gene expression by SREBP-1 and PPAR-alpha [J]. Lipid Res, 2002,43:107-114
[1]Asuncion M, Calvo RM, San Millan JL. A prospective study Of the prevalence of the polycystic ovary syndrome in unselected Caucasian womenfrom Spsan [J].J Clin Endoerinol Metab,2000,85:2434-2438.
[2]Rotterdam E. SHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome [J].Fertil Steril,2004,81(1):19-25.
[3]王继波,侯丽辉,吴效科.肥胖与多囊卵巢综合征关系[J].医学研究杂志2009(4)：127-128
[4]Katsiki N.Georgiadou E, Halzitolios AI. The role of insulin-sensitizing agents in the treatment of polycystic ovary syndrome [J].Drugs,2009,69(11):1417-1431.
[5]李光伟.当前胰岛素敏感性评估及胰岛素抵抗研究中的某些误区[J].中华内科杂志,1998,37(2)：81-83
[6]林金芳,李听,苏椿淋.多囊卵巢综合征患者胰岛素抵抗的诊断方法及治疗策略[J].中国实用妇科与产科杂志,2007,23(9)：663-667.
[7]Mather KJ, Hunt AJ, Steinberg HO, et al. Repeatability character ristics of simple indices of insulin resistance:implications for research applications [J].J Clin Endoerinol Mctab,2001,86(11):5457-5464.
[8]李光伟,Bennett PH糖尿病流行病学研究中应用OGTT资料评估胰岛β细胞功能的可能性—468例非糖尿病Pima印第安人葡萄糖钳研究资料分析[J].中华内分泌代谢杂志,2003,01：8-12
[9]姜荣华,徐望明.多囊卵巢综合征的胰岛素抵抗研究进展[J].国外医学(妇幼保健分册),2004,16(2)：113-116.
[10]Siegel S, Futterweit W, Davies TF, el al. AC/T single nueleotide polymorphism at the tyrogine kinase dommn of the insulin receptor geneis associated with polycystie ovary syndrome[J]. Fertil Steril,2002,78(6):1240-1243.
[11]程庆丰,李卫平.李启富胰岛素抵抗和多囊卵巢综合征[J].中国糖尿病杂志,2007,15(2)：117-119.
[12]Lozzo P,Pratipanawatr T, Pijl H. Physiological hyperinsulinemia impaim insulin-stimulated glycogen synthase activity and glycogen synthesis [J]. Am J Phys Endocrind Metab,2001,280(5):E712-719.
[13]范林霄.郝敏.多囊卵巢综合征患者血清瘦素、胰岛素水平的临床研究[J].山西医药杂志,2007,36(7)：12-14.
[14]Franks S, Gharani N, Waterworth D, et al. Genetics of polycystic ovary syndrome [J]. Mocell Endocrinol,1998,145(1-2):123-128.
[15]Davison RM. New approaches to insulin resistance in polycystic ovary syndrome [J]. Curr Opin Obstet Gynecol,1998,10(3):193.
[16]Nestler JE. Insulin regulation of human ovarian androgens.Hum reprod,1997,12 (suppl):53-62.
[17]Diamanti KE, Dunaif A. New perspectives in polycystic ovary syndrome [J]. Trends Endocfin Metab,.1996,1:267-271.
[18][Pasquali R, Gambineri A. Insulin-sensitizing agents in polycystic ovary syndrome [J]. Eur J Endocrinol,2006,154(6):763-775.
[19]Livingstone C, Collison M. Sex steroids and insulin resistance[J]. Clin Sci(Lond), 2002(2):151-166.
[20]Ibrahim S, Aydin A. Hyperinsulinism and its Interaction with Hyperandrogenism in polycystic ovary syndrome[J]. Obstet Gynecol Surv,2000,55:321-327.
[21]Strowitzki T, Hlser B, Demant T.Body fat distribution, insulin sensitivity, ovarian dysfunction and serum lipoproteins in patients with polycystic ovary syndrome[J]. Gynecol Endocrinol,2002,16 (1):52-51.
[22]王继波,侯丽辉,吴效科.肥胖与多囊卵巢综合征关系[J].医学研究杂志2009(4)：127-128
[23]Bjorntorp P. Abdominal obesity and the metabolic syndrome [J]. Ann Med,1992, 24:465
[24]赵海波,何娅绒,李爱莉,等.多囊卵巢综合征患者二甲双胍治疗前后血清脂联素水平的变化[J].实用妇产科杂志,2007,23(2)：99-101.
[25]胡卫红,乔杰,李美芝.单核细胞趋化蛋白-1与多囊卵巢综合征临床特征的相关性研究[J].中华医学杂志,2007,87(11)：721-724.
[26]Vessby B, Unsitupa M, Hermansen K. Substituting dietary saturated fat for monounsaturated fat impairs insulin sensitivity in healthy men and women:The KANWU Study 2001(03):312-319.
[27]Takayoshi S, Kanami TK, Junko N, et al. Role of the toll-like receptor 4/NF-κB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages changes in both adipocytes and macrophages through NF-κB activation [J]. Arterioscler Thromb Vasc Biol,2007,27:84-91.
[28]Anette D, Thomas ML, Hermansen K, et al.Comparison of the effects on insulin resistance and glucose tolerance of 6-mo high-monounsaturated-fat, low-fat, and control diets[J].Am J Clin Nutr,2008,87:855-862.
[29]Baer DJ, Judd JT, Clevidence BA, et al. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets:randomised crossover study [J]. Am J Clin Nutr,2004,79:969-973.
[30]Ailhaud G,Massicra F,Weill P,et al.Temporal changes in dietary fats:role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity [J].Prog Lipid Res,2006,45(3):203-236.
[31]Taouis M, Dagou C, Ster C, et al. N-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle [J]. Physiol Endocrinol Metab, 2002,282(3):664-671.
[32]史继虹,史虹莉,方京冲等.脂肪酸对糖尿病模型大鼠血磷脂脂肪谱的影响[J].中国公共卫生,2004,20(5)：542-544.
[33]Niamh P, Annalouise O, Tommy KT, et al. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial[J]. Am J Clin Nutr,2011,93(3):652-662.
[34]Novak TE, Babcock TA, Jho DH, et al. NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription [J]. Am J Physiol Lung Cell Mol Physiol.2003,284(1):L84-9.
[35]Mai K, Bobbert T, Kullmann V, et al. Free fatty acids increase androgen precursors in vivo [J]. J Clin Endocrinol Metab.2006,91(4):1501-7.
[36]Diamanti-Kandarakis E, Alezandraki K, Piperi C, et al. Inflammatory and endothelial markers in women with polycystic ovary syndrome [J].Eur J Clin Invest, 2006 (36):691-697.
[37]Harris WS, Muzio F. Fish oil reduces postprandial triglyceride concentrations without accelerating lipidemulsion removal rates [J]. Am J Clin Nutr,1993,58:68-74.
[38]Aitken RJ, Baker HW, Irvine DS, et al. On the nature of semen quality and infertility [J]. Hum Reprod,1995,10:248-249.
[39]Gasperikova D, Demcakova E, Ukropec J, et al. Insulin resistance in the here ditary hypertriglyceridemic rat is associated with an im pairment of delta-6 desaturase expression in liver [J]. Ann NYAcad Sci,2002,967:336-453.
[40]Das UN. Essential fatty acids:biochemistry, physiology and pathology [J]. Biotechnology journal,2006,1:420-439
[41]D.Mozaffarian TP, Hankinson SE,ea al. Dietary intake of trans fatty acids and systemic inflammation in women [J]. Am. J. Clin.Nutr,2004,79:606-612
[42]Matsuzaka T, Shimano H, Yagi N, et al. Dual regulation of mouse Delta5- and Delta6-desaturase gene expression by SREBP-1 and PPAR-alpha [J]. Lipid. Res, 2002,43:107-114.
[43]Cusi K, Defronzo RA, Metformin:a review of its metabolic effects[J].Diabetes Reviews.1998,6(2):98-131.
[44]Laurel A, Benjamin C, Oehninger WS. Should patients with polycystic ovary syndrome be treated with metformin? Benefits of insulin sensitizing drugs in polycystic ovary syndrome beyond ovulation induce [J]. Human Reproduction 2002,17(12):3016-3026.
[45]Attila GR, Rainey WE, Cart BR. Metformin directly inhibits androgen production in human thecal cells [J]. Fertility and sterility,2001,76(3):517-524.
[46]Smith U, Gogg S, Johansson A, et al. Thiazolidinediones(PPARgamma agonists) but not PPARalpha agonists increase IRS-2 gene expression in 3T3. LI and human adipocytes [J]. FASEB J,2001 (1):215-220.
[47]Wu Z, Xie Y, Morrison RF, et al. PPARgamma induces the insulin-dependent glucose transporter GLUT4 in the absence of C/EBPalpha during the conversion of 3T3 fibroblasts into adipocytes [J]. J Clin Invest,1998(1):22-32.
[48]Okuno A, Tamemoto H, Tobe K, et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats[J].J Clin Invest,1998(6):1354-1361.
[49]Arlt W, Auchus RJ, Miller W L. Thiazolidinediones but not metformin directly inhibit the steroidogenic enzymes P450c17 and beta-hydroxysteroid dehydrogenase [J]. J Biol Chem,2001(20):16767-16771.
[50]Baillargeon JP, Jakubowicz DJ, Iuorno MJ, et al. Effect of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity [J]. Fertil Steril.2004, 82:893-902
[2]Hoeger K. Obesity and weight loss in polycystic ovary syndrome [J]. Obstect Gynecol Clin North Am,2001,28(1):85.
[3]Strowitzki T, Hlser B, Demant T.Body fat distribution,insulin sensitivity, ovarian dysfunction and serum lipoproteins in patients with polycystic ovary syndrome [J]. Gynecol Endocrinol,2002,16 (1):52-51.
[4]王继波.侯丽辉.吴效科.肥胖与多囊卵巢综合征关系[J].医学研究杂志2009(4)：127-128
[5]Ovalle F, Azziz R. Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus [J]. Fertil Steril,2002,77:1095-1105.
[6]Davison RM. New approaches to insulin resistance in polycystic ovary syndrome [J]. Curr Opin Obstet Gynecol,1998,10:193.
[7]范乐平,朱杰.多囊卵巢综合征的胰岛索抵抗机制研究进展[J].医学综述,2009,5(15)：1381-1383.
[8]Nestler JE. Role of hyperimulinemia in the pathologenesis of polycystic ovary syndrome and its clinic alimplication [J].Semia Reprod Endoerinol,1997, 15(2):111-122.
[9]Pasquali R,Gambineri A. Insulin-sensitizing agents in polycystic ovary syndrome [J]. Eur J Endocrinol,2006,154(6):763-775.
[10]Nestler JE, Jakubowiez DJ, Evans WS, et al. Effects of metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia,and systolic blood pressure,while facilitateing normal menses pregnancy [J]. polycystic ovary syndrome metabolism,1994(43):647-654
[11]夏丹岚,华凯.二甲双胍在PCOS中的作用[J].国外医学妇产科学分册,2004,31(2)：73-76.
[12]陶建英,徐惠民.罗格列酮治疗多囊卵巢综合征胰岛素抵抗临床研究[J].中国现代医药杂志,2008, 10(3)：45-47.
[13]Shobokshi A Shaarawy M. Correction of insulin resistance and hyperandrogenism in polycystic ovary syndrome by combined rosigitazone and clomiphene citrate therapy[J]. J Soc Gynecol Invesfig,2003(2):99-104.
[14]Rosenstock J, Rood J, Cobitz A, et al. Initial treatment with Rosiglitazone /metformin fixed-dose combination therapy compared with monotherapy with either rosiglitazone or metformin in patients with uncontrolled type 2 diabetes [J]. Diabetes Obes Metab,2007,9(6):914.
[15]Vessby B, Unsitupa M, Hermansen K. Substituting dietary saturated fat for monounsaturated fat impairs insulin sensitivity in healthy men and women [J], The KANWU Study,2001(03):312-319.
[16]Takayoshi S, Kanami TK, Junko N, et al. Role of the toll-like receptor 4/NF-κB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages changes in both adipocytes and macrophages through NF-κB activation [J]. Arterioscler Thromb Vasc Biol,2007,27:84-91.
[17]Anette D,Thomas ML, Kjeld H, et al.Comparison of the effects on insulin resistance and glucose tolerance of 6-mo high-monounsaturated-fat, low-fat, and control diets[J]. Am J Clin Nutr,2008,87:855-862.
[18]Baer DJ, Judd JT, Clevidence BA, Tracey RP. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets:randomised crossover study [J]. Am J Clin Nutr,2004,79:969-973.
[19]Ailhaud G, Massicra F, Weill P, et al.Temporal changes in dietary fats:role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity [J]. Prog Lipid Res,2006,45(3):203-236.
[20]Taouis M, Dagou C, Ster C, et al. N-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle [J].Physiol Endocrinol Metab,2002, 282(3):664-671.
[21]史继虹,史虹莉,方京冲,等.脂肪酸对糖尿病模型大鼠血磷脂脂肪谱的影响[J]. 中国公共卫生,2004,20(5)：542-544.
[22]Niamh P, Annalouise O, Tommy KT, et al. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial[J]. Am J Clin Nutr,2011,93(3):652-662.
[23]Diamanti-Kandarakis E, Alezandraki K, Piperi C, et al. Inflammatory and endothelial markers in women with polycystic ovary syndrome [J].Eur J Clin Invest, 2006 (36):691-697.
[24]Harris WS, Muzio F. Fish oil reduces postprandial triglyceride concentrations without accelerating lipidemulsion removal rates [J].Am J Clin Nutr,1993,58: 68-74.
[25]Aitken RJ, Baker HW, Irvine DS, et al. On the nature of semen quality and infertility [J].Hum Reprod,1995,10:248-249.
[26]Gasperikova D, Demcakova E, Ukropec J, et al. Insulin resistance in the here ditary hypertriglyceridemic rat is associated with an im pairment of delta-6 desaturase expression in liver [J]. Ann NYAcad Sci,2002,967:336-453.
[27]Flegal KM, Graubard BI, Williamson DF, et al. Excess deaths associated with underweight, overweight, and obesity [J]. J AMA,2005.293(15):1861-7.
[28]Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome [J]. Fertil Steril,2004,81(1):19-25.
[29]Wendy Y, Chang MD, Eric S, et al. Phenotypic spectrum of polycystic ovary syndrome:cliniczl and biochemical characterization of the three major clinical subgroups [J]. Fertility and Sterility,2005,83(6):1717-1723.
[30]Codner E, Soto N, Lopez P, et al. Diagnostic Criteria for Polycystic Ovary Syndrome and Ovarian Morphology in Women with Type 1 Diabetes Mellitns [J]. J Clin Endocrinol Metab,2006,91(6):2250--6.
[31]Hatch R, Rosenfield RL, Kim MH, et al. Hirsutism:implications,etiology,and management [J].Am J Obstet Gynecol,1981,140:815-830.
[32]Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome(PCOS) [J].The Rotterdam ESHRE/ASRM Sponsored PCOS consensus workshop group.Hum. Reprod,2004,19(1):41-47
[33]Sobhonslidsuk A.Jongjirasiri S.Thakkinstian A.etal.Visceral fat and insulin resistanc-e as predictors of non-alcoholic steato hepatitis [J]. World J Gastro-enterol. 2007.13 (26):3614-8
[34]李光伟,潘孝仁,Lillioja S,等.检测人群胰岛素敏感性的一项新指数[J].中华内科杂志,1993,32：656-660.
[35]Swanson M, Sauerbrei EE, Cooperberg PL. Medical implications of ultrasonically detected polycystic ovaries [J].J Clin Ultrasound,1981,9:219-222.
[36]LZ Yi, J He, YZ Liang, et al. Plasma fatty acid metabolic profiling and biomarkers of type 2 diabetes mellitus based on GC/MS and PLS-LDA [J]. FEBS Letters, 2006,580:6837-6845.
[37]Cetinkalp, SM, Karadeniz, et al. The effects of rosiglitazone, metformin, and estradiol-cyproterone acetate on lean patients with polycystic ovary syndrome [J]. Endocrinologist,2009,19(3):94-97.
[38]Trolle BA. Flyvbjerg, et al. Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome:a randomized, double-blinded, placebo-controlled cross-over trial [J]. Hum Reprod,2007,22(1):2967-73.
[39]Con JJ, Jacobs HS,Conway CS. The prevalence of polycystic ovades in women with 2 type diabetes mellitus [J]. Clin Eudocrinol(Oxf),2000,52(1):81-86.
[40]Strowitzki T, Halser B. Demant body fat distribution, insulin sensitivity, ovarian dysfunction and serum lipoproteins in patients with polycystic ovary syndrome [J]. Gynecol Endocrinnol,2002,16(1):45-51.
[41]Livingstone C, Collison M. Sex steroids and insulin resistance [J]. Clin Sci (Lond), 2002(2):151-166.
[42]A Yilmaz M, Bifi A, Karakoq A, et al. The effects of rosiglitazone and mefformin on insulin resistance and serum androgen levels in obese and lean patients with polycystie ovary syndrome [J].Endocrinol Invest,2005,28(11):1003·1008
[43]Baillargeon JP, Jakubowicz DJ, Iuorno MJ, et al. Effect of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity [J]. Fertil Steril.2004,82: 893-902
[44]李光伟.当前胰岛素敏感性评估及胰岛素抵抗研究中的某些误区[J].中华内科杂志,1998,,37(2)：81-83
[45]林金芳,李听,苏椿淋.多囊卵巢综合征患者胰岛素抵抗的诊断方法及治疗策略.中国实用妇科与产科杂志,2007,23(9)：663-667.
[46]Mather KJ, Hunt AJ, Steinberg HO, et al. Repeatability character ristics of simple indices of insulin resistance:implications for research applications [J]. J Clin Endoerinol Mctab,2001,86(11):5457-5464.
[47]李光伟,Bennett PH糖尿病流行病学研究中应用OGTT资料评估胰岛β细胞功能的可能性—468例非糖尿病Pima印第安人葡萄糖钳研究资料分析[J].中华内分泌代谢杂志,2003,(01)：8-12.
[48]Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17a activity and serum free testosterone after reduction of insuline secretion in polycystic ovary system [J].N Engl J Med,1996,335:617-623.
[49]Genazzani AD, Battaglia C, Malavasi B, et al. Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome [J].2004, (08):114-119.
[50]Mu YM, Yanase T, Nishi Y, et al. Insulin sensitizer,troglitazone,directly inhibits aromatase activity in human ovarian granulosa cells [J].Biochen Biophys Res Commun,2000,271(3):710-713.
[51]Attila GR, Rainey WE, Cart BR, et al. Mefformin directly inhibits androgen production in human thecal cells [J],2001,76(3):517-524.
[52]Arlt W, Auchus RJ, Miller WL. Thiazolidinediones but not metformin directly inhibit the steroidogenic enzymes P450c17 and beta-hydroxysteroid dehydrogenase [J].J Biol Chem,2001,20:16767-16771.
[53]Storlien LH,Baur LA, Kriketos AD, et al. Dietary fats and insulin action [J]. Diabetologia,1996,39:621-631.
[54]Sidika EK, Rogelio UA, Laura G, et al. Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome [J].J Clin Endocrinol Metab,2004(02):1019-1027
[55]Kalgaonkar S, Almario RU, Gurusinghe D, et al. Differential effects of walnuts vs almonds on improving metabolic and endocrine parameters in PCOS [J]. European J Clinical Nutrition,2011,65:386-393.
[56]Matsuzaka T, Shimano H, Yahagi N, et al. Dual regulation of mouse Delta5- and Delta6-desaturase gene expression by SREBP-1 and PPAR-alpha [J]. Lipid Res, 2002,43:107-114
[1]Asuncion M, Calvo RM, San Millan JL. A prospective study Of the prevalence of the polycystic ovary syndrome in unselected Caucasian womenfrom Spsan [J].J Clin Endoerinol Metab,2000,85:2434-2438.
[2]Rotterdam E. SHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome [J].Fertil Steril,2004,81(1):19-25.
[3]王继波,侯丽辉,吴效科.肥胖与多囊卵巢综合征关系[J].医学研究杂志2009(4)：127-128
[4]Katsiki N.Georgiadou E, Halzitolios AI. The role of insulin-sensitizing agents in the treatment of polycystic ovary syndrome [J].Drugs,2009,69(11):1417-1431.
[5]李光伟.当前胰岛素敏感性评估及胰岛素抵抗研究中的某些误区[J].中华内科杂志,1998,37(2)：81-83
[6]林金芳,李听,苏椿淋.多囊卵巢综合征患者胰岛素抵抗的诊断方法及治疗策略[J].中国实用妇科与产科杂志,2007,23(9)：663-667.
[7]Mather KJ, Hunt AJ, Steinberg HO, et al. Repeatability character ristics of simple indices of insulin resistance:implications for research applications [J].J Clin Endoerinol Mctab,2001,86(11):5457-5464.
[8]李光伟,Bennett PH糖尿病流行病学研究中应用OGTT资料评估胰岛β细胞功能的可能性—468例非糖尿病Pima印第安人葡萄糖钳研究资料分析[J].中华内分泌代谢杂志,2003,01：8-12
[9]姜荣华,徐望明.多囊卵巢综合征的胰岛素抵抗研究进展[J].国外医学(妇幼保健分册),2004,16(2)：113-116.
[10]Siegel S, Futterweit W, Davies TF, el al. AC/T single nueleotide polymorphism at the tyrogine kinase dommn of the insulin receptor geneis associated with polycystie ovary syndrome[J]. Fertil Steril,2002,78(6):1240-1243.
[11]程庆丰,李卫平.李启富胰岛素抵抗和多囊卵巢综合征[J].中国糖尿病杂志,2007,15(2)：117-119.
[12]Lozzo P,Pratipanawatr T, Pijl H. Physiological hyperinsulinemia impaim insulin-stimulated glycogen synthase activity and glycogen synthesis [J]. Am J Phys Endocrind Metab,2001,280(5):E712-719.
[13]范林霄.郝敏.多囊卵巢综合征患者血清瘦素、胰岛素水平的临床研究[J].山西医药杂志,2007,36(7)：12-14.
[14]Franks S, Gharani N, Waterworth D, et al. Genetics of polycystic ovary syndrome [J]. Mocell Endocrinol,1998,145(1-2):123-128.
[15]Davison RM. New approaches to insulin resistance in polycystic ovary syndrome [J]. Curr Opin Obstet Gynecol,1998,10(3):193.
[16]Nestler JE. Insulin regulation of human ovarian androgens.Hum reprod,1997,12 (suppl):53-62.
[17]Diamanti KE, Dunaif A. New perspectives in polycystic ovary syndrome [J]. Trends Endocfin Metab,.1996,1:267-271.
[18][Pasquali R, Gambineri A. Insulin-sensitizing agents in polycystic ovary syndrome [J]. Eur J Endocrinol,2006,154(6):763-775.
[19]Livingstone C, Collison M. Sex steroids and insulin resistance[J]. Clin Sci(Lond), 2002(2):151-166.
[20]Ibrahim S, Aydin A. Hyperinsulinism and its Interaction with Hyperandrogenism in polycystic ovary syndrome[J]. Obstet Gynecol Surv,2000,55:321-327.
[21]Strowitzki T, Hlser B, Demant T.Body fat distribution, insulin sensitivity, ovarian dysfunction and serum lipoproteins in patients with polycystic ovary syndrome[J]. Gynecol Endocrinol,2002,16 (1):52-51.
[22]王继波,侯丽辉,吴效科.肥胖与多囊卵巢综合征关系[J].医学研究杂志2009(4)：127-128
[23]Bjorntorp P. Abdominal obesity and the metabolic syndrome [J]. Ann Med,1992, 24:465
[24]赵海波,何娅绒,李爱莉,等.多囊卵巢综合征患者二甲双胍治疗前后血清脂联素水平的变化[J].实用妇产科杂志,2007,23(2)：99-101.
[25]胡卫红,乔杰,李美芝.单核细胞趋化蛋白-1与多囊卵巢综合征临床特征的相关性研究[J].中华医学杂志,2007,87(11)：721-724.
[26]Vessby B, Unsitupa M, Hermansen K. Substituting dietary saturated fat for monounsaturated fat impairs insulin sensitivity in healthy men and women:The KANWU Study 2001(03):312-319.
[27]Takayoshi S, Kanami TK, Junko N, et al. Role of the toll-like receptor 4/NF-κB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages changes in both adipocytes and macrophages through NF-κB activation [J]. Arterioscler Thromb Vasc Biol,2007,27:84-91.
[28]Anette D, Thomas ML, Hermansen K, et al.Comparison of the effects on insulin resistance and glucose tolerance of 6-mo high-monounsaturated-fat, low-fat, and control diets[J].Am J Clin Nutr,2008,87:855-862.
[29]Baer DJ, Judd JT, Clevidence BA, et al. Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets:randomised crossover study [J]. Am J Clin Nutr,2004,79:969-973.
[30]Ailhaud G,Massicra F,Weill P,et al.Temporal changes in dietary fats:role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity [J].Prog Lipid Res,2006,45(3):203-236.
[31]Taouis M, Dagou C, Ster C, et al. N-3 polyunsaturated fatty acids prevent the defect of insulin receptor signaling in muscle [J]. Physiol Endocrinol Metab, 2002,282(3):664-671.
[32]史继虹,史虹莉,方京冲等.脂肪酸对糖尿病模型大鼠血磷脂脂肪谱的影响[J].中国公共卫生,2004,20(5)：542-544.
[33]Niamh P, Annalouise O, Tommy KT, et al. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial[J]. Am J Clin Nutr,2011,93(3):652-662.
[34]Novak TE, Babcock TA, Jho DH, et al. NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription [J]. Am J Physiol Lung Cell Mol Physiol.2003,284(1):L84-9.
[35]Mai K, Bobbert T, Kullmann V, et al. Free fatty acids increase androgen precursors in vivo [J]. J Clin Endocrinol Metab.2006,91(4):1501-7.
[36]Diamanti-Kandarakis E, Alezandraki K, Piperi C, et al. Inflammatory and endothelial markers in women with polycystic ovary syndrome [J].Eur J Clin Invest, 2006 (36):691-697.
[37]Harris WS, Muzio F. Fish oil reduces postprandial triglyceride concentrations without accelerating lipidemulsion removal rates [J]. Am J Clin Nutr,1993,58:68-74.
[38]Aitken RJ, Baker HW, Irvine DS, et al. On the nature of semen quality and infertility [J]. Hum Reprod,1995,10:248-249.
[39]Gasperikova D, Demcakova E, Ukropec J, et al. Insulin resistance in the here ditary hypertriglyceridemic rat is associated with an im pairment of delta-6 desaturase expression in liver [J]. Ann NYAcad Sci,2002,967:336-453.
[40]Das UN. Essential fatty acids:biochemistry, physiology and pathology [J]. Biotechnology journal,2006,1:420-439
[41]D.Mozaffarian TP, Hankinson SE,ea al. Dietary intake of trans fatty acids and systemic inflammation in women [J]. Am. J. Clin.Nutr,2004,79:606-612
[42]Matsuzaka T, Shimano H, Yagi N, et al. Dual regulation of mouse Delta5- and Delta6-desaturase gene expression by SREBP-1 and PPAR-alpha [J]. Lipid. Res, 2002,43:107-114.
[43]Cusi K, Defronzo RA, Metformin:a review of its metabolic effects[J].Diabetes Reviews.1998,6(2):98-131.
[44]Laurel A, Benjamin C, Oehninger WS. Should patients with polycystic ovary syndrome be treated with metformin? Benefits of insulin sensitizing drugs in polycystic ovary syndrome beyond ovulation induce [J]. Human Reproduction 2002,17(12):3016-3026.
[45]Attila GR, Rainey WE, Cart BR. Metformin directly inhibits androgen production in human thecal cells [J]. Fertility and sterility,2001,76(3):517-524.
[46]Smith U, Gogg S, Johansson A, et al. Thiazolidinediones(PPARgamma agonists) but not PPARalpha agonists increase IRS-2 gene expression in 3T3. LI and human adipocytes [J]. FASEB J,2001 (1):215-220.
[47]Wu Z, Xie Y, Morrison RF, et al. PPARgamma induces the insulin-dependent glucose transporter GLUT4 in the absence of C/EBPalpha during the conversion of 3T3 fibroblasts into adipocytes [J]. J Clin Invest,1998(1):22-32.
[48]Okuno A, Tamemoto H, Tobe K, et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats[J].J Clin Invest,1998(6):1354-1361.
[49]Arlt W, Auchus RJ, Miller W L. Thiazolidinediones but not metformin directly inhibit the steroidogenic enzymes P450c17 and beta-hydroxysteroid dehydrogenase [J]. J Biol Chem,2001(20):16767-16771.
[50]Baillargeon JP, Jakubowicz DJ, Iuorno MJ, et al. Effect of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity [J]. Fertil Steril.2004, 82:893-902