Acupuncture treatment for insulin sensitivity of women with polycystic ovary syndrome and insulin resistance: a study protocol for a randomized controlled trial

Juan Li, Ernest Hung Yu Ng, Elisabet Stener-Victorin, Zhenxing Hu, Xiaoguang Shao, Haiyan Wang, Meifang Li, Maohua Lai, Changcai Xie, Nianjun Su, Chuyi Yu, Jia Liu, Taixiang Wu, Hongxia Ma, Juan Li, Ernest Hung Yu Ng, Elisabet Stener-Victorin, Zhenxing Hu, Xiaoguang Shao, Haiyan Wang, Meifang Li, Maohua Lai, Changcai Xie, Nianjun Su, Chuyi Yu, Jia Liu, Taixiang Wu, Hongxia Ma

Abstract

Background: Our prospective pilot study of acupuncture affecting insulin sensitivity on polycystic ovary syndrome (PCOS) combined with insulin resistance (IR) showed that acupuncture had a significant effect on improving the insulin sensitivity of PCOS. But there is still no randomized controlled trial to determine the effect of acupuncture on the insulin sensitivity in women with PCOS and IR. In this article, we present the protocol of a randomized controlled trial to compare the effect of true acupuncture on the insulin sensitivity of these patients compared with metformin and sham acupuncture. Acupuncture may be an effective therapeutic alternative that is superior to metformin and sham acupuncture in improving the insulin sensitivity of PCOS combined with IR.

Methods: This study is a multi-center, controlled, double-blind, and randomized clinical trial aiming to evaluate the effect of acupuncture on the insulin sensitivity in PCOS combined with IR. In total 342 patients diagnosed with PCOS and IR will be enrolled. Participants will be randomized to one of the three groups: (1) true acupuncture + metformin placebo; (2) sham acupuncture + metformin, and (3) sham acupuncture + metformin placebo. Participants and assessors will be blinded. The acupuncture intervention will be given 3 days per week for a total of 48 treatment sessions during 4 months. Metformin (0.5 g per pill) or placebo will be given, three times per day, and for 4 months. Primary outcome measures are changes in homeostasis model assessment of insulin resistance (HOMA-IR) and improvement rate of HOMA-IR by oral glucose tolerance test (OGTT) and insulin releasing test (Ins). Secondary outcome measures are homeostasis model assessment-β (HOMA-β), area under the curve for glucose and insulin, frequency of regular menstrual cycles and ovulation, body composition, metabolic profile, hormonal profile, questionnaires, side effect profile, and expectation and credibility of treatment. Outcome measures are collected at baseline, at the end of treatments, and 3 months after the last acupuncture treatment. On completion of the screening visit, randomization will be conducted using a central randomization system.

Discussion: This study will investigate the effects of acupuncture on the insulin sensitivity of PCOS and IR women compared with metformin and sham acupuncture. We will test whether true acupuncture with needles placed in skeletal muscles and stimulated manually and by electrical stimulation is more effective than metformin and sham acupuncture with superficial needle placement with no manual or electrical stimulation in improving the insulin sensitivity in PCOS women with IR.

Trial registration: ClinicalTrials.gov, NCT02491333 ; Chinese Clinical Trial Registry, ChiCTR-ICR-15006639. Registered on 24 June 2015.

Keywords: Acupuncture; Insulin resistance; Metformin; Polycystic ovary syndrome; Sham acupuncture.

Figures

Fig. 1
Fig. 1
CONSORT flow diagram of the study. PCOS polycystic ovary syndrome; HOMA homeostatic model assessment; IR insulin resistance; AUC area under the curve

References

    1. Lakkakula BV, Thangavelu M, Godla UR. Genetic variants associated with insulin signaling and glucose homeostasis in the pathogenesis of insulin resistance in polycystic ovary syndrome: a systematic review. J Assist Reprod Genet. 2013;30(7):883–95. doi: 10.1007/s10815-013-0030-1.
    1. Katulski K, Czyzyk A, Podfigurna-Stopa A, Genazzani AR, et al. Pregnancy complications in polycystic ovary syndrome patients. Gynecol Endocrinol. 2014;30:1–5. doi: 10.3109/09513590.2013.879857.
    1. Nestler JE. Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome, and its clinical implications. Semin Reprod Endocrinol. 1997;15(2):111–22. doi: 10.1055/s-2007-1016294.
    1. Farrell K, Antoni MH. Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: biobehavioral mechanisms and interventions. Fertil Steril. 2010;94(5):1565–74. doi: 10.1016/j.fertnstert.2010.03.081.
    1. Bhathena RK. Insulin resistance and the long-term consequences of polycystic ovary syndrome. J Obstet Gynaecol. 2011;31(2):105–10. doi: 10.3109/01443615.2010.539722.
    1. Hernandez-Valencia M, Hernandez-Rosas M, Zarate A. Care of insulin resistance in polycystic ovary syndrome. Ginecol Obstet Mex. 2010;78(11):612–6.
    1. Legro RS, Dodson WC, Kunselman AR, et al. Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS. J Clin Endocrinol Metab. 2016;12:jc20161659.
    1. Franks S. When should an insulin sensitizing agent be used in the treatment of polycystic ovary syndrome? Clin Endocrinol (Oxf) 2011;74(2):148–51. doi: 10.1111/j.1365-2265.2010.03934.x.
    1. Pauli JM, Raja-Khan N, Wu X, et al. Current perspectives of insulin resistance and polycystic ovary syndrome. Diabet Med. 2011;28(12):1445–54. doi: 10.1111/j.1464-5491.2011.03460.x.
    1. Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108:1167–74. doi: 10.1172/JCI13505.
    1. Hwang KR, Choi YM, Kim JJ, et al. Effects of insulin-sensitizing agents and insulin resistance in women with polycystic ovary syndrome. Clin Exp Reprod Med. 2013;40(2):100–5. doi: 10.5653/cerm.2013.40.2.100.
    1. Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(12):4565–92. doi: 10.1210/jc.2013-2350.
    1. Chang CT, Chen YC, Fang JT, et al. Metformin-associated lactic acidosis: case reports and literature review. J Nephrol. 2002;15(4):398–402.
    1. Triggle CR, Ding H. Cardiovascular impact of drugs used in the treatment of diabetes. Ther Adv Chronic Dis. 2014;5(6):245–68. doi: 10.1177/2040622314546125.
    1. Dunaif A. Drug insight: insulin-sensitizing drugs in the treatment of polycystic ovary syndrome-a reappraisal. Nat Clin Pract Endocrinol Metab. 2008;4(5):272–83. doi: 10.1038/ncpendmet0787.
    1. Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010;304(4):411–8. doi: 10.1001/jama.2010.920.
    1. Mamtani R, Haynes K, Bilker WB, et al. Association between longer therapy with thiazolidinediones and risk of bladder cancer: a cohort study. J Natl Cancer Inst. 2012;104(18):1411–21. doi: 10.1093/jnci/djs328.
    1. Betteridge DJ. Thiazolidinediones and fracture risk in patients with type 2 diabetes. Diabet Med. 2011;28(7):759–71. doi: 10.1111/j.1464-5491.2010.03187.x.
    1. Witt CM, Pach D, Brinkhaus B, et al. Safety of acupuncture: results of a prospective observational study with 229,230 patients and introduction of a medical information and consent form. Forsch Komplementmed. 2009;16(2):91–7. doi: 10.1159/000209315.
    1. Stener-Victorin E, Jedel E, Janson PO, et al. Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am J Physiol Regul Integr Comp Physiol. 2009;297(2):R387–95. doi: 10.1152/ajpregu.00197.2009.
    1. Manni L, Rocco ML, Barbaro Paparo S, et al. Electroacupucture and nerve growth factor: potential clinical applications. Arch Ital Biol. 2011;149(2):247–55.
    1. Liang F, Koya D. Acupuncture: is it effective for treatment of insulin resistance? Diabetes Obes Metab. 2010;12(7):555–69. doi: 10.1111/j.1463-1326.2009.01192.x.
    1. Johansson J, Manneras-Holm L, Shao R, et al. Electrical vs manual acupuncture stimulation in a rat model of polycystic ovary syndrome: different effects on muscle and fat tissue insulin signaling. PLoS One. 2013;8(1):e54357. doi: 10.1371/journal.pone.0054357.
    1. Benrick A, Maliqueo M, Johansson J, et al. Enhanced insulin sensitivity and acute regulation of metabolic genes and signaling pathways after a single electrical or manual acupuncture session in female insulin-resistant rats. Acta Diabetol. 2014;51(6):963–72. doi: 10.1007/s00592-014-0645-4.
    1. Yanhua Z, Stener-Victorin E, Ng HE, et al. How does acupuncture affect insulin sensitivity in women with polycystic ovary syndrome and insulin resistance? Study protocol of a prospective pilot study. BMJ Open. 2015;5(4):e007757. doi: 10.1136/bmjopen-2015-007757.
    1. Schulz KF, Altman DG, Moher D, for the CONSORT Group CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. Trials. 2010;11:32. doi: 10.1186/1745-6215-11-32.
    1. Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586. doi: 10.1136/bmj.e7586.
    1. Zhao X, Ni R, Li L, et al. Defining hirsutism in Chinese women: a cross-sectional study. Fertil Steril. 2011;96(3):792–6. doi: 10.1016/j.fertnstert.2011.06.040.
    1. Ni RM, Mo Y, Chen X, et al. Low prevalence of the metabolic syndrome but high occurrence of various metabolic disorders in Chinese women with polycystic ovary syndrome. Eur J Endocrinol. 2009;161(3):411–8. doi: 10.1530/EJE-09-0298.
    1. Chen X, Yang D, Li L, et al. Abnormal glucose tolerance in Chinese women with polycystic ovary syndrome. Hum Reprod. 2006;21(8):2027–32. doi: 10.1093/humrep/del142.
    1. Vincent C, Lewith G. Placebo controls for acupuncture studies. J R Soc Med. 1995;88:199–202.
    1. MacPherson H, Altman DG, Hammerschlag R, et al. Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT statement. PLoS Med. 2010;7(6):e1000261. doi: 10.1371/journal.pmed.1000261.
    1. Stener-Victorin E, Baghaei F, Holm G, et al. Effects of acupuncture and exercise on insulin sensitivity, adipose tissue characteristics, and markers of coagulation and fibrinolysis in women with polycystic ovary syndrome: secondary analyses of a randomized controlled trial. Fertil Steril. 2012;97:501–8. doi: 10.1016/j.fertnstert.2011.11.010.
    1. Kuang H, Li Y, Wu X, et al. Acupuncture and clomiphene citrate for live birth in polycystic ovary syndrome: study design of a randomized controlled trila. Evid Based Complement Alternat Med. 2013;2013:527303. doi: 10.1155/2013/527303.
    1. McHorney CA, Ware JE, Jr, Raczek AE. The MOS 36-Item Short-Form Health Survey (SF-36): II.Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care. 1993;31(3):247–63. doi: 10.1097/00005650-199303000-00006.
    1. Leung KF, Liu FB, Zhao L, et al. Development and validation of the Chinese Quality of Life Instrument. Health Qual Life Outcomes. 2005;3:26. doi: 10.1186/1477-7525-3-26.
    1. Buysse DJ, Reynolds CF, 3rd, Monk TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213. doi: 10.1016/0165-1781(89)90047-4.
    1. Craig CL, Marshall AL, Sjostrom M, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381–95. doi: 10.1249/01.MSS.0000078924.61453.FB.
    1. Borges MB, Morgan CM, Claudino AM, et al. Validation of the Portuguese version of the questionnaire on eating and weight patterns-revised (QEWP-R) for the screening of binge eating disorder. Rev Bras Psiquiatr. 2005;27(4):319–22. doi: 10.1590/S1516-44462005000400012.
    1. Cronin L, Guyatt G, Griffith L, et al. Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS) J Clin Endocrinol Metab. 1998;83(6):1976–87.
    1. Jiang M, Lu C, Zhang C, et al. Syndrome differentiation in modern research of traditional Chinesemedicine. J Ethnopharmacol. 2012;140(3):634–42. doi: 10.1016/j.jep.2012.01.033.
    1. Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9. doi: 10.1007/BF00280883.
    1. Iwata M, Maeda S, Kamura Y, et al. Genetic risk score constructed using 14 susceptibility alleles for type 2 diabetes is associated with the early onset of diabetes and may predict the future requirement of insulin injections among Japanese individuals. Diabetes Care. 2012;35(8):1763–70. doi: 10.2337/dc11-2006.
    1. Kahn SE, Prigeon RL, McCulloch DK, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993;42(11):1663–72. doi: 10.2337/diab.42.11.1663.

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