Efficacy Of GLP-1Receptor Agonist In Women With Both Pofycystic Ovary Syndrome And Insulin Resistance

BACKGROUNDPolycystic ovary syndrome (PCOS) is one of clinical common gynecologicalendocrinepathy syndrome which affects5%~10%of the women at fertile age. PCOSis a complex syndrome of unclear etiopatho-genesis, perhaps included hypothalamicpituitary dysfunction; dyscorticism; Insulin resistance and hyperinsulinemia; heredity;hyperpro-lactinemia. Of which insulin resistance is known as a major mechanism ofPCOS.HOMA-IR is widely used in clinic to evaluate insulin sensitivity and insulinresistance. Oral glucose tolerance test without interference in the physiologicalmechanism of glucose—insulin is conformed with physiology, which simultaneouslyto determine Insulin release curve.To increase insulin sensitivity and improve insulin resistance GLP-1receptoragonist (Exenatide) is effectively as a new medicine for PCOS.Objective(1) To assess different levels of the hormone in PCOS, T2DM and control group.(2) To contrast efficacy of treatment in exenatide or metformin in PCOS withinsulin resistance.(3)To investigate the probable mechanism and to provide a good choice in thetreatment of exenatide in PCOS with insulin resistance.Methods(1) To assess different levels of the hormone:From May2011,42patients in the clear prognosis of polycystic ovarysyndrome in our hospital were recruited, and34were devided into two groups;6female diabetic patients without diabetes complications, and8healthy femalevolunteers: â‘ To divide into2subgroups according to BMI:1）PCOS-Obese group (PO):n=18,25±5years,BMI29.11±2.65kg/m~22)PCOS-Lean(PL):n=16,27±4years,BMI22.18±2.15kg/m~2â‘¡Type2diabetes group(T2DM):n=6,34±3years,BMI25.31±1.57kg/m~2.â‘¢Control group (control):n=8,30±8years,BMI21.42±1.53kg/m~2All the subjects were examined after oral glucose tolerance test, includingblood lipid (TG, TC, LDL, HDL), blood glucose, sex hormone (T, E2, LH, FSH, PRL,PRG), insulin, GLP-1, GIP, HOMA-IR. And do some statistical analysis.（2）To contrast efficacy of treatment in exenatide or metformin in PCOS with insulinresistance: a randomized, double-blinded, placebo-controlled cross-over trialWe selected31PCOS with insulin resistance from34PCOS volunteers in clinicrandom allocation:â‘ GLP/MET group: Exenatide (0.5ug1month,1ug2month), followed with a10-day washout period and metformin (0.5mg TID3month)â‘¡MET/GLP group:, metformin (0.5mg TID3month),followed with a10-daywashout period and Exenatide (0.5ug1month,1ug2month)All the patients were examined after oral glucose tolerance test, includingblood lipid (TG, TC, LDL, HDL), blood glucose, sex hormone (T, E2, LH, FSH, PRL,PRG), insulin, GLP-1, GIP, HOMA-IR. And do some statistical analysis.Results（1）At baseline, BMI, Blood lipids, testosterone and HOMA-IR weresignificantly higher on PO than on other groups（P<0.05）. The level of C-peptide in0’60’120’ and180’ were significantly higher on PO than on Control group（P<0.05）.The level of insulin in0’60’120’and180’ were significantly higher on PO than onT2DM group（P<0.05）. LH was significantly higher on PL than on other groups（P<0.05）（2）In MET/GLP group, Testosterone did not show a significantly change after3months, and after6month Testosterone was significantly lower thanbefore-treatment. In GLP/MET group, Testosterone and LH/FSH shows asignificantly change after3months, but after another3month treatment in MET Testosterone did not show a significantly lower, either LH/FSH show a significantlyhigher than it on3M.In MET/GLP group, insulin only show a significantly change at15min after3months, and after6month show a significantly lower at15min,30min and60min thanbefore-treatment; and c-peptide was significantly lower at15min,30min,60min and180min than on0M. In GLP/MET group, insulin at15min and C-peptide at60minshows a significantly change after3months，and after6month,each time point showsa significantly lower than on0M.In MET/GLP group, only after6month GLP-1show a significantly lower at15min,30min and60min than before-treatment. In GLP/MET group, GLP-1at60minshows a significantly lower than on0M, and after6month shows a significantly lowerat0min,60min and120min.In both the group, INS-AUC shows a significantly lower than on0M.In MET/GLP group, after6month both GLP-1-AUC and GIP-AUC show asignificantly lower than on0M. In GLP/MET group, GLP-1-AUC and GIP-AUCshows a significantly lower than on0M, and HOMA-IR after6month shows asignificantly lower.Conclusion：（１）The major pathogenesis of the PCOS-Obese was insulin resistance. AndLH/FSH plays a leading role in PCOS-Lean. The reason that more secretion of bothGLP-1and GIP in PCOS-Obese maybe GLP-1resistance.（ï¼'）The possible mechanism of Exenatide is to improve insulin resistance,reduce testosterone and LH/FSH, also for the treatment of PCOS provides a newchoice.