利拉鲁肽和二甲双胍:利拉鲁肽联合二甲双胍医治多囊卵巢综合征对妊娠期糖尿病发病率的影响

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中国当代医药
2020年01月13日 05:44

胡晓娜

[摘要]意图 觀察利拉鲁肽联合二甲双胍医治对多囊卵巢综合征(PCOS)妇女妊娠期糖尿病(GDM)发病率的影响。办法 选取2014年10月~2017年4月就诊于辽宁省人民医院内排泄科的确诊为PCOS的60例初度妊娠妇女,依照妊娠前是否运用利拉鲁肽医治分为实验组(n=21)和对照组(n=39)。实验组为利拉鲁肽联合二甲双胍医治超越6个月的妇女,并且妊娠后继续二甲双胍医治。对照组为单纯口服二甲双胍医治的PCOS妊娠妇女,妊娠期间未继续二甲双胍医治。一切研讨目标在妊娠期间进行口服葡萄糖耐量实验(OGTT),调查两组的GDM发病率、剖宫产率、早产率和体重改变状况。成果 实验组在妊娠前的减重率高于对照组,差异有统计学含义(P<0.05)。实验组的GDM发病率低于对照组,差异有统计学含义(P<0.05);实验组妊娠第24、32、36周的体重别离低于对照组,差异有统计学含义(P<0.05)。定论 利拉鲁肽联合二甲双胍医治可防备性下降PCOS妇女GDM发病率。

[关键词]妊娠期糖尿病;多囊卵巢综合征;二甲双胍;利拉鲁肽

[中图分类号] R714.256 [文献标识码] A [文章编号] 1674-4721(2018)4(a)-0019-04

Influence of Liraglutide combined with Metformin in the treatment of polycystic ovary syndrome on the morbidity of gestational diabetes mellitus

HU Xiao-na

The First Department of Endocrinology,People′s Hospital of China Medical University People′s Hospital of Liaoning Province,Shenyang 110015,China

[Abstract]Objective To observe the influence of Liraglutide combined with Metformin treating polycystic ovary syndrome (PCOS) on the morbidity of gestational diabetes mellitus (GDM).Methods Sixty -pregnancy women diagnosed with PCOS who visited the Department of Endocrinology in our hospital from October 2014 to April 2017 were enrolled and divided into the experimental group (n=21) and the control group (n=39) based on whether Liraglutide was used or not before pregnancy.In the experimental group,participants were treated with Liraglutide combined with Metformin for more than 6 months before pregnancy and continued with Metformin after pregnancy.In the control group,oral administration of Metformin alone was adopted for these PCOS women,and did not continue Metformin treatment during pregnancy.All subjects were provided with oral glucose tolerance test (OGTT) during pregnancy.The incidence of GDM,cesarean section rate,premature birth rate and weight change were observed in the two groups.Results The weight loss rate of the experimental group before pregnancy was higher than that of the control group,with significant difference (P<0.05).The incidence of GDM in the experimental group was lower than that in the control group,with significant difference (P<0.05).The body weight of the experimental group at weeks 24,32,and 36 weeks of the pregnancy was lower than that of the control group,with significant difference (P<0.05).Conclusion Liraglutide combined with Metformin can preventively reduce the morbidity of GDM in PCOS women.

[Key words]Gestational diabetes mellitus;Polycystic ovary syndrome;Metformin;Liraglutide

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是育龄期妇女常见的内排泄代谢紊乱疾病之一,以高雄激素血症和胰岛素反抗为首要特征,患有PCOS的妇女发作妊娠期糖尿病(gestational diabetes mellitus,GDM)的危险增高[1]。二甲双胍是2型糖尿病的一线口服降糖药,尽管归于妊娠期B类用药规模,但临床研讨显现,妊娠期运用二甲双胍并未对子代生长发育发作不良影响[2-3]。2015年世界妇产科学联盟引荐二甲双胍可作为妊娠期操控血糖安全有用的用药挑选[4]。二甲双胍可改进胰岛素反抗,下降PCOS妇女空腹胰岛素及雄激素水平。利拉鲁肽是胰高血糖素样肽-1(glucagon-like peptide 1,GLP-1)受体激动剂的一种,GLP-1受体激动剂首要经过按捺摄食中枢以及推迟胃排空来削减食物摄入,然后起到减轻体重的作用[5-6]。研讨显现利拉鲁肽可以减轻肥壮PCOS妇女的体重[7-8],并且二甲双胍联合低剂量利拉鲁肽可增强肥壮PCOS妇女的减重作用[9]。但是妊娠后继续运用二甲双胍能否下降GDM发病率,现仍有争议[10-11]。

现在大多数研讨首要重视PCOS妇女妊娠期间二甲双胍医治对GDM发病率的影响,忽视了妊娠前二甲双胍的医治作用以及减重对PCOS的医治作用。本研讨旨在调查妊娠前二甲双胍与GLP-1受体激动剂联合医治使PCOS妇女减重后妊娠期间继续二甲双胍医治对其GDM发病率的影响。

1材料与办法

1.1一般材料

选取2014年10月~2017年4月就诊于辽宁省人民医院内排泄科的确诊为PCOS的60例初度妊娠妇女,依照妊娠前是否运用利拉鲁肽医治分为实验组(n=21)和对照组(n=39)。归入规范:①契合PCOS确诊规范[12]且初度妊娠的妇女;②年纪21~34岁,无吸烟史;③25 kg/m2≤体重指数(body mass index,BMI)<28 kg/m2,腹围>85 cm;④单胎妊娠。扫除规范:肝肾功用反常、妊娠前患有1型或2型糖尿病、垂体功用反常、高泌乳素血症、肾上腺功用反常者。本研讨取得院内医学道德委员会赞同,医护人员向一切患者具体讲解了本次实验的意图、办法、含义等,取得了一切孕妈妈的知情赞同。两组妊娠妇女的基线年纪、妊娠周数、BMI、体重及空腹血糖(FPG)比较,差异无统计学含义(P>0.05)(表1),具有可比性。对照组妇女妊娠前无运用利拉鲁肽病史。实验组妊娠前二甲双胍均匀运用时刻善于对照组,差异有统計学含义(P<0.05)(表1)。

1.2办法

实验组为利拉鲁肽联合二甲双胍医治超越6个月的妇女,并且妊娠后继续二甲双胍医治。利拉鲁肽医治(诺和诺德公司,出产批号:S20160004)剂量规模为1.2~1.8 mg/d,实验组妇女方案妊娠前停用利拉鲁肽。二甲双胍(中美上海施贵宝制药有限公司,出产批号:H20023370)1500~2000 mg/d,医治继续到妊娠36周或呈现药物不良反应,患者不能耐受停药。

对照组为单纯口服二甲双胍医治的PCOS妊娠妇女,妊娠期间中止二甲双胍医治。妊娠期间一切发作GDM的妇女依据血糖水平断定是否联合胰岛素医治操控血糖。

一切研讨目标别离在妊娠第5~12、19、24、32、36周进行口服葡萄糖耐量实验(OGTT)。检测办法:查看前1 d禁食至少8 h,实验前接连3 d正常饮食,次日给予75 g的葡萄糖粉(辽宁省人民医院,批号:140506)口服,抽取空腹静脉血、服糖后1 h和2 h静脉血。

1.3调查目标及点评规范

75 g OGTT的确诊规范[13]:FPG、餐后1 h葡萄糖(1 h PG)和餐后2 h葡萄糖(2 h PG)3项血糖值应别离<5.1、10.0、8.5 mmol/L,任何一项血糖值到达或超越上述规范即确诊为GDM。

1.4统计学剖析

选用SPSS 19.0统计学软件对数据进行剖析,计数材料选用χ2查验,以率(%)表明;计量材料选用t查验,以均数±规范差(x±s)表明,以P<0.05为差异有统计学含义。

2成果

2.1两组妊娠前期体重改变状况的比较

两组妊娠妇女呈现GDM后依据血糖状况加用胰岛素医治。实验组在妊娠前的减重率高于对照组,差异有统计学含义(P<0.05)(表2)。

表2 两组妊娠前期体重改变状况的比较(n)

2.2两组GDM发病率和妊娠并发症状况的比较

实验组的GDM发病率低于对照组,差异有统计学含义(P<0.05)。两组的妊娠并发症剖宫产及早产发病率比较,差异无统计学含义(P>0.05)(表3)。

表3 两组GDM发病率和妊娠并发症状况的比较[n(%)]

2.3两组妊娠期间体重改变的比较

实验组妊娠妇女第24周、第32周以及第36周的体重别离低于对照组,差异有统计学含义(P<0.05)(表4)。

表4 两组妊娠妇女体重改变的比较(kg,x±s)

3评论

二甲双胍作为一种胰岛素增敏剂被广泛应用于2型糖尿病的医治。二甲双胍可以添加安排对胰岛素的敏感性、按捺肝糖组成、添加外周葡萄糖吸取以及下降胰岛素循环浓度而不影响血糖水平。妊娠是与胰岛素反抗相关的生理进程,正常状况下胰岛素代偿性地添加胰岛素的排泄使血糖保持在正常水平[14]。因为PCOS与GDM具有胰岛素反抗这一一起的病理生理根底,导致PCOS患者妊娠期易发作GDM。胰岛素反抗、肥壮、高雄激素血症可能参加PCOS患者发作GDM的病理生理进程。GDM的病理生理与2型糖尿病类似,都伴有胰岛素反抗增强、肝糖异生添加以及胰岛β细胞功用下降,因而估测二甲双胍可以防备伴有胰岛素反抗的PCOS妇女发作GDM[15]。本研讨成果显现,长时刻口服二甲双胍的PCOS妇女GDM发病率显着下降并且妊娠期间体重显着低于对照组,这与很多研讨定论共同[1,16]。Glueck等[16]的研讨是回忆性研讨,在依据等级上以及可信度上要低于前瞻性研讨,而本研讨为前瞻性研讨,本研讨实验组妊娠妇女二甲双胍医治时刻更长,得出定论依据强度高于其他研讨。现在运动和调整生活办法、操控饮食、减轻体重是公认的PCOS伴胰岛素反抗患者有用的医治办法。约束能量摄入和减轻体重能显着改进PCOS患者的妊娠率及胰岛素反抗。利拉鲁肽是GLP-1受体激动剂,现在用于超重2型糖尿病的医治。根底研讨显现,GLP-1受体激动剂可以维护β细胞(削减β细胞细胞凋亡)[14]。临床研讨成果显现,利拉鲁肽对非糖尿病肥壮患者改进糖耐量、改进β细胞功用以及减重的作用可以保持2年[17-18],并且可以减轻肥壮PCOS妇女的体重[7-8]。本研讨中,实验组二甲双胍联合GLP-1受体激动剂医治使PCOS患者体重在妊娠前期及妊娠期间显着下降,可能改进了PCOS患者的胰岛素反抗[16],然后下降了GDM发病率。但是关于二甲双胍医治GDM的研讨仍需求更大的样本量以及更完善的办法学来调查其对妊娠妇女及新生儿的近期及远期影响[19-20]。

本研讨結果提示,患有PCOS的拟妊娠妇女可延长二甲双胍医治时刻并联合GLP-1受体激动剂医治以减轻体重而防备妊娠期糖尿病的发作。该研讨成果对患有PCOS的拟妊娠妇女在临床医治上有必定的辅导含义,可进行更大样本量的实验取得更高档的医治依据而辅导临床医治。

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(收稿日期:2018-01-09 本文編辑:祁海文)

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