Prevention of gestational diabetes through lifestyle modification before pregnancy

 描述(申请人提供)：妊娠期糖尿病(GDM)与几种急性母亲风险有关，包括先兆子痫、剖腹产、引产和早产，以及2型糖尿病、代谢综合征和心血管疾病的长期风险。患有妊娠期糖尿病的女性更有可能表现出胰岛素抵抗的特征--这是2型糖尿病和心血管疾病(CVD)的强烈先兆。宫内暴露于GDM会增加新生儿的健康风险，包括胎儿死亡、巨大儿、出生创伤和代谢性疾病的长期风险。妊娠期糖尿病复发也很常见，影响到40%-73%的妇女，并增加了相关的孕产妇/胎儿健康风险。流行病学和减肥外科研究的初步数据表明，孕前减轻体重可以预防妊娠期糖尿病及其相关的母婴并发症。我们的初步研究表明，在怀孕前招募女性并在受孕前促进显著减肥是可行的。然而，一项全面的试验从未进行过，以测试孕前母亲的生活方式干预对减轻体重和防止妊娠期糖尿病复发的效果。这项研究的主要目的是确定孕前减轻体重的生活方式干预是否可以减少妊娠期糖尿病的复发，并改善胰岛素抵抗和心血管疾病的生物标志物。这项两个地点的试验计划招募350名有妊娠期糖尿病病史的超重/肥胖女性，她们计划在未来1-2年内再次怀孕。妇女将在现场随机接受为期16周的全面孕前生活方式减肥干预(在怀孕前持续治疗)或教育对照组。评估将在怀孕前(研究开始时、4个月后和怀孕前的简短季度访问)、怀孕期间(怀孕26周)和产后6周分娩时进行。次级目标将检查与治疗相关的产前和围产期并发症的减少以及孕前体重、饮食和活动的变化。如果被证明有效，拟议的生活方式干预可能会将当前的治疗方法转变为受孕期，并提供一种“基于证据的”立即可用的治疗方法，旨在优化生殖结果，预防每年20多万名被诊断为妊娠期糖尿病的美国妇女患上妊娠期糖尿病及相关的慢性病。这项研究也是创新的，因为还没有随机对照试验评估孕前提供的生活方式干预预防妊娠期糖尿病的效果。这项拟议的研究侧重于预防，将直接挑战目前治疗妊娠期糖尿病的传统方法--这种方法侧重于怀孕期间的早期识别和治疗--并将努力转向未孕期。

 DESCRIPTION (provided by applicant): Gestational diabetes mellitus (GDM) is linked with several acute maternal risks, including preeclampsia, caesarean sections, induced deliveries, and pre-term labor, and long-term risks of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Women with GDM are more likely to display features of insulin resistance - a strong precursor to type 2 diabetes and cardiovascular disease (CVD). Intrauterine exposure to GDM raises neonatal health risks, including fetal demise, macrosomia, and birth trauma and long-term risk of metabolic disease. GDM recurrence is also common, affecting 40- 73% of women overall, and augments associated maternal/fetal health risks. Preliminary data from epidemiologic and bariatric surgery studies suggest that reducing body weight before pregnancy can prevent development of GDM and associated maternal/fetal complications. Our preliminary research suggested that it was feasible to recruit women before pregnancy and promote significant weight loss prior to conception. However, a full scale trial to test the effects of maternal lifestyle intervention before pregnancy to reduce body weight and prevent GDM recurrence has never been conducted. The principal aim of this study is to determine whether a lifestyle intervention to reduce body weight before pregnancy can reduce GDM recurrence and improve biomarkers of insulin resistance and cardiovascular disease. This two-site trial proposes to recruit 350 overweight/obese women with previous histories of GDM who plan to have another pregnancy in the next 1-2 years. Women will be randomized within site to a 16-week comprehensive pre-pregnancy lifestyle weight loss intervention (with ongoing treatment until conception) or an educational control group. Assessments will occur before pregnancy (at study entry, after 4 months, and at brief quarterly visits until conception), during pregnancy (at 26 weeks gestation) and at delivery at 6 weeks postpartum. Secondary aims will examine treatment-related reductions in prenatal and perinatal complications and changes in pre- pregnancy weight, eating, and activity. If found effective, the proposed lifestyle interventio could shift current treatment practices towards the interconception period and provide an "evidence based" immediately useable therapy targeted to optimize reproductive outcomes and prevent GDM and associated chronic conditions in the more than 200,000 US women diagnosed with GDM each year. The study is also innovative, as there have been no randomized controlled trials evaluating the effects of a lifestyle intervention delivered before pregnancy to prevent GDM. With a focus on prevention, the proposed study will directly challenge the current conventional approach to GDM - which focuses on early identification and treatment during pregnancy - and shift efforts towards the preconception period.