Gestational Diabetes and Pharmacotherapy (GAP) – A Randomized Controlled Trial Investigating Timing of Pharmacotherapy Initiation for Patients with Gestational Diabetes

项目总结/摘要 妊娠糖尿病（GDM）每年使美国10%的妊娠并发症，并且随着妊娠期糖尿病的发生而急剧上升。 肥胖症流行的结果。GDM和由此产生的母体高血糖导致显著的母体和 新生儿并发症，可以减少血糖控制。所需治疗的程度取决于 母亲对医学营养治疗（MNT）和运动的血糖反应;但至少30-50%的患者 MNT和运动的初始试验将失败，随后需要药物治疗。重要的是要注意， 尚未确定什么是不成功的MNT尝试和练习的定义。 因此，药物治疗的开始由提供者自行决定，在实践中有很大的差异。我们 最近在一项对452名母胎医学提供者（MFM）的全国调查中证明了这种变化， >80%的MFM要求循证建议来指导药物治疗的启动。我们 还表明，在血糖值升高20%时，较早开始药物治疗可改善复合物 新生儿结局然而，这种强化治疗也可能增加小于妊娠的风险。 年龄，并可能对患者报告的结果产生负面影响，如焦虑，抑郁和压力。 最后，缺乏药物治疗启动的标准化指南可能会引入偏倚并导致 按种族和族裔分列的医疗保健服务差异。因此，迫切需要解决这一重大问题， GDM临床实践中的差距，并研究早期GDM的疗效、安全性和患者报告的结局。 开始GDM药物治疗。我们计划通过GDM和药物治疗（GAP）来解决这一差距 研究，一项随机对照试验，416例GDM患者，将比较两个阈值（20%与40%） 在开始胰岛素治疗前血糖值升高。我们的中心假设是，早期开始使用胰岛素， 定义为血糖值升高20%，与对照组相比，定义为血糖值升高40%， 将减少GDM相关的不良结局和GDM管理的差异， 健康后果。我们的假设是根据我们的试点数据制定的，支持20%的阈值 临床结果。根据我们的调查结果，选择的积极控制组为40%， 75%的MFM在血糖值升高40%时开始药物治疗。我们将追求以下三个 具体目的：1）确定早期胰岛素治疗GDM对新生儿不良反应的影响。 妊娠期糖尿病孕妇早期开始胰岛素治疗的安全性 患者及其新生儿;和3）确定早期开始胰岛素治疗对患者报告的 结果使用标准化的措施和定性访谈。差距研究将提供一个高层次的 GDM患者开始药物治疗的证据，并将对临床实践产生直接影响。如果证明 有效和安全，早期开始药物治疗将改善妊娠患者的健康， 并将促进GDM管理的规范化。

PROJECT SUMMARY/ABSTRACT Gestational diabetes (GDM) complicates 10% of pregnancies in the US annually and is rising dramatically as a result of the obesity epidemic. GDM and the resulting maternal hyperglycemia lead to significant maternal and neonatal complications that can be reduced with glycemic control. The extent of treatment needed is based on maternal glycemic response to medical nutrition therapy (MNT) and exercise; yet at least 30-50% of patients will fail the initial trial of MNT and exercise and subsequently require pharmacotherapy. It is crucial to note, that the definition of what constitutes an unsuccessful attempt at MNT and exercise has not been established. Consequently, initiation of pharmacotherapy is at a provider’s discretion with a wide variation in practice. We recently demonstrated this variation in a national survey of 452 Maternal-Fetal Medicine providers (MFMs), with >80% of MFMs requesting evidence-based recommendations to guide initiation of pharmacotherapy. We also showed that earlier pharmacotherapy initiation at 20% elevated glucose values improved composite neonatal outcome. However, such intensified treatment could also increase the risk of a small-for-gestational age and may carry a negative impact on patient reported outcomes such as anxiety, depression and stress. Finally, the lack of standardized guidelines for pharmacotherapy initiation may introduce biases and lead to a variation in healthcare delivery by race and ethnicity. Therefore, there is a critical need to address this major gap in clinical practice of GDM and investigate the efficacy, safety, and patient reported outcomes of earlier pharmacotherapy initiation for GDM. We plan to address this gap with GDM and Pharmacotherapy (GAP) study, a randomized controlled trial of 416 patients with GDM that will compare two thresholds (20% vs. 40%) of elevated glucose values prior to insulin initiation. Our central hypothesis is that initiating insulin earlier, defined as 20% elevated glucose values, compared with controls, defined as 40% elevated glucose values, will result in reduced GDM-related adverse outcomes and disparities in GDM management, without adverse health consequences. Our hypothesis has been formulated based on our pilot data favoring the 20% threshold for clinical outcomes. The active control group chosen to be 40% based on our survey results demonstrating that 75% of MFMs start pharmacotherapy at 40% elevated glucose values. We will pursue the following three specific aims:1) Determine the effect of earlier insulin initiation for GDM management on adverse neonatal and maternal outcomes associated with GDM; 2) Assess the safety of earlier insulin initiation in pregnant patients and their neonates; and 3) Determine the effect of earlier insulin initiation on patient-reported outcomes using standardized measures and qualitative interviews. The GAP study will provide a high-level evidence for pharmacotherapy initiation in GDM and will have a direct impact on clinical practice. If proven effective and safe, earlier pharmacotherapy initiation will improve the health of pregnant patients and their offspring and will promote standardization of GDM management.