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

项目摘要/摘要 在美国，妊娠期糖尿病(GDM)每年导致10%的妊娠并发症，而且作为一种 肥胖症流行的结果。妊娠期糖尿病和由此产生的母体高血糖导致显著的母体和 可通过血糖控制减少的新生儿并发症。所需治疗的程度取决于 母亲对医学营养疗法(MNT)和运动的血糖反应；但至少30%-50%的患者 将不会通过MNT和运动的初步试验，随后需要药物治疗。必须指出的是， 什么是不成功的MNT尝试和练习的定义还没有确定。 因此，药物治疗的启动是提供者的自由裁量权，在实践中有很大的差异。我们 最近在一项对452名母婴医疗提供者(MFM)的全国性调查中证明了这一变异， 80%的MFM要求循证建议以指导药物治疗的启动。我们 研究还表明，在血糖升高20%的情况下尽早开始药物治疗可以改善复合体。 新生儿结局。然而，这种强化治疗也可能增加小于胎龄儿的风险。 年龄，可能会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见，并导致 提供的医疗服务因种族和民族而异。因此，迫切需要解决这一重大问题。 GDM临床实践中的差距，并调查早期GDM的有效性、安全性和患者报告的结果 妊娠期糖尿病的药物治疗启动。我们计划通过GDM和药物疗法(GAP)解决这一差距 研究：对416名妊娠期糖尿病患者进行随机对照试验，比较两种阈值(20%和40%) 在开始使用胰岛素之前血糖升高的情况。我们的中心假设是，更早地启动胰岛素， 定义为血糖值升高20%，与对照组相比，定义为血糖值升高40%， 将减少与妊娠期糖尿病相关的不良后果和妊娠期糖尿病管理方面的差异，而不会产生不利影响 对健康的影响。我们的假设是基于我们的试点数据，支持20%的门槛 看临床结果。根据我们的调查结果，选择了40%的积极控制组 75%的MFM在血糖升高40%的情况下开始药物治疗。我们将进行以下三项工作 具体目标：1)确定早期胰岛素治疗对妊娠期糖尿病不良新生儿的影响 与妊娠期糖尿病相关的母体结局；2)评估妊娠早期应用胰岛素的安全性 患者和他们的新生儿；以及3)确定早期启动胰岛素对患者报告的影响 采用标准化测量和定性访谈的结果。GAP研究将提供高水平的 这是妊娠期糖尿病药物治疗启动的证据，并将对临床实践产生直接影响。如果经过验证 有效和安全，尽早开始药物治疗将改善孕妇和他们的健康 并将促进妊娠期糖尿病管理的标准化。

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.