Metabolic Analysis for Treatment Choice in Gestational Diabetes Mellitus

项目摘要 妊娠期糖尿病(GDM)是一个重大的临床和公共卫生负担，影响着40多万名孕妇 美国每年都有女性。如果没有适当的治疗，患有妊娠期糖尿病的妇女及其婴儿 有很大的发病率风险。正因为如此，专家建议将治疗重点放在 高血糖以改善预后。然而，提供者预测哪种治疗方法的能力有限。 达到血糖控制目标。这导致了基于提供者和患者偏好的选择以及试验和错误 方法，这可能会在诊断之间的短时间(8-10周)内造成血糖控制的延误 和送货。母婴发病率可能与血糖的病理生理学不匹配有关 以及降糖剂的作用机理。事实上，GDM是异质性的，具有优势 50%的女性存在胰岛素抵抗，30%的女性存在胰岛素分泌缺陷，20%的女性同时存在这两种情况。 高血糖的潜在机制。妊娠期糖尿病病理生理学和临床结果的这种变异 支持使用个体化治疗方法。这个项目的总体目标是调查一个 妊娠期糖尿病的个体化治疗方法，根据每个妇女的妊娠期糖尿病机制进行治疗。 具体来说，我们计划透过以下目标进行研究：目标1：我们会评估 对60名妇女进行随机对照试验，比较个体化治疗和常规护理 与GDM一起。目的2：我们将探讨治疗对妊娠期糖尿病发病机制的影响和潜在的作用 协变量。目标3：我们将评估参与者和提供者对随机对照试验的接受度，比较个别化 妊娠期糖尿病的治疗和常规护理。完成K23奖项申请中的这些目标将推进我们的 了解妊娠期糖尿病的潜在机制，为更大规模的临床试验奠定基础 评估妊娠期糖尿病的个体化治疗。研究计划将通过密集的指导来扩大，具体做法是 该领域的专家和匹兹堡大学的教学研究培训。总之，这项研究 在此描述的项目、指导和课程工作将为主要调查员提供基本的职业生涯 在以下方面的发展：1)设计和实施孕妇介入试验，2) 药效学建模以评估治疗对妊娠期糖尿病机制和3)领导力的影响， 管理和研究团队建设。最终，这项工作将为研究评估奠定基础 R01资助的全面研究中的个性化GDM治疗策略，并在 作为未来领导者的主要研究人员专注于转变妊娠期糖尿病护理 个体化治疗模式。

PROJECT ABSTRACT Gestational diabetes (GDM) is a significant clinical and public health burden, affecting over 400,000 pregnant women in the United States each year. Without adequate treatment, women with GDM and their infants are at risk for substantial morbidity. Because of this, experts recommend treatment focused on normalization of hyperglycemia to improve outcomes. However, providers have limited capacity to predict which treatment will achieve glycemic goals. This results in a choice based on provider and patient preference and a trial and error approach, which can create delays in glycemic control within the short (8-10 weeks) window between diagnosis and delivery. Maternal and fetal morbidity may be related to a mismatch between glycemic pathophysiology and the mechanism of action of glucose lowering agents. In fact, GDM is heterogeneous, with predominant insulin resistance in 50%, insulin secretion deficiency in 30%, and a combination of both in 20% of women as underlying mechanisms of hyperglycemia. This variation in GDM pathophysiology and clinical outcomes supports the use of an individualized treatment approach. The overall goal of this project is to investigate an individualized treatment approach for GDM where treatment is based on each woman’s GDM mechanism. Specifically, we plan to study this through the following aims: Aim 1: we will evaluate the feasibility of conducting a pilot randomized controlled trial comparing individualized treatment and usual care in 60 women with GDM. Aim 2: we will explore the effect of treatment on GDM mechanisms and the role of potential covariates. Aim 3: we will assess participant and provider acceptability of an RCT comparing individualized GDM treatment and usual care. Completion of these aims in this K23 award application will advance our knowledge of the underlying mechanisms of GDM and provide the foundation for a larger-scale clinical trial assessing individualized GDM treatment. The research plan will be augmented by intensive mentoring by experts in the field and didactic research training at the University of Pittsburgh. Together, the research project, mentoring and coursework described herein will provide the primary investigator with essential career development in the areas of: 1) design and implementation of interventional trials in pregnant women, 2) pharmacodynamic modeling to assess the effect of treatment on GDM mechanisms and 3) leadership, management, and research team building. Ultimately, this work will set the stage for research evaluating individualized GDM treatment strategies in a comprehensive R01-funded study, and uniquely position the primary investigator as a future leader focused on transforming diabetes care during pregnancy with individualized treatment models.