Metabolic Analysis for Treatment Choice in Gestational Diabetes Mellitus

妊娠糖尿病治疗选择的代谢分析

• 批准号: 10219816
• 负责人: Maisa N Feghali
• 金额: $ 13.5万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-13 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10219816
• 关键词: Adverse effects; Affect; Aftercare; Area; Birth trauma; Body mass index; Caring; Cesarean section; Clinical; Clinical Trials; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Drug usage; Enrollment; Ensure; Fetus; Foundations; Functional disorder; Funding; Future; Gestational Diabetes; Glucose; Glyburide; Glyburide-metformin; Glycemic Index; Goals; Hour; Hyperglycemia; Incidence; Individual; Infant; Insulin; Insulin Resistance; Intervention Trial; Interview; Knowledge; Leadership; Learning; Left; Life Style Modification; Lipids; Maternal Age; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolic; Metabolism; Metformin; Modeling; Morbidity - disease rate; Mothers; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Obesity; Oral; Outcome; Participant; Patient Preferences; Patients; Pharmacotherapy; Pilot Projects; Population Heterogeneity; Positioning Attribute; Pregnancy; Pregnancy Outcome; Pregnant Women; Prenatal care; Procedures; Provider; Public Health; Randomized; Randomized Controlled Trials; Research; Research Personnel; Research Project Grants; Research Training; Risk; Role; Severities; Stress; Structure; Third Pregnancy Trimester; Time; TimeLine; Titrations; Training; United States; Universities; Variant; Weight Gain; Woman; Work; adverse outcome; adverse pregnancy outcome; arm; base; blood glucose regulation; care providers; career development; cost; design; diet and exercise; dietary; early screening; effective therapy; efficacious treatment; expectation; experience; fetal; glycemic control; health of the mother; i(19); implementation intervention; improved; improved outcome; individualized medicine; insulin secretion; maternal outcome; neonatal morbidity; neonatal outcome; offspring; personalized medicine; pharmacodynamic model; preference; pregnancy disorder; racial diversity; satisfaction; treatment as usual; treatment choice; treatment effect; treatment strategy; trial comparing

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.

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，影响超过40万孕妇， 美国女性每年。如果没有适当的治疗，患有GDM的妇女及其婴儿 严重发病的风险。正因为如此，专家建议治疗集中在正常化， 高血糖改善预后。然而，提供者预测哪种治疗将 实现血糖目标。这导致了基于提供者和患者偏好的选择以及试验和错误 这种方法可能会在诊断之间的短时间（8-10周）内造成血糖控制延迟 和交付。母亲和胎儿发病率可能与血糖病理生理学 以及降糖药的作用机制。事实上，GDM是异质的， 50%的女性存在胰岛素抵抗，30%的女性存在胰岛素分泌不足，20%的女性同时存在胰岛素抵抗和胰岛素分泌不足。 高血糖的潜在机制。GDM病理生理学和临床结局的这种变化 支持使用个性化治疗方法。该项目的总体目标是调查一个 GDM的个体化治疗方法，治疗基于每个女性的GDM机制。 具体而言，我们计划通过以下目标进行研究：目标1：我们将评估 在60名妇女中进行了一项试点随机对照试验，比较了个体化治疗和常规护理 关于GDM目的2：探讨治疗对GDM的作用机制及潜在的作用机制。 协变量目标3：我们将评估参与者和提供者对RCT的可接受性， GDM治疗和常规护理。在K23奖项申请中完成这些目标将推动我们的 了解GDM的潜在机制，并为更大规模的临床试验提供基础 评估个体化GDM治疗。研究计划将通过以下人员的密集指导得到加强： 该领域的专家和匹兹堡大学的教学研究培训。在一起，研究 本文所述的项目、指导和课程将为主要研究者提供必要的职业生涯 以下领域的发展：1）设计和实施孕妇干预性试验，2） 药效学建模以评估治疗对GDM机制的影响和3）领导， 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 在一项全面的R 01资助的研究中，个性化的GDM治疗策略，并独特地定位 主要研究者作为未来的领导者，专注于改变妊娠期间的糖尿病护理， 个性化的治疗模式。