Uncovering the Role of Dietary Fat and Protein in Glycemic Physiology in Pregnancy and in Gestational Diabetes

项目总结/摘要 妊娠期糖尿病（GDM）是一种患病率上升的疾病，其一线治疗是饮食疗法， 这些患者的最佳饮食是未知的。指南重点关注GDM中的碳水化合物限制， 一些证据表明母亲和胎儿的结局得到了改善，但人们担心低碳水化合物 饮食可能会对胎儿产生不良影响。研究评估不同的营养宏量营养素， 特别是蛋白质和脂肪，在怀孕和GDM缺乏。拟议研究项目的目标 目的是了解膳食脂肪和蛋白质对妊娠期胰岛素生理学和胰岛素分泌的影响， GDM的目标是发现受GDM影响的女性的最佳饮食。申请人将利用数据 一项关于妊娠期葡萄糖代谢的前瞻性纵向观察研究， 膳食蛋白质和脂肪暴露对孕妇胰岛素生理的影响。申请人还将 在一项干预性交叉研究中，评价蛋白质和脂肪对妊娠期糖尿病女性妊娠的急性影响 两种等热量早餐的随机试验，碳水化合物含量相同，蛋白质含量不同， 脂肪含量（高蛋白/低脂肪，低蛋白/高脂肪）。该项目的目标是： 1.明确孕妇膳食脂肪和蛋白质与胰岛素生理的关系。第一 假设高脂肪饮食与低脂肪饮食相比会导致胰岛素敏感性降低; 第二个假设是高蛋白饮食将导致胰岛素分泌增加（调整为 胰岛素敏感性）。 2.脂肪和蛋白质对女性糖尿病患者餐后血糖反应的急性影响 GDM。假设高蛋白/低脂膳食将导致餐后葡萄糖峰值降低 比高脂肪/低蛋白的膳食水平。 这些研究的结果将确定蛋白质和脂肪对胰岛素生理学和胰岛素分泌的影响。 孕妇和GDM，因此有可能为GDM的临床饮食建议提供信息。 培训计划包括由Ellen Seely博士（赞助商）和Camille博士（赞助商）提供的专门指导 （共同赞助商），每个提供专门知识，适合申请人的需求和目标。此外，申请人将 通过哈佛Catalyst完成生物统计学、营养学和临床研究方面的正式培训 临床/转化科学中心，哈佛T.H.马萨诸塞州Chan公共卫生学院 综合医院临床研究部和美国国立卫生研究院行为和 社会科学研究。这些活动将为申请人提供职业生涯的关键工具， 她是GDM营养和生活方式领域的独立临床研究者。

PROJECT SUMMARY/ABSTRACT The first-line treatment of gestational diabetes (GDM), a disease rising in prevalence, is dietary therapy, yet the optimal diet for these patients is unknown. Guidelines have focused on carbohydrate restriction in GDM, with some evidence suggesting improved maternal and fetal outcomes, yet there is concern that low carbohydrate diets may have adverse fetal consequences. Research evaluating different nutritional macronutrients, specifically protein and fat, in pregnancy and GDM is lacking. The objectives of the proposed research projects are to understand the impact of dietary fat and protein on insulin physiology and glycemia in pregnancy and in GDM with the goal of discovering the optimal diet for women affected by GDM. The applicant will utilize data from a prospective longitudinal observational study of glucose metabolism in pregnancy to investigate the effects of dietary protein and fat exposure on insulin physiology in pregnant women. The applicant will also evaluate the acute effects of protein and fat on glycemia in women with GDM in an interventional cross-over randomized trial of two isocaloric breakfast meals with identical carbohydrate content and varying protein and fat content (high protein/low fat, low protein/high fat). The aims of this project are: 1. Define the relationship of dietary fat and protein with insulin physiology in pregnant women. The first hypothesis is that diets high in fat will lead to reduced insulin sensitivity as compared to diets low in fat; the second hypothesis is that diets high in protein will lead to increased insulin secretion (adjusted for insulin sensitivity) as compared to diets low in protein. 2. Prospectively test the acute effect of fat and protein on post-prandial glycemic response in women with GDM. The hypothesis is that the high protein/low fat meal will lead to lower peak post prandial glucose levels than the high fat/low protein meal. The results of these studies will determine the impact of protein and fat on insulin physiology and glycemia in pregnant women and in GDM and thus have the potential to inform clinical dietary recommendations in GDM. The training plan includes dedicated mentorship by Dr. Ellen Seely MD (sponsor) and Dr. Camille Powe MD (co-sponsor), each offering expertise tailored to the applicant’s needs and goals. Additionally, the applicant will complete formal training in biostatistics, nutrition and clinical research through the Harvard Catalyst Clinical/Translational Science Center, the Harvard T.H. Chan School of Public Health, the Massachusetts General Hospital Division of Clinical Research, and the National Institutes of Health Office of Behavioral and Social Sciences Research. These activities will provide the applicant with the tools critical for a career as an independent clinical researcher in the field of nutritional and lifestyle approaches to GDM.