Role of Macronutrient Diet Composition on Maternal and Infant Metabolic Outcomes

描述（由申请人提供）：尽管妊娠期糖尿病（GDM）的患病率在过去10年中翻了一番，但由于缺乏随机对照试验，饮食管理指南仍然不明确。最近制定的诊断GDM的新诊断标准预计将使所有孕妇的患病率增加到10-15%。越来越多的人认识到GDM对孕产妇患糖尿病的风险具有长期影响，并且宫内GDM环境是儿童肥胖和糖耐量受损的独立危险因素。然而，在人类中，如何使用饮食来改变胎儿的燃料并降低这种风险仍然是未知的。GDM管理的基础是饮食干预，但建议低碳水化合物（CHO），高脂肪饮食的历史实践尚未得到充分的测试。动物和非人类灵长类动物的数据都支持胎儿编程的影响，母体高脂肪饮食可能会促进后代的胰岛素抵抗、葡萄糖耐受不良和肝脏脂肪变性。最近的人类数据表明，高母体甘油三酯（TG）和游离脂肪酸（FFA），对饮食操纵敏感的变量，是胎儿巨大儿和肥胖的独立危险因素。因此，共识团体已经放弃了任何针对GDM女性的具体饮食建议。尽管饮食疗法在GDM的治疗中起着关键作用，但没有随机试验直接比较常规高脂肪饮食与其他饮食的血糖和脂蛋白谱。为了解决这一关键需求，本随机交叉试验的目的是研究高复合碳水化合物/低脂肪饮食（HC/LF; 60% CHO， 25%脂肪，15%蛋白质）与常规护理相比，GDM女性低CHO/高脂肪饮食（LC/HF; 40% CHO， 45%脂肪和15%蛋白质）对以下方面的影响：1)使用受试者连续血糖监测系统进行72小时血糖记录；2)通过测量受试者早餐后5小时内的连续血浆TG和FFA来测定餐后血脂；3) 6-8周饮食治疗后母体脂蛋白、炎症谱和体外脂肪组织脂解。我们还将通过空气置换体积描记仪和新生儿脂质过氧化、炎症和饮食脂肪摄入的新生儿标记物来测量新生儿肥胖。本初步研究将以随机对照的方式直接测试哪种GDM饮食最有效地限制母体高血糖和高脂血症，潜在地优化胎儿底物利用率和胎儿生长。我们的目标是确定哪种饮食干预可能有利于影响一个循环，否则可能使母亲和后代的糖尿病、肥胖和心血管疾病长期存在。

DESCRIPTION (provided by applicant): Despite the doubling in the prevalence of gestational diabetes mellitus (GDM) over the last 10 years, dietary management guidelines remain ambiguous due to the paucity of randomized controlled trials. New diagnostic criteria recently developed for the diagnosis of GDM are expected to increase the prevalence to 10-15% of all pregnant women. There is growing recognition that GDM has long-term implications on maternal risk for diabetes and that the intrauterine GDM environment is an independent risk factor for childhood obesity and impaired glucose tolerance. Yet, how diet can be used to modify fetal fuel and attenuate this risk remains unknown in humans. Fundamental to the management of GDM is dietary intervention, yet the historic practice of advising a low-carbohydrate (CHO), higher-fat diet has not been sufficiently tested. Both animal and non- human primate data support a fetal programming influence that maternal high-fat diets may promote insulin resistance, glucose intolerance, and hepatic steatosis in the offspring. Recent human data suggest that high maternal triglycerides (TG) and free fatty acids (FFA), variables sensitive to dietary manipulation, are independent risk factors for fetal macrosomia and adiposity. As a result, consensus groups have abandoned any specific diet recommendations for women with GDM. Despite the pivotal role of diet therapy in the treatment of GDM, no randomized trials have directly compared glycemic and lipoprotein profiles of the conventional higher-fat diet with any other diet. To address this critical need, the aims of this randomized cross-over trial are to study the effects of a high complex carbohydrate/low-fat diet (HC/LF; 60% CHO, 25% fat, 15% protein) compared to the usual care, low-CHO/higher fat diet (LC/HF; 40% CHO, 45% fat, and 15% protein) in GDM women on: 1) 72-hour glycemic profiles using a continuous glucose monitoring system within subjects; 2) postprandial lipemia by measuring serial plasma TG and FFA over a 5-hour, post-breakfast meal period within subjects; and 3) maternal lipoproteins, inflammatory profiles, and in-vitro adipose tissue lipolysis after 6-8 weeks of diet therapy between subjects. We will also measure neonatal adiposity by air displacement plethysmography and newborn markers of lipid peroxidation, inflammation, and dietary fat intake in the babies born to mothers with GDM. This pilot study will directly test which GDM diet is most effective in limiting maternal hyperglycemia and hyperlipidemia in a randomized controlled fashion, potentially optimizing fetal substrate availability and fetal growth. Our goal is to determine which diet intervention might favorably impact a cycle that could otherwise perpetuate future diabetes, obesity, and CVD in both mother and offspring. PUBLIC HEALTH RELEVANCE: A better understanding of the optimal diet for women with gestational diabetes is fundamental to the management of this rapidly growing problem in pregnancy. Careful comparison studies of the current low- carbohydrate, higher-fat diet versus a diet higher in complex carbohydrate but lower in fat is critical in order to determine which diet results in a more favorable maternal 24-hour glucose, lipid, and inflammatory profile, all of which directly affect optimal fetal growth and may influence the future health of the offspring.