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。最近制定的诊断妊娠期糖尿病的新诊断标准预计将使妊娠期糖尿病的患病率增加到所有孕妇的10%-15%。越来越多的人认识到，妊娠期糖尿病对母亲患糖尿病的风险具有长期影响，宫内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，饮食如何能够改变胎儿的燃料并降低这种风险仍是未知的。GDM管理的基础是饮食干预，然而，建议低碳水化合物(CHO)、高脂肪饮食的历史做法尚未得到充分检验。动物和非人类灵长类动物的数据都支持胎儿编程的影响，即母亲的高脂肪饮食可能会促进后代的胰岛素抵抗、葡萄糖耐受和肝脏脂肪变性。最近的人类数据表明，孕妇高甘油三酯(TG)和游离脂肪酸(FFA)是胎儿巨大儿和肥胖症的独立危险因素，这些变量对饮食控制很敏感。因此，共识团体放弃了任何针对妊娠期糖尿病女性的具体饮食建议。尽管饮食疗法在治疗妊娠期糖尿病中起着关键作用，但没有随机试验直接将传统高脂肪饮食的血糖和脂蛋白谱与任何其他饮食进行比较。为了解决这一关键需求，这项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)与通常护理的低CHO/高脂肪饮食(LC/HF；40%CHO，45%脂肪，15%蛋白质)对以下方面的影响：1)在受试者中使用连续血糖监测系统，72小时血糖谱；2)通过在受试者早餐后5小时内测量连续血浆TG和FFA来测量餐后血脂；3)受试者之间进行6-8周饮食治疗后，母体脂蛋白、炎症状态和体外脂肪组织脂解情况。我们还将通过空气置换体积描记术和新生儿脂质过氧化、炎症和饮食脂肪摄入量的标记物来测量GDM母亲所生婴儿的新生儿肥胖症。这项初步研究将以随机对照的方式直接测试哪种GDM饮食在限制母亲高血糖和高脂血症方面最有效，潜在地优化胎儿底物的供应和胎儿生长。我们的目标是确定哪种饮食干预可能有利地影响一个循环，否则可能会使母亲和子女未来的糖尿病、肥胖症和心血管疾病永久化。 公共卫生相关性：更好地了解妊娠期糖尿病妇女的最佳饮食是管理这一快速增长的妊娠问题的基础。对目前的低碳水化合物、高脂肪饮食与复杂碳水化合物含量较高但脂肪含量较低的饮食进行仔细的比较研究是至关重要的，以确定哪种饮食会产生更有利的孕妇24小时血糖、脂肪和炎症状况，所有这些都直接影响最佳的胎儿生长，并可能影响后代未来的健康。

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.