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Role of Macronutrient Diet Composition on Maternal and Infant Metabolic Outcomes

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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.

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