Role of Macronutrient Diet Composition and Infant Metabolic Outcomes in Gestational Diabetes

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.

Inclusion criteria

Inclusion Criteria. Potential participants will be ≥ 0-36 years old, which includes the offspring of the pregnant mothers with GDM. Pregnant women will be between the ages of 18-40 years and will have a BMI of 26 - 35 kg/m2 at the time of diagnosis, a singleton pregnancy, and will not be taking medication for their GDM on entrance to the study. Subjects will have been diagnosed with GDM according to the criteria established by the ADA and the ACOG (19;35;53), specifically, they will meet the following criteria:

• A 50-gram Glucola in which the one hour reading is >200 mg/dL and the FBG is >95 mg/dL
• Two abnormal values on a 100-gram 3 hour glucose tolerance test based on the Coustan and Carpenter criteria as adopted by the ADA and Fourth International Workshop on Gestational Diabetes (76;77):

• Fasting > or = to 95 mg/dL but <126 mg/dL
• 1 hr >/= 180 mg/dL
• 2 hr >/= 155 mg/dL
• 3 hr >/=140 mg/dL

Exclusion criteria

Those women with overt diabetes and those suspected of having preexisting diabetes by any of the following criteria will be excluded, including:

• Fasting glucose >110 mg/dL, due to the high likelihood of rapidly failing diet and requiring medical treatment (35).
• Random glucose > 200 mg/dL
• Glycosylated hemoglobin A1C > 6.5
• Non-English speaking patient
• Fasting TG > 400 mg/dL

Women who smoke will be excluded since this is the leading cause of low birth weight. In addition, women with other risk factors for placental insufficiency, including hypertension requiring beta-blocker treatment, renal disease, thrombophilias, preeclampsia, steroid use, history of pancreatitis or infectious disease such as hepatitis, or intrauterine growth restriction will be excluded.

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