Trial of Diet in Gestational Diabetes Mellitus: Metabolic Consequences to Mother and Offspring

The rapidly rising incidence of gestational diabetes mellitus in overweight/obese pregnant
women demands that an effective diet strategy be developed due to the high risk of fetal
overgrowth, which places the newborn at increased risk for childhood obesity and metabolic
syndrome. However, the lack of adequate controlled randomized clinical trials for treatment
of gestational diabetes with diet has resulted in consensus panels abandoning any specific
diet recommendation. If effective, diet therapy has the potential to avoid the high costs of
medical treatment and intensified fetal monitoring for this growing population. Although a
low carbohydrate diet has historically been advocated to decrease glucose excursions after
meals, carbohydrate has typically been replaced by higher fat which has been shown in animal
and non-human primate data to promote insulin resistance, glucose intolerance, and liver fat
deposition in the offspring. In fact, recent human data suggest that high maternal
triglycerides and free fatty acids, variables sensitive to dietary manipulation, may be at
least as important as glucose in contributing to excess fetal growth and infant adiposity.
Preliminary data based on an R21, show that compared to a conventional lower-carbohydrate
(higher in fat) diet, providing a higher complex carbohydrate (lower fat) diet effectively
blunts postprandial glucose and improves fasting glucose and insulin after 6-7 weeks, with
less adiposity in the newborn. The investigators global hypothesis is that compared to 8
weeks of a low-carbohydrate/higher fat diet, a higher complex carbohydrate/lower fat diet
will blunt maternal post-prandial free fatty acids and improve insulin resistance. Improved
insulin sensitivity will reduce fetal over-nutrition by decreasing substrate availability and
down-regulating placental nutrient transporters, thereby reducing neonatal adiposity (primary
outcome).This proposal builds on the investigators R21 study, which is the first randomized
clinical trial to provide all meals from the time of gestational diabetes diagnosis
throughout the remainder of pregnancy. The aims of this randomized trial are to compare the
effects of an 8-wk isocaloric higher complex carbohydrate/lower fat diet (60%
carbohydrate/25% fat) vs. a conventional low-carbohydrate (higher fat)(40% carbohydrate/45%
fat) diet on maternal insulin resistance, placental nutrient transporters, and neonatal fat
development. Innovative approaches by the investigators skilled multidisciplinary team
include: maternal insulin resistance systemically (oral glucose tolerance Index) and locally
(adipose tissue lipolysis); intestinal microbiome (transferred to the newborn); and neonatal
intrahepatic fat (magnetic resonance spectroscopy). Persistence of neonatal adiposity is
relevant to understanding obesity risk in these infants. As the investigators pilot data
suggest infant microbiome and breast milk composition impact fat accrual after birth, the
investigators will follow the infants through 1-yr of life accounting for these variables.
Identifying a diet for gestational diabetes that can effectively alter maternal/fetal
metabolism in late pregnancy when fetal growth accelerates is critical to reducing short- and
long-term metabolic risk in this growing cohort of mothers and infants. The study results
could lead to a paradigm shift for diet therapy in gestational diabetes, with potential
widespread application to pregnancies affected by obesity alone.

Inclusion Criteria:

- Pregnant women will be between the ages of 20-36 yrs

- BMI of 26-39 kg/m2 at the time of diagnosis

- singleton pregnancy

- no oral hypoglycemic therapy before entering the study

- diagnosed with Gestational diabetes according to the criteria established by the
American College of Obstetricians and Gynecologists, specifically, they will have 2
abnormal values on a 100-g 3 hr glucose tolerance test 205, 206: Fasting>95 mg/dL but
<105 mg/dL; 1hr> 180 mg/dL; 2 hr>155 mg/dL; 3 hr>140 mg/dL.

Exclusion Criteria:

- extreme hypertriglyceridemia

- overt diabetes

- suspected preexisting diabetes (A1C≥6.5%, Fasting glucose>125 mg/dL, or random glucose
>200/mg/dL)

- women highly likely to fail diet by any of the following criteria will be excluded:1)
Fasting glucose >105 mg/dL, due to the higher likelihood of failing diet and requiring
medical treatment 139; 2) Fasting triglyceride > 400 mg/dL.

- non-English speaking

- Smokers (leading cause of low birth weight)

- Risk factors for placental insufficiency (hypertension, renal disease, thrombophilias,
rheumatologic disease, preeclampsia, steroid use, history of pancreatitis, infectious
disease, or intrauterine growth restriction)

- History of pancreatitis

- History of pre-term labor

- Taking beta blockers/glucocorticoids