The rapidly rising incidence of gestational diabetes (GDM) 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 (RCTs) for treatment of GDM 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diet has historically been advocated to decrease glucose excursions after meals, carbohydrate has typically been replaced by higher fat which has been shown in animal and non-human primate data to promote insulin resistance, glucose intolerance, and liver fat deposition in the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 hig maternal triglycerides (TG) and free fatty acids (FFA), 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-CHO (higher in fat) diet, providing a higher complex CHO (lower fat) diet effectively blunts postprandial glucose and improves fasting glucose and insulin after 6-7 weeks, with less adiposity in the newborn. Our global hypothesis is that compared to 8wks of a low- CHO/higher fat diet, a higher complex CHO/lower fat diet will blunt maternal post-prandial FFA and improve IR. Improved insulin sensitivity will reduce fetal over-nutrition by decreasing substrate availabilty and down-regulating placental nutrient transporters, thereby reducing neonatal adiposity (primary outcome).This proposal builds on our R21 study (in-press, Appendix), which is the first RCT to provide all meals from the time of GDM diagnosis throughout the remainder of pregnancy.
The aims of this RCT are to compare the effects of an 8-wk isocaloric higher complex CHO/lower fat diet (60% CHO/25% fat) vs. a conventional low-CHO (higher fat)(40% CHO/45% fat) diet on maternal insulin resistance, placental nutrient transporters, and neonatal fat development. Innovative approaches by our skilled multidisciplinary team include: maternal IR systemically (Matsuda Index) and locally (AT lipolysis);intestinal microbiome (transferred to the newborn);and neonatal intrahepatic fat (MRS). Persistence of neonatal adiposity is relevant to understanding obesity risk in these infants. As our pilot data suggest infant microbiome and breast milk composition impact fat accrual after birth, we will follow the infants through 1-yr of life accounting for these variables. Identifying a diet for GDM 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 GDM, with potential widespread application to pregnancies affected by obesity alone.

Public Health Relevance

The rapidly rising risk of gestational diabetes (GDM) 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. The aims of this randomized clinical trial are to compare the effects of an 8- wk. isocaloric higher complex carbohydrate/lower fat diet vs. a conventional lower carbohydrate (higher fat) diet on glycemic and lipid profiles, maternal insulin resistance, placenta nutrient transporters, the maternal microbiome, neonatal intrahepatic fat, and neonatal total adiposity (primary outcome). We will then follow the infants for 1-yr and measure maternal breast milk and infant microbiome composition to observe if they impact net fat mass gain differently in infants exposed to one diet vs. the other. Identifying a diet for GDM women that can effectively alter maternal/fetal metabolism is critical to reducing short- and long-term metabolic risk in this growing cohort of mothers and infants and has the potential to be applicable to overweight/obese pregnant women.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01DK101659-01A1
Application #
8817163
Study Section
Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
Program Officer
Silva, Corinne M
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Aurora
State
CO
Country
United States
Zip Code
80045