The incidence of childhood obesity continues to rise and alarmingly, 40% are already estimated to have nonalcoholic fatty liver disease (NAFLD), the leading cause of liver transplantation. An early origin exposure that contributes to NAFLD may be maternal obesity, diet, triglycerides (TG) and free fatty acids (FFA) in-utero, particularly in offspring of mothers with diabetes or gestational diabetes (GDM) who are at high risk for childhood metabolic disorders. In this pilot study, we explored the hypothesis that maternal TG in diet-controlled GDM (A1GDM) is associated with offspring intrahepatic lipid (IHL) accumulation. We randomized newly diagnosed A1GDM women (n=13, BMI 32±2 [mean±SEM]) to eucaloric diets at 32 weeks. Fasting and postprandial (PP) glucose, insulin, TG, FFA, and glycerol were measured in a breakfast test meal study (hourly x5) at baseline and 37 weeks. Newborn IHL content (Magnetic Resonance Spectroscopy; MRS) and body composition (%fat, PEAPOD) were measured at ~10 days. At 32 weeks, but not at 37 weeks, maternal fasting TG (199±17 mg/dL) and the 5-hour TG area-under-the-curve (AUC) were strongly associated with newborn IHL (r=0.69, p=0.01; r=0.75, p=0.003, respectively). The 1-hour and 2-hour PPTG (205-206±19-20 mg/dL) were highly associated with IHL (r=0.69-0.73; p≤0.01) as was the 5-hour glycerol AUC (r=0.65, p=0.01). There was no relationship between IHL and subcutaneous %fat by PEAPOD. We found no associations between maternal pre-pregnancy BMI, gestational weight gain (11±1.6 kg), glucose, insulin, or FFA and IHL. These data are the first in humans to support that maternal TG exposure at the time of GDM diagnosis, when fetal subcutaneous fat depots are early in development, may result in increased liver lipid deposition. If confirmed, MRS newborn liver fat measures and early interventions targeting maternal TG may be indicated to lower fetal liver fat deposition that could potentially be a developmental risk for pediatric NAFLD.
T.L. Hernandez: None. S.S. Farabi: None. N. Hirsch: None. E.Z. Dunn: None. E.A. Haugen: None. D. Brumbaugh: None. M.S. Brown: None. J.E. Friedman: Consultant; Self; Janssen Research & Development. L.A. Barbour: None.
National Institutes of Health