First Trimester Sonographic Assessment of Maternal Abdominal Adiposity and Fatty Liver Disease and the development of Dysglycemia and Gestational Diabetes Mellitus

Obesity leads to insulin resistance (IR) and is part of the pathogenesis of gestational diabetes mellitus (GDM) and subsequent type 2 diabetes mellitus (T2DM) after pregnancy. Regional abdominal adipose tissue (AT) has emerged as a critical pathogenic mediator of IR and consequent metabolic dysfunction. While the mechanistic processes that characterize the pathophysiology of visceral AT (VAT) and IR remain to be elucidated, growing evidence describes the role of pro-inflammatory adipokines, free fatty acid release and changes in adipose tissue morphology that leads to ectopic fat accumulation in organs such as the liver. Hepatic fat deposition results in asymptomatic, but consequential, non-alcoholic fatty liver disease (NAFLD). Like abdominal AT, NAFLD is typically a sub-clinical state that long predates the onset of T2DM. Clinicians routinely screen for GDM in the second trimester, which may be too late to favourably impact maternal and fetal outcomes. Early risk detection might help prevent GDM and its deleterious effects. We conducted a series of prospective studies to measure maternal abdominal AT at the same time each participant underwent routine first-trimester ultrasound assessment of fetal nuchal translucency, to screen for trisomy 21. First, we demonstrated that elevated first-trimester maternal VAT and total adipose tissue (TAT) were each associated with IR at 16 weeks’ gestation. We also observed that TAT and subcutaneous adipose tissue (SAT) were more strongly associated with adiponectin at 16 weeks’ gestation than was body mass index (BMI). Second, with a larger cohort of pregnant women and using the same method of first-trimester sonographic assessment of AT, we found that the highest quartile of first-trimester VAT and TAT, each predicted IR at 24-28 weeks’ gestation, and was most significantly associated with a higher odds of GDM. Finally, we used first-trimester clinical ultrasound to assess for evidence of NAFLD, and found that the presence of one or more sonographic features of NAFLD was associated with dysglycemia and GDM at 24-28 weeks’ gestation. This body of work suggests that first-trimester sonographic assessment of maternal abdominal AT and NAFLD may each provide a novel way to identify in early pregnancy, those women at higher risk for developing GDM.Ph.D