| Popis: |
Intrauterine exposure to metabolic dysfunction leads to offspring metabolic dysfunction in human and rodent models, but underlying mechanisms are unclear. The mediobasal hypothalamus (MBH) is involved in energy homeostasis and weight regulation, and MBH gliosis associates with obesity and insulin resistance. We tested the hypothesis that offspring exposed to gestational diabetes mellitus (GDM) in utero vs those unexposed would demonstrate evidence of MBH gliosis. Participants in the BrainChild Study (age 7-11 years, with confirmed GDM exposure or no GDM exposure) underwent brain magnetic resonance imaging to acquire T2 weighted images. By using the amygdala (AMY) and white matter (WM) as reference regions, MBH:AMY and MBH:WM T2 signal ratios were calculated as a radiologic measure of MBH gliosis. Linear regressions examined associations between GDM exposure (GDM overall, and by timing of GDM exposure (£26 weeks or >26 weeks) and MBH gliosis. Secondary analyses examined associations between pre-pregnancy BMI and child MBH gliosis. There were no differences in T2 signal ratios in children exposed vs unexposed to GDM overall, but children exposed to early GDM (<26 weeks gestation) had higher MBH:WM ratios compared to unexposed (β=0.147, SE 0.06; p=0.03), adjusting for child’s age, sex, BMI z-score and maternal pre-pregnancy BMI; whereas no associations were seen for the control ratio. Pre-pregnancy BMI was not associated with evidence of MBH gliosis. Early exposure to GDM was associated with radiologic evidence of MBH gliosis in children. These data provide mechanistic insight into brain pathways by which exposure to GDM may increase risk for metabolic dysfunction. |
