9358 Maternal Blood Glucose And Hypothalamus Volume: Novel Insights For Intergenerational Transmission Of Endocrine Traits

Abstract Disclosure: C. Marchildon: None. M. Arguin: None. M. Doyon: None. S. Cote: None. A. Michaud: None. J. Huck: None. V. Gingras: None. P. Perron: None. M. Hivert: None. L. Bouchard: None. K. Whittingstall: None. Objective: Several studies have linked maternal hyperglycaemia to diabetes-prone phenotype in the offspring, yet the mechanisms underlying these associations remain unclear. In adults, the hypothalamus is known to play a crucial role in the progression of obesity and diabetes. In utero exposure to maternal hyperglycaemia may thus selectively target the developing hypothalamus. To test this hypothesis, we explored the link between maternal glycemia and offspring brain volumes at 10-12-year-old. Methods: This study was conducted in a subgroup of 48 mother-child pairs from the Gen3G prospective pre-birth cohort. Pregnant women completed a 75g oral glucose tolerance test (OGTT) at 24-30 weeks of pregnancy. Maternal glucose was measured at fasting, 1h, and 2h during the OGTT and area-under-the curve of glucose (AUCgluc) was calculated using the trapezoid method. When participating offspring reached 12 years of age, they were invited back to the clinical research centre to complete a high-resolution structural MRI from which regional brain volumes and hypothalamic subvolumes were quantified using FreeSurfer (Fisch, 2012). Results: Participating mothers were 28.6 (± 4.4) years old at enrolment, their mean BMI was 25.3 (± 6.3) kg/m2, and 6 women had gestational diabetes diagnosed from the IADPSG criteria. At follow-up, offspring were 10.9 (± 0.4) years old, and mean BMI was 18.3 (± 3.3) kg/m2. Our investigation revealed a significant and positive correlation between maternal AUCgluc and total offspring hypothalamic volume (r = 0.41, p = 0.004, n = 48). No significant correlations were observed in other cortical and sub-cortical regions (all p>=0.05). The link between maternal AUCgluc and hypothalamic volume was considerably stronger in female offspring (r = 0.54, p = 0.008, n = 23) than in males (r = 0.26, p = 0.22, n = 25). Conclusions: We found an association between higher maternal glycemia and greater offspring hypothalamic volumes, particularly among females. These results suggest that prenatal exposure to hyperglycaemia may lead to hypothalamic programming in a sex-dependent manner. Considering that recent studies have linked the hypothalamic disturbances to endocrine dysregulation, our findings may lead to a new understanding of obesity and the intergenerational transmission of endocrine traits. Ref:Fischl B. Freesurfer. NeuroImage. 2012 Aug 10;62(2): 774-81. doi:10.1016/j.neuroimage.2012.01.021 Presentation: 6/2/2024