Abstract Body: Background: Congenital heart defects are the most common birth defects, and infants born to mothers with pregestational diabetes mellitus are 3-5 times more likely to develop cardiac anomalies. Among these, hypertrophic cardiomyopathy (HCM) is a serious phenotype observed more frequently in newborns of diabetic mothers. While severe maternal hyperglycemia has been linked to overt structural defects, the effects of mild hyperglycemia on cardiac development and underlying mechanisms are not yet well characterized.
Aim: This study aimed to validate an avian embryo model of mild maternal hyperglycemia for studying diabetes-associated HCM.
Approach: Fertilized white leghorn eggs were exposed to a modest increase in D-glucose (approximately 3-6%) via yolk injection before incubation. Eggs were incubated for 13 days, at which point the yolk’s nutrient supply is nearly exhausted and the heart is fully developed. Embryos underwent echocardiography and images were analyzed using Q Strain software (Medis Medical Imaging) to quantify cardiac function. Dissected hearts were subjected to ex vivo micro-CT to assess structural changes and HCM incidence.
Results: Preliminary data with relatively low sample sizes show that mild D-glucose exposure increased the incidence of HCM but not to a level of statistical significance (Fischer’s p-value = 0.13). HCM was defined by significant thickening of the interventricular septum, left ventricular free wall, or both. In embryos treated with 50 mM D-glucose, HCM occurred in 31% (5/16) and in 40% (4/10) of embryos treated with 100 mM D-glucose. No HCM was observed in embryos treated with 50 mM L-glucose (osmotic control), but 29% (2/7) of embryos treated with 100 mM L-glucose had HCM. HCM was present in 18% (2/11) of vehicle controls dosed with Chick Ringers saline. These results suggest that mild, chronic exposure to metabolically active glucose contributes to HCM development, with some contribution from osmotic effects at higher concentrations.
Conclusion: These findings support the avian embryo as a promising model of mild glucose-induced HCM, demonstrating that even low-level excess glucose can drive structural changes during cardiac development. It also lays the groundwork for future studies to investigate associated changes in cardiac function via hemodynamic analysis, as well as the molecular mechanisms underlying diabetes-associated HCM, ultimately informing strategies for early detection or intervention in diabetic pregnancies.