1246-P: Microcirculatory Circuit of Pancreatic Islets in Diabetic Fetopathy and Congenital Hyperinsulinism

The main cause of diabetes is the loss or dysfunction of beta cells that leads to insulin deficiency and hyperglycemia. However, there are some opposite pathologies, in which insulin secretion results in hypoglycemia. Data on the islets morphology in such diseases may be useful for understanding of the pathogenesis of diabetes. Diabetic fetopathy (DF) is a complication of gestational diabetes or preexisting maternal diabetes mellitus, which is characterized by the accelerated fetal growth and neonatal hypoglycemia. These complications mainly develop due to fetal hyperinsulinemia as a compensatory response to the increased delivery of the glucose to the fetus. Congenital hyperinsulinism (CHI) is a severe genetic disease, in which hypoglycemia is caused by excessive insulin secretion. There are two main CHI forms based on histology: diffuse and focal. Pancreatic samples of 4 newborns with DF from mothers with diabetes, 7 infants with diffuse CHI, and 7 infants with focal CHI were compared to 6 control infants without hypoglycemia. The diagnosis of CHI and histological form were established based on increased insulin level during hypoglycemia, presence of pathologic mutations in ABCC8/KCNJ11 genes, and immunohistochemistry results. All pancreatic samples were examined by immunohistochemistry with antibodies against insulin, glucagon, and vimentin. Histological changes such as nuclei enlargement in some beta-cells, islets hypertrophy, and prominent islets vascularization were observed in the endocrine pancreas of infants with DF as well as in patients with CHI. Swelling of the perivascular space was the distinguishing feature, which was revealed only in newborns with DF. In children with CHI, the abundant vascularization in large islets was not accompanied by swelling. We assume that a long-term increase of blood glucose in fetuses with DF leads to vasodilatation, which subsequently causes impaired endothelial permeability and swelling.