ESPE Yearbook of Paediatric Endocrinology

J Endocrinol. 2020 May;245(2):315–326. doi: 10.1530/JOE-20-0012. PMID: 32171178.

As it is not possible to study the histology of the pancreas post-partum in humans, this study used a mouse model of mild glucose intolerance to assess the changes in pancreatic islets after post-partum and assess the impact of pro-inflammatory cytokines. Mice with glucose intolerance during pregnancy continued to have glucose intolerance after parturition for one month due to ongoing impairments in endocrine pancreas compensation and glucose levels normalized only after 3 months.

Pregnancy is a state characterized by insulin resistance and proinflammation. In a normal pregnancy to combat insulin resistance and prevent hyperglycaemia pancreatic beta-cells undergo hypertrophy and increase in mass leading to increased insulin production. After pregnancy this compensation discontinues so that beta-cell mass is returned to normal. In GDM pregnancies despite the increase in beta-cell mass and increased insulin secretion hyperglycaemia persists. It is known that GDM can lead to type 2 diabetes in the mother later in life but the mechanisms of this are unclear. Progressive beta-cell dysfunction is the most likely underlying mechanism.

In this study, histologically islet quantification demonstrated that the number of small, medium, and large-sized islets varied with time after parturition. At one week of age, there were lower beta-cell and surprisingly alpha-cell fractional areas in the pancreas (beta-cell and alpha-cell mass were not measured). Then at three months of age, there was compensatory increase in the number of small islets with increased insulin to glucagon ratio thus accounting for the normalization of the blood glucose levels. These histological changes were associated with an increase in pro-inflammatory cytokines. The changes in alpha-cell ontogeny observed are novel and suggest that GDM may also lead to possible changes in alpha-cell mass and possible function.

These observations in mice suggest that GDM leads to histological changes in pancreatic beta and alpha-cells which persist after birth and ares associated with an increase in pro-inflammatory cytokines.