To read the full abstract: Endocrinology. 2019 Aug 1;160(8):19071925. PMID: 31237608
Gestational diabetes (GDM) is associated with impaired beta-cell function in the offspring and this leads to increased risk of type 2 diabetes mellitus (1). However, the underlying mechanisms are not well understood. GDM exposure may alter islet gene expression and function in the fetus. Impaired beta-cell function is apparent in the offspring of women with gestational diabetes by age 7 years and in adulthood (2). Beta-cells undergo major structural and functional changes during gestation and early postnatal life. Evidence from animal models shows that maternal hyperglycemia and overnutrition can trigger maladaptive beta-cell growth (3).
This study used a rat model of high fat diet to determine how GDM may program islet structure and function in infancy (day 1) and then in young adulthood (15 weeks of age). The study also examined how the maternal environment interacts with the postnatal diet to affect islet structure and function. Islet size was increased in the newborn pups of GDM dams but there was no change in islet size in young adult rats. The offspring of GDM dams who were fed a high fat diet postnatally also showed no increase in islet size suggesting that GDM exposure impaired the ability of their islets to increase in beta-cell numbers/mass. Mechanistically, GDM leads to defects in the secretion of insulin and glucagon and this might be mediated by altered expression patterns of genes that regulate insulin and glucagon secretion. Consistent with this, unbiased analysis of RNA-seq data revealed significant changes in genes in several categories, including inflammation, mitochondrial function/ oxidative stress resistance, and ribosomal proteins. Further studies will be required to understand the function of these genes and how maternal gestational hyperglycaemia impacts offspring islet function.
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2. Kelstrup L, Damm P, Mathiesen ER, Hansen T, Vaag AA, Pedersen O, Clausen TD. Insulin resistance and impaired pancreatic b-cell function in adult offspring of women with diabetes in pregnancy. J Clin Endocrinol Metab. 2013;98(9):37933801.
3. Singh R, Pearson E, Avery PJ, McCarthy MI, Levy JC, Hitman GA, Sampson M, Walker M, Hattersley AT. Reduced beta cell function in offspring of mothers with young-onset type 2 diabetes. Diabetologia. 2006;49(8):18761880.