Exposure to glucocorticoids in the first part of fetal life is associated with insulin secretory defect in adult humans

Abstract

Prenatal treatment with glucocorticoids (GC) is used in several clinical indications. However, the long-term outcome on offspring metabolic, somatic and cognitive health has raised significant concern. In rodents, high glucocorticoid levels inhibit development of beta cells during fetal life and lead to insulin deficiency in adulthood. To investigate whether similar phenomena occur in humans, Jean-Pierre Riveline and colleagues compared the beta-cell function of adults exposed to glucocorticoids during the first part of fetal life with that of nonexposed subjects. The authors assessed beta cell function using the oral glucose tolerance test (OGTT) and the graded intravenous glucose and arginine tests in adults (n =16) treated with dexamethasone (DEX) during the first trimester of fetal life. They were compared to untreated healthy participants (n =16) with normal glucose tolerance, who were matched for age, sex, and body mass index. Subjects exposed to glucocorticoids were born to mothers who had been treated with DEX 1 – 1.5 mg/day from the sixth gestational week (GW) to prevent genital virilization in children at risk of 21-hydroxylase deficiency (1), but stopped DEX before the 18th GW following negative genotyping of the fetus. Insulin sensitivity was determined by the hyperinsulinemic-euglycemic-clamp.