Gestational hyperglycaemia impacts glucose control and insulin sensitivity in mouse offspring

Gestational diabetes mellitus (GDM) predisposes offspring to the development of obesity and type 2 diabetes. While GDM is studied in the context of maternal obesity and insulin resistance, the consequences of GDM in lean, insulin sensitive women for offspring health are unclear. This preclinical study investigated whether GDM in lean dams characterized by reduced insulin secretion affects offspring metabolic health. Lean GDM was induced by short-term 60% high-fat diet and low-dose streptozotocin injections before mating in mice. The control dams received only high-fat diet (HF) or low-fat diet (LF). Glucose homeostasis was studied in chow-fed offspring. GDM resulted in decreased birth weight, that resolved at postnatal day 15 (PN15). At PN100, higher postprandial glucose responses were found in GDM offspring, while insulin secretion was lower in both GDM and HF offspring. Female GDM offspring showed lower endogenous glucose production and increased liver insulin sensitivity at PN100 compared to controls. No differences in metabolic parameters were observed at PN200 and PN300. Prenatal exposure to elevated maternal glucose levels without maternal obesity modestly affected glucose regulation in mouse offspring during early adulthood. Future studies should clarify if a less favourable postnatal diet may further challenge metabolic health in offspring of GDM dams.