Effects of different gestational diabetes treatments on myo-inositol levels and placental insulin signalling.

Myo-inositol (MI) is a precursor of inositol-3-phosphate, which participates in the insulin receptor pathway. Glucose enhances urinary MI excretion, which could affect gestational diabetes mellitus (GDM) management. The relationship between MI levels and GDM treatment remains unclear, raising questions about potential MI supplementation. The aim of this study was to evaluate MI levels in GDM women treated with either diet or insulin, and their associations with glycaemia and placental insulin signalling. MI was quantified in 23 women with GDM treated with diet (GDM-Diet), 20 GDM treated with insulin (GDM-Insulin) and 25 healthy non-GDM (control). Samples were collected at both the third trimester of pregnancy and at delivery in serum, urine, placenta and cord blood. Placental insulin cascade proteins were assessed by western blot. MI concentration in serum and placenta were decreased in GDM women at delivery, especially in the GDM-diet group. Furthermore, diabetic patients showed greater urinary excretion of MI already at third trimester. Nevertheless, cord MI was not affected by GDM. Placental p-Akt was strongly associated with placental MI (R=0.415, P=0.006), and its levels were lower in GDM-diet group (P=0.031). Insulin treatment tended to normalize maternal MI levels and insulin signalling, whereas GDM treated with diet had lower MI concentrations in both serum and placenta compared to controls. Women with GDM show reduced serum and placental MI concentrations than controls, linked to impaired insulin signalling. Women with GDM managed with diet show the greatest MI deficit and thus may therefore represent a target population for future supplementation trials.