Bioactive milk sugars may play a broader metabolic role beyond infant nutrition during the postpartum period. In a study published in Diabetologia, circulating human milk oligosaccharides (HMOs) persisted weeks after delivery and changed rapidly in response to glucose and insulin exposure, supporting a possible role in maternal metabolic adaptation.

The study included 28 women assessed at 5 to 7 weeks postpartum, including 16 with prior gestational diabetes mellitus (GDM), while 18 were breastfeeding. Participants underwent both a 75 g oral glucose tolerance test (OGTT) and a hyperinsulinemic-euglycemic clamp. Human milk oligosaccharides were quantified in plasma and milk using high-performance liquid chromatography.

Seventeen HMOs were detected in milk, and six were also identified in plasma at concentrations approximately 10,000-fold lower, although levels were strongly correlated between compartments. The lactosamine-based glycans 3′-sialyllactosamine (3′SLN) and 6′-sialyllactosamine (6′SLN) were detected only in plasma.

During the OGTT, plasma levels of the fucosylated HMOs 2′-fucosyllactose (2′FL), lacto-N-fucopentaose 1 (LNFP1), and lacto-N-difucohexaose (LNDFH) decreased significantly, while 3′-sialyllactose (3′SL) increased. During the clamp, all fucosylated HMOs and 3′SL declined, whereas 3′SLN increased as insulin levels rose.

Women with prior GDM had lower fasting HMO concentrations in milk. Lactation status did not significantly affect plasma HMO levels except for lower 6′SLN in breastfeeding women. The findings suggest that HMOs may function as candidate signaling molecules linking lactation with short-term postpartum metabolic regulation.