ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Am J Physiol Endocrinol Metab. 2020 May 1;318(5):E600–E612. doi: 10.1152/ajpendo.00473.2019. Epub 2020 Mar 10. PMID: 32154743

The window of lactation is a critical period during which nutritional and environmental exposures may impact lifelong risks of metabolic diseases (such as type 2 diabetes and obesity). Significant organ and tissue development, organ expansion and maturation of cellular functions occur during the lactation period, making this a vulnerable time during which transient insults may have lasting effects. This period also provides a window of opportunity for possible interventions to improve long-term metabolic health.

In this mouse study, the authors hypothesized that metformin given during the lactational period would improve the metabolic profile of offspring later in life. Metformin was administered to C57BL/6 dams (lactating mothers) from the day of birth to postnatal day 21. Maternal and offspring health were monitored and glucose homeostasis assessed, as well as pancreatic and adipocyte biopsies taken. Maternal exposure to metformin during lactation programmed offspring body composition and glucose homeostasis in a sex-dependent manner. Throughout life, both male and female offspring were leaner. Furthermore, males tended to have lower visceral adiposity with more smaller visceral white adipocytes and an improvement in glucose tolerance that was unrelated to changes in beta-cell mass or function. Females showed no change in adiposity. Both males and females were protected from metabolic impairment when subjected to a high fat diet but this differed between males and females. Lactational metformin had no effect on beta-cell mass or insulin secretion and changes in insulin sensitivity were observed only in the setting of a high fat diet.

How metformin may be mediating its effects is not clear but suggested mechanisms include a direct effect on the gut, on the liver, and by altering maternal milk composition. These data demonstrate long-term metabolic programming in offspring by maternal exposure to metformin during lactation – at least in mice. It will be interesting to understand if similar findings can be replicated in humans.