Breast milk as a new paradigm for preserving offspring born from gestational diabetes-mother against adult diabetes – GDM-MILK

The worldwide prevalence of Gestational Diabetes Mellitus (GDM) has increased steadily over the last decade, affecting up to 10.8 % of the pregnancies in France, mainly due to the rising proportion of women with pre-pregnancy overweight, sedentary lifestyle and advanced maternal age at birth. GDM fuels the type 2 diabetes (T2D) epidemic in the next generation. Whether nutritional interventions during critical time windows in early life, such as breastfeeding could mitigate this risk remains to be explored. Indeed, despite emerging evidence of the infant-health benefit of breastfeeding in GDM, there is still a paucity of data concerning GDM-breast milk (BM) composition in regard with consensual key regulators of energy homeostasis and insulin sensitivity. In original studies, GDM-MILK consortium reported adaptations of BM composition in link with maternal diet or physiological status in human cohorts and in a cross-fostering rodent model of programming. Interestingly, in a pilot study conducted on GDM mothers, using comprehensive human BM (HBM) metabolomics/lipidomics analyses, we evidenced a specific GDM-HBM signature. Based on these preliminary data, GDM-MILK plans to (i) achieve the identification and validation of BM bioactive compounds associated with maternal glycaemia in existing human cohorts and integrate compositional and clinical data, (ii) validate the HBM bioactive components in a pre-clinical rodent model of GDM and explore the mechanisms of adaptations of key maternal organs (pancreas-placenta-mammary gland) impacting GDM-milk composition, and (iii) in vivo using cross-fostering, evaluate the functional impact of a cocktail of milk components previously selected by in vitro studies, on the sensitivity/secretion of insulin in the male and female offspring. This project will provide a major breakthrough in the understanding of lactation period as a sustainable intervention that may curb the T2D pandemic in the next generations and also yield the scientific basis for nutritional recommendations for mothers with GDM and their infants. Therefore, GDM-MILK perfectly fits the research axis Translational Health Research.