Pregnancy Hyperglycemia & Offspring Metabolic Syndrome (PHOMS)
Maternal diabetes during pregnancy poses major long-term health risks for both mother and child. This collaborative project between UMCG and Danone Nutricia Research will evaluate the consequences of gestational diabetes (GDM) for offspring development and -health.
Research within the so-called Developmental Origins of Health and Disease (DOHaD) field support the notion that healthy ageing starts in the womb. Infants born from obese mothers and mothers with GDM are at an increased risk for pregnancy and birth complications as well as later non-communicable disease. The worldwide incidence of GDM is currently estimated to be 14% of all pregnancies, but much higher (>20%) in women having one or more risk factors. On the long term, GDM children have an increased risk to develop obesity and impaired glucose tolerance, two features of metabolic syndrome. Additionally, there are indications that intrauterine exposure to hyperglycemia sensitizes female offspring to also develop GDM when pregnant, suggesting transgenerational effects on glucose metabolism. However, the mechanisms in mother, placenta and child by which GDM induces metabolic programming and subsequently increases later MetS risk are poorly understood. A GDM mouse model was developed that adequately captures the maternal and fetal phenotype of human GDM. This model allows us to study the specific adaptations in maternal physiology, offspring organ function, the contribution of different organ adaptations to later disease risk, as well as the underlying mechanisms that potentially contribute to maternal and offspring disease risk.
Moreover, potential impact of interventions during different windows of opportunity, i.e. during pregnancy (current treatment window), lactation and/or after weaning can be studied in detail. The proposed project will hence contribute to further mechanistic understanding and provide insights to develop intervention strategies that potentially reduce the incidence of GDM and obesity/insulin resistance, thereby contributing to healthy aging in humans.
