Pathophysiology from preconception, during pregnancy, and beyond.

Gestational diabetes is the most common medical complication in pregnancy. Historically, gestational diabetes was considered a pregnancy complication involving treatment of rising glycaemia late in the second trimester. However, recent evidence challenges this view. Pre-pregnancy and pregnancy-specific factors influence gestational glycaemia, with open questions regarding roles of non-glycaemic factors in the aetiology and consequences of gestational diabetes. Varying patterns of insulin secretion and resistance in early and late pregnancy underlie a heterogeneity of gestational diabetes in the timing and pathophysiological subtypes with clinical implications: early gestational diabetes and insulin resistant gestational diabetes subtypes are associated with a higher risk of pregnancy complications. Metabolic perturbations of early gestational diabetes can affect early placental development, affecting maternal metabolism and fetal development. Fetal hyperinsulinaemia can affect the development of multiple fetal tissues, with short-term and long-term consequences. Pregnancy complications are prevented by managing glycaemia in early and late pregnancy in some, but not all women with gestational diabetes. A better understanding of the pathophysiology and heterogeneity of gestational diabetes will help to develop novel management approaches with focus on improved prevention of maternal and offspring short-term and long-term complications, from pre-conception, throughout pregnancy, and beyond.
Competing Interests: Declaration of interests KB received research funding and study devices from Medtronic for the investigator-initiated CRISTAL study; study devices from Dexcom for the investigator-initiated GLORIA-study; study medication from Novo Nordisk for the investigator-initiated SERENA study; consulting fees from AstraZeneca and Lilly; and serves on the speakers bureau for Novo Nordisk, AstraZeneca, and Mundipharma. DS received study devices on loan from Tandem for the CIRCUIT study; and speaker fees from Ascensia and Sanofi. M-FH, PC, HB, CJDM, CLM, GD, AJ, JI, CJN, UR, and AS declare no competing interests.
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