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Despite the substantial public health ramifications, relatively little is known about the pathophysiological mechanisms underlying obesity in these high-risk children, which creates a barrier to successful intervention. While maternal glucose itself is undeniably a major stimulus upon intrauterine growth, the degree of offspring hyperinsulinism and disturbed lipid metabolism in mothers and offspring are also likely to be implicated in the disease process. The aim of this review is to summarise current understanding of the pathophysiology of childhood obesity after intrauterine exposure to maternal hyperglycaemia and to highlight possible opportunities for intervention. I present here a new unified hypothesis for the pathophysiology of childhood obesity in infants born to mothers with diabetes, which involves self-perpetuating twin cycles of pancreatic beta cell hyperfunction and altered lipid metabolism, both acutely and chronically upregulated by intrauterine exposure to maternal hyperglycaemia.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s00125-023-05965-w","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T20:29:57Z","timestamp":1689280197000},"page":"1961-1970","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["An unwelcome inheritance: childhood obesity after diabetes in pregnancy"],"prefix":"10.1007","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4176-8329","authenticated-orcid":false,"given":"Claire L.","family":"Meek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,13]]},"reference":[{"issue":"Suppl 2","key":"5965_CR1","first-page":"B161","volume":"21","author":"BE Metzger","year":"1998","unstructured":"Metzger BE, Coustan DR (1998) Summary and recommendations of the fourth international workshop-conference on gestational diabetes mellitus. 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This was an invited review after a presentation of the same name delivered at the EASD conference in 2022.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"CLM receives funding from Diabetes UK (17\/0005712), the BMA Foundation (Helen H Lawson Award), the European Foundation for the Study of Diabetes\u2013Novo Nordisk Foundation (NNF19SA058974) and the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre (BRC). The views expressed are those of the author and not necessarily those of the NIHR or the Department of Health and Social Care.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The author declares that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"The author was the sole contributor to this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}