Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Diabetologia. 2023 Nov;66(11):1961-1970. doi: 10.1007/s00125-023-05965-w. Epub 2023 Jul 13.
Diabetes in pregnancy affects 20 million women per year and is associated with increased risk of obesity in offspring, leading to insulin resistance and cardiometabolic disease. 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.
妊娠期糖尿病每年影响 2000 万名女性，与后代肥胖风险增加相关，导致胰岛素抵抗和心血管代谢疾病。尽管对公共健康有重大影响，但对于这些高风险儿童肥胖的病理生理机制相对知之甚少，这成为成功干预的障碍。虽然母体葡萄糖本身无疑是宫内生长的主要刺激因素，但母亲和后代中后代高胰岛素血症和脂质代谢紊乱的程度也可能与疾病过程有关。本综述的目的是总结目前对宫内暴露于母体高血糖后儿童期肥胖的病理生理学的理解，并强调干预的可能机会。我在这里提出了一个新的统一假说，即母亲患有糖尿病的婴儿在出生后的儿童肥胖的病理生理学，其中涉及胰腺β细胞功能亢进和脂质代谢改变的自我维持的双循环，这两种循环在宫内暴露于母体高血糖后急性和慢性地上调。
