Szostak-Węgierek Dorota, Szamotulska Katarzyna
Department of Preventive Medicine and Hygiene, Medical University of Warsaw, Warszawa.
Med Wieku Rozwoj. 2011 Jul-Sep;15(3):203-15.
The fetal origin hypothesis of adult cardiovascular diseases, type 2 diabetes, hypertension and dyslipidemia in persons born with low birthweight, independently of their extrauterine risk factors, has been well established in the last decade of the twentieth century. However, mechanisms responsible for this relationship are still under investigation. Insulin resistance resulting from the restriction of intrauterine development of skeletal muscles and other organs is considered as the most important cause of metabolic disturbances and their cardiovascular complications in adult subjects born with intrauterine growth retardation (IUGR). Decline of insulin secretion, overactivation of the hypothalamo-pituitary-adrenal axis, reduced glucose uptake in the liver and raised lipid oxidation in the muscles may also explain this association. On the other hand, abnormal vascular development , increased activity of the sympathetic nervous system, defective endothelial function and/or impaired renal function in growth restricted newborns may contribute to hypertension in their later life. With respect to maternal conditions and life-style factors that may increase cardiovascular risk in adult offspring born with IUGR, the most consistent results concern pregnancy induced hypertension, preeclampsia, undernutrition, smoking during pregnancy, hypercholesterolemia, inflammation and/or enhanced glucocorticoid secretion. Macrosomia of the newborn, a frequent sequel to maternal diabetes and/or obesity, also increases the risk of diabetes and cardiovascular diseases in adulthood. Maternal overnutrition, and particularly high fat and sugar intake, seem to play a key role in fetal programming of cardiovascular risk in subjects born with macrosomia. Epigenetic imprinting underlies the described pathomechanisms. The presented associations are illustrated, among others, with the results of studies performed by the authors of this review.
出生体重低的人成年后发生心血管疾病、2型糖尿病、高血压和血脂异常的胎儿起源假说，独立于其宫外危险因素，在20世纪的最后十年已得到充分证实。然而，这种关系的机制仍在研究中。宫内骨骼肌和其他器官发育受限导致的胰岛素抵抗被认为是宫内生长受限（IUGR）出生的成年受试者代谢紊乱及其心血管并发症的最重要原因。胰岛素分泌下降、下丘脑-垂体-肾上腺轴过度激活、肝脏葡萄糖摄取减少和肌肉脂质氧化增加也可能解释这种关联。另一方面，生长受限新生儿的血管发育异常、交感神经系统活动增加、内皮功能缺陷和/或肾功能受损可能导致其晚年患高血压。关于可能增加IUGR出生的成年后代心血管风险的母亲状况和生活方式因素，最一致的结果涉及妊娠高血压、先兆子痫、营养不良、孕期吸烟、高胆固醇血症、炎症和/或糖皮质激素分泌增加。新生儿巨大儿是母亲糖尿病和/或肥胖的常见后果，也会增加成年后患糖尿病和心血管疾病的风险。母亲营养过剩，尤其是高脂肪和高糖摄入，似乎在巨大儿出生的受试者心血管风险的胎儿编程中起关键作用。表观遗传印记是上述发病机制的基础。除其他外，本综述作者进行的研究结果说明了所呈现的关联。
