Department of Obstetrics and Gynaecology, Children's Health Research Institute and Lawson Research Institute, University of Western Ontario, London, Ontario, Canada.
Semin Reprod Med. 2011 May;29(3):211-24. doi: 10.1055/s-0031-1275522. Epub 2011 Jun 27.
The metabolic syndrome (or syndrome X) is a constellation of risk factors including insulin resistance, hypertension, dyslipidemia, and central obesity that predispose to the development of cardiovascular disease and type 2 diabetes in adult life. Insulin resistance is believed to be a critical pathophysiological event early in the disease process, impacting both skeletal muscle metabolic function and vascular responses. Adverse changes in insulin sensitivity have been found to originate in utero; for instance, prenatal events such as placental insufficiency/oxidative stress leading to altered fetal growth trajectories are associated with increased rates of metabolic syndrome in adult life. Such intrauterine insults result in reduced skeletal muscle mass in conjunction with altered insulin signaling, decreased oxidative fibers, and impaired mitochondrial function. These developmental disturbances set the stage for development of muscle triglyceride accumulation and depressed insulin sensitivity in childhood. Abnormalities of vascular structure and function arising from deprived intrauterine conditions that are exacerbated by insulin resistance account for the progression of hypertension from childhood to adulthood. Arterial changes initiated in utero include reduced endothelial nitric oxide (NO) bioavailability, vascular smooth muscle cell proliferation and inflammation, events leading to endothelial dysfunction, and atherosclerosis that are present in those destined for metabolic syndrome. In addition, the hypertensive phenotype that is a hallmark of metabolic syndrome may also be traced to blunted kidney development and renin-angiotensin system activation in growth-restricted offspring. The summative impact of these intrauterine programmed changes in terms of influencing adult health and disease encompasses dietary and lifestyle factors introduced postnatally. Establishing novel therapeutic interventions aimed at preventing and/or reducing in utero-induced insulin resistance and vascular dysfunction warrants investigation because the numbers of low birthweight babies continue to increase.
代谢综合征（或综合征 X）是一组危险因素，包括胰岛素抵抗、高血压、血脂异常和中心性肥胖，这些因素易导致成年人心血管疾病和 2 型糖尿病的发生。胰岛素抵抗被认为是疾病早期的一个关键病理生理事件，影响骨骼肌代谢功能和血管反应。胰岛素敏感性的不利变化被发现在宫内起源；例如，胎盘功能不全/氧化应激等产前事件导致胎儿生长轨迹改变，与成年代谢综合征的发生率增加有关。这种宫内损伤导致骨骼肌质量减少，同时伴随着胰岛素信号改变、氧化纤维减少和线粒体功能受损。这些发育紊乱为儿童期肌肉甘油三酯积累和胰岛素敏感性降低的发展奠定了基础。由于胰岛素抵抗加剧，宫内条件剥夺引起的血管结构和功能异常导致从儿童期到成年期高血压的进展。在宫内启动的动脉变化包括内皮一氧化氮 (NO) 生物利用度降低、血管平滑肌细胞增殖和炎症，导致内皮功能障碍和动脉粥样硬化的事件，这些都存在于那些注定患有代谢综合征的人群中。此外，代谢综合征的高血压表型也可能归因于生长受限后代的肾脏发育不良和肾素-血管紧张素系统激活。这些宫内编程变化对成年健康和疾病的综合影响包括出生后引入的饮食和生活方式因素。因此，需要研究旨在预防和/或减少宫内诱导的胰岛素抵抗和血管功能障碍的新治疗干预措施，因为低出生体重婴儿的数量仍在继续增加。
