Plagemann A
Clinic of Obstetrics, Charité-University Medicine Berlin, Germany.
Horm Res. 2006;65 Suppl 3:83-9. doi: 10.1159/000091511. Epub 2006 Apr 10.
It is increasingly accepted that alterations of the intrauterine and early postnatal nutritional, metabolic and hormonal environment may predispose individuals to development of diseases in later life. Results from studies of the offspring of diabetic mothers strongly support this hypothesis. It has also been suggested that being light at birth leads to an increased risk of the metabolic syndrome (Syndrome X) in later life (the Barker hypothesis). The pathophysiological mechanisms that underlie this programming are unclear. However, hormones are important environment-dependent organizers of the developing neuroendocrine-immune network, which regulates all the fundamental processes of life. Hormones can act as 'endogenous functional teratogens' when present in non-physiological concentrations, induced by alterations in the intrauterine or neonatal environment during critical periods of perinatal life. Perinatal hyperinsulinism is pathognomic in offspring of diabetic mothers. Early hyperinsulinism also occurs as a result of early postnatal overfeeding. In rats, endogenous hyperinsulinism, as well as peripheral or intrahypothalamic insulin treatment during perinatal development, may lead to 'malprogramming' of the neuroendocrine systems regulating body weight, food intake and metabolism. This results in an increased disposition to become obese and to develop diabetes throughout life. Similar malprogramming may occur due to perinatal hypercortisolism and hyperleptinism. With regard to 'small baby syndrome' and the thrifty phenotype hypothesis, we propose that early postnatal overfeeding of underweight newborns may substantially contribute to their long-term risk of obesity and diabetes. In summary, a complex malprogramming of the central regulation of body weight and metabolism may provide a general aetiopathogenetic concept, explaining perinatally acquired disposition to later disease and, thereby, opening a wide field for primary prevention.
越来越多的人认为，子宫内和出生后早期的营养、代谢和激素环境改变可能使个体在晚年易患疾病。对糖尿病母亲后代的研究结果有力地支持了这一假说。也有人提出，出生时体重较轻会增加晚年患代谢综合征（X综合征）的风险（巴克假说）。这种编程背后的病理生理机制尚不清楚。然而，激素是发育中的神经内分泌 - 免疫网络重要的环境依赖性组织者，该网络调节生命的所有基本过程。当在围产期生命的关键时期子宫内或新生儿环境发生改变，导致激素以非生理浓度存在时，激素可作为“内源性功能性致畸剂”。围产期高胰岛素血症是糖尿病母亲后代的特征。出生后早期过度喂养也会导致早期高胰岛素血症。在大鼠中，围产期发育期间的内源性高胰岛素血症以及外周或下丘脑内胰岛素治疗可能导致调节体重、食物摄入和代谢的神经内分泌系统“编程错误”。这导致终生肥胖和患糖尿病的倾向增加。由于围产期高皮质醇血症和高瘦素血症，可能会发生类似的编程错误。关于“小婴儿综合征”和节俭表型假说，我们提出出生后早期对体重不足的新生儿过度喂养可能会显著增加他们肥胖和糖尿病的长期风险。总之，体重和代谢的中枢调节的复杂编程错误可能提供一个一般的病因发病学概念，解释围产期获得的晚年疾病易感性，从而为一级预防开辟广阔领域。
