Plagemann Andreas
Experimental Obstetrics, Clinic of Obstetrics, Charité, University Medicine Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
Physiol Behav. 2005 Dec 15;86(5):661-8. doi: 10.1016/j.physbeh.2005.08.065. Epub 2005 Nov 8.
It is increasingly accepted that alterations of the intrauterine and early postnatal nutritional, metabolic, and hormonal environment may cause predispositions for the development of diseases in later life. Studies in the offspring of diabetic mothers have decisively contributed to this perception. Alterations of the fetal and neonatal environment which offspring of diabetic mothers 'experience' seem to program a disposition to develop obesity, diabetes mellitus and Syndrome X-like alterations throughout later life. Underweight at birth is also suggested to lead to an increased risk of Syndrome X in later life ('Barker hypothesis'). Pathophysiological mechanisms are unclear. Hormones are important environment-dependent organizers of the developing neuro-endocrine-immune network, which finally regulates all fundamental processes of life. When present in non-physiological concentrations during 'critical periods' of perinatal life, induced by alterations in the intrauterine or neonatal environment, hormones can act as 'endogenous functional teratogens'. Perinatal hyperinsulinism is pathognomonic in the offspring of diabetic mothers. Early hyperinsulinism also occurs as a result of early postnatal overfeeding. In rats, endogenous hyperinsulinism, as well as peripheral or only intrahypothalamic insulin treatment during perinatal development, may lead to 'malprogramming' of neuroendocrine systems regulating body weight, food intake and metabolism. This results in an increased disposition to become obese and to develop diabetes throughout life. In conclusion, a complex malprogramming of the central regulation of body weight and metabolism may provide a general etiopathogenetic concept, explaining perinatally acquired dispositions, thereby opening a wide field of primary prevention.
越来越多的人认为，子宫内及出生后早期的营养、代谢和激素环境改变可能导致日后患疾病的倾向。对糖尿病母亲后代的研究对这一认识起到了决定性作用。糖尿病母亲的后代所“经历”的胎儿和新生儿环境改变似乎会在其一生中形成发展为肥胖、糖尿病和类X综合征改变的倾向。出生时体重过轻也被认为会增加日后患X综合征的风险（“巴克假说”）。病理生理机制尚不清楚。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，该网络最终调节生命的所有基本过程。在围产期生命的“关键时期”，当激素以非生理浓度存在时，由子宫内或新生儿环境改变所诱发，激素可作为“内源性功能性致畸剂”。围产期高胰岛素血症在糖尿病母亲的后代中具有特征性。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仅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”。这导致一生中肥胖和患糖尿病的倾向增加。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概念，解释围产期获得的易感性，从而开辟了一个广泛的一级预防领域。
