Phillips D I
Medical Research Council Metabolic Programming Group, Southampton General Hospital, U.K.
Diabetes Care. 1998 Aug;21 Suppl 2:B150-5.
Recent studies in Europe, North America, and the developing world have shown that low birth weight and other indices of abnormal fetal growth in babies born at term are linked with a higher prevalence of glucose intolerance and NIDDM in adult life. Reduced fetal growth is also associated with a higher prevalence of the metabolic syndrome (in particular, hypertension and vascular disease) and with insulin resistance in adult life. Because birth size is determined largely by nongenetic factors, these findings have led to the "fetal origins" hypothesis, which proposes that fetal adaptations to an adverse intrauterine environment that reduces fetal growth program lifelong physiological changes. These changes in turn predispose to diabetes and the metabolic syndrome. The mechanisms are unknown, but evidence from animal studies and preliminary human evidence suggests that adverse events in early life may influence the neuroendocrine development of the fetus. This results in long-term alterations in the setpoint of several major hormonal axes, including an increase in adrenal glucocorticoid secretion. These hormonal alterations may contribute to the predisposition to diabetes and the metabolic syndrome in people who were small at birth.
欧洲、北美及发展中世界的近期研究表明，足月出生婴儿的低出生体重及其他胎儿生长异常指标与成年后葡萄糖耐量异常及非胰岛素依赖型糖尿病（NIDDM）的较高患病率相关。胎儿生长受限还与成年后代谢综合征（尤其是高血压和血管疾病）的较高患病率以及胰岛素抵抗相关。由于出生体重很大程度上由非遗传因素决定，这些发现导致了“胎儿起源”假说，该假说提出胎儿对不利于胎儿生长的子宫内不良环境的适应性变化会编程终身的生理改变。这些改变进而易患糖尿病和代谢综合征。其机制尚不清楚，但动物研究证据和初步人体证据表明，生命早期的不良事件可能影响胎儿的神经内分泌发育。这导致几个主要激素轴的设定点发生长期改变，包括肾上腺糖皮质激素分泌增加。这些激素改变可能促使出生时体重较轻的人易患糖尿病和代谢综合征。
