Metzger B E
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
Diabetes. 1991 Dec;40 Suppl 2:99-105. doi: 10.2337/diab.40.2.s99.
More than a decade ago, Norbert Freinkel postulated that alterations in the maternal metabolic milieu at any time during gestation can influence intrauterine development and also may have long-term consequences for certain tissues such as adipocytes, myocytes, pancreatic beta-cells, and neurons. This review illustrates that metabolic alterations early in gestation, such as those that occur in diabetes mellitus, may impair growth of the embryo and increase the risk of dysmorphogenesis. Such delayed growth of the embryo may in turn influence size at birth. In midgestation, metabolic perturbations may accelerate functional maturation of fetal pancreatic beta-cells. Fetal beta-cell development is very sensitive to alterations in the nutrient milieu and may be enhanced in gestational diabetes mellitus (GDM) with only minimal elevations of plasma glucose and minor alterations in other nutrient fuels, including insulinogenic amino acids. Data are reviewed that suggest that the ensuing fetal hyperinsulinemia may promote the development of macrosomia even if metabolic control is satisfactory during late gestation. The overall potential influences of metabolic alterations on intrauterine growth are different in pregnancies complicated by diabetes mellitus throughout gestation (pregestational) and GDM. However, the implications in an individual pregnancy may be defined by the degree of metabolic control at the specific stages of gestation when growth of the embryo, development of fetal beta-cell function, and growth of insulin-sensitive tissues are most critically influenced by the metabolic milieu.
十多年前，诺伯特·弗赖因克尔提出，孕期任何时候母体代谢环境的改变都可能影响子宫内发育，并且可能对某些组织，如脂肪细胞、肌细胞、胰腺β细胞和神经元产生长期影响。这篇综述表明，孕期早期的代谢改变，如糖尿病时发生的改变，可能会损害胚胎生长并增加畸形发生的风险。胚胎的这种生长延迟反过来可能会影响出生时的体重。在妊娠中期，代谢紊乱可能会加速胎儿胰腺β细胞的功能成熟。胎儿β细胞发育对营养环境的改变非常敏感，在妊娠期糖尿病（GDM）中，即使血浆葡萄糖仅有轻微升高，其他营养物质（包括胰岛素原性氨基酸）仅有微小改变，胎儿β细胞发育也可能会增强。本文回顾的资料表明，即使在妊娠晚期代谢控制良好，随之而来的胎儿高胰岛素血症也可能促进巨大儿的发生。在整个妊娠期患有糖尿病（孕前糖尿病）和GDM的妊娠中，代谢改变对子宫内生长的总体潜在影响是不同的。然而，个体妊娠中的影响可能取决于妊娠特定阶段的代谢控制程度，此时胚胎生长、胎儿β细胞功能发育以及胰岛素敏感组织的生长最受代谢环境的关键影响。
