Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Diabetologia. 2021 Apr;64(4):717-726. doi: 10.1007/s00125-021-05386-7. Epub 2021 Feb 11.
In 1998 the fetal insulin hypothesis proposed that lower birthweight and adult-onset type 2 diabetes are two phenotypes of the same genotype. Since then, advances in research investigating the role of genetics affecting insulin secretion and action have furthered knowledge of fetal insulin-mediated growth and the biology of type 2 diabetes. In this review, we discuss the historical research context from which the fetal insulin hypothesis originated and consider the position of the hypothesis in light of recent evidence. In summary, there is now ample evidence to support the idea that variants of certain genes which result in impaired pancreatic beta cell function and reduced insulin secretion contribute to both lower birthweight and higher type 2 diabetes risk in later life when inherited by the fetus. There is also evidence to support genetic links between type 2 diabetes secondary to reduced insulin action and lower birthweight but this applies only to loci implicated in body fat distribution and not those influencing insulin resistance via obesity or lipid metabolism by the liver. Finally, we also consider how advances in genetics are being used to explore alternative hypotheses, namely the role of the maternal intrauterine environment, in the relationship between lower birthweight and adult cardiometabolic disease.
1998 年，胎儿胰岛素假说提出，低出生体重和成年 2 型糖尿病是同一基因型的两种表型。此后，研究遗传因素对胰岛素分泌和作用影响的研究进展进一步加深了人们对胎儿胰岛素介导生长和 2 型糖尿病生物学的认识。在这篇综述中，我们讨论了胎儿胰岛素假说产生的历史研究背景，并根据最近的证据考虑了该假说的地位。总之，现在有充分的证据支持这样一种观点，即某些基因的变异导致胰腺β细胞功能受损和胰岛素分泌减少，这些变异不仅会导致胎儿出生体重较低，而且在以后的生活中患 2 型糖尿病的风险更高。也有证据支持与胰岛素作用降低导致的 2 型糖尿病和低出生体重相关的遗传联系，但这仅适用于与体脂分布相关的基因座，而不适用于通过肥胖或肝脏脂质代谢影响胰岛素抵抗的基因座。最后，我们还考虑了遗传学的进展如何被用于探索替代假说，即子宫内环境在低出生体重与成年心脏代谢疾病之间的关系中的作用。
