Endocrine Abstracts

Low birth weight is associated with adult disorders characterised by insulin resistance such as type 2 diabetes, hypertension, dyslipidaemia and coronary heart disease. However the mechanism of this established association is still uncertain and controversial. For the past decade research has principally focused on the role of the intra-uterine environment. It has been proposed that under nutrition in utero results in a permanent re-programming of the fetal metabolism. Genetic factors are not part of this thrifty phenotype hypothesis but there is a significant body of evidence suggesting that they are important both as determinants of birth weight and adult diseases like Type 2 diabetes. We have proposed the fetal insulin hypothesis: that low birth weight and type 2 diabetes are two phenotypes of the same insulin resistant genotype. Evidence for this comes from several sources: i) rare genetic disorders of the beta-cell such as maturity onset diabetes of the young, transient neonatal diabetes and persistant hyperinsulinaeima alter birthweight ii) paternal diabetes is associated with low birthweight whilst maternal diabetes results in high birthweight. The fetal insulin hypothesis and thrifty phenotype hypothesis are not exclusive and it is likely that the adult phenotype of diseases like Type 2 diabetes is a reflection of the genotype and the intra-uterine and the post natal environment with different factors having different predominance in different individuals.