Developmental Aspects in the Pathogenesis of Type 2 Diabetes

Low birthweight is linked to increased risk of adulthood type 2 diabetes and this risk may be secondary to adaptive metabolic/endocrine mechanisms in the fetus which ensure survival during undernutrition. Thrifty genotypes, which enhance these adaptations to undernutrition may further protect survival from fetal life to reproductive age, but at the expense of longer-term disease risk. Potential fetal thrifty genotypes include the insulin gene variable number of tandem repeats class III/III genotype which is associated with larger size at birth and type 2 diabetes in adults and these effects may relate to paternally inherited genotypes. In contrast, mechanisms, which restrain fetal growth and protect maternal survival may be inherited on mitochondrial DNA or maternally expressed imprinted genes such as IGF2R. Finally, larger early postnatal size is also important for survival and some genotypes may promote infancy growth, but in affluent societies may predispose to obesity and increased risks for adulthood type 2 diabetes.