Two decades since the fetal insulin hypothesis: what have we learned from genetics? – published online 11/02/2021

Alice E. Hughes, Andrew T. Hattersley, Sarah E. Flanagan, Rachel M. Freathy

In 1998, the fetal insulin hypothesis proposed that lower birthweight and adult-onset type 2 diabetes are two phenotypes of the same genotype. In this issue, Hughes et al (https://doi.org/10.1007/s00125-021-05386-7) review evidence from recent genetics research relevant to the fetal insulin hypothesis. People with monogenic diabetes not only have early-onset diabetes that results from reduced insulin secretion, but also usually have low birthweight. The authors highlight that genome-wide association studies have established overlap between common genetic variants associated with lower birthweight and higher risk of type 2 diabetes. There is strong evidence that certain risk alleles associated with reduced pancreatic beta cell function or metabolically unfavourable patterns of adiposity are associated with lower birthweight when inherited, but fetal risk alleles associated with obesity do not alter birthweight. The authors conclude that it is likely that further advances in genetics research will help us better understand the complex relationship between fetal growth and type 2 diabetes risk, which has both genetic and epigenetic components. The figures from this review are available as a downloadable slideset.

All News