Purpose of review: Smaller size at birth is associated with a higher risk of type 2 diabetes in later life, but the mechanisms behind this association are poorly understood. Genetic variants which influence susceptibility to type 2 diabetes via effects on insulin secretion or action are good candidates for association with birth weight because foetal insulin is a key foetal growth factor. This review will focus on recent progress in identifying associations between common genetic variants and birth weight.

Recent findings: Foetal genetic variants at two loci (near CCNL1 and in ADCY5) were robustly associated with birth weight via the foetal genotype in the first genome-wide association study of birth weight. The birth weight-lowering allele at ADCY5 also predisposes to type 2 diabetes. In addition, evidence from studies of other type 2 diabetes loci is accumulating for association between the foetal risk alleles at CDKAL1 and HHEX-IDE and lower birth weight, and the maternal risk alleles at GCK and TCF7L2 and higher birth weight.

Summary: The associations with birth weight at ADCY5, CDKAL1 and HHEX-IDE support the foetal insulin hypothesis, which proposed that type 2 diabetes and lower birth weight could be two phenotypes of the same genotype. The associations at GCK and TCF7L2 illustrate that maternal genes are also important determinants of birth weight.