Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

PURPOSE OF REVIEW: In observational epidemiology, both low and high birth weights are associated with later type 2 diabetes. The mechanisms underlying the associations are poorly understood. We review evidence for the roles of genetic and non-genetic factors linking both sides of the birth weight distribution to risk of type 2 diabetes, focusing on contributions made by the most recent genome-wide association studies (GWAS) of birth weight. RECENT FINDINGS: There are now nine genetic loci robustly implicated in both fetal growth and type 2 diabetes. At many of these, the same alleles are associated both with a higher risk of type 2 diabetes and a lower birth weight. This supports the Fetal Insulin Hypothesis and reflects a general pattern for type 2 diabetes susceptibility alleles: genome-wide, there is an inverse genetic correlation with birth weight, and initial estimates suggest genetic factors explain a large part of the covariance between the two traits. However, the associations at individual loci show heterogeneity; some fetal risk alleles are associated with higher birth weight. For most of these, the association reflects their correlation with the maternal risk allele which raises maternal glucose, thus increasing fetal insulin-mediated growth. GWAS have improved our understanding of the mechanisms underlying associations between type 2 diabetes and birth weight but questions remain about the relative importance of genetic versus non-genetic factors and of maternal versus fetal genotypes. To answer these questions, future work will require well-powered analyses of parents and offspring.

Original publication

DOI

10.1007/s11892-017-0852-9

Type

Journal article

Journal

Curr Diab Rep

Publication Date

04/2017

Volume

17

Keywords

Birth weight, Fetal, Genetics, Genome-wide association study, Maternal, Type 2 diabetes, Birth Weight, Diabetes Mellitus, Type 2, Fetal Development, Genetic Loci, Genome-Wide Association Study, Genotype, Humans