Association of birthweight and penetrance of diabetes in individuals with HNF4A-MODY: a cohort study
2022
Abstract
Mutations in HNF4A, which encodes hepatocyte nuclear factor-4 α, cause maturity-onset diabetes of the young (MODY). HNF4A-MODY is also associated with congenital hyperinsulinism (CHI) and neonatal hypoglycaemia [2].
Our understanding of the transition from hyperinsulinism to diabetes is limited. One hypothesis is higher fetal insulin secretion triggers apoptosis and results in accelerated postnatal beta cell failure.
Alternatively, HNF4A deficiency could cause distinct transcriptional defects in early and late life, leading to the contrasting insulin phenotypes. These two hypotheses differ as to whether hypersecretion of insulin in utero precipitates beta cell failure later in life.