Maternal type 1 diabetes and relative protection against offspring transmission

Type 1 diabetes is around twice as common in the offspring of men with type 1 diabetes than in the offspring of women with type 1 diabetes, but the reasons for this difference are unclear. This Review summarises the evidence on the rate of transmission of type 1 diabetes to the offspring of affected fathers compared with affected mothers. The findings of nine major studies are presented, describing the magnitude of the effect observed and the relative strengths and weaknesses of these studies. This Review also explores possible underlying mechanisms for this effect, such as genetic mechanisms (eg, the selective loss of fetuses with high-risk genes in mothers with type 1 diabetes, preferential transmission of susceptibility genes from fathers, and parent-of-origin effects influencing gene expression), environmental exposures (eg, exposure to maternal hyperglycaemia, exogenous insulin exposure, and transplacental antibody transfer), and maternal microchimerism. Understanding why type 1 diabetes is more common in the offspring of men versus women with type 1 diabetes will help in the identification of individuals at high risk of the disease and can pave the way in the development of interventions that mimic the protective elements of maternal type 1 diabetes to reduce the risk of disease in individuals at high risk.