Abstract
OBJECTIVE: Our objective was to assess the prospective association between breastfeeding and the risk of type 2 diabetes (T2D) in offspring and to investigate the joint effects of breastfeeding and genetic susceptibility on T2D risk. METHODS: We included 364,562 participants free from prevalent T2D from the UK Biobank. Cox proportional hazards models were employed to evaluate the association between breastfeeding and incident T2D. RESULTS: Over a median follow-up of 12 years, 12,795 cases of incident T2D were recorded. Ever breastfeeding was associated with a significantly lower risk of T2D compared with never breastfeeding (hazard ratio = 0.94, 95% CI: 0.89-0.99). Additionally, significant interaction effects on T2D risk were observed between breastfeeding and T2D genetic risk score (T2D-GRS), both multiplicatively and additively. The association between T2D-GRS and risk of T2D was stronger in participants who were never breastfed compared with those who were breastfed (p for multiplicative interaction = 0.040). The risk of T2D associated with never breastfeeding combined with a high T2D-GRS was greater than the sum of the risks associated with each individual factor (p for additive interaction = 0.007). CONCLUSIONS: Breastfeeding is associated with a lower risk of incident T2D in offspring, showing both multiplicative and additive interactions with T2D-GRS.