High Concentrations of Immunoglobulin G Against Cow Milk Proteins and Frequency of Cow Milk Consumption Are Associated With the Development of Islet Autoimmunity and Type 1 Diabetes—The Trial to Reduce Insulin-dependent Diabetes Mellitus (IDDM) in the Genetically at Risk (TRIGR) Study

Abstract

BackgroundThe Trial to Reduce IDDM in the Genetically at Risk (TRIGR) (NCT00179777) found no difference type 1 diabetes risk between hydrolyzed and regular infant formula. However, cow's milk consumption during childhood is consistently linked to type 1 diabetes risk in prospective cohort studies. ObjectiveOur primary aim was to study whether humoral immune responses to cow’s milk and cow’s milk consumption are associated with type 1 diabetes in TRIGR children. MethodsTRIGR comprised 2159 children with genetic susceptibility to type 1 diabetes born between 2002-2007 in 15 countries. Children were randomized into groups receiving extensively hydrolyzed casein or a regular cow’s milk formula and followed until age 10. Type 1 diabetes related autoantibodies and antibodies to cow’s milk proteins were analyzed. Infant formula intake was measured by structured dietary interviews and milk consumption with a food frequency questionnaire. Associations of milk antibodies and milk consumption with the risk to develop type 1 diabetes were analysed by Cox survival model. ResultsCow’s milk antibody levels both in cord blood [HR for islet autoimmunity 1.30 (95% CI 1.05-1.61); type 1 diabetes 1.32 (1.02-1.71)] and longitudinally from birth to 3 years [islet autoimmunity 1.39 (1.07-1.81); type 1 diabetes 1.43 (1.04-1.96)] were associated with increased risk of developing type 1 diabetes. The amount of regular infant formula was associated with a reduced islet autoimmunity risk in the regular infant formula group [0.92 (0.85-0.99)]. Furthermore, frequent liquid milk consumption after infancy was associated with an increased risk of islet autoimmunity or type 1 diabetes. ConclusionsElevated cow's milk antibody levels and high consumption of liquid milk after infancy are related to type 1 diabetes development in children with an increased genetic susceptibility to type 1 diabetes. Enhanced antibody levels to cow’s milk may provide a biomarker of immune system prone to develop islet autoimmunity. Trial registry numberNCT00179777