{"doi":"10.1016/j.tjnut.2024.06.005","title":"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":"BACKGROUND: The 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 milk consumption during childhood is consistently linked to type 1 diabetes risk in prospective cohort studies. OBJECTIVES: Our primary aim was to study whether humoral immune responses to cow milk and cow milk consumption are associated with type 1 diabetes in TRIGR children. METHODS: TRIGR comprised 2159 children with genetic susceptibility to type 1 diabetes born between 2002 and 2007 in 15 countries. Children were randomly assigned into groups receiving extensively hydrolyzed casein or a regular cow milk formula and followed up until age 10 y. Type 1 diabetes-related autoantibodies and antibodies to cow 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 risk to develop type 1 diabetes were analyzed using Cox survival model. RESULTS: Cow milk antibody concentrations both in cord blood [hazards ratio (HR) for islet autoimmunity: 1.30; 95% CI: 1.05, 1.61; HR for type 1 diabetes: 1.32; 95% CI: 1.02, 1.71] and longitudinally from birth to 3 years (HR for islet autoimmunity: 1.39; 95% CI: 1.07, 1.81; HR for type 1 diabetes: 1.43; 95% CI: 1.04, 1.96) were associated with increased risk of developing type 1 diabetes. The amount of regular infant formula was associated with reduced islet autoimmunity risk in the regular infant formula group (HR: 0.92; 95% CI: 0.85, 0.99). Furthermore, frequent liquid milk consumption after infancy was associated with increased risk of islet autoimmunity or type 1 diabetes. CONCLUSIONS: Elevated cow milk antibody concentrations 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 concentrations to cow milk may provide a biomarker of immune system prone to develop islet autoimmunity. This trial was registered at clinicaltrials.gov as NCT00179777.","journal":"Journal of Nutrition","year":2024,"id":465757,"datarank":0.25369016818753076,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.012274481322415697,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.012274481322415697,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.964,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT00179777"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":328459,"name":"David Cuthbertson","orcid":"0000-0002-3785-9834","position":1,"is_corresponding":false},{"id":467293,"name":"Maija E. Miettinen","orcid":"0000-0002-5587-7227","position":2,"is_corresponding":false},{"id":678202,"name":"Leena Hakola","orcid":"0000-0001-7115-6035","position":3,"is_corresponding":false},{"id":467296,"name":"Anita Nucci","orcid":"0000-0001-8823-7384","position":4,"is_corresponding":false},{"id":1297151,"name":"Tuuli E. Korhonen","orcid":"0000-0003-0334-3618","position":5,"is_corresponding":false},{"id":95838,"name":"Heikki Hyöty","orcid":"0000-0003-0370-4145","position":6,"is_corresponding":false},{"id":5970,"name":"Jeffrey P. Krischer","orcid":"0000-0003-4526-888X","position":7,"is_corresponding":false},{"id":468479,"name":"Outi Vaarala","orcid":null,"position":8,"is_corresponding":false},{"id":344344,"name":"Mikael Knip","orcid":"0000-0003-0474-0033","position":9,"is_corresponding":false},{"id":779051,"name":"Erkki Savilahti","orcid":null,"position":10,"is_corresponding":false},{"id":344341,"name":"Suvi Μ. Virtanen","orcid":"0000-0001-8928-0878","position":11,"is_corresponding":false},{"id":467294,"name":"Sari Niinistö","orcid":"0000-0003-2041-6241","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:04:50.328230Z","pmid":"38906178","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}