An exploration of Glo-3A antibody levels in children at increased risk for type 1 diabetes mellitus

Aims To determine whether Glo-3A, (formerly referred to as homologue of Glb1 or Glb1) antibodies are associated with islet autoimmunity (IA) in children at increased risk for type 1 diabetes (T1D) and to investigate their relation with environmental correlates of T1D. Methods We selected a sample from the Diabetes Autoimmunity Study in the Young (DAISY), a prospective study of children at increased risk for T1D. Cases were positive for insulin, glutamic acid decarboxylase (GAD), or insulinoma-associated antigen-2 (IA-2) autoantibodies on two consecutive visits and either diagnosed with diabetes mellitus or still autoantibody positive when selected. Controls were from the same increased risk group, of similar age as the cases but negative for autoantibodies. Sera from 91 IA cases and 82 controls were analyzed in a blinded manner for immunoglobulin G (IgG) antibodies to Glo-3A by ELISA. Results Adjusting for family history of T1D and human leukocyte antigen (HLA)-DR4 positivity, Glo-3A antibodies were not associated with IA case status (OR: 1.01, 95% CI: 0.99-1.03). Adjusting for age, family history of T1D, and HLA-DR4 positivity, Glo-3A antibody levels were inversely associated with breast-feeding duration (beta = -0.08, p = 0.001) and directly associated with current intake of foods containing gluten (beta = 0.24, p = 0.007) in IA cases but not in controls. Zonulin, a biomarker of gut permeability, was directly associated with Glo-3A antibody levels in cases (beta = 0.73, p = 0.003) but not in controls. Conclusion Differing correlates of Glo-3A antibodies in IA cases and controls suggest an underlying difference in mucosal immune response.