title: Neonatal and infant beta cell hormone concentrations in relation to type 1 diabetes risk.
abstract: Type 1 diabetes is preceded by the appearance of islet autoantibodies. Seroconversion to islet autoantibodies is greatest around 1 yr of age and is more frequent in children born to fathers with type 1 diabetes as compared to children born to mothers with type 1 diabetes. Here we asked whether changes in beta-cell function in the neonate and infant reflect variations in the incidence of islet autoantibody seroconversion. Insulin, proinsulin, and c-peptide concentrations were measured in sequential samples taken from birth to age 2 yr in 103 children who had a first degree relative with type 1 diabetes and who had been followed for islet autoantibody seroconversion. Serum insulin and proinsulin concentrations were highest at birth declining by age 3 months and stable thereafter until age 2 yr. C-peptide concentrations, proinsulin/insulin, and proinsulin/c-peptide ratios were stable from age 3 months. No differences were observed between children who developed islet autoantibodies and children who remained islet autoantibody negative. Children born to a mother with type 1 diabetes had higher birth concentrations of insulin (p = 0.005) and proinsulin (p = 0.014) as compared with children of non-diabetic mothers. Increased insulin concentrations in children of type 1 diabetes mothers persisted until age 6 months. In conclusion, we could not relate excursions in beta-cell hormones to autoantibody development, but suggest that the higher exposure to insulin and proinsulin in neonates born to mothers with type 1 diabetes may be linked to the relative protection against islet autoantibody seroconversion observed in these children.
authors.affiliation: DFG Research Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stumpp
authors.forename: Andreas
authors.initials: A
authors.lastname: Beyerlein
authors.forename: Anette-Gabriele
authors.initials: AG
authors.lastname: Ziegler
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
mesh_terms: D001323:Autoantibodies / Q000032:analysis*; D015551:Autoimmunity; D002096:C-Peptide / Q000097:blood*; D002657:Child Development; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D005260:Female; D047109:Fetal Development; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000276:immunology / Q000503:physiopathology; D011384:Proinsulin / Q000097:blood* / Q000378:metabolism; D012306:Risk
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin
keywords: autoantibodies; insulin; proinsulin; type 1 diabetes