title: Characteristics of the pre-diabetic period in children with high risk of type 1 diabetes recruited from the general Swedish population-The ABIS study.
abstract: There is a need for increased understanding of the pre-diabetic period in individuals with high risk of type 1 diabetes from the general population.
  
  
  
  High-risk children (n = 21) positive for multiple islet autoantibodies were identified by autoantibody screening within the All Babies in Southeast Sweden study. The children and their parents were enrolled in a 2-year prospective follow-up study aiming to characterize the pre-diabetic period. Blood samples were collected every 6 months for measurement of C-peptide, HbA1c, fasting glucose, and autoantibodies. Human leukocyte antigen-genotype was determined, and oral glucose tolerance test was performed every 12 months.
  
  
  
  Despite positivity for multiple autoantibodies, 9 out of 21 individuals had low-risk human leukocyte antigen-genotypes. Children who progressed to manifest diabetes (progressors, n = 12) had higher levels of IA2A and ZnT8A than children who did not (non-progressors, n = 9). Impaired glucose tolerance and impaired fasting glucose was observed to the same extent in progressors and non-progressors, but HbA1c increased over time in progressors in spite of increased C-peptide.
  
  
  
  Autoantibodies to IA2 and ZnT8 may be useful discriminators for disease progression in at-risk children from the general population. Dysglycemia was observed long before diagnosis, and difficulties in maintaining glucose homeostasis despite increased C-peptide indicate that insulin resistance might be an important accelerator of disease in risk individuals.
authors.affiliation: Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Linda
authors.identifier: 0000-0003-1504-3655
authors.initials: L
authors.lastname: Åkerman
authors.affiliation: Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.|Pediatric Clinic, County Council of Östergötland, Linköping, Sweden.
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
authors.affiliation: Division of Diabetes and Celiac disease, Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Ulrica
authors.initials: U
authors.lastname: Swartling
authors.affiliation: Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Rosaura
authors.initials: R
authors.lastname: Casas
mesh_terms: D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: D001323:Autoantibodies
keywords: T1D high-risk; islet autoantibodies; pre-diabetes; type 1 diabetes