title: Complex multi-block analysis identifies new immunologic and genetic disease progression patterns associated with the residual β-cell function 1 year after diagnosis of type 1 diabetes.
abstract: The purpose of the present study is to explore the progression of type 1 diabetes (T1D) in Danish children 12 months after diagnosis using Latent Factor Modelling. We include three data blocks of dynamic paraclinical biomarkers, baseline clinical characteristics and genetic profiles of diabetes related SNPs in the analyses. This method identified a model explaining 21.6% of the total variation in the data set. The model consists of two components: (1) A pattern of declining residual β-cell function positively associated with young age, presence of diabetic ketoacidosis and long duration of disease symptoms (P = 0.0004), and with risk alleles of WFS1, CDKN2A/2B and RNLS (P = 0.006). (2) A second pattern of high ZnT8 autoantibody levels and low postprandial glucagon levels associated with risk alleles of IFIH1, TCF2, TAF5L, IL2RA and PTPN2 and protective alleles of ERBB3 gene (P = 0.0005). These results demonstrate that Latent Factor Modelling can identify associating patterns in clinical prospective data--future functional studies will be needed to clarify the relevance of these patterns.
authors.affiliation: Department of Pediatrics, Herlev Hospital, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark. ml.max.andersen@dadlnet.dk
authors.forename: Marie Louise Max
authors.initials: ML
authors.lastname: Andersen
authors.forename: Morten Arendt
authors.initials: MA
authors.lastname: Rasmussen
authors.forename: Sven
authors.initials: S
authors.lastname: Pörksen
authors.forename: Jannet
authors.initials: J
authors.lastname: Svensson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vikre-Jørgensen
authors.forename: Jane
authors.initials: J
authors.lastname: Thomsen
authors.forename: Niels Thomas
authors.initials: NT
authors.lastname: Hertel
authors.forename: Jesper
authors.initials: J
authors.lastname: Johannesen
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
authors.forename: Jacob Sten
authors.initials: JS
authors.lastname: Petersen
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.forename: Henrik Bindesbøl
authors.initials: HB
authors.lastname: Mortensen
authors.forename: Lotte Brøndum
authors.initials: LB
authors.lastname: Nielsen
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D001323:Autoantibodies / Q000097:blood; D002096:C-Peptide / Q000097:blood; D027682:Cation Transport Proteins / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D027682:Cation Transport Proteins; D006442:Glycated Hemoglobin; D000075703:Zinc Transporter 8; C492522:SLC30A8 protein, human; C517652:hemoglobin A1c protein, human