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

PLoS One. 2013 Jun 5;8(6):e64632. doi: 10.1371/journal.pone.0064632. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Alleles
  • Autoantibodies / blood
  • C-Peptide / blood
  • Cation Transport Proteins / immunology
  • Child
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Glycated Hemoglobin / metabolism
  • Humans
  • Insulin-Secreting Cells / pathology
  • Insulin-Secreting Cells / physiology*
  • Male
  • Models, Biological
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Risk
  • Zinc Transporter 8

Substances

  • Autoantibodies
  • C-Peptide
  • Cation Transport Proteins
  • Glycated Hemoglobin A
  • SLC30A8 protein, human
  • Zinc Transporter 8
  • hemoglobin A1c protein, human

Grants and funding

The present study is a part of an industrial PhD project funded by Novo Nordisk A/S and the Danish Agency for Science, Technology and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.