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Early prediction of autoimmune (type 1) diabetes

Regnell, Simon E. LU and Lernmark, Åke LU (2017) In Diabetologia 60(8). p.1370-1381
Abstract

Underlying type 1 diabetes is a genetic aetiology dominated by the influence of specific HLA haplotypes involving primarily the class II DR-DQ region. In genetically predisposed children with the DR4-DQ8 haplotype, exogenous factors, yet to be identified, are thought to trigger an autoimmune reaction against insulin, signalled by insulin autoantibodies as the first autoantibody to appear. In children with the DR3-DQ2 haplotype, the triggering reaction is primarily against GAD signalled by GAD autoantibodies (GADA) as the first-appearing autoantibody. The incidence rate of insulin autoantibodies as the first-appearing autoantibody peaks during the first years of life and declines thereafter. The incidence rate of GADA as the... (More)

Underlying type 1 diabetes is a genetic aetiology dominated by the influence of specific HLA haplotypes involving primarily the class II DR-DQ region. In genetically predisposed children with the DR4-DQ8 haplotype, exogenous factors, yet to be identified, are thought to trigger an autoimmune reaction against insulin, signalled by insulin autoantibodies as the first autoantibody to appear. In children with the DR3-DQ2 haplotype, the triggering reaction is primarily against GAD signalled by GAD autoantibodies (GADA) as the first-appearing autoantibody. The incidence rate of insulin autoantibodies as the first-appearing autoantibody peaks during the first years of life and declines thereafter. The incidence rate of GADA as the first-appearing autoantibody peaks later but does not decline. The first autoantibody may variably be followed, in an apparently non-HLA-associated pathogenesis, by a second, third or fourth autoantibody. Although not all persons with a single type of autoantibody progress to diabetes, the presence of multiple autoantibodies seems invariably to be followed by loss of functional beta cell mass and eventually by dysglycaemia and symptoms. Infiltration of mononuclear cells in and around the islets appears to be a late phenomenon appearing in the multiple-autoantibody-positive with dysglycaemia. As our understanding of the aetiology and pathogenesis of type 1 diabetes advances, the improved capability for early prediction should guide new strategies for the prevention of type 1 diabetes.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autoimmunity, Beta cells, diabetes mellitus, Glutamic acid decarboxylase autoantibodies, HLA, Insulin autoantibodies, Insulin secretion, Insulinoma-associated antingen-2 autoantibodies, Next-generation sequencing, Review, Type 1 diabetes, ZnT8 autoantibodies
in
Diabetologia
volume
60
issue
8
pages
1370 - 1381
publisher
Springer Verlag
external identifiers
  • scopus:85019673045
  • wos:000404354900002
ISSN
0012-186X
DOI
10.1007/s00125-017-4308-1
language
English
LU publication?
yes
id
c3eb31a0-7449-4297-9f0f-280578d7fc25
date added to LUP
2017-06-21 16:05:22
date last changed
2018-01-07 12:08:38
@article{c3eb31a0-7449-4297-9f0f-280578d7fc25,
  abstract     = {<p>Underlying type 1 diabetes is a genetic aetiology dominated by the influence of specific HLA haplotypes involving primarily the class II DR-DQ region. In genetically predisposed children with the DR4-DQ8 haplotype, exogenous factors, yet to be identified, are thought to trigger an autoimmune reaction against insulin, signalled by insulin autoantibodies as the first autoantibody to appear. In children with the DR3-DQ2 haplotype, the triggering reaction is primarily against GAD signalled by GAD autoantibodies (GADA) as the first-appearing autoantibody. The incidence rate of insulin autoantibodies as the first-appearing autoantibody peaks during the first years of life and declines thereafter. The incidence rate of GADA as the first-appearing autoantibody peaks later but does not decline. The first autoantibody may variably be followed, in an apparently non-HLA-associated pathogenesis, by a second, third or fourth autoantibody. Although not all persons with a single type of autoantibody progress to diabetes, the presence of multiple autoantibodies seems invariably to be followed by loss of functional beta cell mass and eventually by dysglycaemia and symptoms. Infiltration of mononuclear cells in and around the islets appears to be a late phenomenon appearing in the multiple-autoantibody-positive with dysglycaemia. As our understanding of the aetiology and pathogenesis of type 1 diabetes advances, the improved capability for early prediction should guide new strategies for the prevention of type 1 diabetes.</p>},
  author       = {Regnell, Simon E. and Lernmark, Åke},
  issn         = {0012-186X},
  keyword      = {Autoimmunity,Beta cells, diabetes mellitus,Glutamic acid decarboxylase autoantibodies,HLA,Insulin autoantibodies,Insulin secretion,Insulinoma-associated antingen-2 autoantibodies,Next-generation sequencing,Review,Type 1 diabetes,ZnT8 autoantibodies},
  language     = {eng},
  month        = {05},
  number       = {8},
  pages        = {1370--1381},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Early prediction of autoimmune (type 1) diabetes},
  url          = {http://dx.doi.org/10.1007/s00125-017-4308-1},
  volume       = {60},
  year         = {2017},
}