The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study

Jeffrey P. Krischer, Kristian F. Lynch, Desmond A. Schatz, Jorma Ilonen, Åke Lernmark, William A. Hagopian, Marian J. Rewers, Jin-Xiong She, Olli G. Simell, Jorma Toppari, Anette G. Ziegler, Beena Akolkar, Ezio Bonifacio

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Aims/hypothesis: Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both. Methods: Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter. Results: Autoantibodies appeared in 549/8,503 (6.5%) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1%) and 6 (0.2%) months of age were rare. Of the 549, 43.7% had islet autoantibodies to insulin (IAA) only, 37.7% had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8% had both GADA and IAA only, 1.6% had insulinoma antigen-2 only and 3.1% had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children. Conclusions/interpretation: Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.

Original languageEnglish (US)
Pages (from-to)980-987
Number of pages8
JournalDiabetologia
Volume58
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

Autoantibodies
Incidence
Glutamate Decarboxylase
HLA-DR Antigens
Genotype
HLA-DR3 Antigen
HLA-DR4 Antigen
HLA-DQ Antigens
Insulinoma
Environmental Exposure
Type 1 Diabetes Mellitus
Blood Glucose
Insulin
Antigens

Keywords

  • Autoimmunity
  • Diabetes in young children
  • HLA-DR-DQ genotypes
  • Incidence
  • Islet autoantibodies
  • Type 1 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Krischer, J. P., Lynch, K. F., Schatz, D. A., Ilonen, J., Lernmark, Å., Hagopian, W. A., ... Bonifacio, E. (2015). The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia, 58(5), 980-987. https://doi.org/10.1007/s00125-015-3514-y

The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children : the TEDDY study. / Krischer, Jeffrey P.; Lynch, Kristian F.; Schatz, Desmond A.; Ilonen, Jorma; Lernmark, Åke; Hagopian, William A.; Rewers, Marian J.; She, Jin-Xiong; Simell, Olli G.; Toppari, Jorma; Ziegler, Anette G.; Akolkar, Beena; Bonifacio, Ezio.

In: Diabetologia, Vol. 58, No. 5, 01.05.2015, p. 980-987.

Research output: Contribution to journalArticle

Krischer, JP, Lynch, KF, Schatz, DA, Ilonen, J, Lernmark, Å, Hagopian, WA, Rewers, MJ, She, J-X, Simell, OG, Toppari, J, Ziegler, AG, Akolkar, B & Bonifacio, E 2015, 'The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study', Diabetologia, vol. 58, no. 5, pp. 980-987. https://doi.org/10.1007/s00125-015-3514-y
Krischer, Jeffrey P. ; Lynch, Kristian F. ; Schatz, Desmond A. ; Ilonen, Jorma ; Lernmark, Åke ; Hagopian, William A. ; Rewers, Marian J. ; She, Jin-Xiong ; Simell, Olli G. ; Toppari, Jorma ; Ziegler, Anette G. ; Akolkar, Beena ; Bonifacio, Ezio. / The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children : the TEDDY study. In: Diabetologia. 2015 ; Vol. 58, No. 5. pp. 980-987.
@article{6dd6dffceeca411eaf33686f225b4901,
title = "The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study",
abstract = "Aims/hypothesis: Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both. Methods: Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter. Results: Autoantibodies appeared in 549/8,503 (6.5{\%}) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1{\%}) and 6 (0.2{\%}) months of age were rare. Of the 549, 43.7{\%} had islet autoantibodies to insulin (IAA) only, 37.7{\%} had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8{\%} had both GADA and IAA only, 1.6{\%} had insulinoma antigen-2 only and 3.1{\%} had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children. Conclusions/interpretation: Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.",
keywords = "Autoimmunity, Diabetes in young children, HLA-DR-DQ genotypes, Incidence, Islet autoantibodies, Type 1 diabetes",
author = "Krischer, {Jeffrey P.} and Lynch, {Kristian F.} and Schatz, {Desmond A.} and Jorma Ilonen and {\AA}ke Lernmark and Hagopian, {William A.} and Rewers, {Marian J.} and Jin-Xiong She and Simell, {Olli G.} and Jorma Toppari and Ziegler, {Anette G.} and Beena Akolkar and Ezio Bonifacio",
year = "2015",
month = "5",
day = "1",
doi = "10.1007/s00125-015-3514-y",
language = "English (US)",
volume = "58",
pages = "980--987",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children

T2 - the TEDDY study

AU - Krischer, Jeffrey P.

AU - Lynch, Kristian F.

AU - Schatz, Desmond A.

AU - Ilonen, Jorma

AU - Lernmark, Åke

AU - Hagopian, William A.

AU - Rewers, Marian J.

AU - She, Jin-Xiong

AU - Simell, Olli G.

AU - Toppari, Jorma

AU - Ziegler, Anette G.

AU - Akolkar, Beena

AU - Bonifacio, Ezio

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Aims/hypothesis: Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both. Methods: Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter. Results: Autoantibodies appeared in 549/8,503 (6.5%) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1%) and 6 (0.2%) months of age were rare. Of the 549, 43.7% had islet autoantibodies to insulin (IAA) only, 37.7% had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8% had both GADA and IAA only, 1.6% had insulinoma antigen-2 only and 3.1% had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children. Conclusions/interpretation: Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.

AB - Aims/hypothesis: Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both. Methods: Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter. Results: Autoantibodies appeared in 549/8,503 (6.5%) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1%) and 6 (0.2%) months of age were rare. Of the 549, 43.7% had islet autoantibodies to insulin (IAA) only, 37.7% had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8% had both GADA and IAA only, 1.6% had insulinoma antigen-2 only and 3.1% had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children. Conclusions/interpretation: Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.

KW - Autoimmunity

KW - Diabetes in young children

KW - HLA-DR-DQ genotypes

KW - Incidence

KW - Islet autoantibodies

KW - Type 1 diabetes

UR - http://www.scopus.com/inward/record.url?scp=84939961476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939961476&partnerID=8YFLogxK

U2 - 10.1007/s00125-015-3514-y

DO - 10.1007/s00125-015-3514-y

M3 - Article

C2 - 25660258

AN - SCOPUS:84939961476

VL - 58

SP - 980

EP - 987

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 5

ER -