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Contribution of antibodies against 1A-2β and zinc transporter 8 to classification of diabetes diagnosed under 40 years of age

Ilse Vermeulen, Ilse Weets, Milca Asanghanwa, Johannes Ruige UGent, Luc Van Gaal, Chantal Mathieu, Bart Keymeulen, Vito Lampasona, Janet M Wenzlau and John C Hutton, et al. (2011) DIABETES CARE. 34(8). p.1760-1765
abstract
OBJECTIVE-We investigated whether measuring autoantibodies against zinc transporter 8 (ZnT8A) and IA-2 beta (IA-2 beta A) may improve classification of new-onset type 1 diabetic patients based on detection of autoantibodies against insulin (IAA), GAD (GADA), and IA-2 (IA-2A). In addition, we studied the correlation of IA-2 beta A and ZnT8A with other biological and demographic variables. RESEARCH DESIGN AND METHODS-Circulating autoantibodies were determined by liquid-phase radiobinding assays from 761 healthy control subjects and 655 new-onset (<1 week insulin) diabetic patients (aged 0-39 years) with clinical type 1 diabetes phenotype consecutively recruited by the Belgian Diabetes Registry. RESULTS-At diagnosis, IA-2 beta A and ZnT8A prevalences were 41 and 58%, respectively. In IAA-negative, GADA-negative, and IA-2A negative patients, one IA-2 beta A positive and eleven ZnT8A-positive individuals were identified at the expense of eight and seven additional positive control subjects (1%), respectively, for each test. ZnT8A or IA-2 beta A screening increased (P < 0.001; McNemar) the number of patients with >= 2 antibodies both under (from 78 to 87% for ZnT8A and 82% for IA-2 beta A) and above age 15 (from 51 to 63% for ZnT8A and 56% for IA-2 beta A) versus 0% in control subjects. IA-2 beta A and ZnT8A were preferentially associated with IA-2A, and with younger age at diagnosis. Unlike ZnT8A, IA-2 beta A levels were positively correlated with HLA-DQ8 and negatively with HLA-DQ2. ZnT8A could replace IAA for classification of patients above age 10 without loss of sensitivity or specificity. CONCLUSIONS-ZnT8A, and to a lesser degree IA-2 beta A, may usefully complement GADA, IA-2A, and IAA for classifying insulin-treated diabetes under age 40 years.
Please use this url to cite or link to this publication:
author
organization
alternative title
Contribution of antibodies against 1A-2 beta and zinc transporter 8 to classification of diabetes diagnosed under 40 years of age
year
type
journalArticle (original)
publication status
published
subject
keyword
CLINICAL ONSET, PROTEIN-TYROSINE-PHOSPHATASE, TYPE-1, MELLITUS, AUTOANTIBODIES, ZNT8, RISK, IDENTIFICATION, AUTOANTIGEN, REGISTRIES
journal title
DIABETES CARE
Diabetes Care
volume
34
issue
8
pages
1760 - 1765
Web of Science type
Article
Web of Science id
000294035400015
JCR category
ENDOCRINOLOGY & METABOLISM
JCR impact factor
8.087 (2011)
JCR rank
8/121 (2011)
JCR quartile
1 (2011)
ISSN
0149-5992
DOI
10.2337/dc10-2268
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2021536
handle
http://hdl.handle.net/1854/LU-2021536
date created
2012-02-07 09:27:24
date last changed
2012-02-13 16:58:54
@article{2021536,
  abstract     = {OBJECTIVE-We investigated whether measuring autoantibodies against zinc transporter 8 (ZnT8A) and IA-2 beta (IA-2 beta A) may improve classification of new-onset type 1 diabetic patients based on detection of autoantibodies against insulin (IAA), GAD (GADA), and IA-2 (IA-2A). In addition, we studied the correlation of IA-2 beta A and ZnT8A with other biological and demographic variables. 
RESEARCH DESIGN AND METHODS-Circulating autoantibodies were determined by liquid-phase radiobinding assays from 761 healthy control subjects and 655 new-onset ({\textlangle}1 week insulin) diabetic patients (aged 0-39 years) with clinical type 1 diabetes phenotype consecutively recruited by the Belgian Diabetes Registry. 
RESULTS-At diagnosis, IA-2 beta A and ZnT8A prevalences were 41 and 58\%, respectively. In IAA-negative, GADA-negative, and IA-2A negative patients, one IA-2 beta A positive and eleven ZnT8A-positive individuals were identified at the expense of eight and seven additional positive control subjects (1\%), respectively, for each test. ZnT8A or IA-2 beta A screening increased (P {\textlangle} 0.001; McNemar) the number of patients with {\textrangle}= 2 antibodies both under (from 78 to 87\% for ZnT8A and 82\% for IA-2 beta A) and above age 15 (from 51 to 63\% for ZnT8A and 56\% for IA-2 beta A) versus 0\% in control subjects. IA-2 beta A and ZnT8A were preferentially associated with IA-2A, and with younger age at diagnosis. Unlike ZnT8A, IA-2 beta A levels were positively correlated with HLA-DQ8 and negatively with HLA-DQ2. ZnT8A could replace IAA for classification of patients above age 10 without loss of sensitivity or specificity. 
CONCLUSIONS-ZnT8A, and to a lesser degree IA-2 beta A, may usefully complement GADA, IA-2A, and IAA for classifying insulin-treated diabetes under age 40 years.},
  author       = {Vermeulen, Ilse and Weets, Ilse and Asanghanwa, Milca and Ruige, Johannes and Van Gaal, Luc and Mathieu, Chantal and Keymeulen, Bart and Lampasona, Vito and Wenzlau, Janet M and Hutton, John C and Pipeleers, Daniel G and Gorus, Frans K},
  issn         = {0149-5992},
  journal      = {DIABETES CARE},
  keyword      = {CLINICAL ONSET,PROTEIN-TYROSINE-PHOSPHATASE,TYPE-1,MELLITUS,AUTOANTIBODIES,ZNT8,RISK,IDENTIFICATION,AUTOANTIGEN,REGISTRIES},
  language     = {eng},
  number       = {8},
  pages        = {1760--1765},
  title        = {Contribution of antibodies against 1A-2\ensuremath{\beta} and zinc transporter 8 to classification of diabetes diagnosed under 40 years of age},
  url          = {http://dx.doi.org/10.2337/dc10-2268},
  volume       = {34},
  year         = {2011},
}

Chicago
Vermeulen, Ilse, Ilse Weets, Milca Asanghanwa, Johannes Ruige, Luc Van Gaal, Chantal Mathieu, Bart Keymeulen, et al. 2011. “Contribution of Antibodies Against 1A-2β and Zinc Transporter 8 to Classification of Diabetes Diagnosed Under 40 Years of Age.” Diabetes Care 34 (8): 1760–1765.
APA
Vermeulen, I., Weets, I., Asanghanwa, M., Ruige, J., Van Gaal, L., Mathieu, C., Keymeulen, B., et al. (2011). Contribution of antibodies against 1A-2β and zinc transporter 8 to classification of diabetes diagnosed under 40 years of age. DIABETES CARE, 34(8), 1760–1765.
Vancouver
1.
Vermeulen I, Weets I, Asanghanwa M, Ruige J, Van Gaal L, Mathieu C, et al. Contribution of antibodies against 1A-2β and zinc transporter 8 to classification of diabetes diagnosed under 40 years of age. DIABETES CARE. 2011;34(8):1760–5.
MLA
Vermeulen, Ilse, Ilse Weets, Milca Asanghanwa, et al. “Contribution of Antibodies Against 1A-2β and Zinc Transporter 8 to Classification of Diabetes Diagnosed Under 40 Years of Age.” DIABETES CARE 34.8 (2011): 1760–1765. Print.