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Zinc transporter 8 autoantibody (ZnT8A) by ELISA for diagnosing type 1 diabetes among Chinese people

  • Xuan Qiu
  • Cuili Ning
  • Lin Xiao
  • Jianmin Jing
  • Zhenyun Mu
  • Kuanzhi LiuEmail author
Original Article
  • 26 Downloads

Abstract

This study aimed to evaluate the utility of enzyme-linked immunosorbent assay (ELISA) to measure ZnT8A for diagnosing type 1 diabetes among Chinese people. We recruited a group of 95 patients with type 1 diabetes, 130 patients with type 2 diabetes, and 110 subjects without diabetes. We measured ZnT8A level by ELISA and glutamic acid decarboxylase antibody (GADA) level by radioimmunoassay. We collected data on their history-based variables, body mass index (BMI), fasting blood glucose, glycosylated hemoglobin, and lipid levels. 24.2% were positive for ZnT8A in type 1 diabetics, compared to 0.0% in type 2 diabetics and 0.9% in the participants without diabetes (both p < 0.001). And the type 1 diabetics had higher ZnT8A level compared with the latter two groups (both p < 0.001). The frequency of ZnT8A in the “classical” type 1 diabetics was higher than that in patients with latent autoimmune diabetes in adults (45.0 vs. 18.7%, p < 0.05). The frequency/level of ZnT8A was higher in the youngest group (all p < 0.05). The ROC curve area was 0.892. The combination of ZnT8A and GADA increased the diagnostic sensitivity. The ZnT8A level was correlated with the GADA level. ZnT8A-positive type 1 diabetics had younger age at diagnosis (p = 0.022), lower BMI scores (p = 0.016), and more frequent ketosis (p = 0.034) and needed more insulin (p = 0.041) than ZnT8A-negative type 1 diabetics. This study demonstrated the value of ZnT8A in addition to GADA for the diagnosis of type 1 diabetes.

Keywords

Zinc transporter 8 autoantibody Enzyme-linked immunosorbent assay Glutamic acid decarboxylase antibody Type 1 diabetes mellitus Chinese 

Notes

Acknowledgements

We thank all of the participants who made this study possible.

Authors’ contributions

Xuan Qiu: literature search, design, clinical studies, statistical analysis, manuscript preparation; Cuili Ning: clinical studies, data acquisition, manuscript editing; Lin Xiao: data analysis, manuscript editing; Zhenyun Mu: data analysis, statistical analysis, manuscript editing; Kuanzhi Liu: concepts, design, definition of intellectual content, manuscript review. All authors have read and contributed to the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Wenzlau JM, Frisch LM, Gardner TJ, Sarkar S, Hutton JC, Davidson HW. Novel antigens in type 1 diabetes: the importance of ZnT8. Curr Diabetes Rep. 2009;9:105–12.CrossRefGoogle Scholar
  2. 2.
    Fabris M, Zago S, Liguori M, Trevisan MT, Zanatta M, Comici A, et al. Anti-zinc transporter protein 8 autoantibodies significantly improve the diagnostic approach to type 1 diabetes: an Italian multicentre study on paediatric patients. Auto Immun Highlights. 2015;6:17–22.CrossRefGoogle Scholar
  3. 3.
    Gomes KF, Semzezem C, Batista R, Fukui RT, Santos AS, Correia MR, et al. Importance of zinc transporter 8 autoantibody in the diagnosis of type 1 diabetes in Latin Americans. Sci Rep. 2017;7:207.CrossRefGoogle Scholar
  4. 4.
    Hussein H, Ibrahim F, Sobngwi E, Gautier JF, Boudou P. Zinc transporter 8 autoantibodies assessment in daily practice. Clin Biochem. 2017;50:94–6.CrossRefGoogle Scholar
  5. 5.
    Garnier L, Marchand L, Benoit M, Nicolino M, Bendelac N, Wright C, et al. Screening of ZnT8 autoantibodies in the diagnosis of autoimmune diabetes in a large French cohort. Clin Chim Acta. 2018;478:162–5.CrossRefGoogle Scholar
  6. 6.
    Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26(Suppl 1):S5–20.Google Scholar
  7. 7.
    Chinese Medical Association Diabetes Branch. Chinese guidelines for diagnosis and treatment of type 1 diabetes. 1st ed. Beijing: People's Medical Publishing House; 2012.Google Scholar
  8. 8.
    Fourlanos S, Dotta F, Greenbaum CJ, Palmer JP, Rolandsson O, Colman PG, et al. Latent autoimmune diabetes in adults (LADA) should be less latent. Diabetologia. 2005;48:2206–12.CrossRefGoogle Scholar
  9. 9.
    Kawasaki E, Maruyama T, Imagawa A, Awata T, Ikegami H, Uchigata Y, et al. Diagnostic criteria for acute-onset type 1 diabetes mellitus (2012): report of the Committee of Japan Diabetes Society on the research of fulminant and acute-onset type 1 diabetes mellitus. J Diabetes Investig. 2014;5:115–8.CrossRefGoogle Scholar
  10. 10.
    Milicic T, Jotic A, Markovic I, Lalic K, Jeremic V, Lukic L, et al. High risk first degree relatives of type 1 diabetics: an association with increases in CXCR3 (+) T memory cells reflecting an enhanced activity of Th1 autoimmune response. Int J Endocrinol. 2014;2014:1–9.  https://doi.org/10.1155/2014/589360.CrossRefGoogle Scholar
  11. 11.
    Scott-Algara D, Truong LX, Versmisse P, David A, Luong TT, Nguyen NV, et al. Cutting edge: increased NK cell activity in HIV-1-exposed but uninfected Vietnamese intravascular drug users. J Immunol. 2003;171:5663–7.CrossRefGoogle Scholar
  12. 12.
    Kawasaki E. ZnT8 and type 1 diabetes. Endocr J. 2012;59:531–7.CrossRefGoogle Scholar
  13. 13.
    Dunseath G, Ananieva-Jordanova R, Coles R, Powell M, Amoroso M, Furmaniak J, et al. Bridging-type enzyme-linked immunoassay for zinc transporter 8 autoantibody measurements in adult patients with diabetes mellitus. Clin Chim Acta. 2015;447:90–5.CrossRefGoogle Scholar
  14. 14.
    Faccinetti NI, Guerra LL, Penas SA, Iacono RF, Frechtel GD, Trifone L, et al. Characterization of zinc transporter 8 (ZnT8) antibodies in autoimmune diabetic patients from Argentinian population using monomeric, homodimeric, and heterodimeric ZnT8 antigen variants. Eur J Endocrinol. 2016;174:157–65.CrossRefGoogle Scholar
  15. 15.
    Kawasaki E, Uga M, Nakamura K, Kuriya G, Satoh T, Fujishima K, et al. Association between anti-ZnT8 autoantibody specificities and SLC30A8 Arg325Trp variant in Japanese patients with type 1 diabetes. Diabetologia. 2008;51:2299–302.CrossRefGoogle Scholar
  16. 16.
    Shivaprasad C, Mittal R, Dharmalingam M, Kumar PK. Zinc transporter-8 autoantibodies can replace IA-2 autoantibodies as a serological marker for juvenile onset type 1 diabetes in India. Indian J Endocrinol Metab. 2014;18:345–9.CrossRefGoogle Scholar
  17. 17.
    Yang L, Luo S, Huang G, Peng J, Li X, Yan X, et al. The diagnostic value of zinc transporter 8 autoantibody (ZnT8A) for type 1 diabetes in Chinese. Diabetes Metab Res Rev. 2010;26:579–84.CrossRefGoogle Scholar
  18. 18.
    Delitala AP, Pes GM, Fanciulli G, Maioli M, Secchi G, Sanciu F, et al. Organ-specific antibodies in LADA patients for the prediction of insulin dependence. Endocr Res. 2016;41:207–12.CrossRefGoogle Scholar
  19. 19.
    Sørgjerd EP, Skorpen F, Kvaløy K, Midthjell K, Grill V. Prevalence of ZnT8 antibody in relation to phenotype and SLC30A8 polymorphism in adult autoimmune diabetes: results from the HUNT study, Norway. Autoimmunity. 2013;46:74–9.CrossRefGoogle Scholar
  20. 20.
    Lampasona V, Petrone A, Tiberti C, Capizzi M, Spoletini M, di PS, et al. Zinc transporter 8 antibodies complement GAD and IA-2 antibodies in the identification and characterization of adult-onset autoimmune diabetes: non insulin requiring autoimmune diabetes (NIRAD) 4. Diabetes Care. 2010;33:104–8.CrossRefGoogle Scholar
  21. 21.
    Vaziri-Sani F, Oak S, Radtke J, Lernmark K, Lynch K, Agardh CD, et al. ZnT8 autoantibody titers in type 1 diabetes patients decline rapidly after clinical onset. Autoimmunity. 2010;43:598–606.CrossRefGoogle Scholar
  22. 22.
    Juusola M, Parkkola A, Härkönen T, Siljander H, Ilonen J, Åkerblom HK, et al. Positivity for zinc transporter 8 autoantibodies at diagnosis is subsequently associated with reduced β-cell function and higher exogenous insulin requirement in children and adolescents with type 1 diabetes. Diabetes Care. 2016;39:118–21.CrossRefGoogle Scholar
  23. 23.
    Vermeulen I, Weets I, Asanghanwa M, Ruige J, Van Gaal L, Mathieu C, et al. Contribution of antibodies against IA-2β and zinc transporter 8 to classification of diabetes diagnosed under 40 years of age. Diabetes Care. 2011;34:1760–5.CrossRefGoogle Scholar
  24. 24.
    Wenzlau JM, Liu Y, Yu L, Moua O, Fowler KT, Rangasamy S, et al. A common nonsynonymous single nucleotide polymorphism in the SLC30A8 gene determines ZnT8 autoantibody specificity in type 1 diabetes. Diabetes. 2008;57:2693–7.CrossRefGoogle Scholar
  25. 25.
    Lampasona V, Schlosser M, Mueller PW, Williams AJ, Wenzlau JM, Hutton JC, et al. Diabetes antibody standardization program: first proficiency evaluation of assays for autoantibodies to zinc transporter 8. Clin Chem. 2011;57:1693–702.CrossRefGoogle Scholar
  26. 26.
    Wenzlau JM, Moua O, Sarkar SA, Yu L, Rewers M, Eisenbarth GS, et al. SlC30A8 is a major target of humoral autoimmunity in type 1 diabetes and a predictive marker in prediabetes. Ann N Y Acad Sci. 2008;1150:256–9.CrossRefGoogle Scholar
  27. 27.
    Huang G, Xiang Y, Pan L, Li X, Luo S, Zhou Z. Zinc transporter 8 autoantibody (ZnT8A) could help differentiate latent autoimmune diabetes in adults (LADA) from phenotypic type 2 diabetes mellitus. Diabetes Metab Res Rev. 2013;29:363–8.CrossRefGoogle Scholar
  28. 28.
    Mbanya A, Ngandeu A, Kamwa V, Donfack OT, Lontchi É, Leke R, et al. Metabolic features associated with positivity to ZnT8 autoantibody in sub-Saharan African young-onset diabetes patients. Diabetes Metab. 2016;42:204–6.CrossRefGoogle Scholar
  29. 29.
    Buzzetti R, Spoletini M, Zampetti S, Campagna G, Marandola L, Panimolle F, et al. Tyrosine phosphatase-related islet antigen 2 (256-760) autoantibodies, the only marker of islet autoimmunity that increases by increasing the degree of BMI in obese subjects with type 2 diabetes. Diabetes Care. 2015;38:513–20.CrossRefGoogle Scholar

Copyright information

© Research Society for Study of Diabetes in India 2018

Authors and Affiliations

  • Xuan Qiu
    • 1
  • Cuili Ning
    • 2
  • Lin Xiao
    • 3
    • 4
  • Jianmin Jing
    • 5
  • Zhenyun Mu
    • 6
  • Kuanzhi Liu
    • 1
    Email author
  1. 1.Department of EndocrinologyThird Hospital of Hebei Medical UniversityShijiazhuangPeople’s Republic of China
  2. 2.Department of EndocrinologySecond Hospital of ShijiazhuangShijiazhuangChina
  3. 3.Department of PhysiologyHebei Medical UniversityShijiazhuangChina
  4. 4.Hebei Key Laboratory of Animal ScienceHebei Medical UniversityShijiazhuangChina
  5. 5.Department of Nuclear MedicineThird Hospital of Hebei Medical UniversityShijiazhuangChina
  6. 6.Department of Epidemiology and Health Statistics, School of Public HealthHeibei Medical UniversityShijiazhuangChina

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