Journal of the Formosan Medical Association
Volume 108, Issue 11 , Pages 856-861, November 2009

β-Cell Autoantibodies and Their Function in Taiwanese Children With Type 1 Diabetes Mellitus

  • Yi-Ching Tung

      Affiliations

    • Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
    • ,
  • Mei-Huei Chen

      Affiliations

    • Department of Pediatrics, Yung Ho Branch of Cardinal Tien Hospital, Taipei, Taiwan
    • ,
  • Cheng-Ting Lee

      Affiliations

    • Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
    • ,
  • Wen-Yu Tsai

      Affiliations

    • Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Wen-Yu Tsai, Department of Pediatrics, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan

Received 10 July 2008; received in revised form 3 December 2008; accepted 29 June 2009.

Article Outline

Background/Purpose

To understand the importance of autoimmunity in the development of type 1 diabetes in Taiwanese children, we evaluated the presence of β-cell autoantibodies and their correlation with residual β-cell function.

Methods

From 1989 to 2006, 157 Taiwanese children with newly diagnosed type 1 diabetes were enrolled in this study. We determined the presence of β-cell autoantibodies, such as glutamic acid decarboxylase autoantibodies (GADAs), insulinoma antigen 2 autoantibodies (IA-2As), and insulin autoantibodies (IAAs). A 6-minute glucagon test was also performed at diagnosis.

Results

At diagnosis, 73% of children tested positive for GADAs, 76% for IA-2As and 21% for IAAs. Ninety-two percent of them had at least one of the β-cell autoantibodies detected. Positivity for IAAs was more frequent in patients younger than 5 years than in those older than 5 years (45% vs. 13%). Using multiple regression analysis, the presence of GADAs or IAAs, or age of onset of these patients was an independent factor for residual β-cell function. Younger patients and those with GADAs had less residual β-cell function at disease onset, whereas those with IAAs had more insulin reserve.

Conclusion

Autoimmunity plays an important role in the pathogenesis of type 1 diabetes in Taiwanese children, and the presence of IAAs tends to be more common in younger children.

Key Words:  autoantibodies , C-peptide , glucagon test , type 1 diabetes mellitus

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References 

  1. Wei JN , Sung FC , Lin CC , et al.   National surveillance for type 2 diabetes mellitus in Taiwanese children . JAMA . 2003;290:1345–1350
  2. Tseng CH , Tseng CP , Chong CK , et al.   Increasing incidence of diagnosed type 2 diabetes in Taiwan: analysis of data from a national cohort . Diabetologia . 2006;49:1755–1760
  3. Tseng CH . Incidence of type 1 diabetes in children aged 0–14 years during 1992–1998 in Taiwan . Acta Pediatr . 2008;97:392–393
  4. Esienbarth GS . Type 1 diabetes: a chronic autoimmune disease . N Engl J Med . 1986;314:1360–1368
  5. Baekkeskov S , Aanstoot HJ , Christgau S , et al.   Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase . Nature . 1990;347:151–156
  6. Lan MS , Wasserfall C , Maclaren NK , et al.   IA-2, a transmembrane protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus . Proc Natl Acad Sci USA . 1996;93:6367–6370
  7. Palmer JP . Insulin autoantibodies: their role in the pathogenesis of IDDM . Diabetes Metab Rev . 1987;3:1005–1015
  8. Hagopian WA , Sanjeevi CB , Kockum I , et al.   Glutamate decarboxylase-, insulin-and islet cell-antibodies and HLA typing to detect diabetes in a general population-based study of Swedish children . J Clin Invest . 1995;95:1501–1511
  9. Bingley PJ , Bonifacio E , Williams AJ , et al.   Prediction of IDDM in the general population: strategies based on combinations of autoantibody markers . Diabetes . 1997;46:1701–1710
  10. Gorus FK , Goubert P , Semakula C , et al.   IA-2-autoantibodies complement GAD65-autoantibodies in new-onset IDDM patients and help predict impending diabetes in their siblings. The Belgian Diabetes Registry . Diabetologia . 1997;40:95–99
  11. Diabetes Epidemiology Research International Group  . Geographic pattern of childhood insulin-dependent diabetes mellitus . Diabetes . 1988;37:1113–1119
  12. Park Y . Why is type 1 diabetes uncommon in Asia . Ann N Y Acad Sci . 2006;1079:31–40
  13. Park Y , Lee H , Takino H , et al.   Evaluation of the efficacy of the combination of multiple autoantibodies to islet-specific antigens in Korean type 1 diabetic patients . Acta Diabetol . 2001;38:51–56
  14. Sera Y , Kawasaki E , Abiru N , et al.   Autoantibodies to multiple islet autoantigens in patients with abrupt onset type 1 diabetes and diabetes diagnosed with urinary glucose screening . J Autoimmun . 1999;13:257–265
  15. Ko GTC , Chan JCN , Yeung VTF , et al.   Autoantibodies to glutamic acid decarboxylase in young Chinese diabetic patients . Ann Clin Biochem . 1998;35:761–767
  16. Ng WY , Lee YS , Todd AL , et al.   Tyrosine phosphatase-like protein (IA-2) and glutamic acid decarboxylase (GAD65) autoantibodies: a study of Chinese patients with diabetes mellitus . Autoimmunity . 2002;35:119–124
  17. Chang YH , Shiau MY , Tsai ST , et al.   Autoantibodies against IA-2, GAD, and topoisomerase II in type 1 diabetic patients . Biochem Biophys Res Commun . 2004;320:802–809
  18. Chen BH , Chung SB , Chiang W , et al.   GAD65 antibody prevalence and association with thyroid antibodies, HLADR in Chinese children with type a diabetes mellitus . Diabetes Res Clin Pract . 2001;54:27–32
  19. Wang JP , Zhou ZG , Lin J , et al.   Islet autoantibodies are associated with HLA-DQ genotypes in Han Chinese patients with type 1 diabetes and their relatives . Tissue Antigens . 2007;70:369–375
  20. The 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 . 1997;20:1183–1197
  21. Tanner JM , Whitehouse RH . Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty . Arch Dis Child . 1976;51:170–179
  22. Tung YC , Lee JS , Tsai WY , et al.   Evaluation of β-cell function in diabetic Taiwanese children using a 6-minute glucagon test . Eur J Pediatr . 2008;167:801–805
  23. Bingley PJ , Bonifacio E , Mueller PW . Diabetes Antibody Standardization Program: first assay proficiency evaluation . Diabetes . 2003;52:1128–1136
  24. Sabbah E , Savoka K , Kulmala P , et al.   Diabetes-associated autoantibodies in relation to clinical characteristics and natural course in children with newly diagnosed type 1 diabetes . J Clin Endocrinol Metab . 1999;84:1534–1539
  25. Graham J , Hagopian WA , Kockum I , et al.   Diabetes Incidence in Sweden Study Group; Swedish Childhood Diabetes Study Group: genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes . Diabetes . 2002;51:1346–1355
  26. Feeney SJ , Myers MA , Mackay IR , et al.   Evaluation of ICA512As in combination with other islet cell autoantibodies at the onset of IDDM . Diabetes Care . 1997;20:1403–1407
  27. Bilbao JR , Rica I , Vázquez JA , et al.   Influence of sex and age at onset on autoantibodies against insulin, GAD65 and IA2 in recent onset type 1 diabetic patients . Horm Res . 2000;54:181–185
  28. Sochett EB , Daneman D , Clarson C , et al.   Factors affecting and patterns of residual insulin secretion during the first year of type 1 (insulin-dependent) diabetes mellitus in children . Diabetologia . 1987;30:453–459
  29. Kimpimaki T , Kulmala P , Savola K , et al.   Natural history of β-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population . J Clin Endocrinol Metab . 2002;87:4572–4579
  30. Stene LC , Witsø E , Torjesen PA , et al.   Islet autoantibody development during follow-up of high-risk children from the general Norwegian population from three months of age: design and early results from the MIDIA study . J Autoimmun . 2007;9:44–51
  31. Hoeldtke RD , Bryner KD , Horvath GG , et al.   Antibodies to GAD and glycemic control in recent-onset IDDM . Diabetes Care . 1997;20:1900–1903
  32. Petersen JS , Dyrberg T , Karlsen AE , et al.   Glutamic acid decarboxylase (GAD65) autoantibodies in prediction of beta-cell function and remission in recent-onset IDDM after cyclosporin treatment. The Canadian-European Randomized Control Trial Group . Diabetes . 1994;43:1291–1296
  33. Decochez K , Keymeulen B , Somers G , et al.   Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset . Diabetes Care . 2000;23:1072–1078

PII: S0929-6646(09)60417-4

doi:10.1016/S0929-6646(09)60417-4

Journal of the Formosan Medical Association
Volume 108, Issue 11 , Pages 856-861, November 2009

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