Abstract
Objectives
Type 1 diabetes is an autoimmune disease. Its most important immunologic markers are pancreatic beta-cell autoantibodies. This study aimed to determine diabetes mellitus antibodies frequency among children and adolescents with type 1 diabetes.
Methods
This descriptive study evaluated the frequency of four diabetes autoantibodies (glutamic acid decarboxylase 65 autoantibodies [GADA], islet cell autoantibodies [ICA], insulin autoantibodies [IAA], tyrosine phosphatase–like insulinoma antigen-2 antibodies [IA-2A]) and their serum level in children and adolescents diagnosed with type 1 diabetes mellitus at the diabetes department of Bou-Ali-Sina Hospital and Baghban Clinic, Sari, Iran, from March 2012 to March 2018. The relationship between the level of different antibodies and age, gender, and diabetes duration were determined. A two-sided p value less than 0.05 indicated statistical significance.
Results
One hundred forty-two eligible patient records were screened. The average age at diabetes diagnosis was 4.2 ± 4.4 years. The median duration of diabetes was 34.0 (12.7–69.7) months. 53.5% of patients were female, and 81.7% of them had at least one positive autoantibody, and ICA in 66.2%, GADA in 56.3%, IA-2A in 40.1%, and IAA in 21.8% were positive. The type of the autoantibodies and their serum level was similar between females and males but there was a higher rate of positive autoantibodies in females. The level of IA-2A and ICA were in positive and weak correlation with age at diagnosis.
Conclusions
More than 80% of pediatric and adolescent patients with type 1 diabetes were autoantibody-positive. ICA and GADA were the most frequently detected autoantibodies. The presence of antibodies was significantly higher in females.
Funding source: Mazandran University of Medical Sciences
- Research funding: The source of financial grants and other funding was supported by Research Vice Chancellor of Mazandaran University of Medical Sciences. 
- Author contributions: Zamanfar D. conceptualized and designed the study; Aarabi M. designed and analyzed the data; Amini M. collected the data and Zamanfar D. and Monajati M. drafted the initial manuscript. All authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. 
- Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication. 
- Informed consent: Informed consent was obtained from all individuals included in this study. 
- Ethical approval: The study was approved by the Ethics Committee of the Mazandaran University of Medical Science. Data were collected anonymously. All the principles, outlined in the Helsinki Declaration, were followed during the investigation. 
References
1. Bluestone, JA, Herold, K, Eisenbarth, G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature 2010;464:1293. https://doi.org/10.1038/nature08933.Suche in Google Scholar
2. Simmons, KM, Youngkin, E, Alkanani, A, Miao, D, McDaniel, K, Yu, L, et al. Screening children for type 1 diabetes-associated antibodies at community health fairs. Pediatr Diabetes 2019;20:909–14. https://doi.org/10.1111/pedi.12902.Suche in Google Scholar
3. Raab, J, Haupt, F, Scholz, M, Matzke, C, Warncke, K, Lange, K, et al. Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: design and initial results of the Fr1da study. BMJ Open 2016;6:e011144. https://doi.org/10.1136/bmjopen-2016-011144.Suche in Google Scholar
4. Watkins, RA, Evans-Molina, C, Blum, JS, DiMeglio, LA. Established and emerging biomarkers for the prediction of type 1 diabetes: a systematic review. Transl Res 2014;164:110–21. https://doi.org/10.1016/j.trsl.2014.02.004.Suche in Google Scholar
5. Atkinson, MA, Maclaren, NK. The pathogenesis of insulin-dependent diabetes mellitus. N Engl J Med 1994;331:1428–36.10.1056/NEJM199411243312107Suche in Google Scholar
6. Ellis, TM, Schatz, DA, Ottendorfer, EW, Lan, MS, Wasserfall, C, Salisbury, PJ, et al. The relationship between humoral and cellular immunity to IA-2 in IDDM. Diabetes 1998;47:566–9. https://doi.org/10.2337/diabetes.47.4.566.Suche in Google Scholar
7. Bingley, PJ. Clinical applications of diabetes antibody testing. J Clin Endocrinol Metab 2010;95:25–33. https://doi.org/10.1210/jc.2009-1365.Suche in Google Scholar
8. Ziegler, AG, Bonifacio, E. Group tB-BS. Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia 2012;55:1937–43. https://doi.org/10.1007/s00125-012-2472-x.Suche in Google Scholar
9. Atkinson, MA, Eisenbarth, GS, Michels, AW. Type 1 diabetes. Lancet 2014;383:69–82. https://doi.org/10.1016/s0140-6736(13)60591-7.Suche in Google Scholar
10. Zamanfar, D, Yazdani, P, Aarabi, M, Pournorooz, H. The prevalence of type 1 diabetes in children of Mazandaran province. Iran J Health Sci 2018;6:1–10. https://doi.org/10.18502/jhs.v6i2.45.Suche in Google Scholar
11. Mayer-Davis, EJ, Kahkoska, AR, Jefferies, C, Dabelea, D, Balde, N, Gong, CX, et al. ISPAD clinical practice consensus guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes 2018;19:7–19. https://doi.org/10.1111/pedi.12773.Suche in Google Scholar
12. Wolfsdorf, JI, Glaser, N, Agus, M, Fritsch, M, Hanas, R, Rewers, A, et al. ISPAD clinical practice consensus guidelines 2018: diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes 2018;19:155–77. https://doi.org/10.1111/pedi.12701.Suche in Google Scholar
13. Hattersley, AT, Greeley, SAW, Polak, M, Rubio-Cabezas, O, Njølstad, PR, Mlynarski, W, et al. ISPAD clinical practice consensus guidelines 2018: the diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2018;27:47–63. https://doi.org/10.1111/pedi.12772.Suche in Google Scholar
14. Mayer-Davis, EJ, Lawrence, JM, Dabelea, D, Divers, J, Isom, S, Dolan, L, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002–2012. N Engl J Med 2017;376:1419–29. https://doi.org/10.1056/nejmoa1610187.Suche in Google Scholar
15. Mirbolouk, M, Derakhshan, A, Charkhchi, P, Guity, K, Azizi, F, Hadaegh, F. Incidence and predictors of early adulthood pre-diabetes/type 2 diabetes, among Iranian adolescents: the Tehran lipid and glucose study. Pediatr Diabetes 2016;17:608–16. https://doi.org/10.1111/pedi.12343.Suche in Google Scholar
16. Unnikrishnan, AG, Bhatia, E, Bhatia, V, Bhadada, SK, Sahay, RK, Kannan, A, et al. Type 1 diabetes versus type 2 diabetes with onset in persons younger than 20 years of age. Ann N Y Acad Sci 2008;1150:239–44. https://doi.org/10.1196/annals.1447.056.Suche in Google Scholar
17. Damanhouri, LH, Dromey, JA, Christie, MR, Nasrat, HA, Ardawi, MS, Robins, RA, et al. Autoantibodies to GAD and IA-2 in Saudi Arabian diabetic patients. Diabet Med 2005;22:448–52. https://doi.org/10.1111/j.1464-5491.2005.01438.x.Suche in Google Scholar
18. Wan Nazaimoon, WM, Faridah, I, Singaraveloo, M, Ismail, IS, Wan Mohamad, WB, Letchuman, R, et al. Prevalence of glutamic acid decarboxylase antibodies amongst young Malaysian diabetics. Diabetes Res Clin Pract 1999;43:59–66. https://doi.org/10.1016/s0168-8227(98)00108-9.Suche in Google Scholar
19. Lutale, JJK, Thordarson, H, Holm, PI, Eide, GE, Vetvik, K. Islet cell autoantibodies in African patients with type 1 and type 2 diabetes in Dar es Salaam Tanzania: a cross sectional study. J Autoimmune Dis 2007;4. https://doi.org/10.1186/1740-2557-4-4.Suche in Google Scholar
20. Tung, YC, Chen, MH, Lee, CT, Tsai, WY. Beta-cell autoantibodies and their function in Taiwanese children with type 1 diabetes mellitus. J Formos Med Assoc 2009;108:856–61. https://doi.org/10.1016/s0929-6646(09)60417-4.Suche in Google Scholar
21. Panz, VR, Kalk, WJ, Zouvanis, M, Joffe, BI. Distribution of autoantibodies to glutamic acid decarboxylase across the spectrum of diabetes mellitus seen in South Africa. Diabet Med 2000;17:524–7. https://doi.org/10.1046/j.1464-5491.2000.00324.x.Suche in Google Scholar PubMed
22. Thunander, M, Petersson, C, Jonzon, K, Fornander, J, Ossiansson, B, Torn, C, et al. Incidence of type 1 and type 2 diabetes in adults and children in Kronoberg, Sweden. Diabetes Res Clin Pract 2008;82:247–55. https://doi.org/10.1016/j.diabres.2008.07.022.Suche in Google Scholar PubMed
23. Hagopian, WA, Sanjeevi, CB, Kockum, I, Landin-Olsson, M, Karlsen, AE, Sundkvist, G, 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;95:1505–11. https://doi.org/10.1172/jci117822.Suche in Google Scholar
24. Marandi, LY, Rajaii, M, Aliasgarzadeh, A, Sadeghi-Bazargani, H. Islet cell autoantibodies in patients younger than 20 years of age with recently diagnosed diabetes in Northwest of Iran. Int J Diabetes Dev C 2011;31:70–5. https://doi.org/10.1007/s13410-011-0015-5.Suche in Google Scholar
25. Keihani, MD, Nakhjavani, M. The role of GAD65 autoantibody in diabetes mellitus and their first-degree relatives and comparison with healthy persons. Tehran Univ Med J 2001;59:21–5.Suche in Google Scholar
26. Aljabri, KS, Bokhari, SA, Alqurashi, K. The prevalence of autoantibodies in Saudish patients with type1 diabetes mellitus. OJEMD 2013;3:132–6. https://doi.org/10.4236/ojemd.2013.32020.Suche in Google Scholar
27. Howson, JMM, Stevens, H, Smyth, DJ, Walker, NM, Chandler, KA, Bingley, PJ, et al. Evidence that HLA class I and II associations with type 1 diabetes, autoantibodies to GAD and autoantibodies to IA-2, are distinct. Diabetes 2011;60:2635–44. https://doi.org/10.2337/db11-0131.Suche in Google Scholar PubMed PubMed Central
28. Glowinska-Olszewska, B, Michalak, J, Luczynski, W, Del Pilar Larosa, M, Chen, S, Furmaniak, J, et al. Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes. J Pediatr Endocrinol Metab 2016;29:647–56. https://doi.org/10.1515/jpem-2015-0190.Suche in Google Scholar PubMed
29. Dayal, D, Samprati, M, Kaur, N, Minz, RW, Jayaraman, D. Prevalence of beta-cell, thyroid and celiac autoimmunity in North Indian children with recent onset type 1 diabetes (T1D). J Clin Diagn Res 2015;9:Sm01–2. https://doi.org/10.7860/jcdr/2015/11960.5711.Suche in Google Scholar
30. Verge, CF, Gianani, R, Kawasaki, E, Yu, L, Pietropaolo, M, Chase, HP, et al. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 1996;45:926–33. https://doi.org/10.2337/diab.45.7.926.Suche in Google Scholar PubMed
31. Al-Hassani, N, Chedid, F, Hadi, S, Kaplan, W. Prevalence of autoantibodies in type 1 diabetes patients and its association with the clinical presentation – UAE Eastern region experience. J Pediatr Endocrinol Metab 2014;27:1157–9. https://doi.org/10.1515/jpem-2013-0430.Suche in Google Scholar PubMed
32. Bravis, V, Kaur, A, Walkey, HC, Godsland, IF, Misra, S, Bingley, PJ, et al. Relationship between islet autoantibody status and the clinical characteristics of children and adults with incident type 1 diabetes in a UK cohort. BMJ Open 2018;8:e020904. https://doi.org/10.1136/bmjopen-2017-020904.Suche in Google Scholar PubMed PubMed Central
33. Verkauskiene, R, Danyte, E, Dobrovolskiene, R, Stankute, I, Simoniene, D, Razanskaite-Virbickiene, D, et al. The course of diabetes in children, adolescents and young adults: does the autoimmunity status matter?. BMC Endocr Disord 2016;16:61. https://doi.org/10.1186/s12902-016-0145-3.Suche in Google Scholar PubMed PubMed Central
34. Khashan, AS, Kenny, LC, Lundholm, C, Kearney, PM, Gong, T, McNamee, R, et al. Gestational age and birth weight and the risk of childhood type 1 diabetes: a population-based cohort and sibling design study. Diabetes Care 2015;38:2308–15. https://doi.org/10.2337/dc15-0897.Suche in Google Scholar PubMed
35. Ziegler, AG, Nepom, GT. Prediction and pathogenesis in type 1 diabetes. Immunity 2010;32:468–78. https://doi.org/10.1016/j.immuni.2010.03.018.Suche in Google Scholar PubMed PubMed Central
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Research Articles
- Analysis of the alpha galactosidase gene: mutation profile and description of two novel mutations with extensive literature review in Turkish population
- Cascade screening and treatment of children with familial hypercholesterolemia in Turkey
- Risk of adrenal insufficiency following intra-articular or periarticular corticosteroid injections among children with chronic arthritis
- Vitamin D status is related to severity at onset of diabetes and worse glycemic control
- Reassessing vitamin D supplementation in preterm infants: a prospective study and review of the literature
- Mutations in PMM2 gene in four unrelated Spanish families with polycystic kidney disease and hyperinsulinemic hypoglycemia
- Liraglutide pharmacokinetics and exposure-response in pediatric patients with type 2 diabetes
- Identification of nucleotide polymorphism within the NeuroD1 candidate gene and its association with type 1 diabetes susceptibility in Iranian people by polymerase chain reaction-restriction fragment length polymorphism
- Prevalence of autoantibodies in type 1 diabetes mellitus pediatrics in Mazandaran, North of Iran
- Clinical features of the diabetes eating problem survey–revised Turkish version in children and adolescent with type 1 diabetes
- Ambulatory blood pressure profile in office normotensive obese children: prevalence of masked hypertension and impact of parental hypertension
- Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review
- Short Communication
- Screening for imprinting disorders in 58 patients with clinically diagnosed idiopathic short stature
- Case Reports
- ROHHAD syndrome – A still unrecognized cause of childhood obesity: report of three cases
- Carbonic anhydrase VA deficiency: a very rare case of hyperammonemic encephalopathy
- Idiopathic infantile hypercalcemia: mutations in SLC34A1 and CYP24A1 in two siblings and fathers
- GCK-MODY in a child with cystic fibrosis: the doubt of the treatment plan
Artikel in diesem Heft
- Frontmatter
- Research Articles
- Analysis of the alpha galactosidase gene: mutation profile and description of two novel mutations with extensive literature review in Turkish population
- Cascade screening and treatment of children with familial hypercholesterolemia in Turkey
- Risk of adrenal insufficiency following intra-articular or periarticular corticosteroid injections among children with chronic arthritis
- Vitamin D status is related to severity at onset of diabetes and worse glycemic control
- Reassessing vitamin D supplementation in preterm infants: a prospective study and review of the literature
- Mutations in PMM2 gene in four unrelated Spanish families with polycystic kidney disease and hyperinsulinemic hypoglycemia
- Liraglutide pharmacokinetics and exposure-response in pediatric patients with type 2 diabetes
- Identification of nucleotide polymorphism within the NeuroD1 candidate gene and its association with type 1 diabetes susceptibility in Iranian people by polymerase chain reaction-restriction fragment length polymorphism
- Prevalence of autoantibodies in type 1 diabetes mellitus pediatrics in Mazandaran, North of Iran
- Clinical features of the diabetes eating problem survey–revised Turkish version in children and adolescent with type 1 diabetes
- Ambulatory blood pressure profile in office normotensive obese children: prevalence of masked hypertension and impact of parental hypertension
- Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review
- Short Communication
- Screening for imprinting disorders in 58 patients with clinically diagnosed idiopathic short stature
- Case Reports
- ROHHAD syndrome – A still unrecognized cause of childhood obesity: report of three cases
- Carbonic anhydrase VA deficiency: a very rare case of hyperammonemic encephalopathy
- Idiopathic infantile hypercalcemia: mutations in SLC34A1 and CYP24A1 in two siblings and fathers
- GCK-MODY in a child with cystic fibrosis: the doubt of the treatment plan