Document Type : original article

Authors

1 Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Department of Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

5 Pediatric Endocrinology Ward, Akbar Children's Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

10.22038/ijp.2023.73844.5329

Abstract

Background: Type 1 diabetes mellitus results from autoimmune destruction of the insulin-producing beta cells in the islets of Langerhans in pancreas. It is one of the most common chronic diseases in childhood. This process occurs in genetically susceptible subjects and is probably triggered by one or more environmental agents. Viral agents especially enteroviruses are under special focus as the environmental triggering factors and many studies all around the world have evaluated their role in the pathogenesis of type 1 diabetes. As the prevalence of viral infections varies in different geographical regions, this study was planned to evaluate the frequency of enterovirus infection in the population of diabetic children in North East of Iran.
Methods: 35 children between 1 to 18 years who were newly diagnosed with type 1 diabetes were investigated for enterovirus RNA using RT-PCR in their serum and stool, and 31 nondiabetic children who were also negative for other autoimmune disorders were also evaluated.
Results: Enterovirus RNA RT-PCR was negative in serum of all case and control samples. Stool samples were also negative in the case group and only one stool sample was positive in the control group. The patient was totally asymptomatic and had received polio vaccine 2 weeks before.
Conclusion: Results of this study show that presence of enterovirus RNA at the time of the clinical presentation of diabetes is not common in our population of diabetic patients and more extensive studies are needed to establish a relationship.

Keywords

  1. Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, Imperatore G, Linder B, Marcovina S, Pettitt DJ, Pihoker C, Saydah S, Wagenknecht L; SEARCH for Diabetes in Youth Study. Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002-2012. N Engl J Med. 2017; 376(15):1419-1429.
  2. Mayer-Davis EJ, Kahkoska AR, Jefferies C, Dabelea D, Balde N, Gong CX, Aschner P, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents. Pediatr Diabetes. 2018; 19 Suppl 27(Suppl 27):7-19.
  3. Tuomilehto J, Ogle GD, Lund-Blix NA, Stene LC. Update on Worldwide Trends in Occurrence of Childhood Type 1 Diabetes in 2020. Pediatric endocrinology reviews: PER. 2020 Mar 1; 17(Suppl 1):198-209.
  4. Wang K, Ye F, Chen Y, Xu J, Zhao Y, Wang Y, Lan T. Association Between Enterovirus Infection and Type 1 Diabetes Risk: A Meta-Analysis of 38 Case-Control Studies. Front Endocrinol (Lausanne). 2021; 12:706964.
  5. Oikarinen S, Krogvold L, Edwin B, Buanes T, Korsgren O, Laiho JE, Oikarinen M, Ludvigsson J, Skog O, Anagandula M, Frisk G, Hyöty H, Dahl-Jørgensen K. Characterisation of enterovirus RNA detected in the pancreas and other specimens of live patients with newly diagnosed type 1 diabetes in the DiViD study. Diabetologia. 2021 Nov; 64(11):2491-501.
  6. Hober D, Sauter P. Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host. Nature Reviews Endocrinology. 2010 May; 6(5):279-89.
  7. Isaacs SR, Foskett DB, Maxwell AJ, Ward EJ, Faulkner CL, Luo JY, Rawlinson WD, Craig ME, Kim KW. Viruses and type 1 diabetes: from enteroviruses to the virome. Microorganisms. 2021 Jul 16; 9(7):1519.
  8. Romero, J.R. Pediatric Group B Coxsackievirus Infections. In Group B Coxsackieviruses; Springer: Berlin/Heidelberg, Germany, 2008; Volume 323, pp. 223–239.
  9. Chehadeh W, Kerr-Conte J, Pattou F, Alm G, Lefebvre J, Wattré P, Hober D. Persistent infection of human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesis in β cells. Journal of virology. 2000 Nov 1; 74(21):10153-64.
  10. Nekoua MP, Bertin A, Sane F, Alidjinou EK, Lobert D, Trauet J, Hober C, Engelmann I, Moutairou K, Yessoufou A, Hober D. Pancreatic beta cells persistently infected with coxsackievirus B4 are targets of NK cell-mediated cytolytic activity. Cellular and Molecular Life Sciences. 2020 Jan; 77(1):179-94.
  11. Schulte BM, Bakkers J, Lanke KH, Melchers WJ, Westerlaken C, Allebes W, Aanstoot HJ, Bruining GJ, Adema GJ, Van Kuppeveld FJ, Galama JM. Detection of enterovirus RNA in peripheral blood mononuclear cells of type 1 diabetic patients beyond the stage of acute infection. Viral Immunol. 2010 Feb; 23(1):99-104. doi: 10.1089/vim.2009.0072. PMID: 20121407.
  12. Cinek O, Tapia G, Witsø E, Kramna L, Holkova K, Rasmussen T, Stene LC, Rønningen KS. Enterovirus RNA in peripheral blood may be associated with the variants of rs1990760, a common type 1 diabetes associated polymorphism in IFIH1. PLoS One. 2012; 7(11):e48409. doi: 10.1371/journal.pone.0048409. Epub 2012 Nov 7. PMID: 23144876; PMCID: PMC3492349.
  13. Alidjinou EK, Sane F, Lefevre C, Baras A, Moumna I, Engelmann I, Vantyghem MC, Hober D. Enteroviruses in blood of patients with type 1 diabetes detected by integrated cell culture and reverse transcription quantitative real-time PCR. Acta Diabetol. 2017 Nov; 54(11):1025-1029. doi: 10.1007/s00592-017-1041-7. Epub 2017 Aug 31. PMID: 28861621.
  14. Hyöty H. Enterovirus infections and type 1 diabetes. Annals of medicine. 2002 Jan 1; 34(3):138-47.
  15. Haverkos HW, Battula N, Drotman DP, Rennert OM. Enteroviruses and type 1 diabetes mellitus. Biomedicine & pharmacotherapy. 2003 Nov 1; 57(9):379-85.
  16. Maha MM, Ali MA, Abdel-Rehim SE, Abu-Shady EA, El-Naggar BM, Maha YZ. The role of coxsackieviruses infection in the children of insulin dependent diabetes mellitus. The Journal of the Egyptian Public Health Association. 2003 Jan 1; 78(3-4):305-18.
  17. Sarmiento L, Cabrera-Rode E, Lekuleni L, Cuba I, Molina G, Fonseca M, Heng-Hung L, Borroto AD, Gonzalez P, Mas-Lago P, Diaz-Horta O. Occurrence of enterovirus RNA in serum of children with newly diagnosed type 1 diabetes and islet cell autoantibody-positive subjects in a population with a low incidence of type 1 diabetes. Autoimmunity. 2007 Jan 1; 40(7):540-5.
  18. Sarmiento L, Cabrera E, Díaz O, Fonseca M, Molina G, Más P, Díaz LH, Resik S. Association between enterovirus infection and type 1 diabetes: new findings from Cuban studies. Biotecnología Aplicada. 2009 Dec; 26(4):349-51.
  19. Kendall EK, Olaker VR, Kaelber DC, Xu R, Davis PB. Association of SARS-CoV-2 Infection with New-Onset Type 1 Diabetes among Pediatric Patients from 2020 to 2021. JAMA Netw Open. 2022; 5(9):e2233014. doi:10.1001/ jamanetworkopen
  20. Gottesman BL, Yu J, Tanaka C, Longhurst CA, Kim JJ. Incidence of new-onset type 1 diabetes among US children during the COVID-19 global pandemic. JAMA pediatrics. 2022 Apr 1; 176(4):414-5.
  21. Qeadan F, Tingey B, Egbert J, Pezzolesi MG, Burge MR, Peterson KA, Honda T. The associations between COVID-19 diagnosis, type 1 diabetes, and the risk of diabetic ketoacidosis: A nationwide cohort from the US using the Cerner Real-World Data. Plos one. 2022 Apr 19; 17(4):e0266809.
  22. Vlad A, Serban V, Timar R, Sima A, Botea V, Albai O, Timar B, Vlad M. Increased incidence of type 1 diabetes during the COVID-19 pandemic in Romanian children. Medicina. 2021 Sep 16; 57(9):973.
  23. Boddu SK, Aurangabadkar G, Kuchay MS. New onset diabetes, type 1 diabetes and COVID-19. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020 Nov 1; 14(6):2211-7.
  24. Caruso P, Longo M, Esposito K, Maiorino MI. Type 1 diabetes triggered by covid-19 pandemic: A potential outbreak? Diabetes research and clinical practice. 2020 Jun 1; 164.
  25. Alidjinou EK, Sane F, Lefevre C, Baras A, Moumna I, Engelmann I, Vantyghem MC, Hober D. Enteroviruses in blood of patients with type 1 diabetes detected by integrated cell culture and reverse transcription quantitative real-time PCR. Acta Diabetol. 2017; 54(11):1025-1029.
  26. Wang K, Ye F, Chen Y, Xu J, Zhao Y, Wang Y, Lan T. Association Between Enterovirus Infection and Type 1 Diabetes Risk: A Meta-Analysis of 38 Case-Control Studies. Front Endocrinol (Lausanne). 2021; 12:706964.