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Type 1 Diabetes Mellitus: Epidemiology, Genetics, Pathogenesis, and Clinical Manifestations

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Abstract

Type 1 diabetes (type 1 DM) is characterized by an absolute deficiency of insulin secretion, a relatively rapid onset, and dependence on exogenous insulin at the time of diagnosis. Patients with type 1 DM are also prone to ketosis [1].

Insulin deficiency in type 1a diabetes is caused by immune-mediated destruction of beta cells and is associated with evidence of autoimmunity. A smaller group of type 1 diabetic patients exhibit no evidence of autoimmunity and the cause of insulin deficiency remains undefined. These cases are categorized as type 1b diabetes or idiopathic type 1 diabetes and are relatively more common in African and Asian populations [2]. This category is heterogeneous, may be caused by different mechanisms in different populations, and remains poorly understood at this time. This chapter focuses on autoimmune type 1a diabetes unless otherwise specified.

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References

  1. American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2016;39 Suppl 1:S13–22. doi:10.2337/dc16-S005. Review. PMID: 26696675.

    Google Scholar 

  2. Abiru N, Kawasaki E, Eguch K. Current knowledge of Japanese type 1 diabetic syndrome. Diabetes Metab Res Rev. 2002;18:357–66.

    Article  CAS  PubMed  Google Scholar 

  3. Diabetes in the Young in International Diabetes Federation. IDF diabetes atlas. Brussels: International Diabetes Federation; 2011.

    Google Scholar 

  4. Casu A, Pascutto C, Bernardinelli L, et al. Type 1 diabetes among Sardinian children is increasing: the Sardinian diabetes register for children aged 0–14 years (1989–1999). Diabetes Care. 2004;27:1623–9.

    Article  PubMed  Google Scholar 

  5. Borchers AT, Uibo R, Gershwin ME. The geoepidemiology of type 1 diabetes. Autoimmun Rev. 2010;9(5):A355–65. doi:10.1016/j.autrev.2009.12.003. PMID: 19969107, Epub 2009 Dec 5. Review.

    Article  PubMed  Google Scholar 

  6. Stanescu DE, Lord K, Lipman TH. The epidemiology of type 1 diabetes in children. Endocrinol Metab Clin North Am. 2012;41(4):679–94. doi:10.1016/j.ecl.2012.08.001. PMID: 23099264, Epub 2012 Sep 27. Review.

    Article  PubMed  Google Scholar 

  7. Pundziute-Lycka A, Dahlquist G, Nystrom L, et al. Type I diabetes in the 0–34 years group in Sweden. Diabetologia. 2002;45:783–91.

    Article  CAS  PubMed  Google Scholar 

  8. Svensson J, Carstensen B, Molbak A, et al. Increased risk of childhood type 1 diabetes in children born after 1985. Diabetes Care. 2002;25:2197–201.

    Article  PubMed  Google Scholar 

  9. Mohr SB, Garland CF, Gorham ED, Garland FC. The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Diabetologia. 2008;51(8):1391–8. Epub 2008 Jun 12.

    Article  CAS  PubMed  Google Scholar 

  10. Diamond Project Group. Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabet Med. 2006;23:857–66.

    Article  Google Scholar 

  11. Rytkönen M, Moltchanova E, Ranta J, Taskinen O, Tuomilehto J, Karvonen M, SPAT Study Group, Finnish Childhood Diabetes Registry Group. The incidence of type 1 diabetes among children in Finland – rural–urban difference. Health Place. 2003;9(4):315–25.

    Article  PubMed  Google Scholar 

  12. Holmqvist BM, Lofman O, Samuelsson U. A low incidence of type 1 diabetes between 1977 and 2001 in south-eastern Sweden in areas with high population density and which are more deprived. Diabet Med. 2008;25(3):255–60. Epub 2008 Jan 14.

    Article  PubMed  Google Scholar 

  13. Staines A, Bodansky HJ, McKinney PA, et al. Small area variation in the incidence of childhood insulin-dependent diabetes mellitus in Yorkshire, UK: links with overcrowding and population density. Int J Epidemiol. 1997;6:1307–13.

    Article  Google Scholar 

  14. Patterson CC, Carson DJ, Hadden DR. Epidemiology of childhood IDDM in Northern Ireland 1989–1994: low incidence in areas with highest population density and most household crowding. Northern Ireland Diabetes Study Group. Diabetologia. 1996;9:1063–9.

    Article  Google Scholar 

  15. Cherubini V, Carle F, Gesuita R, et al. Large incidence variation of type 1 diabetes in central-southern Italy 1990–1995: lower risk in rural areas. Diabetologia. 1999;7:789–92.

    Article  Google Scholar 

  16. Pundziute-Lycka A, Urbonaite B, Ostrauskas R, Zalinkevicius R, Dahlquist GG. Incidence of type 1 diabetes in Lithuanians aged 0–39 years varies by the urban–rural setting, and the time change differs for men and women during 1991–2000. Diabetes Care. 2003;3:671–6.

    Article  Google Scholar 

  17. Schober E, Rami B, Waldhoer T, Austrian Diabetes Incidence Study Group. Steep increase of incidence of childhood diabetes since 1999 in Austria. Time trend analysis 1979–2005. A nationwide study. Eur J Pediatr. 2008;167(3):293–7. Epub 2007 Apr.

    Article  PubMed  Google Scholar 

  18. Stipancic G, La Grasta Sabolic L, Malenica M, Radica A, Skrabic V, Tiljak MK. Incidence and trends of childhood type 1 diabetes in Croatia from 1995 to 2003. Diabetes Res Clin Pract. 2008;80(1):122–7. Epub 2007 Dec.

    Article  CAS  PubMed  Google Scholar 

  19. Barat P, Valade A, Brosselin P, Alberti C, Maurice-Tison S, Lévy-Marchal C. The growing incidence of type 1 diabetes in children: the 17-year French experience in Aquitaine. Diabet Metab. 2008;34(6 Pt 1):601–5. Epub 2008 Oct 25.

    Article  CAS  Google Scholar 

  20. Ehehalt S, Blumenstock G, Willasch AM, Hub R, Ranke MB, Neu A, DIARY-Study Group Baden-Württemberg. Continuous rise in incidence of childhood type 1 diabetes in Germany. Diabet Med. 2008;25(6):755–7.

    Article  CAS  PubMed  Google Scholar 

  21. Harjutsalo V, Sjöberg L, Tuomilehto J. Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet. 2008;371(9626):1777–82.

    Article  PubMed  Google Scholar 

  22. Newhook LA, Grant M, Sloka S, et al. Very high and increasing incidence of type 1 diabetes mellitus in Newfoundland and Labrador, Canada. Pediatr Diabetes. 2008;9((3 Pt 2)):62–8. Epub 2008 Jan.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang H, Xia W, Yu Q, et al. Increasing incidence of type 1 diabetes in children aged 0–14 years in Harbin, China (1990–2000). Prim Care Diabetes. 2008;2(3):121–6. Epub 2008 Jul 16.

    Article  PubMed  Google Scholar 

  24. Harjutsalo V, Sund R, Knip M, Groop PH. Incidence of type 1 diabetes in Finland. JAMA. 2013;310:427–8.

    Article  CAS  PubMed  Google Scholar 

  25. Cinek O, Kulich M, Sumnik Z. The incidence of type 1 diabetes in young Czech children stopped rising. Pediatr Diabetes. 2012;13(7):559–63. doi:10.1111/j.1399-5448.2012.00858.x. PMID: 22487027, Epub 2012 Apr 5.

    Article  PubMed  Google Scholar 

  26. Patterson C. Behalf of the EURODIAB collaboration of childhood type 1 diabetes registers. 15 year trends in the incidence of type 1 diabetes in Europe. Pediatr Diabetes. 2007;8 Suppl 7:7.

    Google Scholar 

  27. Chobot A, Polanska J, Deja G, Jarosz-Chobot P. Incidence of type 1 diabetes among Polish children ages 0-14 years from 1989 to 2012. Acta Diabetol. 2015;52(3):483–8. doi:10.1007/s00592-014-0682-z. PMID: 25381194, Epub 2014 Nov 8.

    Article  PubMed  Google Scholar 

  28. Jansson SP, Andersson DK, Svärdsudd K. Prevalence and incidence rate of diabetes mellitus in a Swedish community during 30 years of follow-up. Diabetologia. 2007;50(4):703–10. Epub 2007 Feb 1.

    Article  CAS  PubMed  Google Scholar 

  29. Skrivarhaug T, Stene LC, Drivvoll AK, Strøm H, Joner G, Norwegian Childhood Diabetes Study Group. Incidence of type 1 diabetes in Norway among children aged 0–14 years between 1989 and 2012: has the incidence stopped rising? Results from the Norwegian Childhood Diabetes Registry. Diabetologia. 2014;57(1):57–62. doi:10.1007/s00125-013-3090-y. PMID: 24149838, Epub 2013 Oct 23.

    Article  PubMed  Google Scholar 

  30. Raymond NT, Jones JR, Swift PG, et al. Comparative incidence of type 1 diabetes in children aged under 15 years from South Asian and white or other ethnic backgrounds in Leicestershire, UK, 1989 to 1998. Diabetologia. 2001;44 Suppl 3:B32–6.

    Article  PubMed  Google Scholar 

  31. Gillespie KM, Bain SC, Barnett AH, et al. The rising incidence of childhood type 1 diabetes and reduced contributions of high-risk HLA haplotypes. Lancet. 2004;364:1699–700.

    Article  PubMed  Google Scholar 

  32. Muntoni S, Fonte MT, Stoduto S, et al. Incidence of insulin-dependent diabetes mellitus among Sardinian-heritage children born in Lazio region, Italy. Lancet. 1997;349(9046):160–2.

    Article  CAS  PubMed  Google Scholar 

  33. Haller MJ, Atkinson MA, Schatz D. Type 1 diabetes mellitus: etiology, presentation, and management. Pediatr Clin North Am. 2005;52(6):1553–78.

    Article  PubMed  Google Scholar 

  34. Rewers M, Stone RA, LaPorte RE, et al. Poisson regression modeling of temporal variation in incidence of childhood insulin-dependent diabetes mellitus in Allegheny County, Pennsylvania, and Wielkopolska, Poland, 1970–1985. Am J Epidemiol. 1989;129:569–81.

    Article  CAS  PubMed  Google Scholar 

  35. Siemiatycki J, Colle E, Campbell S, Dewar RA, Belmonte MM. Case–control study of IDDM. Diabetes Care. 1989;12:209–16.

    Article  CAS  PubMed  Google Scholar 

  36. Larenas G, Montecinos A, Manosalva M, et al. Incidence of insulin-dependent diabetes mellitus in the IX region of Chile: ethnic differences. Diabetes Res Clin Pract. 1996;34:S147–51.

    Article  PubMed  Google Scholar 

  37. Koton S, Israel IDDM Registry Study Group – IIRSG. Incidence of type 1 diabetes mellitus in the 0- to 17-yr-old Israel population, 1997–2003. Pediatr Diabetes. 2007;8(2):60–6.

    Article  PubMed  Google Scholar 

  38. Kondrashova A, Viskari H, Kulmala P, et al. Signs of beta-cell autoimmunity in nondiabetic schoolchildren: a comparison between Russian Karelia with a low incidence of type 1 diabetes and Finland with a high incidence rate. Diabetes Care. 2007;30(1):95–100.

    Article  CAS  PubMed  Google Scholar 

  39. Willis JA, Scott RS, Darlow BA, Lewy H, Ashkenazi I, Laron Z. Seasonality of birth and onset of clinical disease in children and adolescents (0–19 years) with type 1 diabetes mellitus in Canterbury, New Zealand. J Pediatr Endocrinol Metab. 2002;15(5):645–7.

    PubMed  Google Scholar 

  40. Levy-Marchal C, Patterson C, Green A. Variation by age group and seasonality at diagnosis of childhood IDDM in Europe. The EURODIAB ACE Study Group. Diabetologia. 1995;38:823–30.

    Article  CAS  PubMed  Google Scholar 

  41. Green A, Patterson CC. Trends in the incidence of childhood-onset diabetes in Europe 1989–1998. Diabetologia. 2001;44 Suppl 3:B3–8.

    Article  PubMed  Google Scholar 

  42. Svensson J, Lyngaae-Jørgensen A, Carstensen B, Simonsen LB, Mortensen HB. Long-term trends in the incidence of type 1 diabetes in Denmark: the seasonal variation changes over time. Pediatr Diabetes. 2008;10(4):248–54.

    Article  PubMed  Google Scholar 

  43. Ye J, Chen RG, Ashkenazi I, Laron Z. Lack of seasonality in the month of onset of childhood IDDM (0.7–15 years) in Shanghai, China. J Pediatr Endocrinol Metab. 1998;11:461–4.

    Article  CAS  PubMed  Google Scholar 

  44. Kida K, Mimura G, Ito T, Murakami K, Ashkenazi I, Laron Z. Incidence of type 1 diabetes mellitus in children aged 0–14 in Japan, 1986–1990, including an analysis for seasonality of onset and month of birth: JDS study. The Data Committee for Childhood Diabetes of the Japan Diabetes Society (JDS). Diabet Med. 2000;17:59–63.

    Article  CAS  PubMed  Google Scholar 

  45. Laron Z, Lewy H, Wilderman I, et al. Seasonality of month of birth of children and adolescents with type 1 diabetes mellitus in homogenous and heterogeneous populations. Isr Med Assoc J. 2005;7(6):381–4.

    PubMed  Google Scholar 

  46. Laron Z. Interplay between heredity and environment in the recent explosion of type 1 childhood diabetes mellitus. Am J Med Genet. 2002;115(1):4–7.

    Article  PubMed  Google Scholar 

  47. Gale EA, Gillespie KM. Diabetes and gender. Diabetologia. 2001;44:3–15.

    Article  CAS  PubMed  Google Scholar 

  48. Karvonen M, Pitkäniemi M, Pitkäniemi J, Kohtamäki K, Tajima N, Tuomilehto J. Sex difference in the incidence of insulin-dependent diabetes mellitus: an analysis of the recent epidemiological data. World Health Organization DIAMOND Project Group. Diabetes Metab Rev. 1997;13(4):275–91. Review.

    Article  CAS  PubMed  Google Scholar 

  49. Kawasaki E, Matsuura N, Eguchi K. Type 1 diabetes in Japan. Diabetologia. 2006;49(5):828–36. Epub 2006 Mar 28.

    Article  CAS  PubMed  Google Scholar 

  50. Kalk WJ, Huddle KR, Raal FJ. The age of onset and sex distribution of insulin-dependent diabetes mellitus in Africans in South Africa. Postgrad Med J. 1993;69(813):552–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Heinonen MT, Moulder R, Lahesmaa R. New Insights and biomarkers for type 1 diabetes: review for Scandinavian Journal of Immunology. Scand J Immunol. 2015;82(3):244–53. doi:10.1111/sji.12338.

    Article  CAS  PubMed  Google Scholar 

  52. Hämäläinen AM, Knip M. Autoimmunity and familial risk of type 1 diabetes. Curr Diab Rep. 2002;2(4):347–53.

    Article  PubMed  Google Scholar 

  53. Redondo MJ, Eisenbarth GS. Genetic control of autoimmunity in type I diabetes and associated disorders. Diabetologia. 2002;45:605–22.

    Article  CAS  PubMed  Google Scholar 

  54. Warram JH, Krolewski AS, Gottlieb MS, Ronald Kahn C. Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. N Engl J Med. 1984;311:149–52. doi:10.1056/NEJM198407193110304.

    Article  CAS  PubMed  Google Scholar 

  55. Harjutsalo V, Lammi N, Karvonen M, Groop PH. Age at onset of type 1 diabetes in parents and recurrence risk in offspring. Diabetes. 2010;59(1):210–4. doi:10.2337/db09-0344. Epub 2009 Oct 15.

    Article  CAS  PubMed  Google Scholar 

  56. Kyvik KO, Green A, Beck-Nielsen H. Concordance rates of insulin dependent diabetes mellitus: a population based study of young Danish twins. BMJ. 1995;311(7010):913–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Redondo MJ, Jeffrey J, Fain PR, Eisenbarth GS, Orban T. Concordance for islet autoimmunity among monozygotic twins. N Engl J Med. 2008;359(26):2849–50.

    Article  CAS  PubMed  Google Scholar 

  58. Tait BD. The ever-expanding list of HLA alleles: changing HLA nomenclature and its relevance to clinical transplantation. Transplant Rev (Orlando). 2011;25(1):1–8. doi:10.1016/j.trre.2010.08.001. Epub 2010 Oct 27.

    Article  Google Scholar 

  59. Milius RP, Mack SJ, Hollenbach JA, Pollack J, Heuer ML, Gragert L, Spellman S, Guethlein LA, Trachtenberg EA, Cooley S, Bochtler W, Mueller CR, Robinson J, Marsh SG, Maiers M. Genotype List String: a grammar for describing HLA and KIR genotyping results in a text string. Tissue Antigens. 2013;82(2):106–12. doi:10.1111/tan.12150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gragert L, Madbouly A, Freeman J, Maiers M. Six-locus high resolution HLA haplotype frequencies derived from mixed-resolution DNA typing for the entire US donor registry. Hum Immunol. 2013;74(10):1313–20. doi:10.1016/j.humimm.2013.06.025. Epub 2013 Jun 24.

    Article  CAS  PubMed  Google Scholar 

  61. Noble JA. Immunogenetics of type 1 diabetes: a comprehensive review. J Autoimmun. 2015;64:101–12. doi:10.1016/j.jaut.2015.07.014. Epub 2015 Aug 10. Review.

    Article  CAS  PubMed  Google Scholar 

  62. Aly TA, Ide A, Jahromi MM, et al. Extreme genetic risk for type 1A diabetes. Proc Natl Acad Sci U S A. 2006;103(38):14074–9. Epub 2006 Sept 11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Erlich H, Valdes AM, Noble J, et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes. 2008;57:1084–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Redondo MJ, Fain PR, Eisenbarth GS. Genetics of type 1A diabetes. Recent Prog Horm Res. 2001;56:69–89.

    Article  CAS  PubMed  Google Scholar 

  65. Todd JA, Bell JI, McDevitt HO. HLA-DQβ gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987;329:599–604.

    Article  CAS  PubMed  Google Scholar 

  66. Morel PA, Dorman JS, Todd JA, McDevitt HO, Trucco M. Aspartic acid at position 57 of the HLA-DQ beta chain protects against type I diabetes: a family study. Proc Natl Acad Sci U S A. 1988;85(21):8111–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kwok WW, Domeier ME, Johnson ML, Nepom GT, Koelle DM. HLA-DQB1 codon 57 is critical for peptide binding and recognition. J Exp Med. 1996;183(3):1253–8.

    Article  CAS  PubMed  Google Scholar 

  68. Lee HC, Ikegami H, Fujisawa T, et al. Role of HLA class II alleles in Korean patients with IDDM. Diabetes Res Clin Pract. 1996;31(1–3):9–15.

    Article  CAS  PubMed  Google Scholar 

  69. Awata T, Kuzuya T, Matsuda A, et al. High frequency of aspartic acid at position 57 of HLA-DQ B-chain in Japanese IDDM patients and nondiabetic subjects. Diabetes. 1990;39(2):266–9.

    Article  CAS  PubMed  Google Scholar 

  70. Nejentsev S, Howson JM, Walker NM, et al. Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A. Nature. 2007;450(7171):887–92. Epub 2007 Nov 14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Park Y. Why is type 1 diabetes uncommon in Asia? Ann N Y Acad Sci. 2006;1079:31–40.

    Article  PubMed  Google Scholar 

  72. Bennett ST, Todd JA. Human type 1 diabetes and the insulin gene: principles of mapping polygenes. Annu Rev Genet. 1996;30:343–70.

    Article  CAS  PubMed  Google Scholar 

  73. Bell GI, Selby MJ, Rutter WJ. The highly polymorphic region near the human insulin gene is composed of simple tandemly repeating sequences. Nature. 1982;295(5844):31–5.

    Article  CAS  PubMed  Google Scholar 

  74. Stead JD, Hurles ME, Jeffreys AJ. Global haplotype diversity in the human insulin gene region. Genome Res. 2003;13:2101–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Pugliese A, Zeller M, Fernandez Jr A, et al. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet. 1997;15(3):293–7.

    Article  CAS  PubMed  Google Scholar 

  76. Vafiadis P, Grabs R, Goodyer CG, Colle E, Polychronakos C. A functional analysis of the role of IGF2 in IDDM2-encoded susceptibility to type 1 diabetes. Diabetes. 1998;47(5):831–6.

    Article  CAS  PubMed  Google Scholar 

  77. Bottini N, Musumeci L, Alonso A, et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet. 2004;36:337–8.

    Article  CAS  PubMed  Google Scholar 

  78. Bottini N, Vang T, Cucca F, Mustelin T. Role of PTPN22 in type 1 diabetes and other autoimmune diseases. Semin Immunol. 2006;18(4):207–13. Epub 2006 May 11.

    Article  CAS  PubMed  Google Scholar 

  79. Rieck M, Arechiga A, Onengut-Gumuscu S, Greenbaum C, Concannon P, Buckner JH. Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes. J Immunol. 2007;179:4704–10.

    Article  CAS  PubMed  Google Scholar 

  80. Nisticò L, Buzzetti R, Pritchard LE, et al. The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry. Hum Mol Genet. 1996;5(7):1075–80.

    Article  PubMed  Google Scholar 

  81. Chistiakov DA, Turakulov RI. CTLA-4 and its role in autoimmune thyroid disease. J Mol Endocrinol. 2003;31(1):21–36. Review.

    Article  CAS  PubMed  Google Scholar 

  82. Lowe CE, Cooper JD, Brusko T, et al. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet. 2007;39(9):1074–82.

    Article  CAS  PubMed  Google Scholar 

  83. Smyth DJ, Cooper JD, Bailey R, et al. A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nat Genet. 2006;38(6):617–9.

    Article  CAS  PubMed  Google Scholar 

  84. Kato H, Takeuchi O, Sato S, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006;441(7089):101–5. Epub 2006 Apr 9.

    Article  CAS  PubMed  Google Scholar 

  85. Bailey R, Cooper JD, Zeitels L, et al. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes. 2007;56(10):2616–21. Epub 2007 Jul 2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Todd JA, Walker NM, Cooper JD, et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007;39(7):857–64. Epub 2007 Jun 6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661–78.

    Article  CAS  Google Scholar 

  88. Conrad B, Weissmahr RN, Böni J, Arcari R, Schüpbach J, Mach B. A human endogenous retroviral superantigen as candidate autoimmune gene in type 1 diabetes. Cell. 1997;90(2):303–13.

    Article  CAS  PubMed  Google Scholar 

  89. Knerr I, Repp R, Dotsch J, et al. Quantitation of gene expression by real-time PCR disproves a “retroviral hypothesis” for childhood-onset diabetes mellitus. Pediatr Res. 1999;46(1):57–60.

    Article  CAS  PubMed  Google Scholar 

  90. Stefan M, Zhang W, Concepcion E, Yi Z, Tomer Y. DNA methylation profiles in type 1 diabetes twins point to strong epigenetic effects on etiology. J Autoimmun. 2014;50:33–7.

    Article  CAS  PubMed  Google Scholar 

  91. Belot MP, Fradin D, Mai N, Le Fur S, Zelenika D, Kerr-Conte J, et al. CpG methylation changes within the IL2RA promoter in type 1 diabetes of childhood onset. PLoS One. 2013;8, e68093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Bell CG, Teschendorff AE, Rakyan VK, Maxwell AP, Beck S, Savage DA. Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus. BMC Med Genomics. 2010;3:33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Wang Y, Zheng C, Hou L, Yang X, Li JL, et al. DNA methylation impairs TLR9 induced Foxp3 expression by attenuating IRF-7 binding activity in fulminant type 1 diabetes. J Autoimmun. 2013;41:50–9.

    Article  PubMed  CAS  Google Scholar 

  94. Nakhooda AF, Like AA, Chappel CI, et al. The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diabetes. 1977;26:100–12.

    Article  CAS  PubMed  Google Scholar 

  95. Rayfield EJ, Kelly KJ, Yoon JW. Rubella virus-induced diabetes in the hamster. Diabetes. 1986;35:1278–81.

    Article  CAS  PubMed  Google Scholar 

  96. Tauriainen S, Salminen K, Hyoty H. Can enteroviruses cause type 1 diabetes? Ann N Y Acad Sci. 2003;1005:13–22.

    Article  PubMed  Google Scholar 

  97. Yoon JW, Austin M, Onodera T, et al. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med. 1979;300:1173–9.

    Article  CAS  PubMed  Google Scholar 

  98. Champsaur HF, Bottazzo GF, Bertrams J, et al. Virologic, immunologic, and genetic factors in insulin-dependent diabetes mellitus. J Pediatr. 1982;100:15–20.

    Article  CAS  PubMed  Google Scholar 

  99. Harkonen T, Lankinen H, Davydova B, et al. Enterovirus infection can induce immune responses that cross-react with beta-cell autoantigen tyrosine phosphatase IA-2/IAR. J Med Virol. 2002;66:340–50.

    Article  CAS  PubMed  Google Scholar 

  100. Horwitz MS, Bradley LM, Harbertson J, et al. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med. 1998;4:781–5.

    Article  CAS  PubMed  Google Scholar 

  101. Viskari H, Ludvigsson J, Uibo R, et al. Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies: time trends and geographical variation. Diabetologia. 2005;48:1280–7.

    Article  CAS  PubMed  Google Scholar 

  102. Menser MA, Forrest JM, Bransby RD. Rubella infection and diabetes-mellitus. Lancet. 1978;1:57–60.

    Article  CAS  PubMed  Google Scholar 

  103. Helmke K, Otten A, Willems W. Islet cell antibodies in children with mumps infection. Lancet. 1980;2:211–2.

    Article  CAS  PubMed  Google Scholar 

  104. Hyoty H, Leinikki P, Reunanen A, et al. Mumps infections in the etiology of type 1 (insulin-dependent) diabetes. Diabetes Res. 1988;9:111–6.

    CAS  PubMed  Google Scholar 

  105. Altobelli E, Petrocelli R, Verrotti A, Valenti M. Infections and risk of type I diabetes in childhood: a population-based case–control study. Eur J Epidemiol. 2003;18(5):425–30.

    Article  PubMed  Google Scholar 

  106. Coulson BS, Witterick PD, Tan Y, et al. Growth of rotaviruses in primary pancreatic cells. J Virol. 2002;76:9537–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Honeyman MC, Stone NL, Harrison LC. T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents. Mol Med. 1998;4:231–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Munakata Y, Kodera T, Saito T, et al. Rheumatoid arthritis, type 1 diabetes, and Graves’ disease after acute parvovirus B19 infection. Lancet. 2005;366:780.

    Article  PubMed  Google Scholar 

  109. Jenson AB, Rosenberg HS, Notkins AL. Pancreatic islet-cell damage in children with fatal viral-infections. Lancet. 1980;2:354–8.

    CAS  PubMed  Google Scholar 

  110. Pak CY, Cha CY, Rajotte RV, et al. Human pancreatic-islet cell specific 38 kilodalton autoantigen identified by cytomegalovirus-induced monoclonal islet cell autoantibody. Diabetologia. 1990;33:569–72.

    Article  CAS  PubMed  Google Scholar 

  111. Graves PM, Barriga KJ, Norris JM, et al. Lack of association between early childhood immunizations and beta-cell autoimmunity. Diabetes Care. 1999;22:1694–7.

    Article  CAS  PubMed  Google Scholar 

  112. EURODIAB Substudy 2 Study Group. Infections and vaccinations as risk factors for childhood type I (insulin-dependent) diabetes mellitus: a multicentre case–control investigation. Diabetologia. 2000;43:47–53.

    Article  Google Scholar 

  113. DeStefano F, Mullooly JP, Okoro CA, et al. Childhood vaccinations, vaccination timing, and risk of type 1 diabetes mellitus. Pediatrics. 2001;108, E112.

    Article  CAS  PubMed  Google Scholar 

  114. Cardwell CR, Carson DJ, Patterson CC. No association between routinely recorded infections in early life and subsequent risk of childhood-onset type 1 diabetes: a matched case–control study using the UK General Practice Research Database. Diabet Med. 2008;25(3):261–7. Epub 2008 Jan 14.

    Article  CAS  PubMed  Google Scholar 

  115. Pundziute-Lyckå A, Urbonaite B, Dahlquist G. Infections and risk of type I (insulin-dependent) diabetes mellitus in Lithuanian children. Diabetologia. 2000;43(10):1229–34.

    Article  PubMed  Google Scholar 

  116. Cooke A, Tonks P, Jones FM, et al. Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol. 1999;21:169–76.

    Article  CAS  PubMed  Google Scholar 

  117. Bras A, Aguas AP. Diabetes-prone NOD mice are resistant to Mycobacterium avium and the infection prevents autoimmune disease. Immunology. 1996;89:20–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Saunders KA, Raine T, Cooke A, Lawrence CE. Inhibition of autoimmune type 1 diabetes by gastrointestinal helminth infection. Infect Immun. 2007;75:397–407.

    Article  CAS  PubMed  Google Scholar 

  119. Rosenbauer J, Herzig P, Giani G. Early infant feeding and risk of type 1 diabetes mellitus – a nationwide population-based case–control study in pre-school children. Diabetes Metab Res Rev. 2008;24(3):211–22.

    Article  CAS  PubMed  Google Scholar 

  120. Ziegler AG, Schmid S, Huber D, et al. Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA. 2003;290:1721–8.

    Article  CAS  PubMed  Google Scholar 

  121. Norris JM, Barriga K, Klingensmith G, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA. 2003;290:1713–20.

    Article  CAS  PubMed  Google Scholar 

  122. Goldfarb MF. Relation of time of introduction of cow milk protein to an infant and risk of type-1 diabetes mellitus. J Proteome Res. 2008;7(5):2165–7. Epub 2008 Apr 15.

    Article  CAS  PubMed  Google Scholar 

  123. Karjalainen J, Martin JM, Knip M, et al. A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus [see comments]. N Engl J Med. 1992;327:302–7.

    Article  CAS  PubMed  Google Scholar 

  124. Rayfield EJ, Ishimura K. Environmental factors and insulin dependent diabetes mellitus. Diabetes Metab Rev. 1987;3:925–57.

    Article  CAS  PubMed  Google Scholar 

  125. Dahlquist GG, Blom LG, Persson L-Å, Sandström AIM, Wall SGI. Dietary factors and the risk of developing insulin dependent diabetes in childhood. Br Med J. 1990;300:1302–6.

    Article  CAS  Google Scholar 

  126. Winkler C, Mollenhauer U, Hummel S, Bonifacio E, Ziegler AG. Exposure to environmental factors in drinking water: risk of islet autoimmunity and type 1 diabetes – the BABYDIAB study. Horm Metab Res. 2008;40(8):566–71. Epub 2008 May 21.

    Article  CAS  PubMed  Google Scholar 

  127. Karavanaki K, Tsoka E, Liacopoulou M, et al. Psychological stress as a factor potentially contributing to the pathogenesis of type 1 diabetes mellitus. J Endocrinol Invest. 2008;31(5):406–15.

    Article  CAS  PubMed  Google Scholar 

  128. Wilkin TJ. The accelerator hypothesis: weight gain as the missing link between type I and type II diabetes. Diabetologia. 2001;44:914–22.

    Article  CAS  PubMed  Google Scholar 

  129. Daneman D. Is the ‘accelerator hypothesis’ worthy of our attention? Diabet Med. 2005;22(2):115–7.

    Article  CAS  PubMed  Google Scholar 

  130. Betts PR, Mulligan J, Ward P, Smith B, Wilkin T. Increasing body weight predicts the earlier onset of insulin-dependent diabetes in childhood: testing the ‘accelerator hypothesis’. Diabet Med. 2005;2:144–51.

    Article  Google Scholar 

  131. Mejía-León ME, Barca AM. Diet, microbiota and immune system in type 1 diabetes development and evolution. Nutrients. 2015;7(11):9171–84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Zaccardi F, Webb DR, Yates T, Davies MJ. Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective. Postgrad Med J. 2015;pii: postgradmedj-2015-133281. doi:10.1136/postgradmedj-2015-133281. [Epub ahead of print] Review. PMID:26621825.

    Google Scholar 

  133. Ziegler AG, Hummel M, Schenker M, Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes. 1999;48:460–8.

    Article  CAS  PubMed  Google Scholar 

  134. Achenbach P, Bonifacio E, Koczwara K, Ziegler AG. Natural history of type 1 diabetes. Diabetes. 2005;54 Suppl 2:S25–31.

    Article  CAS  PubMed  Google Scholar 

  135. Mallone R, van Endert P. T cells in the pathogenesis of type 1 diabetes. Curr Diabetes Rep. 2008;8(2):101–6.

    Article  CAS  Google Scholar 

  136. Gepts W, Lecompte PM. The pancreatic islets in diabetes. Am J Med. 1981;70:105–15.

    Article  CAS  PubMed  Google Scholar 

  137. Hanninen A, Jalkanen S, Salmi M, et al. Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus. J Clin Invest. 1992;90:1901–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. von Herrath M, Sanda S, Herold K. Type 1 diabetes as a relapsing–remitting disease? Nat Rev Immunol. 2007;7:988–94.

    Article  CAS  Google Scholar 

  139. Siljander HT, Veijola R, Reunanen A, Virtanen SM, Akerblom HK, Knip M. Prediction of type 1 diabetes among siblings of affected children and in the general population. Diabetologia. 2007;50(11):2272–5.

    Article  CAS  PubMed  Google Scholar 

  140. Hummel M, Bonifacio E, Schmid S, Walter M, Knopff A, Ziegler AG. Brief communication: early appearance of islet autoantibodies predicts childhood type 1 diabetes in offspring of diabetic parents. Ann Intern Med. 2004;140(11):882–6.

    Article  PubMed  Google Scholar 

  141. Gullstrand C, Wahlberg J, Ilonen J, Vaarala O, Ludvigsson J. Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study. Pediatr Diabetes. 2008;9(3 Pt 1):182–90. Epub 2008 Mar 5.

    Article  PubMed  Google Scholar 

  142. Knip M, Karjalainen J, Akerblom HK. Islet cell antibodies are less predictive of IDDM among unaffected children in the general population than in sibs of children with diabetes. The Childhood Diabetes in Finland Study Group. Diabetes Care. 1998;21(10):1670–3.

    Article  CAS  PubMed  Google Scholar 

  143. Matveyenko AV, Butler PC. Relationship between beta-cell mass and diabetes onset. Diabetes Obes Metab. 2008;10 Suppl 4:23–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Sherry NA, Tsai EB, Herold KC. Natural history of beta-cell function in type 1 diabetes. Diabetes. 2005;54 Suppl 2:S32–9.

    Article  CAS  PubMed  Google Scholar 

  145. Roche EF, Menon A, Gill D, Hoey H. Clinical presentation of type 1 diabetes. Pediatr Diabetes. 2005;6(2):75–8.

    Article  PubMed  Google Scholar 

  146. Lévy-Marchal C, Patterson CC, Green A, EURODIAB ACE Study Group. Geographical variation of presentation at diagnosis of type I diabetes in children: the EURODIAB study (European and Diabetes). Diabetologia. 2001;44 Suppl 3:B75–80.

    Article  PubMed  Google Scholar 

  147. Hekkala A, Knip M, Veijola R. Ketoacidosis at diagnosis of type 1 diabetes in children in northern Finland: temporal changes over 20 years. Diabetes Care. 2007;30(4):861–6.

    Article  CAS  PubMed  Google Scholar 

  148. Dunger DB, Sperling MA, Acerini CL, et al. ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child. 2004;89(2):188–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Hanafusa T, Imagawa A. Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab. 2007;3(1):36–45.

    Article  CAS  PubMed  Google Scholar 

  150. Cho YM, Kim JT, Ko KS, et al. Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes. Diabetologia. 2007;50(11):2276–9. Epub 2007 Aug 28.

    Article  CAS  PubMed  Google Scholar 

  151. Endo T, Takizawa S, Tanaka S, et al. Amylase {alpha}-2A autoantibodies: novel marker of autoimmune pancreatitis and fulminant type 1 diabetes mellitus. Diabetes. 2008;58:732–7.

    Article  PubMed  CAS  Google Scholar 

  152. Martin S, Pawlowski B, Greulich B, Zieglen A, Mandrup-Poulsen T, Mahan J. Natural course of remission in IDDM during 1st year after diagnosis. Diabetes Care. 1992;15:66–74.

    Article  CAS  PubMed  Google Scholar 

  153. Wallensteen M, Dahlguiat G, Persson B, et al. Factors influencing the magnitude, duration and rate of fall of β cell function in type 1 (insulin-dependent) diabetic children followed for two years from their clinical diagnosis. Diabetologia. 1988;31:664–9.

    Article  CAS  PubMed  Google Scholar 

  154. Dost A, Herbst A, Kintzel K, et al. Shorter remission period in young versus older children with diabetes mellitus type 1. Exp Clin Endocrinol Diabetes. 2007;115(1):33–7.

    Article  CAS  PubMed  Google Scholar 

  155. Skrivarhaug T, Bangstad HJ, Stene LC, Sandvik L, Hanssen KF, Joner G. Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway. Diabetologia. 2006;49:298–305.

    Article  CAS  PubMed  Google Scholar 

  156. Laing SP, Swerdlow AJ, Slater SD, et al. Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia. 2003;46:760–5.

    Article  CAS  PubMed  Google Scholar 

  157. Dahl-Jorgensen K, Larsen JR, Hanssen KF. Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment? Diabetologia. 2005;48:1445–53.

    Article  CAS  PubMed  Google Scholar 

  158. Krantz JS, Mack WJ, Hodis HN, Liu CR, Liu CH, Kaufman FR. Early onset of subclinical atherosclerosis in young persons with type 1 diabetes. J Pediatr. 2004;145:452–7.

    Article  PubMed  Google Scholar 

  159. Libby P, Nathan DM, Abraham K, et al. Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases working group on cardiovascular complications of type 1 diabetes mellitus. Circulation. 2005;111:3489–93.

    Article  PubMed  Google Scholar 

  160. Lorini R, D‘Annunzio G, Vitali L, Scaramuzza A. IDDM and autoimmune thyroid disease in the pediatric age group. J Pediatr Endocrinol Metab. 1996;9:89–94.

    PubMed  Google Scholar 

  161. Kordonouri O, Klinghammer A, Lang EB, Grueters-kieslich A, Grabert M, Holl RW. Thyroid autoimmunity in children and adolescents with type 1 diabetes. Diabetes Care. 2002;25:1346–50.

    Article  PubMed  Google Scholar 

  162. Sumnik Z, Cinek O, Bratanic N, et al. Thyroid autoimmunity in children with coexisting type 1 diabetes mellitus and celiac disease: a multicenter study. J Pediatr Endocrinol Metab. 2006;19:517–22.

    CAS  PubMed  Google Scholar 

  163. Cronin C, Shanahan F. Insulin-dependent diabetes mellitus and coeliac disease. Lancet. 1997;349:1096–7.

    Article  CAS  PubMed  Google Scholar 

  164. Crone J, Rami B, Huber WD, Granditsch G, Schober E. Prevalence of coeliac disease and follow-up of EMA in children and adolescents with type 1 diabetes mellitus. J Pediatr Gastroenterol Nutr. 2003;37:67–71.

    Article  CAS  PubMed  Google Scholar 

  165. Freemark M, Levitsky LL. Screening for celiac disease in children with type 1 diabetes. Diabetes Care. 2003;26:1932–9.

    Article  PubMed  Google Scholar 

  166. Fröhlich-Reiterer EE, Hofer S, Kaspers S, et al. Screening frequency for celiac disease and autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus – data from a German/Austrian multicentre survey. Pediatr Diabetes. 2008;9(6):546–53.

    Article  PubMed  Google Scholar 

  167. TRIGR Study Group. Study design of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR). Pediatr Diabetes. 2007;8(3):117–37.

    Article  Google Scholar 

  168. Schmid S, Buuck D, Knopff A, Bonifacio E, Ziegler AG. BABYDIET, a feasibility study to prevent the appearance of islet autoantibodies in relatives of patients with type 1 diabetes by delaying exposure to gluten. Diabetologia. 2004;47(6):1130–1.

    Article  CAS  PubMed  Google Scholar 

  169. Stene LC, Joner G, Norwegian Childhood Diabetes Study Group. Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case–control study. Am J Clin Nutr. 2003;78(6):1128–34.

    CAS  PubMed  Google Scholar 

  170. Gale EA, Bingley PJ, Emmett CL, Collier T, European Nicotinamide Diabetes Intervention Trial (ENDIT) Group. European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet. 2004;363(9413):925–31.

    Article  CAS  PubMed  Google Scholar 

  171. Diabetes Prevention Trial-Type 1 Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med. 2002;346:1685–91.

    Article  Google Scholar 

  172. Näntö-Salonen K, Kupila A, Simell S, et al. Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial. Lancet. 2008;372:1746–55.

    Article  PubMed  CAS  Google Scholar 

  173. Diabetes Prevention Trial-Type 1 Diabetes Study Group. Effects of oral insulin in relatives of patients with type 1 diabetes mellitus. Diabetes Care. 2005;28:1068–76.

    Article  Google Scholar 

  174. Mandrup-Poulsen TR, Mølvig JC, Andersen V, et al. Immunosuppression with cyclosporin induces clinical remission and improved beta cell function in patients with newly diagnosed insulin-dependent diabetes. A national and international multicenter study. Ugeskr Laeger. 1990;152(27):1963–9.

    CAS  PubMed  Google Scholar 

  175. Herold KC, Hagopian W, Auger JA, et al. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002;346(22):1692–8.

    Article  CAS  PubMed  Google Scholar 

  176. Li L, Yi Z, Tisch R, Wang B. Immunotherapy of type 1 diabetes. Arch Immunol Ther Exp (Warsz). 2008;56(4):227–36.

    Article  CAS  Google Scholar 

  177. Sadauskaite-Kuehne V, Ludvigsson J, Padaiga Z, Jasinskiene E, Samuelsson U. Longer breastfeeding is an independent protective factor against development of type 1 diabetes mellitus in childhood. Diabetes Metab Res Rev. 2004;20(2):150–7.

    Article  PubMed  Google Scholar 

  178. Hägglöf B, Blom L, Dahlquist G, Lönnberg G, Sahlin B. The Swedish childhood diabetes study: indications of severe psychological stress as a risk factor for type 1 (insulin-dependent) diabetes mellitus in childhood. Diabetologia. 1991;34(8):579–83.

    Article  PubMed  Google Scholar 

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Ali, O. (2017). Type 1 Diabetes Mellitus: Epidemiology, Genetics, Pathogenesis, and Clinical Manifestations. In: Poretsky, L. (eds) Principles of Diabetes Mellitus. Springer, Cham. https://doi.org/10.1007/978-3-319-18741-9_12

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