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Q: “What causes an immune response that will destroy the pancreas’ ability to produce insulin as in Type 1 diabetes?”Come up with the definitive answer to that, and there’s a Nobel Peace Prize in Medicine in your future. That said… we’ve some pretty good ideas. In short… T1 is a genetic condition, but MUST be “triggered” (by one of several known - or as yet unknown - environmental factors), and it MUST be at a susceptible time - when the gut microbiome is in a weakened state, or simply not “in prime condition”.BUT FIRST… it is ABSOLUTELY NECESSARY to carry the genetic markers that bestow susceptibility; without those, you WILL NOT develop T1 - whether exposed to a “trigger” or not. AND… even in identical twins, T1 is NOT consistent; having a T1 relative - even an identical twin - does NOT mean you will get the disease; as a matter of fact, in more than 50% of those that develop T1 that have an identical twin, the identical twin never develops the disease.It is important to understand that there is NO single gene that causes susceptibility to T1; it is a combination of certain genetic alleles that bestows the risk upon an individual, and that alone is NOT enough to cause the disease. AND… there are several causative combinations of alleles, though some confer more risk than others.On “triggers” that initiate the disease development…Many viruses have been linked to T1; the most common ones are the family of enteroviruses. This “family” is the largest family of viruses that plague humans, though most of them are relatively harmless, causing little more than mild cold symptoms, and readily overcome. Except, of course, in those cases where they trigger the T1 autoimmune response. A few other common viruses that have been identified as triggers of T1 are mumps, rubella, rotavirus, cytomegalovirus, and ljunganvirus.AND… several bacteria are suspected triggers of T1. The gut microbiome is a key component of the immune system - and issues therein can make a carrier of the genetic risk factors more susceptible to development of the disease. SO… not only do you have to carry the genetic risk factors, AND be exposed to an environmental trigger, but ALSO that exposure must happen at a susceptible time vis-a-vis the gut microbiome.AND… several dietary habits are suspected sources of “triggers” for T1. AND a few other environmental factors.In short - this is a very complex issue, and involves a LOT of factors. It is likely that many more years of study will be required to even begin to identify who’s “really” at risk for the disease, and then, many more years of research to identify the actual diseases progression “steps” in order to intervene effectively.For a more in-depth understanding of these issues… here’s a short reading list:Åkerblom HK, Vaarala O, Hyöty H, Ilonen J, Knip M 2002. Environmental factors in the etiology of type 1 diabetes. Am J Med Genet 115: 18–29 [PubMed] [Google Scholar]Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, Cheng G, Yamasaki S, Saito T, Ohba Y, et al. 2011. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331: 337–341 [PMC free article] [PubMed] [Google Scholar]Barnett AH, Eff C, Leslie RDG, Pyke DA 1981. Diabetes in identical twins. A study of 200 pairs. Diabetologia 20: 87–93 [PubMed] [Google Scholar]Blomquist M, Juhela S, Erkkilä S, Korhonen S, Simell T, Kupila A, Vaarala O, Simell O, Knip M, Ilonen J 2002. Rotavirus infections and development of diabetes-associated autoantibodies during the first 2 years of life. Clin Exp Immunol 128: 511–515 [PMC free article] [PubMed] [Google Scholar]Brown CT, Davis-Richardson AG, Giongo A, Gano KA, Crabb DB, Mukherjee N, Casella G, Drew JC, Ilonen J, Knip M, et al. 2011. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS ONE 6: e25792. [PMC free article] [PubMed] [Google Scholar]Chase HP, Lescheck R, Rafkin-Mervis L, Krause-Steinrauf H, Chritton S, Asare S, Adams S, Skyler JS, Clare-Salzier M, Type 1 Diabetes Trialnet NIP Study Group 2009. Nutritional intervention to prevent (NIP) type 1 diabetes: A pilot trial. Infant Child Adolesc Nutr 1: 99–107 [Google Scholar]Dahlquist GG, Blom L, Persson LÅ, Sandström AI, Wall SG 1990. Dietary factors and the risk of developing insulin dependent diabetes in childhood. Br Med J 300: 1302–1306 [PMC free article] [PubMed] [Google Scholar]Fuchtenbusch M, Irnstetter A, Jager G, Ziegler AG 2001. No evidence for an association of coxsackie virus infections during pregnancy and early childhood with development of islet autoantibodies in offspring of mothers or fathers with type 1 diabetes. J Autoimmun 17: 333–340 [PubMed] [Google Scholar]Gillespie KM, Bain SC, Barnett AH, Bingley PJ, Christie MR, Gill GV, Gale EA 2004. The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes. Lancet 364: 1699–1700 [PubMed] [Google Scholar]Giongo A, Mukherjee N, Gano KA, Crabb DB, Casella G, Drew JC, Ilonen J, Knip M, Hyöty H, Veijola R, et al. 2011. Toward defining the autoimmune microbiome for type 1 diabetes. ISME J 5: 82–91 [PMC free article] [PubMed] [Google Scholar]Graves PM, Rotbart HA, Nix WA, Pallansch MA, Erlich HA, Norris JM, Hoffman M, Eisenbarth GS, Rewers M 2003. Prospective study of enteroviral infections and development of β-cell autoimmunity. Diabetes autoimmunity study in the young (DAISY). Diabetes Res Clin Pract 59: 51–61 [PubMed] [Google Scholar]Hermann R, Knip M, Veijola R, Simell O, Laine AP, Åkerblom HK, Groop PH, Forsblom C, Petterson-Fernholm K, Ilonen J, et al. 2003. Temporal changes in the frequencies of HLA genotypes in patients with type 1 diabetes—indication of an increased environmental pressure? Diabetologia 46: 420–425 [PubMed] [Google Scholar]Hindmarsh PC, Matthews DR, Di Silvio L, Kurz AB, Brook CG 1988. Relation between height velocity and fasting insulin concentrations. Arch Dis Child 63: 665–666 [PMC free article] [PubMed] [Google Scholar]Holmberg H, Wahlberg J, Vaarala O, Ludvigsson J, the ABIS studygroup 2007. Short duration of breast-feeding as a risk factor for β-cell autoantibodies in 5-year-old children from the general population. Br J Nutr 97: 111–116 [PubMed] [Google Scholar]Honeyman MC, Stone NL, Harrison LC 1998. T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: Potential for mimicry with rotavirus and other environmental agents. Mol Med 4: 231–239 [PMC free article] [PubMed] [Google Scholar]Honeyman MC, Coulson BS, Stone NL, Gellert SA, Goldwater PN, Steele CE, Couper JJ, Tait BD, Colman PG, Harrison LC 1999. Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. Diabetes 49: 1319–1324 [PubMed] [Google Scholar]Honeyman MC, Stone NL, Falk BA, Nepom G, Harrison LC 2010. Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J Immunol 184: 2204–2210 [PubMed] [Google Scholar]Hummel M, Bonifacio E, Naserke HE, Ziegler AG 2002. Elimination of dietary gluten does not reduce titers of type 1 diabetes-associated autoantibodies in high-risk subjects. Diabetes Care 25: 1111–1116 [PubMed] [Google Scholar]Hummel S, Pflüger M, Hummel M, Bonifacio E, Ziegler AG 2011. Primary dietary intervention study to reduce the risk of islet autoimmunity in children at increased risk for type 1 diabetes: The BABYDIET study. Diabetes Care 34: 1301–1305 [PMC free article] [PubMed] [Google Scholar]Hyöty H, Taylor KW 2002. The role of viruses in human diabetes. Diabetologia 45: 1353–1361 [PubMed] [Google Scholar]Hyppönen E, Kenward MG, Virtanen SM, Piitulainen A, Virta-Autio P, Knip M, Åkerblom HK, the Childhood Diabetes in Finland Study Group 1999. Infant feeding, early weight gain and risk of type 1 diabetes. Diabetes Care 22: 1961–1965 [PubMed] [Google Scholar]Hyppönen E, Virtanen SM, Kenward MG, Knip M, Åkerblom HK, the Childhood Diabetes in Finland Study Group 2000. Obesity, increased linear growth and risk of type 1 diabetes mellitus in children. Diabetes Care 23: 1755–1760 [PubMed] [Google Scholar]Hyppönen E, Läärä E, Järvelin MR, Virtanen SM 2001. Intake of vitamin D and risk of type 1 diabetes: A birth cohort study. Lancet 358: 1500–1504 [PubMed] [Google Scholar]Kaprio J, Tuomilehto J, Koskenvuo M, Romanov K, Reunanen A, Eriksson J, Stengård J, Kesäniemi YA 1992. Concordance for Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Diabetologia 35: 1060–1067 [PubMed] [Google Scholar]Kim CY, Quarsten H, Bergseng E, Khosla C, Sollid LM 2004. Structural basis for HLA-DQ2-mediated presentation of gluten epitopes in celiac disease. Proc Natl Acad Sci 101: 4175–4179 [PMC free article] [PubMed] [Google Scholar]Kimpimäki T, Kupila A, Hämäläinen A-M, Kukko M, Kulmala P, Savola K, Simell T, Muona P, Ilonen J, Simell O, et al. 2001a. The first signs of ß-cell autoimmunity appear in infancy in genetically susceptible children from the general population: The Finnish Type 1 Diabetes Prediction and Prevention Study. J Clin Endocrinol Metab 86: 4782–4788 [PubMed] [Google Scholar]Kimpimäki T, Erkkola M, Korhonen S, Kupila A, Virtanen SM, Ilonen J, Simell O, Knip M 2001b. Short exclusive breast-feeding predisposes young children with increased genetic risk of type 1 diabetes to progressive β-cell autoimmunity. Diabetologia 44: 63–69 [PubMed] [Google Scholar]Knip M 2011. Pathogenesis of type 1 diabetes: Implications for incidence trends. Horm Res 76: 57–64 [PubMed] [Google Scholar]Knip M, Hyöty H 2008. Environmental determinants: The role of viruses and standard of hygiene. In Epidemiology of Pediatric and Adolescent Diabetes (ed. Dabelea D, Klingensmith GJ), pp. 63–64 Informa Healthcare, New York [Google Scholar]Knip M, Siljander H 2008. Autoimmune mechanisms in type 1 diabetes. Autoimmun Rev 7: 550–557 [PubMed] [Google Scholar]Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Åkerblom HK 2005. Environmental triggers and determinants of β-cell autoimmunity and type 1 diabetes. Diabetes 54: S125–S136 [PubMed] [Google Scholar]Knip M, Korhonen S, Kulmala P, Veijola R, Reunanen A, Raitakari OT, Viikari J, Åkerblom HK 2010a. Prediction of type 1 diabetes in the general population. Diabetes Care 33: 1206–1212 [PMC free article] [PubMed] [Google Scholar]Knip M, Virtanen SM, Åkerblom HK 2010b. Infant feeding and risk of type 1 diabetes. Am J Clin Nutr 91: 1506S–1513S [PMC free article] [PubMed] [Google Scholar]Knip M, Virtanen SM, Seppä K, Ilonen J, Savilahti E, Vaarala O, Reunanen A, Teramo K, Hämäläinen AM, Paronen J, et al. 2010c. Dietary intervention in infancy and later signs of β-cell autoimmunity. N Engl J Med 363: 1900–1908 [PMC free article] [PubMed] [Google Scholar]Kondrashova A, Reunanen A, Romanov A, Karvonen A, Viskari H, Vesikari T, Ilonen J, Knip M, Hyöty H 2005. A sixfold gradient in the incidence of type 1 diabetes at the eastern border of Finland. Ann Med 37: 67–72 [PubMed] [Google Scholar]Kostraba JN, Cruickshanks KJ, Lawler-Heavner J, Jobim LF, Rewers MJ, Gay EC, Chase HP, Klingensmith G, Hamman RF 1993. Early exposure to cow's milk and solid foods in infancy, genetic predisposition, and risk of IDDM. Diabetes 42: 288–295 [PubMed] [Google Scholar]Kukko M, Virtanen SM, Toivonen A, Erkkilä S, Korhonen S, Ilonen J, Simell O, Knip M 2004. Geographic variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of β-cell autoimmunity within a high incidence country. Diabetes Care 27: 676–681 [PubMed] [Google Scholar]Kukko M, Kimpimäki T, Korhonen S, Kupila A, Simell S, Veijola R, Simell T, Ilonen J, Simell O, Knip M 2005. Dynamics of diabetes-associated autoantibodies in young children with HLA-conferred risk of type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 90: 2712–2717 [PubMed] [Google Scholar]Lamb MM, Yin X, Barriga K, Hoffman MR, Barón AE, Eisenbarth GS, Rewers M, Norris JM 2008. Dietary glycemic index, development of islet autoimmunity, and subsequent progression to type 1 diabetes in young children. J Clin Endocrinol Metab 93: 3936–3942 [PMC free article] [PubMed] [Google Scholar]Lamb MM, Yin X, Zerbe GO, Klingensmith GJ, Dabelea D, Fingerlin TE, Rewers M, Norris JM 2009. Height growth velocity, islet autoimmunity and type 1 diabetes development: The Diabetes Autoimmunity Study in the Young. Diabetologia 52: 2064–2071 [PMC free article] [PubMed] [Google Scholar]Lempainen J, Vaarala O, Mäkelä M, Veijola R, Simell O, Knip M, Hermann R, Ilonen J 2009. Interplay between genetic and dietary factors in type 1 diabetes. J Autoimmun 33: 155–163 [PubMed] [Google Scholar]Lempainen J, Tauriainen S, Vaarala O, Mäkelä M, Honkanen H, Marttila J, Veijola R, Simell O, Hyöty H, Knip M, et al. 2012. Interaction of enterovirus infection and cow's milk based formula nutrition in type 1 diabetes-associated autoimmunity. Diabetes Metab Res Rev 28: 177–185 [PubMed] [Google Scholar]Lipponen K, Gombos Z, Kiviniemi M, Siljander H, Hermann R, Veijola R, Simell O, Knip M, Ilonen J 2010. Effect of HLA class I and class II alleles on progression from autoantibody positivity to overt type 1 diabetes. Diabetes 59: 3253–3256 [PMC free article] [PubMed] [Google Scholar]Lönnrot M, Korpela K, Knip M, Ilonen J, Simell O, Korhonen S, Savola K, Muona P, Simell T, Koskela P, et al. 2000. Enterovirus infection as a risk factor for ß-cell autoimmunity in a prospectively observed birth cohort—The Finnish Diabetes Prediction and Prevention (DIPP) Study. Diabetes 49: 1314–1318 [PubMed] [Google Scholar]Mrena S, Savola K, Kulmala P, Åkerblom HK, Knip M, the Childhood Diabetes in Finland Study Group 2003. Natural course of preclinical Type 1 diabetes in siblings of affected children. Acta Paediatr 92: 1403–1410 [PubMed] [Google Scholar]Norris JM, Barriga K, Klingensmith G, Hoffman M, Eisenbarth GS, Erlich HA, Rewers M 2003. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 290: 1713–1720 [PubMed] [Google Scholar]Norris JM, Yin X, Lamb MM, Barriga K, Seifert J, Hoffman M, Orton HD, Barón AE, Clare-Salzler M, Chase HP, et al. 2007. Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA 298: 1420–1428 [PubMed] [Google Scholar]Oikarinen S, Martiskainen M, Tauriainen S, Huhtala H, Ilonen J, Veijola R, Simell O, Knip M, Hyöty H 2011. Enterovirus RNA in blood is linked to the development of type 1 diabetes. Diabetes 60: 276–279 [PMC free article] [PubMed] [Google Scholar]Orešič M, Simell S, Sysi-Aho M, Nänto-Salonen K, Seppänen-Laakso T, Parikka V, Mattila I, Keskinen P, Katajamaa M, Yetukuri L, et al. 2008. Dysregulation of lipid and amino acid metabolism precedes autoimmunity in children who later progress to type 1 diabetes. J Exp Med 205: 2975–2984 [PMC free article] [PubMed] [Google Scholar]Palmer JP, Helquist S, Spinas GA, Mølvig J, Mandrup-Poulsen T, Andersen HU, Nerup J 1989. Interaction of β-cell activity and IL-1 concentration and exposure time in isolated rat islets of Langerhans. Diabetes 38: 1211–1216 [PubMed] [Google Scholar]Parikka V, Näntö-Salonen K, Saarinen M, Simell T, Ilonen J, Hyöty H, Veijola R, Knip M, Simell O 2012. Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk. Diabetologia 10.1007/s00125-012-2523-3 [PubMed] [CrossRef] [Google Scholar]Pastore MR, Bazzigaluppi E, Belloni C, Arcovio C, Bonifacio E, Bosi E 2003. Six months of gluten-free diet do not influence autoantibody titers, but improve insulin secretion in subjects at high risk for type 1 diabetes. J Clin Endocrinol Metab 88: 162–165 [PubMed] [Google Scholar]Peng H, Hagopian W 2006. Environmental factors in the development of Type 1 diabetes. Rev Endocr Metab Disord 7: 149–162 [PubMed] [Google Scholar]Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, McGee PF, Moran AM, et al. 2009. Rituximab, B-lymphocyte depletion, and preservation of β-cell function. N Engl J Med 361: 2143–2152 [PMC free article] [PubMed] [Google Scholar]Pflueger M, Seppänen-Laakso T, Suortti T, Hyötyläinen T, Achenbach P, Bonifacio E, Oresic M, Ziegler AG 2011. Age- and islet autoimmunity-associated differences in amino acid and lipid metabolites in children at risk for type 1 diabetes. Diabetes 60: 2740–2747 [PMC free article] [PubMed] [Google Scholar]Pociot F, Akolkar B, Concannon P, Erlich HA, Julier C, Morahan G, Nierras CR, Todd JA, Rich S, Nerup J 2010. Genetics of type 1 diabetes: What's next? Diabetes 59: 1561–1571 [PMC free article] [PubMed] [Google Scholar]Räsänen M, Kronberg-Kippilä C, Ahonen S, Uusitalo L, Kautiainen S, Erkkola M, Veijola R, Knip M, Kaila M, Virtanen SM 2006. Intake of vitamin D by Finnish children aged 3 months to 3 years in relation to sociodemographic factors. Eur J Clin Nutr 60: 1317–1322 [PubMed] [Google Scholar]Sabbah E, Savola K, Ebeling T, Kulmala P, Vähäsalo P, Salmela P, Knip M 2000. Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset Type 1 diabetes mellitus. Diabetes Care 23: 1326–1332 [PubMed] [Google Scholar]Siljander H, Simell S, Hekkala A, Lähde J, Simell T, Vähäsalo P, Veijola R, Ilonen J, Simell O, Knip M 2009. Predictive value of diabetes-associated autoantibodies among children with HLA-conferred disease susceptibility recruited from the general population. Diabetes 58: 2835–2842 [PMC free article] [PubMed] [Google Scholar]Simonen-Tikka ML, Pflueger M, Klemola P, Savolainen-Kopra C, Smura T, Hummel S, Kaijalainen S, Nuutila K, Natri O, Roivainen M, et al. 2011. Human enterovirus infections in children at increased risk for type 1 diabetes: The Babydiet study. Diabetologia 54: 2995–3002 [PubMed] [Google Scholar]Simpson M, Brady H, Yin X, Seifert J, Barriga K, Hoffman M, Bugawan T, Barón AE, Sokol RJ, Eisenbarth G, et al. 2011. No association of vitamin D intake or 25-hydroxyvitamin D levels in childhood with risk of islet autoimmunity and type 1 diabetes: The Diabetes Autoimmunity Study in the Young (DAISY). Diabetologia 54: 2779–2788 [PMC free article] [PubMed] [Google Scholar]Stene LC, Joner G, Norwegian Childhood Diabetes Study Group 2003. 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 78: 1128–1134 [PubMed] [Google Scholar]Stene LC, Thorsby PM, Berg JP, Rønningen KS, Joner G, Norwegian Childhood Diabetes Study Group 2008. Peroxisome proliferator-activated receptor-γ2 Pro12Ala polymorphism, cod liver oil and risk of type 1 diabetes. Pediatr Diabetes 9: 40–45 [PubMed] [Google Scholar]Stene LC, Oikarinen S, Hyöty H, Barriga KJ, Norris JM, Klingensmith G, Hutton JC, Erlich HA, Eisenbarth GS, Rewers M 2010. Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: The Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes 39: 3174–3180 [PMC free article] [PubMed] [Google Scholar]Streng J 1946. Over de beoordeling van de voedingstoestand in de praktijk (in Dutch, summary in English). Maandschrift v Kindergen 14: 67–78 [Google Scholar]Sysi-Aho M, Ermolov A, Tripathi A, Seppänen-Laakso T, Ruohonen ST, Toukola L, Yetukuri L, Härkönen T, Lindfors E, Nikkilä J, et al. 2011. Metabolic regulation in progression to autoimmune diabetes. PLoS Comput Biol 7: e1002257. [PMC free article] [PubMed] [Google Scholar]Tauriainen S, Oikarinen S, Oikarinen M, Hyöty H 2011. Enteroviruses in the pathogenesis of type 1 diabetes. Semin Immunopathol 33: 45–55 [PubMed] [Google Scholar]The EURODIAB ACE Study Group and The EURODIAB ACE Substudy 2 Study Group 1998. Familial risk of Type I diabetes in European children. Diabetologia 41: 1151–1156 [PubMed] [Google Scholar]The EURODIAB ACE Study Group 2000. Variation and trends in incidence of childhood diabetes in Europe. Lancet 355: 873–876 [PubMed] [Google Scholar]The EURODIAB Substudy 2 Study Group 1999. Vitamin D supplement in early childhood and risk of Type I (insulin-dependent) diabetes mellitus. Diabetologia 42: 51–54 [PubMed] [Google Scholar]The EURODIAB Substudy 2 Study Group 2001. Rapid early growth is associated with increased risk of childhood type 1 diabetes in various European populations. Diabetes Care 25: 1755–1760 [PubMed] [Google Scholar]The TRIGR Study Group 2011. The Trial to Reduce IDDM in the Genetically at Risk (TRIGR ) study: Recruitment, intervention and follow-up. Diabetologia 54: 627–633 [PMC free article] [PubMed] [Google Scholar]Vaarala O, Knip M, Paronen J, Hämäläinen A-M, Muona P, Väätäinen M, Ilonen J, Simell O, Åkerblom HK 1999. Cow milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes. Diabetes 48: 1389–1394 [PubMed] [Google Scholar]Vaarala O, Atkinson MA, Neu J 2008. The “perfect storm” for type 1 diabetes: The complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Diabetes 57: 2555–2562 [PMC free article] [PubMed] [Google Scholar]Vaarala O, Ilonen J, Ruohtula T, Pesola J, Virtanen SM, Härkönen T, Koski M, Kallioinen H, Tossavainen O, Poussa T, et al. 2012. Removal of bovine insulin from cow's milk formula and early initiation of β-cell autoimmunity. Arch Pediat Adol Med 10.1001/archpediatrics.2011.1559 [PubMed] [CrossRef] [Google Scholar]Verge CF, Howard NJ, Irwig L, Simpson JM, Mackerras D, Silink M 1994. Environmental factors in childhood IDDM: A population-based case-control study. Diabetes Care 17: 1381–1389 [PubMed] [Google Scholar]Virtanen SM, Knip M 2003. Nutritional risk predictors of β cell autoimmunity and type 1 diabetes at a young age. Am J Clin Nutr 78: 1053–1067 [PubMed] [Google Scholar]Virtanen SM, Räsänen L, Aro A, Lindström J, Sippola H, Lounamaa R, Toivanen L, Tuomilehto J, Akerblom HK 1991. Infant feeding in Finnish children <7 yr of age with newly diagnosed IDDM. Diabetes Care 14: 415–417 [PubMed] [Google Scholar]Virtanen SM, Räsänen L, Ylönen K, Aro A, Clayton D, Langholz B, Pitkäniemi J, Savilahti E, Lounamaa R, Tuomilehto J, et al. 1993. Early introduction of dairy products associated with increased risk of IDDM in Finnish children. Diabetes 42: 1786–1790 [PubMed] [Google Scholar]Virtanen SM, Hyppönen E, Läärä E, Vähäsalo P, Kulmala P, Savola K, Räsänen L, Knip M, Åkerblom HK, the Childhood Diabetes in Finland Study Group 1998. Cow's milk consumption, disease associated autoantibodies and Type 1 diabetes mellitus: A follow-up study in siblings of diabetic children. Diabetic Med 15: 730–738 [PubMed] [Google Scholar]Virtanen SM, Kenward MG, Erkkola M, Kautiainen S, Kronberg-Kippilä C, Hakulinen T, Ahonen S, Uusitalo L, Veijola R, Simell OG, et al. 2006. Age at introduction of new foods and advanced β-cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes. Diabetologia 49: 1512–1521 [PubMed] [Google Scholar]Virtanen SM, Nevalainen J, Kronberg-Kippilä C, Ahonen S, Tapanainen H, Uusitalo L, Takkinen HM, Niinistö S, Ovaskainen M-L, Kenward MG, et al. 2012. Food consumption during childhood and advanced β-cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes: A nested case-control study. Am J Clin Nutr 95: 471–478 [PubMed] [Google Scholar]Viskari H, Kondrashova A, Koskela P, Knip M, Hyöty H 2006. Circulating vitamin D concentrations in two neighboring populations with markedly different incidence of type 1 diabetes. Diabetes Care 49: 1458–1459 [PubMed] [Google Scholar]Wadsworth EJK, Shield JPH, Hunt LP, Baum JD 1997. A case-control study of environmental factors associated with diabetes in the under 5s. Diabet Med 14: 390–396 [PubMed] [Google Scholar]Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, et al. 2008. Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455: 1109–1113 [PMC free article] [PubMed] [Google Scholar]Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, Rewers M, Eisenbarth GS, Jensen J, Davidson HW, et al. 2007. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci 104: 17040–17045 [PMC free article] [PubMed] [Google Scholar]Wilkin TJ 2001. The accelerator hypothesis: Weight gain as the missing link between type 1 and type 2 diabetes. Diabetologia 44: 914–922 [PubMed] [Google Scholar]Yeung WC, Rawlinson WD, Craig M 2011. Enterovirus infection and type 1 diabetes mellitus: Systematic review and meta-analysis of observational molecular studies. BMJ 342: d35 [PMC free article] [PubMed] [Google Scholar]Ziegler A-G, Hummel M, Schenker M, Bonifacio E 1999. 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 48: 460–468 [PubMed] [Google Scholar]Ziegler A-G, Schmid S, Huber D, Hummel M, Bonifacio E 2003. Early infant feeding and risk of developing Type 1 diabetes-associated autoantibodies. JAMA 290: 1721–1728 [PubMed] [Google Scholar]Zipitis CS, Akobeng AK 2008. Vitamin D supplementation in early childhood and risk of type 1 diabetes: A systematic review and meta-analysis. Arch Dis Childr 93: 512–517 [PubMed] [Google Scholar]