1 Children’s Hospital (MK), University of Helsinki and Helsinki University Central Hospital, FI-00014 Helsinki, Finland; Folkhälsan Research Center (MK), FI-00290 Helsinki, Finland; Department of Pediatrics (MK), Tampere University Hospital, FI-33520 Tampere, Finland; and Department of Pediatrics (OS), University of Turku and Turku University Hospital, FI-20014 Turku, Finland
Author and Copyright Information
- Details about the Author
- Copyright and Licensing Information
Type 1 diabetes (T1D) is a progressive autoimmune disease with a preclinical phase, potentially activated by infectious agents or dietary substances. Genetic predisposition is a factor, alongside triggers like dietary elements and changes in gut microbiome.
T1D is characterized by the specific loss of insulin-producing β cells in genetically vulnerable individuals. External factors, such as lifestyle and geographical differences, impact the disease’s occurrence. Studies on migrants and alterations in HLA genotypes suggest that environmental triggers contribute to disease advancement.
Recent findings propose that the onset of the disease process leading to T1D may occur before the age of 3, with varying rates of progression. Genetic and non-genetic factors, particularly HLA genes, influence the transition to autoantibody positivity, leading to clinical diabetes.
Progression to Clinical T1D
Autoantibodies signify the progression of β-cell autoimmunity, with identified markers predicting T1D. A proinflammatory state precedes the presence of autoantibodies, possibly influenced by factors like chronic infections, diet, and alterations in gut microbiome.
Evidence indicates early initiation of β-cell autoimmunity, with initial autoantibodies appearing before 3 months of age. Potential environmental triggers suggest a complex interaction between genetic susceptibility and external elements in T1D development.
Additional Information
Further research is being conducted to explore the role of environmental factors in T1D development. Factors such as air pollution, chemical exposure, and stress are being investigated for their potential impact on autoimmune diabetes.
In addition to viral infections, genetic predisposition also plays a significant role in the development of T1D. Identifying genetic markers associated with the disease can help in early detection and personalized treatment approaches.
Educating families about the early signs and symptoms of T1D is crucial for timely diagnosis and management. Increased awareness and screening programs can aid in identifying at-risk individuals and implementing preventive measures.
Collaborative efforts between researchers, healthcare professionals, and policymakers are essential in advancing our understanding of T1D and developing effective prevention strategies. Continued funding and support for research initiatives are vital in combating the rising prevalence of autoimmune diabetes.
Overall, a holistic approach that considers both genetic and environmental factors is needed to address the complex nature of T1D. By integrating various disciplines and perspectives, we can work towards better outcomes for individuals at risk of developing autoimmune diabetes.
INTERACTIONS
Understanding the complex interactions among various factors involved in β-cell autoimmunity and T1D development is crucial. Gene-gene, gene-environment, and environment-environment interactions play roles in the disease process leading to overt T1D. Unraveling these interplays is key to comprehending the disease’s progression.
Studies like the DIPP study have illustrated how gene and environment interactions impact T1D. For instance, the correlation between the predisposing PTPN22 polymorphism and infant feeding influenced the rate of transitioning to autoantibodies. Similarly, a study highlighted interactions between early exposure to enteroviruses and infant feeding. Further investigations are needed to identify these interactions in T1D development.
CONCLUDING REMARKS
Identifying environmental triggers of β-cell autoimmunity and T1D is vital for intervention and prevention. Delving into the role of environmental factors in disease pathogenesis is critical, as altering the environment can be an effective strategy in preventing T1D. Research indicates that environmental modifications can impact the natural progression of preclinical T1D, underscoring the necessity for additional studies.
Research backed by various foundations and organizations has enhanced our understanding of T1D development, emphasizing the significance of environmental factors and gene interactions in the disease process.
Continued research in this area is essential for advancing our knowledge and developing targeted interventions to prevent T1D. By addressing environmental factors and gene interactions, we can work towards reducing the incidence of this autoimmune disease and improving the quality of life for individuals at risk.
Collaboration between researchers, healthcare providers, and public health officials is crucial in implementing effective prevention strategies and promoting early detection of T1D. Education and awareness initiatives can also play a key role in empowering individuals to make healthy lifestyle choices and reduce their risk of developing T1D.
ACKNOWLEDGMENTS
This study received funding from numerous organizations, supporting the exploration of preventing and managing T1D. We would like to express our gratitude to the following organizations:
- Diabetes Research Institute Foundation
- American Diabetes Association
- JDRF (Juvenile Diabetes Research Foundation)
Footnotes
Editors: Jeffrey A. Bluestone, Mark A. Atkinson, and Peter Arvan
Discover more insights on Type 1 Diabetes at www.perspectivesinmedicine.org
REFERENCES
- Research on environmental factors in the etiology of type 1 diabetes emphasizes the importance of identifying disease triggers.
- A study on native Clostridium species suggests potential mechanisms for regulating T cells in the colon.
- Diabetes in identical twins and its implications for the disease are under investigation.
- Exploration of rotavirus infections and autoantibody development in children.
- Analysis of the gut microbiome sheds light on autoimmune processes in type 1 diabetes.
- Testing nutritional interventions to prevent type 1 diabetes.
- Investigating dietary factors and the risk of insulin-dependent diabetes in childhood.
- Exploring viral infections and their role in autoimmunity development.
- Studying the incidence of childhood type 1 diabetes and its correlation with HLA haplotypes.
- Defining the autoimmune microbiome in type 1 diabetes is a current research focus.
..
– Hypponen E, Virtanen SM, Kenward MG, Knip M, Akerblom 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 [DOI] [PubMed] [Google Scholar]
– (2001) is taken out
– Kaprio J, Tuomilehto J, Koskenvuo M, Romanov K, Reunanen A, Eriksson J, Stengard J, Kesaniemi 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 [DOI] [PubMed] [Google Scholar]
– Kim CY, Quarsten H, Bergseng E, Khosla C, Sollid LM 2004. Understanding how gluten epitopes in celiac disease are presented through HLA-DQ2. Proc Natl Acad Sci 101: 4175–4179 [DOI] [PMC free article] [PubMed] [Google Scholar]
– Kimpimaki T, Kupila A, Hamalainen A-M, Kukko M, Kulmala P, Savola K, Simell T, Muona P, Ilonen J, Simell O, et al. 2001. Identification of initial beta-cell autoimmunity signs in genetically susceptible infants: Insights from the Finnish Type 1 Diabetes Prediction and Prevention Study. J Clin Endocrinol Metab 86: 4782–4788 [DOI] [PubMed] [Google Scholar]
– Kimpimaki T, Erkkola M, Korhonen S, Kupila A, Virtanen SM, Ilonen J, Simell O, Knip M 2001. Increased risk of progressive β-cell autoimmunity in young children with genetic susceptibility to type 1 diabetes who were exclusively breastfed. Diabetologia 44: 63–69 [DOI] [PubMed] [Google Scholar]
– and so on.
– Sabbah E, Savola K, Ebeling T, Kulmala P, Vähäsalo P, Salmela P, Knip M 2000. Characteristics of childhood and adult-onset Type 1 diabetes mellitus from a genetic and autoimmune perspective. Diabetes Care 23: 1326–1332 [DOI] [PubMed] [Google Scholar]
– Siljander H, Simell S, Hekkala A, Lähde J, Simell T, Vähäsalo P, Veijola R, Ilonen J, Simell O, Knip M 2009. Diabetes-associated autoantibodies as predictors among children with HLA-conferred susceptibility. Diabetes 58: 2835–2842 [DOI] [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. Impact of human enterovirus infections on children at high risk for type 1 diabetes: Insights from the Babydiet study. Diabetologia 54: 2995–3002 [DOI] [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 correlation found between vitamin D intake or levels in childhood and the risk of islet autoimmunity and type 1 diabetes: Results from the Diabetes Autoimmunity Study in the Young (DAISY). Diabetologia 54: 2779–2788 [DOI] [PMC free article] [PubMed] [Google Scholar]
– Stene LC, Joner G, Norwegian Childhood Diabetes Study Group 2003. Association between cod liver oil use in the first year of life and reduced risk of childhood-onset type 1 diabetes: Evidence from a large, population-based, case-control study. Am J Clin Nutr 78: 1128–1134 [DOI] [PubMed] [Google Scholar]
– Stene LC, Thorsby PM, Berg JP, Rønningen KS, Joner G, Norwegian Childhood Diabetes Study Group 2008. Examination of the peroxisome proliferator-activated receptor-γ2 Pro12Ala polymorphism, cod liver oil consumption, and type 1 diabetes risk. Pediatr Diabetes 9: 40–45 [DOI] [PubMed] [Google Scholar]
– Stene LC, Oikarinen S, Hyöty H, Barriga KJ, Norris JM, Klingensmith G, Hutton JC, Erlich HA, Eisenbarth GS, Rewers M 2010. Impact of enterovirus infection on the progression from islet autoimmunity to type 1 diabetes: Findings from the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes 39: 3174–3180 [DOI] [PMC free article] [PubMed] [Google Scholar]
– Streng J 1946. Evaluation of nutritional status in practice (in Dutch, summary in English). Maandschrift v Kindergen 14: 67–78 [Google]
– 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. Regulation of metabolism in the development of autoimmune diabetes. PLoS Comput Biol 7: e1002257. [DOI] [PMC free article] [PubMed] [Google Scholar]
– Tauriainen S, Oikarinen S, Oikarinen M, Hyöty H 2011. Exploring the role of enteroviruses in the onset of type 1 diabetes. Semin Immunopathol 33: 45–55 [DOI] [PubMed] [Google Scholar]
– The EURODIAB ACE Study Group and The EURODIAB ACE Substudy 2 Study Group 1998. Familial predisposition to Type I diabetes in children throughout Europe. Diabetologia 41: 1151–1156 [DOI] [PubMed] [Google Scholar]
– The EURODIAB ACE Study Group 2000. Analysis of the incidence of childhood diabetes in Europe. Lancet 355: 873–876 [PubMed] [Google Scholar]
– The EURODIAB Substudy 2 Study Group 1999. Impact of vitamin D supplementation in early childhood on the risk of Type I (insulin-dependent) diabetes mellitus. Diabetologia 42: 51–54 [DOI] [PubMed] [Google Scholar]
– The EURODIAB Substudy 2 Study Group 2001. Early rapid growth linked to increased risk of childhood type 1 diabetes in different European populations. Diabetes Care 25: 1755–1760 [DOI] [PubMed] [Google Scholar]
– The TRIGR Study Group 2011. Recruiting, intervening, and following up in The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study. Diabetologia 54: 627–633 [DOI] [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. Initial exposure to cow milk formula triggers immune responses to insulin in infants with genetic predisposition for type 1 diabetes. Diabetes 48: 1389–1394 [DOI] [PubMed] [Google Scholar]
– Vaarala O, Atkinson MA, Neu J 2008. Unraveling the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity in the development of type 1 diabetes. Diabetes 57: 2555–2562 [DOI] [PMC free article] [PubMed] [Google Scholar]
– Vaarala O, Ilonen J, Ruotula T, Pesola J, Virtanen SM, Härkönen T, Koski M, Kallioinen H, Tossavainen O, Poussa T, et al. 2012. Elimination of bovine insulin from cow’s milk formula and early onset of β-cell autoimmunity. Arch Pediat Adol Med 10.1001/archpediatrics.2011.1559 [DOI] [PubMed] [Google Scholar]
– Verge CF, Howard NJ, Irwig L, Simpson JM, Mackerras D, Silink M 1994. Examining environmental factors contributing to childhood IDDM: Results from a population-based case-control study. Diabetes Care 17: 1381–1389 [DOI] [PubMed] [Google Scholar]
– Virtanen SM, Knip M 2003. Predictors of nutritional risks associated with β cell autoimmunity and type 1 diabetes in young individuals. Am J Clin Nutr 78: 1053–1067 [DOI] [PubMed] [Google Scholar]
– Virtanen SM, Räsänen L, Aro A, Lindström J, Sippola H, Lounamaa R, Toivanen L, Tuomilehto J, Akerblom HK 1991. Infant feeding practices in Finnish children
– Virtanen SM, Räsänen L, Ylönen K, Aro A, Clayton D, Langholz B, Pitkäniemi J, Savilahti E, Lounamaa R, Tuomilehto J, et al. 1993. Association between early introduction of dairy products and increased risk of IDDM in Finnish children. Diabetes 42: 1786–1790 [DOI] [PubMed] [Google Scholar]
– Virtanen SM, Hyppönen E, Läära E, Vähäsalo P, Kulmala P, Savola K, Räsänen L, Knip M, Åkerblom HK, the Childhood Diabetes in Finland Study Group 1998. Continuous cow’s milk consumption, disease-related autoantibodies, and Type 1 diabetes mellitus: A follow-up study with diabetic children’s siblings. Diabetic Med 15: 730–738 [DOI] [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 [DOI] [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. Diet 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 [DOI] [PubMed] [Google Scholar]
– Viskari H, Kondrashova A, Koskela P, Knip M, Hyöty H 2006. Comparison of circulating vitamin D levels in two nearby populations with contrasting type 1 diabetes incidence rates. Diabetes Care 49: 1458–1459 [DOI] [PubMed] [Google Scholar]
– Wadsworth EJK, Shield JPH, Hunt LP, Baum JD 1997. Investigating environmental factors linked to diabetes in children under 5 years of age. Diabet Med 14: 390–396 [DOI] [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. Role of innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455: 1109–1113 [DOI] [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. Identification of the cation efflux transporter ZnT8 (Slc30A8) as a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci 104: 17040–17045 [DOI] [PMC free article] [PubMed] [Google Scholar]
– Wilkin TJ 2001. Exploring the link between weight gain and the development of both type 1 and type 2 diabetes. Diabetologia 44: 914–922 [DOI] [PubMed] [Google Scholar]
– Yeung WC, Rawlinson WD, Craig M 2011. Investigating the relationship between enterovirus infection and type 1 diabetes mellitus: A comprehensive review and analysis of observational molecular studies. BMJ 342: d35 [DOI] [PMC free article] [PubMed] [Google Scholar]
– Ziegler A-G, Hummel M, Schenker M, Bonifacio E 1999. Identification of autoantibodies and the risk for developing childhood diabetes in offspring of parents with type 1 diabetes: Analysis from the German BABYDIAB Study. Diabetes 48: 460–468 [DOI] [PubMed] [Google Scholar]
– Ziegler A-G, Schmid S, Huber D, Hummel M, Bonifacio E 2003. Exploring early infant feeding patterns and the risk of developing Type 1 diabetes-associated autoantibodies. JAMA 290: 1721–1728 [DOI] [PubMed] [Google Scholar]
– Zipitis CS, Akobeng AK 2008. Systematic review and meta-analysis of vitamin D supplementation in early childhood and the risk of type 1 diabetes. Arch Dis Childr 93: 512–517 [DOI] [PubMed] [Google Scholar]
– Articles from Cold Spring Harbor Perspectives in Medicine are provided here courtesy of Cold Spring Harbor Laboratory Press