Show Summary Details
Page of

Genetics of type 1 diabetes mellitus 

Genetics of type 1 diabetes mellitus
Genetics of type 1 diabetes mellitus

David A. Savage

and Stephen C. Bain

Page of

PRINTED FROM OXFORD MEDICINE ONLINE ( © Oxford University Press, 2022. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy and Legal Notice).

date: 26 May 2022

Type 1 diabetes, previously known as insulin-dependent diabetes mellitus, is a common chronic T-cell-mediated disease in which there is selective autoimmune destruction of the insulin-producing β‎ cells of the pancreas. Although the mechanisms underlying this process are not fully understood, type 1 diabetes occurs as a result of complex interactions between multiple genes (reviewed in references 1–3) and environmental influences, which may both promote and protect against disease. Type 1 diabetes clusters in some families, but with no distinct pattern of inheritance. The concordance rates in monozygotic twins for type 1 diabetes can reach 50%, compared to 6% for dizygotic twins. The sibling recurrence risk ratio (λ‎s) (risk to siblings ÷ risk to general population) value for type 1 diabetes is 15 (6.0 ÷ 0.4 or 6% ÷ 0.4%), and twin studies suggest that 80% to 85% of familial aggregation is accounted for by genes. Type 1 diabetes has been noted to coexist with other autoimmune diseases—notably, Graves’ disease and coeliac disease—in certain families, implying the involvement of common autoimmune pathways.

Improved understanding of the so-called ‘allelic architecture’ (the identity of disease-associated gene variants, their frequencies, and size of the risk conferred by each variant) and biological pathways involved in type 1 diabetes is expected to facilitate the identification of new therapeutic targets for the development of new treatments. DNA biomarkers could also assist risk prediction at a population level. This is clinically relevant since individuals can survive with only 20% intact β‎-cell mass, and the time to reach this level of destruction can be considerably delayed in some individuals, offering a window of opportunity for intervention therapy. Furthermore, clinical trials should be improved by only focusing on those patients at highest risk of developing type 1 diabetes.

Early prediction, improved treatments, and, ultimately, prevention of type 1 diabetes are major goals because incidence rates are increasing. A recent study by the EURODIAB Study Group, involving 20 population-based registries across 17 European countries, has assessed incidence trends in children diagnosed with type 1 diabetes under the age of 15 between 1989 and 2003: an overall increase of 3.9% per year was reported, and, in the under 5 age group, an increase of 5.4% per year was observed (4).

Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription.

Please subscribe or login to access full text content.

If you have purchased a print title that contains an access token, please see the token for information about how to register your code.

For questions on access or troubleshooting, please check our FAQs, and if you can't find the answer there, please contact us.