Type 1 Diabetes
- Author(s)
- Harrison, LC;
- Journal Title
- In Clinical Immunology: Principels and Practices 6th ed
- Publication Type
- Book Chapter
- Abstract
- The clinical metabolic syndrome of type 1 diabetes results from insulin deficiency secondary to pancreatic β-cell destruction. The disease has been classified as type 1A or 1B, depending on the presence or absence, respectively, of circulating pancreatic islet autoantibodies as well as natural history. Type 1A, the most common form in populations of Northern European origin, is viewed as having a sub-clinical prodrome reflecting progressive islet autoimmunity, whereas type 1B has a more acute onset. These distinctions should not be viewed as absolute because types 1A and 1B have overlapping pathologic features. Type 1A is an autoimmune disease in which islet autoantibodies are detectable in the first few years of life in the majority of children who subsequently develop clinical disease. Susceptibility is polygenic, but alleles at the human leukocyte antigen (HLA) locus account for about half the lifetime risk. The second most significant genetic locus is the insulin gene, and insulin is a key autoantigen that drives β-cell destruction. The incidence of type 1A is rising as a result of environmental influences, which appear to have enhanced the penetrance of lower risk HLA alleles. The type 1A stereotype of the thin juvenile now overlaps with the type 2 diabetes stereotype of the obese, insulin-resistant adult. The gut microbiome, a bellwether of the external environment, is altered in type 1A and its modification may be an approach to primary prevention. Recognition that type 1A is primarily an autoimmune β-cell disorder that progresses latently from early childhood to an end-stage metabolic syndrome expands therapeutic options for early intervention and prevention. © 2023 Elsevier Ltd. All rights reserved.
- Publisher
- Elsevier
- Keywords
- autoimmune; Diabetes types 1 A and 1B; environment; immune therapy; insulin; islet autoantibodies; microbiome; polygenic; prevention; β-cell
- Publisher's Version
- https://doi.org/10.1016/B978-0-7020-8165-1.00071-X
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-06-26 09:53:26
Last Modified: 2023-06-26 10:01:11