Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Autoimmunity plays a role in the onset of diabetes after 40 years of age
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.ORCID iD: 0000-0002-1341-6828
Show others and affiliations
2019 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428Article in journal (Refereed) Epub ahead of print
Abstract [en]

Aims/hypothesis: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort.

Methods: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression.

Results: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors.

Conclusions/interpretation: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

Place, publisher, year, edition, pages
Springer, 2019.
Keywords [en]
Autoantibody, Autoimmunity, Genetic risk score, Incident diabetes, Type 1 diabetes, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:umu:diva-165777DOI: 10.1007/s00125-019-05016-3ISI: 000495684900003PubMedID: 31713011OAI: oai:DiVA.org:umu-165777DiVA, id: diva2:1375249
Funder
Västerbotten County CouncilSwedish Research CouncilAvailable from: 2019-12-04 Created: 2019-12-04 Last updated: 2019-12-04Bibliographically approved

Open Access in DiVA

fulltext(1550 kB)18 downloads
File information
File name FULLTEXT01.pdfFile size 1550 kBChecksum SHA-512
98d6577f2f462c6fc6e5b3bdfe6ed3fa51dfde598561d2ed20174393d99c8e93c8fb46a676da877c815e11d73dd6e448b44980ddd5b495491810d43a0148bc13
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Rolandsson, OlovOvervad, Kim
By organisation
Family Medicine
In the same journal
Diabetologia
Endocrinology and Diabetes

Search outside of DiVA

GoogleGoogle Scholar
Total: 18 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 18 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf