Autoimmunity plays a role in the onset of diabetes after 40 years of age
<p><strong>Aims/hypothesis:</strong> 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 relati...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Springer Verlag
2019
|
| _version_ | 1826274360363581440 |
|---|---|
| author | Rolandsson, O Hampe, CS Sharp, SJ Ardanaz, E Boeing, H Fagherazzi, G Mancini, FR Nilsson, PM Overvad, K Chirlaque, M-D Dorronsoro, M Gunter, MJ Kaaks, R Key, TJ Khaw, K-T Krogh, V Kühn, T Palli, D Panico, S Sacerdote, C Sánchez, M-J Severi, G Spijkerman, AMW Tumino, R van der Schouw, YT Riboli, E Forouhi, NG Langenberg, C Wareham, NJ |
| author_facet | Rolandsson, O Hampe, CS Sharp, SJ Ardanaz, E Boeing, H Fagherazzi, G Mancini, FR Nilsson, PM Overvad, K Chirlaque, M-D Dorronsoro, M Gunter, MJ Kaaks, R Key, TJ Khaw, K-T Krogh, V Kühn, T Palli, D Panico, S Sacerdote, C Sánchez, M-J Severi, G Spijkerman, AMW Tumino, R van der Schouw, YT Riboli, E Forouhi, NG Langenberg, C Wareham, NJ |
| author_sort | Rolandsson, O |
| collection | OXFORD |
| description | <p><strong>Aims/hypothesis:</strong> 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.</p>
<p><strong>Methods:</strong> 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 (<em>n</em> = 15,802) and in incident diabetes cases (<em>n</em> = 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.</p>
<p><strong>Results:</strong> 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.</p>
<p><strong>Conclusions/interpretation:</strong> 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.</p> |
| first_indexed | 2024-03-06T22:42:15Z |
| format | Journal article |
| id | oxford-uuid:5bf98e64-a04f-492b-8196-de00a88f27f9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:42:15Z |
| publishDate | 2019 |
| publisher | Springer Verlag |
| record_format | dspace |
| spelling | oxford-uuid:5bf98e64-a04f-492b-8196-de00a88f27f92022-03-26T17:25:31ZAutoimmunity plays a role in the onset of diabetes after 40 years of ageJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5bf98e64-a04f-492b-8196-de00a88f27f9EnglishSymplectic ElementsSpringer Verlag2019Rolandsson, OHampe, CSSharp, SJArdanaz, EBoeing, HFagherazzi, GMancini, FRNilsson, PMOvervad, KChirlaque, M-DDorronsoro, MGunter, MJKaaks, RKey, TJKhaw, K-TKrogh, VKühn, TPalli, DPanico, SSacerdote, CSánchez, M-JSeveri, GSpijkerman, AMWTumino, Rvan der Schouw, YTRiboli, EForouhi, NGLangenberg, CWareham, NJ<p><strong>Aims/hypothesis:</strong> 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.</p> <p><strong>Methods:</strong> 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 (<em>n</em> = 15,802) and in incident diabetes cases (<em>n</em> = 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.</p> <p><strong>Results:</strong> 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.</p> <p><strong>Conclusions/interpretation:</strong> 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.</p> |
| spellingShingle | Rolandsson, O Hampe, CS Sharp, SJ Ardanaz, E Boeing, H Fagherazzi, G Mancini, FR Nilsson, PM Overvad, K Chirlaque, M-D Dorronsoro, M Gunter, MJ Kaaks, R Key, TJ Khaw, K-T Krogh, V Kühn, T Palli, D Panico, S Sacerdote, C Sánchez, M-J Severi, G Spijkerman, AMW Tumino, R van der Schouw, YT Riboli, E Forouhi, NG Langenberg, C Wareham, NJ Autoimmunity plays a role in the onset of diabetes after 40 years of age |
| title | Autoimmunity plays a role in the onset of diabetes after 40 years of age |
| title_full | Autoimmunity plays a role in the onset of diabetes after 40 years of age |
| title_fullStr | Autoimmunity plays a role in the onset of diabetes after 40 years of age |
| title_full_unstemmed | Autoimmunity plays a role in the onset of diabetes after 40 years of age |
| title_short | Autoimmunity plays a role in the onset of diabetes after 40 years of age |
| title_sort | autoimmunity plays a role in the onset of diabetes after 40 years of age |
| work_keys_str_mv | AT rolandssono autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT hampecs autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT sharpsj autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT ardanaze autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT boeingh autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT fagherazzig autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT mancinifr autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT nilssonpm autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT overvadk autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT chirlaquemd autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT dorronsorom autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT guntermj autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT kaaksr autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT keytj autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT khawkt autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT kroghv autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT kuhnt autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT pallid autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT panicos autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT sacerdotec autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT sanchezmj autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT severig autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT spijkermanamw autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT tuminor autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT vanderschouwyt autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT ribolie autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT forouhing autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT langenbergc autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage AT warehamnj autoimmunityplaysaroleintheonsetofdiabetesafter40yearsofage |