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HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later
AIMS/HYPOTHESIS: HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15–34 year old individuals. METHODS: The cohort was identified in 199...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055880/ https://www.ncbi.nlm.nih.gov/pubmed/21412422 http://dx.doi.org/10.1371/journal.pone.0017569 |
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author | Jensen, Richard A. Agardh, Elisabet Lernmark, Åke Gudbjörnsdottir, Soffia Smith, Nicholas L. Siscovick, David S. Törn, Carina |
author_facet | Jensen, Richard A. Agardh, Elisabet Lernmark, Åke Gudbjörnsdottir, Soffia Smith, Nicholas L. Siscovick, David S. Törn, Carina |
author_sort | Jensen, Richard A. |
collection | PubMed |
description | AIMS/HYPOTHESIS: HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15–34 year old individuals. METHODS: The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry. RESULTS: The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR. CONCLUSIONS: Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials. |
format | Text |
id | pubmed-3055880 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30558802011-03-16 HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later Jensen, Richard A. Agardh, Elisabet Lernmark, Åke Gudbjörnsdottir, Soffia Smith, Nicholas L. Siscovick, David S. Törn, Carina PLoS One Research Article AIMS/HYPOTHESIS: HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15–34 year old individuals. METHODS: The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry. RESULTS: The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR. CONCLUSIONS: Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials. Public Library of Science 2011-03-11 /pmc/articles/PMC3055880/ /pubmed/21412422 http://dx.doi.org/10.1371/journal.pone.0017569 Text en Jensen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Jensen, Richard A. Agardh, Elisabet Lernmark, Åke Gudbjörnsdottir, Soffia Smith, Nicholas L. Siscovick, David S. Törn, Carina HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later |
title | HLA Genes, Islet Autoantibodies and Residual C-Peptide at the
Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years
Later |
title_full | HLA Genes, Islet Autoantibodies and Residual C-Peptide at the
Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years
Later |
title_fullStr | HLA Genes, Islet Autoantibodies and Residual C-Peptide at the
Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years
Later |
title_full_unstemmed | HLA Genes, Islet Autoantibodies and Residual C-Peptide at the
Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years
Later |
title_short | HLA Genes, Islet Autoantibodies and Residual C-Peptide at the
Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years
Later |
title_sort | hla genes, islet autoantibodies and residual c-peptide at the
clinical onset of type 1 diabetes mellitus and the risk of retinopathy 15 years
later |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055880/ https://www.ncbi.nlm.nih.gov/pubmed/21412422 http://dx.doi.org/10.1371/journal.pone.0017569 |
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