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Class II HLA genotype association with first-phase insulin response is explained by islet autoantibodies |
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| Author: | Koskinen, Maarit K.1; Lempainen, Johanna1,2; Löyttyniemi, Eliisa3; |
| Organizations: |
1Department of Pediatrics, University of Turku and Turku University Hospital, FI-20520 Turku, Finland 2Immunogenetics Laboratory, Institute of Biomedicine, University of Turku and Turku University Hospital, FI-20520 Turku, Finland 3Department of Biostatistics, University of Turku, FI-20520 Turku, Finland
4Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital and University of Oulu, FI-90014 Oulu, Finland
5Children ’ s Hospital, University of Helsinki and Helsinki University Hospital, FI-00290 Helsinki, Finland 6Research Programs Unit, Diabetes and Obesity, University of Helsinki, FI-00290 Helsinki, Finland 7Folkhälsan Research Center, FI-00290 Helsinki, Finland 8Tampere Center for Child Health Research, Tampere University Hospital, FI-33014 Tampere, Finland 9Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, FI-20520 Turku, Finland |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 1.9 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe2019092029147 |
| Language: | English |
| Published: |
Endocrine society,
2018
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| Publish Date: | 2019-09-20 |
| Description: |
AbstractContext: A declining first-phase insulin response (FPIR) is characteristic of the disease process leading to clinical type 1 diabetes. It is not known whether reduced FPIR depends on class II human leukocyte antigen (HLA) genotype, islet autoimmunity, or both. Objective: To dissect the role of class II HLA DR-DQ genotypes and biochemical islet autoantibodies in the compromised FPIR. Design, Setting, Participants: A total of 438 children with defined HLA DR-DQ genotype in the prospective Finnish Type 1 Diabetes Prediction and Prevention Study were analyzed for FPIR in a total of 1149 intravenous glucose tolerance tests and were categorized by their HLA DR-DQ genotype and the number of biochemical islet autoantibodies at the time of the first FPIR. Age-adjusted hierarchical linear mixed models were used to analyze repeated measurements of FPIR. Main Outcome Measure: The associations between class II HLA DR-DQ genotype, islet autoantibody status, and FPIR. Results: A strong association between the degree of risk conferred by HLA DR-DQ genotype and positivity for islet autoantibodies existed (P < 0.0001). FPIR was inversely associated with the number of biochemical autoantibodies (P < 0.0001) irrespective of HLA DR-DQ risk group. FPIR decreased over time in children with multiple autoantibodies and increased in children with no biochemical autoantibodies (P < 0.0001 and P = 0.0013, respectively). Conclusions: The class II HLA DR-DQ genotype association with FPIR was secondary to the association between HLA and islet autoimmunity. Declining FPIR was associated with positivity for multiple islet autoantibodies irrespective of class II HLA DR-DQ genotype. see all
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| Series: |
Journal of clinical endocrinology & metabolism |
| ISSN: | 0021-972X |
| ISSN-E: | 1945-7197 |
| ISSN-L: | 0021-972X |
| Volume: | 103 |
| Issue: | 8 |
| Pages: | 2870 - 2878 |
| DOI: | 10.1210/jc.2017-02040 |
| OADOI: | https://oadoi.org/10.1210/jc.2017-02040 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3121 General medicine, internal medicine and other clinical medicine |
| Subjects: | |
| Funding: |
This study was funded by the Juvenile Diabetes Research Foundation; the European Union; the Novo Nordisk Foundation, the Special Research Funds for Turku, Oulu, and Tampere University Hospitals in Finland; the Academy of Finland; the National Technology Agency of Finland; Finnish Office for Health Technology Assessment; the Turku University Foundation; the University of Turku Graduate School Doctoral Programme; the Diabetes Research Foundation in Finland; the Sigrid Juselius Foundation; the Päivikki and Sakari Sohlberg Foundation; the Emil Aaltonen Foundation; the Jalmari and Rauha Ahokas Foundation; the Signe and Ane Gyllenberg Foundation; the Research Foundation of Orion Corporation; the Foundation for Pediatric Research; and the Alma and KA Snellman Foundation. |
| Copyright information: |
© 2018 Endocrine Society. This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/). |
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https://creativecommons.org/licenses/by/4.0/ |