Class II HLA Genotype Association With First-Phase Insulin Response Is Explained by Islet Autoantibodies

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http://hdl.handle.net/10138/243592

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Koskinen , M K , Lempainen , J , Löyttyniemi , E , Helminen , O , Hekkala , A , Härkönen , T , Kiviniemi , M , Simell , O , Knip , M , Ilonen , J , Toppari , J & Veijola , R 2018 , ' Class II HLA Genotype Association With First-Phase Insulin Response Is Explained by Islet Autoantibodies ' , Journal of Clinical Endocrinology and Metabolism , vol. 103 , no. 8 , pp. 2870-2878 . https://doi.org/10.1210/jc.2017-02040

Title: Class II HLA Genotype Association With First-Phase Insulin Response Is Explained by Islet Autoantibodies
Author: Koskinen, Maarit K.; Lempainen, Johanna; Löyttyniemi, Eliisa; Helminen, Olli; Hekkala, Anne; Härkönen, Taina; Kiviniemi, Minna; Simell, Olli; Knip, Mikael; Ilonen, Jorma; Toppari, Jorma; Veijola, Riitta
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Clinicum
Date: 2018-08
Language: eng
Number of pages: 9
Belongs to series: Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
URI: http://hdl.handle.net/10138/243592
Abstract: Context: 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.
Subject: ANTIBODY-POSITIVE RELATIVES
BETA-CELL AUTOIMMUNITY
1ST-DEGREE RELATIVES
RISK-FACTORS
CHILDREN
PROGRESSION
PREDICTION
SECRETION
IDDM
SUSCEPTIBILITY
3121 General medicine, internal medicine and other clinical medicine
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