Refereed journal article or data article (A1)

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




List of AuthorsKoskinen MK, Lempainen J, Loyttyniemi E, Helminen O, Hekkala A, Harkonen T, Kiviniemi M, Simell O, Knip M, Ilonen J, Toppari J, Veijola R

PublisherENDOCRINE SOC

Publication year2018

JournalJournal of Clinical Endocrinology and Metabolism

Journal name in sourceJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Journal acronymJ CLIN ENDOCR METAB

Volume number103

Issue number8

Start page2870

End page2878

Number of pages9

ISSN0021-972X

eISSN1945-7197

DOIhttp://dx.doi.org/10.1210/jc.2017-02040

URLhttps://academic.oup.com/jcem/article/103/8/2870/4780809#


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.


Last updated on 2021-24-06 at 11:55