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Class II HLA Genotype Association With First-Phase Insulin Response Is Explained by Islet Autoantibodies
Tekijät: Koskinen MK, Lempainen J, Loyttyniemi E, Helminen O, Hekkala A, Harkonen T, Kiviniemi M, Simell O, Knip M, Ilonen J, Toppari J, Veijola R
Kustantaja: ENDOCRINE SOC
Julkaisuvuosi: 2018
Journal: Journal of Clinical Endocrinology and Metabolism
Tietokannassa oleva lehden nimi: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Lehden akronyymi: J CLIN ENDOCR METAB
Vuosikerta: 103
Numero: 8
Aloitussivu: 2870
Lopetussivu: 2878
Sivujen määrä: 9
ISSN: 0021-972X
eISSN: 1945-7197
DOI: https://doi.org/10.1210/jc.2017-02040
Verkko-osoite: https://academic.oup.com/jcem/article/103/8/2870/4780809#
Tiivistelmä
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.
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.
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