Get started
Work

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

Year: 2017
Type: article
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.
DOI: 10.1210/jc.2017-02040
Authors: Maarit K Koskinen, Johanna Lempainen, Eliisa Löyttyniemi, Olli Helminen, Anne Hekkala, Taina Härkönen, Minna Kiviniemi, Olli Simell, Mikael Knip, Jorma Ilonen, Jorma Toppari, Riitta Veijola
Institutions: University of Turku, Turku University Hospital, Oulu University Hospital, University of Oulu, University of Helsinki, Helsinki University Hospital, Tampere University Hospital, Folkhälsans Forskningscentrum
Language: English
Subfield: Genetics
Open Access status: hybrid
Estimated APC paid: $1,699
Funders: Jalmari ja Rauha Ahokkaan Säätiö, European Commission, Academy of Finland, Novo Nordisk, Signe ja Ane Gyllenbergin Säätiö, Emil Aaltosen Säätiö, Turun Yliopisto, Lastentautien Tutkimussäätiö, Novo Nordisk Fonden, Fonds Spéciaux de Recherche, Turun Yliopistosäätiö, Turun yliopiston tutkijakoulu
OpenAlex ID: W2775981144
FWCI: 0.726
Cites: 27
Cited by: 9
Related to: 10