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Updated: Feb 16, 2026

Electrochemiluminescence Assays for Human Islet Autoantibodies
Published on: March 23, 2018
Class II HLA Genotype Association With First-Phase Insulin Response Is Explained by Islet Autoantibodies
Maarit K Koskinen1, Johanna Lempainen1,2, Eliisa Löyttyniemi3
1Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.
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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