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Updated: May 13, 2026
Electrochemiluminescence Assays for Human Islet Autoantibodies
Published on: March 23, 2018
Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention
Cecilia Andersson1, Annelie Carlsson, Corrado Cilio
1Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmö, Sweden. Cecilia_K.Andersson@med.lu.se
Insights
Children with islet autoantibodies show variable glucose metabolism, impacting type 1 diabetes prevention studies. ZnT8 autoantibodies and HLA-DQ2/8 are linked to impaired glucose metabolism in these children.
Area of Science:
- Pediatric Endocrinology
- Immunology
- Metabolic Disorders
Background:
- Type 1 diabetes (T1D) prevention studies require understanding metabolic control in at-risk children.
- Children with T1D risk and islet autoantibodies are candidates for secondary prevention trials.
Purpose of the Study:
- To assess metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children at risk for T1D.
- To identify factors influencing glucose metabolism in children with islet autoantibodies.
Main Methods:
- Recruited 47 healthy children with GADA and other islet autoantibodies.
- Performed intravenous glucose tolerance test (IvGTT) and oral glucose tolerance test (OGTT).
- Measured hemoglobin A1c, plasma glucose, serum insulin, and C-peptide.
Main Results:
- 20/47 children exhibited impaired glucose metabolism.
- Impaired first-phase insulin response (FPIR) observed in 14/20 children; impaired glucose tolerance in 11/20 via OGTT.
- Increased frequency and levels of ZnT8 autoantibodies (ZnT8QA) and carriage of HLA-DQ2/8 were associated with impaired glucose metabolism (p=0.03).
Conclusions:
- Baseline glucose metabolism in children with islet autoantibodies is variable, complicating T1D secondary prevention studies.
- Comprehensive metabolic evaluation using both IvGTT and OGTT is crucial before trial randomization.
- Analysis of all autoantibody tests, including ZnT8QA, is recommended.
Aims:
Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children.
Methods:
In 47 healthy children with GADA and at least one additional islet autoantibody, intravenous glucose tolerance test (IvGTT) and oral glucose tolerance test (OGTT) were performed 8-65 d apart. Hemoglobin A1c, plasma glucose as well as serum insulin and C-peptide were determined at fasting and during IvGTT and OGTT.
Results:
All children aged median 5.1 (4.0-9.2) yr had autoantibodies to two to six of the beta-cell antigens GAD65, insulin, IA-2, and the three amino acid position 325 variants of the ZnT8 transporter. In total, 20/47 children showed impaired glucose metabolism. Decreased (≤ 30 μU/mL insulin) first-phase insulin response (FPIR) was found in 14/20 children while 11/20 had impaired glucose tolerance in the OGTT. Five children had both impaired glucose tolerance and FPIR ≤ 30 μU/mL insulin. Number and levels of autoantibodies were not associated with glucose metabolism, except for an increased frequency (p = 0.03) and level (p = 0.01) of ZnT8QA in children with impaired glucose metabolism. Among the children with impaired glucose metabolism, 13/20 had HLA-DQ2/8, compared to 9/27 of the children with normal glucose metabolism (p = 0.03).
Conclusion:
Secondary prevention studies in children with islet autoantibodies are complicated by variability in baseline glucose metabolism. Evaluation of metabolic control with both IvGTT and OGTT is critical and should be taken into account before randomization. All currently available autoantibody tests should be analyzed, including ZnT8QA.
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