Slowly progressive insulin-dependent (type 1) diabetes positive for anti-GAD antibody ELISA test may be strongly associated with a future insulin-dependent state
Open accessAbstract
Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM), believed to be caused by β-cell destruction through islet-cell autoimmunity, gradually progresses to an insulin-dependent state over time. Although the presence of anti-glutamic acid decarboxylase antibody (GADA) is required for the diagnosis of SPIDDM, a recent change in the GADA assay kit from radioimmunoassay (RIA) to enzyme-linked immunosorbent assay (ELISA) yields mismatched GADA test results between the two kits, leading to confusion in understanding the pathological conditions of SPIDDM in Japan. Thus, this study aimed to clarify the difference in the clinical characteristics of GADA-ELISA-positive and GADA-ELISA-negative patients originally diagnosed as SPIDDM by GADA-RIA test. As a result, 42 of 63 original GADA-RIA-positive SPIDDM patients (66.7%) were found to be GADA-ELISA-positive, whereas the remaining 21 patients (33.3%) were found to be GADA-ELISA-negative. In patients with shorter disease duration, GADA-ELISA-positive patients showed significantly lower serum C-peptide levels than GADA-ELISA-negative patients. Meanwhile, in patients with longer disease duration, serum C-peptide levels were comparably decreased in GADA-ELISA-positive and GADA-ELISA-negative patients. A significant inverse correlation between serum C-peptide level and disease duration was observed in GADA-ELISA-negative patients, but not in GADA-ELISA-positive patients, suggesting that insulin secretory capacity may be gradually impaired over time also in GADA-ELISA-negative SPIDDM patients. In conclusion, physicians should be aware that GADA-ELISA-positive SPIDDM may be strongly associated with a future insulin-dependent state. Meanwhile, physicians should be careful in treating GADA-ELISA-negative SPIDDM patients diagnosed as type 2 DM, and cautiously follow the clinical course, in accordance with SPIDDM.
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Autoantibody markers plus clinical presentation can help distinguish type 1 from type 2 diabetes in children and adults.
“The presence or absence of autoimmune markers (autoantibodies to glutamic acid decarboxylase [GAD65], pancreatic islet b cells [tyrosine phosphatase IA-2], and IA-2b zinc transporter [ZnT8], and/or insulin) in addition to the clinical presentation may help establish the correct diagnosis to distinguish between T1D and T2D in children or adults.22–27”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [25]
The introductory passage under the Abstract heading identifies GAD, IA-2, insulin, and ZnT8 autoantibodies as important in diagnosing type 1 diabetes and says GAD or islet-cell antibodies can suggest slowly progressive type 1 diabetes in a non-insulin-dependent patient. But the study compares adult patients with slowly progressive type 1 and type 2 diabetes; it does not establish the claimed approach for children, and the Discussion says it could not investigate the other listed autoantibodies. Page numbers were not available in our copy. (LLM, conf=0.84)
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Blonde, L., Umpierrez, G. E., Reddy, S. S., McGill, J. B., Berga, S. L., Bush, M., Chandrasekaran, S., DeFronzo, R. A., Einhorn, D., Galindo, R. J., et al. (2022) · Endocrine Practice · doi:10.1016/j.eprac.2022.08.002 · Cited by 507 · see citing works
- Authors
- Oikawa, Y., Tanaka, H., Uchida, J., Atsumi, Y., Osawa, M., Katsuki, T., Kawai, T., & Shimada, A.
- Affiliations
- Saiseikai Central Hospital (JP)
- Saitama Medical University (JP)
- Venue
- Endocrine Journal
- Publisher
- Japan Endocrine Society
- Published
- 2017
- Volume
- 64
- Issue
- 2
- Pages
- 163-170
- ISSN
- 0918-8959 (ISSN-L)
- 1348-4540
- OpenAlex
- W2533492047
- Cited by
- 17
- References
- 14
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 6 · 2018: 3
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Endocrine Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, glutamic acid decarboxylase antibodies, islet autoimmunity, beta cell destruction, C-peptide, disease duration, type 2 diabetes misdiagnosis
- MeSH terms
- Aged, Autoantibodies, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Enzyme-Linked Immunosorbent Assay, Female, Glutamate Decarboxylase, Humans, Insulin, Male, Middle Aged, Risk Factors, Autoimmunity, Disease Progression
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