Diabetes & Metabolism Journal

Short Communication

Pathophysiology
Glutamic Acid Decarboxylase and Tyrosine Phosphatase-Related Islet Antigen-2 Positivity among Children and Adolescents with Diabetes in Korea: Ka Young Kim, Min Seung Kim, Yun Jeong Lee, Young Ah Lee, Seong Yong Lee, Choong Ho Shin, Jae Hyun Kim; Diabetes Metab J. 2022;46(6):948-952. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0332

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Autoantibodies against glutamic acid decarboxylase (GADA), tyrosine phosphatase-related islet antigen 2 (IA2A), insulin (INSA), and islet cells (ICA) are critical for determining the type of diabetes and management strategy in new-onset diabetes mellitus (NODM), but there have been few reports of all diabetes-associated autoantibody (DAA) in Korea. We retrospectively analyzed 193 patients with NODM aged 0 to 18 years who were followed at two tertiary centers in Korea (2017 to 2021). Patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) were 93 (48.2%) and 100 (51.8%), respectively. In T1DM patients, the DAA positivity rate was 94.6%; prevalence of GADA, IA2A, INSA, and ICA was 71.0%, 71.0%, 31.2%, and 10.8%, respectively; and IA2A added 10.7% point autoantibody positivity (83.9% for GADA+INSA+ICA and 94.6% for GADA+INSA+ICA+IA2A). Among the patients with T2DM, 12 (12.0%) were positive for DAA, and all were positive for INSA. These findings suggest that DAA at diagnosis, especially GADA and IA2A, is useful for classifying diabetes in Korean children and adolescents.

Citations

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Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice
Yun Kyung Cho, Chang Hee Jung
Diabetes & Metabolism Journal.2023; 47(6): 757. CrossRef
Diagnostic and Therapeutic Strategies of Type 2 Diabetes Mellitus in Youth
Hwa Young Kim, Jae Hyun Kim
The Ewha Medical Journal.2022;[Epub] CrossRef

Original Articles

Technology/Device
Glutamic Acid Decarboxylase Autoantibody Detection by Electrochemiluminescence Assay Identifies Latent Autoimmune Diabetes in Adults with Poor Islet Function: Yuxiao Zhu, Li Qian, Qing Liu, Jing Zou, Ying Zhou, Tao Yang, Gan Huang, Zhiguang Zhou, Yu Liu; Diabetes Metab J. 2020;44(2):260-266. Published online November 12, 2019; DOI: https://doi.org/10.4093/dmj.2019.0007

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Background

The detection of glutamic acid decarboxylase 65 (GAD65) autoantibodies is essential for the prediction and diagnosis of latent autoimmune diabetes in adults (LADA). The aim of the current study was to compare a newly developed electrochemiluminescence (ECL)-GAD65 antibody assay with the established radiobinding assay, and to explore whether the new assay could be used to define LADA more precisely.

Methods

Serum samples were harvested from 141 patients with LADA, 95 with type 1 diabetes mellitus, and 99 with type 2 diabetes mellitus, and tested for GAD65 autoantibodies using both the radiobinding assay and ECL assay. A glutamic acid decarboxylase antibodies (GADA) competition assay was also performed to assess antibody affinity. Furthermore, the clinical features of these patients were compared.

Results

Eighty-eight out of 141 serum samples (62.4%) from LADA patients were GAD65 antibody-positive by ECL assay. Compared with ECL-GAD65 antibody-negative patients, ECL-GAD65 antibody-positive patients were leaner (P<0.0001), had poorer β-cell function (P<0.05), and were more likely to have other diabetes-associated autoantibodies. The β-cell function of ECL-GAD65 antibody-positive patients was similar to that of type 1 diabetes mellitus patients, whereas ECL-GAD65 antibody-negative patients were more similar to type 2 diabetes mellitus patients.

Conclusion

Patients with ECL-GAD65 antibody-negative share a similar phenotype with type 2 diabetes mellitus patients, whereas patients with ECL-GAD65 antibody-positive resemble those with type 1 diabetes mellitus. Thus, the detection of GADA using ECL may help to identify the subtype of LADA.

Citations

Citations to this article as recorded by

2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes—2024
Nuha A. ElSayed, Grazia Aleppo, Raveendhara R. Bannuru, Dennis Bruemmer, Billy S. Collins, Laya Ekhlaspour, Jason L. Gaglia, Marisa E. Hilliard, Eric L. Johnson, Kamlesh Khunti, Ildiko Lingvay, Glenn Matfin, Rozalina G. McCoy, Mary Lou Perry, Scott J. Pil
Diabetes Care.2024; 47(Supplement): S20. CrossRef
2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes—2023
Nuha A. ElSayed, Grazia Aleppo, Vanita R. Aroda, Raveendhara R. Bannuru, Florence M. Brown, Dennis Bruemmer, Billy S. Collins, Jason L. Gaglia, Marisa E. Hilliard, Diana Isaacs, Eric L. Johnson, Scott Kahan, Kamlesh Khunti, Jose Leon, Sarah K. Lyons, Mary
Diabetes Care.2023; 46(Supplement): S19. CrossRef
Determination of autoantibodies in type 2 diabetes: one simple way to improve classification
Johnny Ludvigsson
Diabetologia.2023; 66(5): 955. CrossRef
2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2022

Diabetes Care.2022; 45(Supplement): S17. CrossRef
Screening Strategy for Islet Autoantibodies in Diabetes Patients of Different Ages
Xixi Nan, Xia Li, Yufei Xiang, Xiang Yan, Houde Zhou, Xiaohan Tang, Jin Cheng, Xiaohong Niu, Jing Liu, Qiuhe Ji, Linong Ji, Gan Huang, Zhiguang Zhou
Diabetes Technology & Therapeutics.2022; 24(3): 212. CrossRef
Atypical Diabetes and Management Considerations
Shivajirao Prakash Patil
Primary Care: Clinics in Office Practice.2022; 49(2): 225. CrossRef
Latent autoimmune diabetes in adults: a focus on β-cell protection and therapy
Wenfeng Yin, Shuoming Luo, Zilin Xiao, Ziwei Zhang, Bingwen Liu, Zhiguang Zhou
Frontiers in Endocrinology.2022;[Epub] CrossRef
Analysis of detrended fluctuation function derived from continuous glucose monitoring may assist in distinguishing latent autoimmune diabetes in adults from T2DM
Liyin Zhang, Qi Tian, Keyu Guo, Jieru Wu, Jianan Ye, Zhiyi Ding, Qin Zhou, Gan Huang, Xia Li, Zhiguang Zhou, Lin Yang
Frontiers in Endocrinology.2022;[Epub] CrossRef
Prevalence of antibodies targeting ubiquitin-conjugating enzyme 2L3 and eukaryote translation elongation factor 1 α1 in Chinese Han and American Caucasian populations with type 1 diabetes
Li Qian, Yuxiao Zhu, Yan Luo, Mu Zhang, Liping Yu, Yu Liu, Tao Yang
Endocrine Connections.2022;[Epub] CrossRef
2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2021

Diabetes Care.2021; 44(Supplement): S15. CrossRef
High-Affinity ZnT8 Autoantibodies by Electrochemiluminescence Assay Improve Risk Prediction for Type 1 Diabetes
Xiaofan Jia, Ling He, Dongmei Miao, Kathleen Waugh, Cristy Geno Rasmussen, Fran Dong, Andrea K Steck, Marian Rewers, Liping Yu
The Journal of Clinical Endocrinology & Metabolism.2021;[Epub] CrossRef
Lada or Type 2 Diabetes Mellitus - A Challenging Diagnosis in Clinical Approach
Lucia Mihaela Custură, Oana Deteşan, Raluca Maria Tilinca, Reka Annamaria Schmiedt, Brigitta Irén Bacso, Mariana Cornelia Tilinca
Acta Medica Transilvanica.2021; 26(3): 55. CrossRef
A fluorescence enhancement assay for measurement of glutamate decarboxylase activity
Messripour Manoochehr, Mesripour Azadeh
Open Journal of Analytical and Bioanalytical Chemistry.2020; : 007. CrossRef

The Level of Autoantibodies Targeting Eukaryote Translation Elongation Factor 1 α1 and Ubiquitin-Conjugating Enzyme 2L3 in Nondiabetic Young Adults: Eunhee G. Kim, Soo Heon Kwak, Daehee Hwang, Eugene C. Yi, Kyong Soo Park, Bo Kyung Koo, Kristine M. Kim; Diabetes Metab J. 2016;40(2):154-160. Published online November 13, 2015; DOI: https://doi.org/10.4093/dmj.2016.40.2.154

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Background

The prevalence of novel type 1 diabetes mellitus (T1DM) antibodies targeting eukaryote translation elongation factor 1 alpha 1 autoantibody (EEF1A1-AAb) and ubiquitin-conjugating enzyme 2L3 autoantibody (UBE2L3-AAb) has been shown to be negatively correlated with age in T1DM subjects. Therefore, we aimed to investigate whether age affects the levels of these two antibodies in nondiabetic subjects.

Methods

EEF1A1-AAb and UBE2L3-AAb levels in nondiabetic control subjects (n=150) and T1DM subjects (n=101) in various ranges of age (18 to 69 years) were measured using an enzyme-linked immunosorbent assay. The cutoff point for the presence of each autoantibody was determined based on control subjects using the formula: [mean absorbance+3×standard deviation].

Results

In nondiabetic subjects, there were no significant correlations between age and EEF1A1-AAb and UBE2L3-AAb levels. However, there was wide variation in EEF1A1-AAb and UBE2L3-AAb levels among control subjects <40 years old; the prevalence of both EEF1A1-AAb and UBE2L3-AAb in these subjects was 4.4%. When using cutoff points determined from the control subjects <40 years old, the prevalence of both autoantibodies in T1DM subjects was decreased (EEFA1-AAb, 15.8% to 8.9%; UBE2L3-AAb, 10.9% to 7.9%) when compared to the prevalence using the cutoff derived from the totals for control subjects.

Conclusion

There was no association between age and EEF1A1-AAb or UBE2L3-AAb levels in nondiabetic subjects. However, the wide variation in EEF1A1-AAb and UBE2L3-AAb levels apparent among the control subjects <40 years old should be taken into consideration when determining the cutoff reference range for the diagnosis of T1DM.

Citations

Citations to this article as recorded by

An autoantigen-ome from HS-Sultan B-Lymphoblasts offers a molecular map for investigating autoimmune sequelae of COVID-19
Julia Y. Wang, Wei Zhang, Victor B. Roehrl, Michael W. Roehrl, Michael H. Roehrl, Mibel Aguilar
Australian Journal of Chemistry.2023; 76(8): 525. CrossRef
An Autoantigen Atlas From Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19
Julia Y. Wang, Wei Zhang, Victor B. Roehrl, Michael W. Roehrl, Michael H. Roehrl
Frontiers in Immunology.2022;[Epub] CrossRef
Prevalence of antibodies targeting ubiquitin-conjugating enzyme 2L3 and eukaryote translation elongation factor 1 α1 in Chinese Han and American Caucasian populations with type 1 diabetes
Li Qian, Yuxiao Zhu, Yan Luo, Mu Zhang, Liping Yu, Yu Liu, Tao Yang
Endocrine Connections.2022;[Epub] CrossRef
An autoantigen profile of human A549 lung cells reveals viral and host etiologic molecular attributes of autoimmunity in COVID-19
Julia Y. Wang, Wei Zhang, Michael W. Roehrl, Victor B. Roehrl, Michael H. Roehrl
Journal of Autoimmunity.2021; 120: 102644. CrossRef

Review

Challenges in Diagnosing Type 1 Diabetes in Different Populations: Marian Rewers; Diabetes Metab J. 2012;36(2):90-97. Published online April 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.2.90

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Diabetes affects today an estimated 366 million people world-wide, including 20 million to 40 million of patients with type 1 diabetes (T1D). While T1D accounts for 5% to 20% of those with diabetes, it is associated with higher morbidity, mortality and health care cost than the more prevalent type 2 diabetes. Patients with T1D require exogenous insulin for survival and should be identified as soon as possible after diagnosis to avoid high morbidity due to a delay in insulin treatment. It is also important to present to the patient correct prognosis that differs by the type of diabetes. From the research point of view, correct classification should help to identify the etiologies and to develop specific prevention for T1D. This review summarizes evidence that may be helpful in diagnosing T1D in various ethnic groups. Challenges in interpretation of results commonly used to determine the type of diabetes are highlighted.

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Original Article

Measurement of Anti-38kD Antibody in Korean patients with Insulin-Dependent Diabetes Mellitus by Western Blot Analysis.: Sun Ja Kwon, Hong Kyu Lee, Hyeon Kyu Kim; Korean Diabetes J. 1998;22(2):135-144. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Insulin-dependent diabetes mellitus (IDDM) is characterized by the destruction of pancreatic b-cells, which is associated with the genetic susceptibility and the production of antibodies to a numter of islet cell antigens(ICA). A possible target antigen, 38kD antigen, was suggested by the proliferation of CD4 T cells frorn a newly diagnosed patient in response to a 38kD polypeptide of the insulin-secretory-granule membrane. Autoantibody to a rat islet cell -protein of 38kD was detectable in the sera of diabetes-prone biobreeding rats by both immunoprecipitation and differential Westem blot analysis. Anti-38kD antibodies were also found to have a 76% sensitivity at the time of diagnosis in diabetic children by immunoprecipitation. In the Asian populations, it has been reported that clinical and immunologic characteristics of IDDM are quite different from those of Caucasians, say low prevalence of ICA. In Korean, there has never been reported the presence of the anti-38kD antibody. Moreover, the time-consuming and laborious nature of assay, such as T-cell proliferation and immuno-precipitation, makes it difficult to use for large population screenings. In the present study, we aimed to evaluate the prevalence of anti-38kD antibody as a immunologic marker in Korean IDDM patients by Western blot analysis. METHODS: Anti-38kD antibody was detected by Western blot analysis using the lysate of rat insulinoma cell line(RINmSF) as an antigenic source. ICA was determined by enzymatic immunohistochemical analysis. The prevalence of anti-38kD antibody and ICA was measured in 38 cases of IDDM, whose mean age at diagnosis and mean duration of IDDM were 25.2+14.2 years and 0.66+0.97 years, respectively. RESULTS: Using Western blot analysis with the lysate fraction of RIN cell, the prevalence of anti-38kD autoantibody(21.1%) in the IDDM paients was significantly higher than that in the control subjects(0.0%, P<0.05). Clinical characteristics between anti-38kD antibody-positive and -negative IDDM patients were not different. In immunohisto-chemical staining, ICA was detected in 18.2% of the IDDM patients, but not in the control subjects. The prevalence of anti-38kD antibody was 21.7%, 28.6% and 12.5% in the patients of less 1 year, 1 year and 2~4 years, respectively, showing no statistically significant difference in the prevalence according to the duration of IDDM. As previously reported, however, the prevalence of ICA decreased with increasing duration of IDDM. CONCLUSION: These results suggested that the anti-38kD autoantibody is a candidate of autoantibodies for the immunologic markers of Korean IDDM We expect the development of the more methods for the detection of anti-38kD in the future.

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