Glutamic Acid Decarboxylase Autoantibody Detection by Electrochemiluminescence Assay Identifies Latent Autoimmune Diabetes in Adults with Poor Islet Function

Zhu, Yuxiao; Li, Qian; Liu, Qing; Zou, Jing; Zhou, Ying; Yang, Tao; Huang, Gan; Zhang, Zhou; Liu, Yu

doi:10.4093/dmj.2019.0007

Cited by 13 publications

(8 citation statements)

References 21 publications

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“…For the purpose of this classification, all forms of diabetes mediated by autoimmune b-cell destruction are included under the rubric of type 1 diabetes. Use of the term LADA is common and acceptable in clinical practice and has the practical impact of heightening awareness of a population of adults likely to have progressive autoimmune b-cell destruction (16), thus accelerating insulin initiation prior to deterioration of glucose control or development of DKA (6,17).…”

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confidence: 99%

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2022

2021

Diabetes Care

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655

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The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.

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confidence: 99%

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2022

2021

Diabetes Care

1,418

655

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“…The term LADA is acceptable in clinical practice for its practical impact of highlighting proper treatment and insulin initiation prior to beta-cell function failure ( 16 – 18 ). Jones et al.…”

Section: Discussionmentioning

confidence: 99%

Analysis of detrended fluctuation function derived from continuous glucose monitoring may assist in distinguishing latent autoimmune diabetes in adults from T2DM

Zhang

Tian²,

Guo³

et al. 2022

Front. Endocrinol.

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BackgroundWe aimed to explore the performance of detrended fluctuation function (DFF) in distinguishing patients with latent autoimmune diabetes in adults (LADA) from type 2 diabetes mellitus (T2DM) with glucose data derived from continuous glucose monitoring.MethodsIn total, 71 LADA and 152 T2DM patients were enrolled. Correlations between glucose parameters including time in range (TIR), mean glucose, standard deviation (SD), mean amplitude of glucose excursions (MAGE), coefficient of variation (CV), DFF and fasting and 2-hour postprandial C-peptide (FCP, 2hCP) were analyzed and compared. Receiver operating characteristics curve (ROC) analysis and 10-fold cross-validation were employed to explore and validate the performance of DFF in diabetes classification respectively.ResultsPatients with LADA had a higher mean glucose, lower TIR, greater SD, MAGE and CV than those of T2DM (P<0.001). DFF achieved the strongest correlation with FCP (r = -0.705, P<0.001) as compared with TIR (r = 0.485, P<0.001), mean glucose (r = -0.337, P<0.001), SD (r = -0.645, P<0.001), MAGE (r = -0.663, P<0.001) and CV (r = -0.639, P<0.001). ROC analysis showed that DFF yielded the greatest area under the curve (AUC) of 0.862 (sensitivity: 71.2%, specificity: 84.9%) in differentiating LADA from T2DM as compared with TIR, mean glucose, SD, MAGE and CV (AUC: 0.722, 0.650, 0.800, 0.820 and 0.807, sensitivity: 71.8%, 47.9%, 63.6%, 72.7% and 78.8%, specificity: 67.8%, 83.6%, 80.9%, 80.3% and 72.4%, respectively). The kappa test indicated a good consistency between DFF and the actual diagnosis (kappa = 0.551, P<0.001). Ten-fold cross-validation showed a stable performance of DFF with a mean AUC of 0.863 (sensitivity: 78.8%, specificity: 77.8%) in 10 training sets and a mean AUC of 0.866 (sensitivity: 80.9%, specificity: 84.1%) in 10 test sets.ConclusionsA more violent glucose fluctuation pattern was marked in patients with LADA than T2DM. We first proposed the possible role of DFF in distinguishing patients with LADA from T2DM in our study population, which may assist in diabetes classification.

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“…We believe that, by using a more disease-specific assay with high sensitivity like the ECL assay, the predictive value of IAbs will be greatly enhanced overall and, particularly, a single IAb identified in such a high-affinity assay will be expected as a reliable biomarker for early prediction and disease staging of T1D. This new methodology of ECL assay for IAbs has recently been implemented by several other laboratories with the results demonstrated at the 2020 IASP workshop (unpublished data) and a recent published study of the Latent Autoimmune Diabetes of Adults cohort ( 20 ). Several other IAb assay methods, in addition to RBA, like the enzyme-linked immunosorbent assay ( 21 ), antibody detection by agglutination–polymerase chain reaction ( 22 ), and the luciferase immunoprecipitation system ( 23 ) have been reported.…”

Section: Discussionmentioning

confidence: 99%

High-Affinity ZnT8 Autoantibodies by Electrochemiluminescence Assay Improve Risk Prediction for Type 1 Diabetes

Jia

Miao

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Background The risk of progression to type 1 diabetes (T1D) in subjects positive only for ZnT8 autoantibody (ZnT8A) is currently not known. Methods We developed an electrochemiluminescence (ECL) assay to detect high-affinity ZnT8A and validated it in three populations: 302 patients newly diagnosed with T1D, 135 non-diabetic children positive for ZnT8A by standard radio-binding assay (RBA) among 23400 children screened by the Autoimmunity Screening for Kids (ASK), and 123 non-diabetic children multiple autoantibody positive or single ZnT8A positive by RBA participating in the Diabetes Autoimmunity Study in the Young (DAISY). Results In 302 patients with T1D at diagnosis, the positivity for ZnT8A was 62% in both RBA and ECL. Among ASK 135 participants positive for RBA-ZnT8A, 64 were detected ZnT8A as the only islet autoantibody. Of these 64, only 9 were confirmed by ECL-ZnT8A, found to be of high affinity with increased T1D risk. Overall positive predictive value of ECL-ZnT8A for T1D risk was 87.1%, significantly higher than that of RBA-ZnT8A (53.5%, P<0.0001). In DAISY, 11/2547 children who had no positivity previously detected for other islet autoantibodies were identified as single ZnT8A by RBA; of these, three were confirmed positive by ECL-ZnT8A and all three progressed to clinical T1D. Conclusions Large proportion of ZnT8A by RBA are single ZnT8A with low T1D risk while ZnT8A by ECL were of high-affinity and high prediction for T1D development.

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Glutamic Acid Decarboxylase Autoantibody Detection by Electrochemiluminescence Assay Identifies Latent Autoimmune Diabetes in Adults with Poor Islet Function

Cited by 13 publications

References 21 publications

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2022

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2022

Analysis of detrended fluctuation function derived from continuous glucose monitoring may assist in distinguishing latent autoimmune diabetes in adults from T2DM

High-Affinity ZnT8 Autoantibodies by Electrochemiluminescence Assay Improve Risk Prediction for Type 1 Diabetes

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