Evidence map›Paper›PMID 34272582›Full record

ArticleDiabetologia2021

Improving clinical utility of GAD65 autoantibodies by electrochemiluminescence assay and clinical phenotype when identifying autoimmune adult-onset diabetes.

Yong Gu, Xiaofan Jia, Tanwi Vartak, Dongmei Miao, Fran Dong, Samuel T Jerram, Marian Rewers, Assiamira Ferrara, Jean M Lawrence, Liping Yu and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 25 citations in OpenAlex.

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  12. Adult-onset autoimmune diabetes.Nature reviews. Disease primers · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 6 institutions in 3 countries.

Yong GuBarbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
Xiaofan JiaBarbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
Tanwi VartakCentre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Dongmei MiaoBarbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
Fran DongBarbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
Samuel T JerramCentre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Marian RewersBarbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
Assiamira FerraraDivision of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
Jean M LawrenceDepartment of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.
Liping YuBarbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. Liping.yu@cuanschutz.edu.ORCID 0000-0003-0664-2154
R David LeslieCentre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK. r.d.g.leslie@qmul.ac.uk.ORCID 0000-0002-1786-1531
Action LADA consortium and the Diabetes in Young Adults (DiYA) Study Group
Kaiser Permanente · USQueen Mary University of London · GBUniversity of Colorado Denver · USUniversity of Colorado Health · USBeijing Hospital · CNNanjing Medical University · CN

Funding

University of Colorado Anschutz Medical Campus DRCP30DK116073 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI PETER J DEMPSEY · 2020 to 2026
$10.8M
Natural History of Pre-Diabetic Autoimmunity (DAISY)R01DK032493 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI REWERS, MARIAN J · 1986 to 2024
$9.3M
Multiple Autoantigens/Multiple Epitopes of Type 1DMR01DK032083 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI MICHELS, AARON W · 1986 to 2025
$6.9M
STUDY TO ASSESS THE INCIDENCE OF TYPE 1 DIABETES IN YOUNG ADULTSU18DP006289 · DP · KAISER FOUNDATION RESEARCH INSTITUTE · PI LAWRENCE, JEAN MARIE · 2016 to 2017
$2.1M
MULTIPLE AUTOANTIGENS OF PRETYPE I DMR37DK032083 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI EISENBARTH, GEORGE S · 1992 to 1999
–
ACL HHS U18DP006289NCCDPHP CDC HHS U18 DP006289NIDDK NIH HHS P30 DK116073NIDDK NIH HHS R01 DK032083NIDDK NIH HHS R01 DK032493NIDDK NIH HHS R37 DK032083
6 · The paper itself

Abstract

aims/hypothesisIt is important to differentiate the two major phenotypes of adult-onset diabetes, autoimmune type 1 diabetes and non-autoimmune type 2 diabetes, especially as type 1 diabetes presents in adulthood. Serum GAD65 autoantibodies (GADA) are the most sensitive biomarker for adult-onset autoimmune type 1 diabetes, but the clinical value of GADA by current standard radiobinding assays (RBA) remains questionable. The present study focused on the clinical utility of GADA differentiated by a new electrochemiluminescence (ECL) assay in patients with adult-onset diabetes.

methodsTwo cohorts were analysed including 771 diabetic participants, 30-70 years old, from the Action LADA study (n = 6156), and 2063 diabetic participants, 20-45 years old, from the Diabetes in Young Adults (DiYA) study. Clinical characteristics of participants, including requirement of early insulin treatment, BMI and development of multiple islet autoantibodies, were analysed according to the status of RBA-GADA and ECL-GADA, respectively, and compared between these two assays.

resultsGADA was the most prevalent and predominant autoantibody, >90% in both cohorts. GADA positivity by either RBA or ECL assay significantly discriminated clinical type 1 from type 2 diabetes. However, in both cohorts, participants with ECL-GADA positivity were more likely to require early insulin treatment, have multiple islet autoantibodies, and be less overweight (for all p < 0.0001). However, clinical phenotype, age at diagnosis and BMI independently improved positive predictive value (PPV) for the requirement of insulin treatment, even augmenting ECL-GADA. Participants with GADA detectable by RBA, but not confirmed by ECL, had a phenotype more similar to type 2 diabetes. These RBA-GADA positive individuals had lower affinity GADA compared with participants in which GADA was confirmed by ECL assay. CONCLUSIONS/

interpretationDetection of GADA by ECL assay, given technical advantages over RBA-GADA, identified adult-onset diabetes patients at higher risk of requiring early insulin treatment, as did clinical phenotype, together allowing for more accurate clinical diagnosis and management.

Indexed as

Diabetes Mellitus, Type 1Diabetes Mellitus, Type 2AdultAutoantibodiesGlutamate DecarboxylaseHumansPhenotypeAutoantibodiesGlutamate DecarboxylaseAdult-onset diabetesAutoantibodiesBiomarkerECL assay

Identifiers

PMID34272582
PMCPMC8382643
OpenAlexW3180043680

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.