Diagnostic Accuracy of Serologic Screening Tests for Celiac Disease in Asymptomatic Adults and Children with Type 1 Diabetes
Bibliographic record
Abstract
Background: As related autoimmune conditions, celiac disease (CD) is more common in individuals with type 1 diabetes (T1D) and is frequently asymptomatic. Despite this association, evidence as to the diagnostic accuracy of screening as well as the potential benefits or harms of screening for CD is limited in asymptomatic patients with T1D. Methods: T1D patients, aged 8-45 years, were serologically screened for CD at multiple centers across Ontario, Canada as part of the Celiac Disease and Diabetes Dietary Intervention and Evaluation Trial (CD-DIET). Patients were deemed asymptomatic on the basis of the absence of GI symptoms, weight changes, anemia and other CD-related clinical features. Screening was conducted in 2,386 patients using chemiluminescent (CL, BioFlash™) and/or ELISA (Celikey™) tissue transglutaminase (TTG) IgA assays, yielding 140 positives. Of these, 104 patients had a duodenal biopsy with CD confirmation (Marsh ≥2). Receiver operating characteristic (ROC) curve analysis was conducted and positive predictive values (PPV) of available screening tests for CD were evaluated. Results: CL and ELISA data were available for 100/104 and 36/104 patients, respectively. The area under the curve of the ROC for CL TTG was 0.918, while the PPV using the manufacturer referenced upper limit (RUL) of 30 CU was 85.9% (95% CI: 82.3-90.8%). According to our data, an optimal cut-off of 156.5 CU, or 5.2 times the RUL, showed an improved PPV of 95.8% (95% CI: 92.4-100.0%). With respect to ELISA TTG, the PPV was 94.4% at the RUL of 8 U/ml and reached to 100% at the optimal cut-off determined by our analysis of 58.7 U/ml, which translates to 7.3 times the RUL. Conclusion: Results from serologic CL and ELISA TTG assays that were greater than 5 times the reported upper limit showed a high PPV for biopsy-confirmed CD in asymptomatic adult and pediatric T1D patients, which may help guide diagnostic evaluation in this population. Disclosure M. Gould: None. F.H. Mahmud: None. A.B. Clarke: None. E. Assor: None. A. Parikh: None. A. Advani: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Other Relationship; Self; Boehringer Ingelheim GmbH. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc.. B.R. Shah: None. C.S. Zuijdwijk: None. C. McDonald: None. D. Mack: None. D. Koltin: None. E. Hsieh: None. E.M. Szentgyorgyi: None. F. Saibil: None. G. Mukerji: None. H.A. Lochnan: Research Support; Self; Amylin Pharmaceuticals, Boston Therapeutics, Inc., Sanofi. J. Gilbert: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi. K. Bax: None. M.L. Lawson: None. M.D. Beaton: Advisory Panel; Self; Takeda Canada Inc., Janssen Pharmaceuticals, Inc., AbbVie Inc.. N.A. Saloojee: None. O. Lou: None. P.H. Gallego: None. R.L. Houlden: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., AstraZeneca, Eli Lilly and Company. R. Aronson: Other Relationship; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi, AstraZeneca. Research Support; Self; Eli Lilly and Company, Becton, Dickinson and Company, Merck & Co., Inc., Senseonics, Boehringer Ingelheim Pharmaceuticals, Inc.. S.E. Kirsch: None. W.G. Paterson: None. Z. Punthakee: Research Support; Self; Amgen, Astra Zeneca/Bristol Myers Squibb, Lexicon, Merck, NovoNordisk, Sanofi. Speaker's Bureau; Self; Abbott, Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Sanofi. Advisory Panel; Self; Astra Zeneca/Bristol Myers Squibb, Boehringer Ingelheim/Eli Lilly, Dexcom, Janssen, Medtronic, NovoNordisk, Pfizer, Sanofi. M.A. Marcon: None.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.014 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".