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Hyperglycemic clamp and oral glucose tolerance test for 3-year prediction of clinical onset in persistently autoantibody-positive offspring and siblings of type 1 diabetic patients

Tijdschriftbijdrage - Tijdschriftartikel

CONTEXT AND OBJECTIVE: In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among oral glucose tolerance test (OGTT)- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb(+)) offspring and siblings of patients with type 1 diabetes (T1D).

DESIGN: The design is a registry-based study.

SETTING: Functional tests were performed in a hospital setting.

PARTICIPANTS: Persistently autoAb(+) first-degree relatives of patients with T1D (n = 81; age 5-39 years).

MAIN OUTCOME MEASURES: We assessed 3-year predictive ability of OGTT- and clamp-derived markers using receiver operating characteristics (ROC) and Cox regression analysis. Area under the curve of clamp-derived first-phase C-peptide release (AUC(5-10 min); min 5-10) was determined in all relatives and second-phase release (AUC(120-150 min); min 120-150) in those aged 12-39 years (n = 62).

RESULTS: Overall, the predictive ability of AUC(5-10 min) was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80-0.98] vs 0.81 [0.70-0.93]). Fasting blood glucose (FBG) and AUC(5-10 min) provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84-1.00]). In multivariate Cox regression analysis, AUC(5-10 min)) (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC(5-10 min) below percentile 10 of controls was associated with 50-70% progression to T1D regardless of age. Similar results were obtained for AUC(120-150 min).

CONCLUSIONS: Clamp-derived first-phase C-peptide release can be used as an efficient and simple screening strategy in persistently autoAb(+) offspring and siblings of T1D patients to predict impending diabetes.

Tijdschrift: J Clin Endocrinol Metab
ISSN: 0021-972X
Issue: 2
Volume: 100
Pagina's: 551-560
Aantal pagina's: 10
Jaar van publicatie:2015
Trefwoorden:Adolescent, Adult, Autoantibodies, Child, Child of Impaired Parents, Child, Preschool, Diabetes Mellitus, Type 1, Female, Glucose Intolerance, Glucose Tolerance Test, Humans, Insulin, Male, Predictive Value of Tests, ROC Curve, Siblings, Young Adult
  • DOI: https://doi.org/10.1210/jc.2014-2035
  • Scopus Id: 84922508014
  • WoS Id: 000353350900059
  • ORCID: /0000-0002-9007-5203/work/58116994
  • ORCID: /0000-0001-5099-8962/work/60549495
  • ORCID: /0000-0002-9007-6177/work/60767442
  • ORCID: /0000-0002-8671-4527/work/61349278
  • ORCID: /0000-0002-6440-2485/work/61423349
  • ORCID: /0000-0003-2304-5298/work/61726056
  • ORCID: /0000-0001-7179-1717/work/83057860