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

Eric V Balti, Evy Vandemeulebroucke, Ilse Weets, Ursule Van De Velde, Annelien Van Dalem, Simke Demeester, Katrijn Verhaeghen, Pieter Gillard, Christophe De Block, Johannes Ruige, Bart Keymeulen, Daniel Pipeleers, Katelijn Decochez, Frans K Gorus, Belgian Diabetes Registry

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8 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)551-560
Aantal pagina's10
TijdschriftJournal of Clinical Endocrinology and Metabolism
Volume100
Nummer van het tijdschrift2
DOI's
StatusPublished - feb 2015

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