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
Balti, Eric V × Vandemeulebroucke, Evy Weets, Ilse Van De Velde, Ursule Van Dalem, Annelien Demeester, Simke Verhaeghen, Katrijn Gillard, Pieter De Block, Christophe Ruige, Johannes Keymeulen, Bart Pipeleers, Daniel G Decochez, Katelijn Gorus, Frans K The Belgian Diabetes Registry #
Issued for the Endocrine Society by the Williams & Wilkins Co.
Journal of Clinical Endocrinology & Metabolism vol:100 issue:2 pages:551-560
Context and Objective: In preparation of future prevention trials, we aimed to identify predictors of 3-year diabetes onset among OGTT- and hyperglycemic clamp-derived metabolic markers in persistently islet autoantibody positive (autoAb(+)) offspring and siblings of patients with type 1 diabetes (T1D). Design: Registry-based study. Setting: Functional tests were performed in 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 (AUC5-10min; min 5-10) was determined in all relatives and second-phase release (AUC120-150min; min 120-150) in those aged 12-39 years (n=62). Results: Overall, the predictive ability of AUC5-10min 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 AUC5-10min provided the best combination of markers for prediction of diabetes within three years; (ROC-AUC [95%CI]: 0.92 [0.84-1.00]). In multivariate Cox regression analysis, AUC5-10min (P=.001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC5-10min below percentile 10 of controls was associated with 50-70% progression to T1D regardless age. Similar results were obtained for AUC120-150min 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.