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

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 pati...

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Published in:The journal of clinical endocrinology and metabolism 2015-02, Vol.100 (2), p.551-560
Main Authors: 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
Format: Article
Language:English
Subjects:
Adolescent
Adult
Autoantibodies - blood
Child
Child of Impaired Parents
Child, Preschool
Diabetes Mellitus, Type 1 - blood
Diabetes Mellitus, Type 1 - immunology
Female
Glucose Intolerance
Glucose Tolerance Test
Humans
Insulin - blood
Male
Predictive Value of Tests
ROC Curve
Siblings
Young Adult
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Summary: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 (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 3 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 of 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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2014-2035