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 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-p...