Eric V Balti1, 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 G Pipeleers, Katelijn Decochez, Frans K Gorus. 1. Diabetes Research Center (E.V.B., E.V., I.W., A.V., S.D., P.G., B.K., D.G.P., K.D., F.K.G.), Brussels Free University-VUB, Brussels, Belgium; Department of Clinical Chemistry and Radio-Immunology (E.V.B., I.W., A.V., S.D., K.V., F.K.G.), University Hospital Brussels-UZ Brussel, Brussels, Belgium; Diabetes Clinic (E.V., U.V., B.K., K.D.), University Hospital Brussels-UZ Brussel, Brussels, Belgium; Department of Clinical and Experimental Medicine (P.G.), University of Leuven-KUL and University Hospital Leuven, Leuven, Belgium; Department of Endocrinology (C.D.), Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium; and Department of Endocrinology (J.R.), University of Ghent, Ghent, Belgium.
Abstract
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.
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.
Authors: Annelien Van Dalem; Simke Demeester; Eric V Balti; Katelijn Decochez; Ilse Weets; Evy Vandemeulebroucke; Ursule Van de Velde; An Walgraeve; Nicole Seret; Christophe De Block; Johannes Ruige; Pieter Gillard; Bart Keymeulen; Daniel G Pipeleers; Frans K Gorus Journal: Diabetologia Date: 2015-09-26 Impact factor: 10.122
Authors: Simke Demeester; Bart Keymeulen; Leonard Kaufman; Annelien Van Dalem; Eric V Balti; Ursule Van de Velde; Patrick Goubert; Katrijn Verhaeghen; Howard W Davidson; Janet M Wenzlau; Ilse Weets; Daniel G Pipeleers; Frans K Gorus Journal: Diabetes Care Date: 2015-01-12 Impact factor: 19.112
Authors: Annelien Van Dalem; Simke Demeester; Eric V Balti; Bart Keymeulen; Pieter Gillard; Bruno Lapauw; Christophe De Block; Pascale Abrams; Eric Weber; Ilse Vermeulen; Pieter De Pauw; Daniël Pipeleers; Ilse Weets; Frans K Gorus Journal: PLoS One Date: 2016-12-01 Impact factor: 3.240
Authors: Michael G Voss; David D Cuthbertson; Mario M Cleves; Ping Xu; Carmella Evans-Molina; Jerry P Palmer; Maria J Redondo; Andrea K Steck; Markus Lundgren; Helena Larsson; Wayne V Moore; Mark A Atkinson; Jay M Sosenko; Heba M Ismail Journal: Diabetes Care Date: 2021-08-06 Impact factor: 17.152