{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:43:52Z","timestamp":1790066632998,"version":"4.0.1"},"reference-count":40,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context and Objective:<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design:<\/jats:title>\n                  <jats:p>The design is a registry-based study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting:<\/jats:title>\n                  <jats:p>Functional tests were performed in a hospital setting.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants:<\/jats:title>\n                  <jats:p>Persistently autoAb+ first-degree relatives of patients with T1D (n = 81; age 5\u201339 years).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures:<\/jats:title>\n                  <jats:p>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\u201310min; min 5\u201310) was determined in all relatives and second-phase release (AUC120\u2013150min; min 120\u2013150) in those aged 12\u201339 years (n = 62).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Overall, the predictive ability of AUC5\u201310min was better than that of peak C-peptide, the best predictor among OGTT-derived parameters (ROC-AUC [95%CI]: 0.89 [0.80\u20130.98] vs 0.81 [0.70\u20130.93]). Fasting blood glucose (FBG) and AUC5\u201310min provided the best combination of markers for prediction of diabetes within 3 years; (ROC-AUC [95%CI]: 0.92 [0.84\u20131.00]). In multivariate Cox regression analysis, AUC5\u201310min (P = .001) was the strongest independent predictor and interacted significantly with all tested OGTT-derived parameters. AUC5\u201310min below percentile 10 of controls was associated with 50\u201370% progression to T1D regardless of age. Similar results were obtained for AUC120\u2013150min.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2014-2035","type":"journal-article","created":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T18:38:55Z","timestamp":1416335935000},"page":"551-560","source":"Crossref","is-referenced-by-count":12,"title":["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"],"prefix":"10.1210","volume":"100","author":[{"given":"Eric V.","family":"Balti","sequence":"first","affiliation":[{"name":"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"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evy","family":"Vandemeulebroucke","sequence":"additional","affiliation":[{"name":"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"},{"name":"Diabetes Clinic (E.V., U.V., B.K., K.D.), University Hospital Brussels-UZ Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse","family":"Weets","sequence":"additional","affiliation":[{"name":"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"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursule","family":"Van De Velde","sequence":"additional","affiliation":[{"name":"Diabetes Clinic (E.V., U.V., B.K., K.D.), University Hospital Brussels-UZ Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelien","family":"Van Dalem","sequence":"additional","affiliation":[{"name":"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"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simke","family":"Demeester","sequence":"additional","affiliation":[{"name":"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"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrijn","family":"Verhaeghen","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Gillard","sequence":"additional","affiliation":[{"name":"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"},{"name":"Department of Clinical and Experimental Medicine (P.G.), University of Leuven-KUL and University Hospital Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"De Block","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (C.D.), Diabetology and Metabolism, Antwerp University Hospital, Edegem, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Ruige","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (J.R.), University of Ghent, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Keymeulen","sequence":"additional","affiliation":[{"name":"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"},{"name":"Diabetes Clinic (E.V., U.V., B.K., K.D.), University Hospital Brussels-UZ Brussel, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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