Michael G Voss1, David D Cuthbertson2, Mario M Cleves2, Ping Xu2, Carmella Evans-Molina3, Jerry P Palmer4, Maria J Redondo5, Andrea K Steck6, Markus Lundgren7, Helena Larsson7, Wayne V Moore8, Mark A Atkinson9, Jay M Sosenko10, Heba M Ismail. 1. Department of Medicine, Indiana University, School of Medicine, Indianapolis, IN. 2. Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida. 3. Department of Pediatrics, Indiana University, School of Medicine, Indianapolis, IN. 4. Veterans Affairs Puget Sound Health Care System, Seattle, WA. 5. Texas Children's Hospital, Baylor College of Medicine, Houston, TX. 6. Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO. 7. Unit for Pediatric Endocrinology, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden. 8. Division of Endocrinology and Diabetes, Children's Mercy Hospital, University of Missouri-Kansas City School of Medicine, Kansas City, MO. 9. Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL. 10. Division of Endocrinology, Diabetes, and Metabolism, University of Miami, Miami, FL.
Abstract
OBJECTIVE: To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody-positive relatives of people with type 1 diabetes. RESEARCH DESIGN AND METHODS: We examined 2-h OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (mean ± SD age, 13.84 ± 9.53 years; BMI Z-score, 0.33 ± 1.07; 56.1% male) and 3,720 PTP participants (age, 16.01 ± 12.33 years; BMI Z-score, 0.66 ± 1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-score, HOMA-insulin resistance, and peak glucose/C-peptide levels, respectively) were performed. RESULTS: In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose >30 min and time to peak C-peptide >60 min (P < 0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: χ2 = 25.76 vs. χ2 = 8.62; PTP: χ2 = 149.19 vs. χ2 = 79.98; all P < 0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time. CONCLUSIONS: In two independent at-risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression.
OBJECTIVE: To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody-positive relatives of people with type 1 diabetes. RESEARCH DESIGN AND METHODS: We examined 2-h OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (mean ± SD age, 13.84 ± 9.53 years; BMI Z-score, 0.33 ± 1.07; 56.1% male) and 3,720 PTP participants (age, 16.01 ± 12.33 years; BMI Z-score, 0.66 ± 1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-score, HOMA-insulin resistance, and peak glucose/C-peptide levels, respectively) were performed. RESULTS: In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose >30 min and time to peak C-peptide >60 min (P < 0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: χ2 = 25.76 vs. χ2 = 8.62; PTP: χ2 = 149.19 vs. χ2 = 79.98; all P < 0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time. CONCLUSIONS: In two independent at-risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression.
Authors: Jay M Sosenko; Jerry P Palmer; Carla J Greenbaum; Jeffrey Mahon; Catherine Cowie; Jeffrey P Krischer; H Peter Chase; Neil H White; Bruce Buckingham; Kevan C Herold; David Cuthbertson; Jay S Skyler Journal: Diabetes Care Date: 2006-03 Impact factor: 19.112
Authors: Heli T Siljander; Robert Hermann; Anne Hekkala; Jyrki Lähde; Laura Tanner; Päivi Keskinen; Jorma Ilonen; Olli Simell; Riitta Veijola; Mikael Knip Journal: Eur J Endocrinol Date: 2013-09-14 Impact factor: 6.664
Authors: Jay M Sosenko; Jerry P Palmer; Lisa E Rafkin; Jeffrey P Krischer; David Cuthbertson; Carla J Greenbaum; George Eisenbarth; Jay S Skyler Journal: Diabetes Care Date: 2009-12-23 Impact factor: 17.152