title: Trends of earlier and later responses of C-peptide to oral glucose challenges with progression to type 1 diabetes in diabetes prevention trial-type 1 participants.
abstract: OBJECTIVE We studied the C-peptide response to oral glucose with progression to type 1 diabetes in Diabetes Prevention Trial-Type 1 (DPT-1) participants. RESEARCH DESIGN AND METHODS Among 504 DPT-1 participants <15 years of age, longitudinal analyses were performed in 36 progressors and 80 nonprogressors. Progressors had oral glucose tolerance tests (OGTTs) at baseline and every 6 months from 2.0 to 0.5 years before diagnosis; nonprogressors had OGTTs over similar intervals before their last visit. Sixty-six progressors and 192 nonprogressors were also studied proximal to and at diagnosis. RESULTS The 30-0 min C-peptide difference from OGTTs performed 2.0 years before diagnosis in progressors was lower than the 30-0 min C-peptide difference from OGTTs performed 2.0 years before the last visit in nonprogressors (P < 0.01) and remained lower over time. The 90-60 min C-peptide difference was positive at every OGTT before diagnosis in progressors, whereas it was negative at every OGTT before the last visit in nonprogressors (P < 0.01 at 2.0 years). The percentage whose peak C-peptide occurred at 120 min was higher in progressors at 2.0 years (P < 0.05); this persisted over time (P < 0.001 at 0.5 years). However, the peak C-peptide levels were only significantly lower at 0.5 years in progressors (P < 0.01). The timing of the peak C-peptide predicted type 1 diabetes (P < 0.001); peak C-peptide levels were less predictive (P < 0.05). CONCLUSIONS A decreased early C-peptide response to oral glucose and an increased later response occur at least 2 years before the diagnosis of type 1 diabetes.
authors.affiliation: Division of Endocrinology, University of Miami, Miami, Florida, USA. jsosenko@med.miami.edu
authors.forename: Jay M
authors.initials: JM
authors.lastname: Sosenko
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Rafkin
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
authors.forename: David
authors.initials: D
authors.lastname: Cuthbertson
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: George
authors.initials: G
authors.lastname: Eisenbarth
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002096:C-Peptide / Q000187:drug effects / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011236:Prediabetic State / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
chemical_list: D002096:C-Peptide; D005947:Glucose