Predictive Value of C-Peptide Measures for Clinical Outcomes of β-Cell Replacement Therapy in Type 1 Diabetes: Report From the Collaborative Islet Transplant Registry (CITR).
- Resource Type
- Academic Journal
- Authors
- Baidal DA; Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.; Ballou CM; Collaborative Islet Transplant Registry Coordinating Center, The EMMES Company, LLC, Rockville, MD.; Rickels MR; Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.; Berney T; Division of Transplantation, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland.; Pattou F; Department of General and Endocrine Surgery, Centre Hospitalier Universitaire de Lille, Translational Research for Diabetes, INSERM, Université de Lille, Lille, France.; Payne EH; Collaborative Islet Transplant Registry Coordinating Center, The EMMES Company, LLC, Rockville, MD.; Barton FB; Collaborative Islet Transplant Registry Coordinating Center, The EMMES Company, LLC, Rockville, MD.; Alejandro R; Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
- Source
- Publisher: American Diabetes Association Country of Publication: United States NLM ID: 7805975 Publication Model: Print Cited Medium: Internet ISSN: 1935-5548 (Electronic) Linking ISSN: 01495992 NLM ISO Abbreviation: Diabetes Care Subsets: MEDLINE
- Subject
- Language
- English
Objective: To determine C-peptide measures and levels associated with positive glycemic control outcomes following islet transplant (ITx) in type 1 diabetes.
Research Design and Methods: We evaluated Collaborative Islet Transplant Registry (CITR) islet-alone recipients with pretransplant C-peptide <0.1 nmol/L and mean follow-up of 4.6 ± 1.1 years (n = 677). Receiver operating characteristic area under the curve (ROC-AUC) was used to evaluate the predictive value of fasting and stimulated glucose and C-peptide measures for seven primary outcomes: 1) absence of severe hypoglycemic events (ASHEs); 2) HbA1c <7.0%; 3) HbA1c <7.0% and ASHEs; 4) HbA1c ≤6.5%; 5) HbA1c ≤6.5% and ASHEs; 6) insulin independence; and 7) ASHEs, HbA1c ≤6.5%, and insulin independence (the optimal outcome). Measures with the highest ROC-AUC were selected for determination of optimal cut points.
Results: Fasting C-peptide was highly predictive for ASHE (ROC-AUC 0.906; optimal cut point 0.070 nmol/L) and the optimal outcome (ROC-AUC 0.845; optimal cut point 0.33 nmol/L). Mixed-meal tolerance test (MMTT)-stimulated C-peptide-to-glucose ratio (CPGR) outperformed both fasting and stimulated C-peptide for all outcomes except ASHE. The optimal cut point for the optimal outcome was 0.12 nmol/mmol for MMTT-stimulated CPGR and 0.97 nmol/L for MMTT-stimulated C-peptide.
Conclusions: Fasting C-peptide reliably predicts ITx primary outcomes. MMTT-stimulated CPGR provides marginally better prediction for composite ITx outcomes, including insulin independence. In the absence of an MMTT, a fasting C-peptide ≥0.33 nmol/L is a reassuring measure of optimal islet graft function. C-peptide targets represent excellent and easily determinable means to predict glycemic control outcomes after ITx and should be considered as potential goals of β-cell replacement.
(© 2023 by the American Diabetes Association.)