American Diabetes Association
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Predictive Value of C-peptide Measures for Clinical Outcomes of Beta Cell Replacement Therapy in Type 1 Diabetes: Report from the Collaborative Islet Transplant Registry (CITR)

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posted on 2023-01-17, 19:31 authored by David A. Baidal, Cassandra M. Ballou, Michael R. Rickels, Thierry Berney, Francois Pattou, Elizabeth H. Payne, Franca B. Barton, Rodolfo Alejandro, the CITR Investigators


To determine C-peptide measures and levels associated with positive glycemic control outcomes following islet transplantation (ITx) in type 1 diabetes.

We evaluated Collaborative Islet Transplant Registry (CITR) Islet-Alone recipients with pre-transplant C-peptide <0.1 nmol/L and mean follow up of 4.6±1.1 years (n=677). Area under the curve of receiver-operator characteristics (ROC-AUC) were used to evaluate predictive value of fasting and stimulated glucose and C-peptide measures for 7 primary outcomes: a) absence of severe hypoglycemic events (ASHE); b) HbA1c<7.0%; c) HbA1c<7.0% & ASHE; d) HbA1c≤6.5%; e) HbA1c≤6.5% & ASHE; f) insulin independence; and g) ASHE, HbA1c≤6.5% & insulin independence (the optimal outcome). Measures with the highest ROC-AUC were selected for determination of optimal cut points.

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. 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.

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 a 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 beta cell replacement. 


The CITR is funded by the NIDDK, National Institutes of Health (1UCHDK098086-01, 1UC4DK114839-01) and by a supplemental grant from the JDRF International. MRR is supported in part by Public Health Service Research Grant R01 DK 091331-10.