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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.)

Objective: To determine the impact of islet transplantation (ITx) on hypoglycemia awareness in patients with unstable type 1 diabetes and its relation to islet function., Research Design and Methods: A total of 31 ITx recipients were studied. Hypoglycemia unawareness was assessed using the Clarke hypoglycemic score (0 = no hypoglycemia; >or=4 = hypoglycemia unawareness). Subjects were grouped based on graft function: off-insulin (n = 8), graft dysfunction (on-insulin and stimulated C-peptide >or=0.3 ng/ml, n = 13), and graft failure (stimulated C-peptide <0.3 ng/ml, n = 10, evaluated 11.5 +/- 14.5 months after graft failure)., Results: The hypoglycemia score improved after ITx when compared with baseline values (before vs. after: 5.29 +/- 1.51 vs. 1.35 +/- 1.92, P < 0.001). This result was sustained even after patient stratification based on islet function (pre vs. post off-insulin: 5.63 +/- 2.00 vs. no hypoglycemia reported; graft dysfunction: 5.31 +/- 1.49 vs. 1.15 +/- 1.63, P < 0.001; and graft failure: 5.00 +/- 1.16 vs. 2.70 +/- 2.26, P = 0.014)., Conclusions: The improved metabolic control achieved with ITx can restore hypoglycemia awareness in patients with type 1 diabetes, persisting even after islet graft failure.