Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
Collaborative Islet Transplant Registry Coordinating Center, The EMMES Company, LLC, Rockville, MD.
Diabetes Care. 2023 Apr 1;46(4):697-703. doi: 10.2337/dc22-1155.
To determine C-peptide measures and levels associated with positive glycemic control outcomes following islet transplant (ITx) in type 1 diabetes.
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.
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.
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.
确定与 1 型糖尿病胰岛移植（ITx）后血糖控制良好结果相关的 C 肽测量值和水平。
我们评估了协作胰岛移植登记处（CITR）的胰岛单独移植受者，这些受者在移植前 C 肽 <0.1 nmol/L，平均随访 4.6 ± 1.1 年（n = 677）。我们使用接受者操作特征曲线（ROC）下面积（AUC）来评估空腹和刺激后葡萄糖和 C 肽测量值对七种主要结果的预测价值：1）无严重低血糖事件（ASHEs）；2）HbA1c <7.0%；3）HbA1c <7.0%和 ASHEs；4）HbA1c ≤6.5%；5）HbA1c ≤6.5%和 ASHEs；6）胰岛素独立性；7）ASHEs、HbA1c ≤6.5%和胰岛素独立性（最佳结果）。选择 AUC 最高的测量值来确定最佳切点。
空腹 C 肽对 ASHE（ROC-AUC 0.906；最佳切点 0.070 nmol/L）和最佳结果（ROC-AUC 0.845；最佳切点 0.33 nmol/L）具有高度预测性。混合餐耐量试验（MMTT）刺激的 C 肽与血糖比值（CPGR）在除 ASHE 以外的所有结果中均优于空腹和刺激后的 C 肽。最佳结果的最佳切点为 MMTT 刺激 CPGR 为 0.12 nmol/mmol，MMTT 刺激 C 肽为 0.97 nmol/L。
空腹 C 肽可靠地预测 ITx 的主要结果。MMTT 刺激的 CPGR 对复合 ITx 结果（包括胰岛素独立性）提供了略有更好的预测。在没有 MMTT 的情况下，空腹 C 肽≥0.33 nmol/L 是胰岛移植物功能良好的可靠指标。C 肽目标是预测 ITx 后血糖控制结果的极好且易于确定的手段，应被视为β细胞替代的潜在目标。
