Wang Chia-Hao, Orr Christopher, Hacker-Stratton Jeannette, El-Shahawy Mohamed, Omori Keiko, Qi Meirigeng, Kandeel Fouad
Department of Translational Research & Cellular Therapeutics, Arthur Riggs Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA, USA.
Cell Transplant. 2025 Jan-Dec;34:9636897241310989. doi: 10.1177/09636897241310989.
Although islet transplantation is effective in reducing severe hypoglycemia events and controlling blood glucose in patients with type 1 diabetes, maintaining islet graft function long-term is a significant challenge. Islets from multiple donors are often needed to achieve insulin independence, and even then, islet function can decline over time when metabolic demand exceeds islet mass/insulin secretory capacity. We previously developed a method that calculated the islet graft function index (GFI) and a patient's predicted insulin requirement (PIR) using mathematical nonlinear regression. Both PIR and GFI could be used by physicians as tools to monitor islet graft function and to guide supplementing the patient with exogenous insulin to prevent beta-cell exhaustion. This study investigates the factors relating to the islet preparation process, as well as donor and recipient characteristics, and assessed their associations with PIR and GFI after transplantation. The goal is to determine the most relevant factors that influence islet graft function after transplantation. We examined the effects of donor and recipient characteristics, and islet processing factors on posttransplanted PIR and GFI. The PIR and GFI at 3 months were calculated using patients' baseline insulin intake, posttransplant 2-h postprandial blood glucose, and glucagon-stimulated C-peptide. Thirteen transplants that resulted in progressive decline in patients' weekly averaged insulin intake over the initial weeks after transplant (assuming constant glucose level) with available 3-month PIR and GFI data were chosen for the investigation. Univariate analyses were performed to assess the effects of donor and recipient characteristics and islet processing factors on islet graft function as reflected by PIR and GFI. The PIR and GFI were treated as continuous response variables in separate linear regression models. Shorter digestion time of isolated donor islets were associated with lower PIR ( = 0.014) and a higher GFI ( = 0.027) after transplantation. Islet injury related to digestion enzyme exposure influenced islet function as estimated using PIR and GFI post-transplantation.
尽管胰岛移植在减少1型糖尿病患者严重低血糖事件及控制血糖方面有效，但长期维持胰岛移植功能是一项重大挑战。通常需要多个供体的胰岛才能实现胰岛素自主分泌，即便如此，当代谢需求超过胰岛质量/胰岛素分泌能力时，胰岛功能会随时间下降。我们之前开发了一种方法，利用数学非线性回归计算胰岛移植功能指数（GFI）和患者的预测胰岛素需求量（PIR）。医生可将PIR和GFI都用作监测胰岛移植功能以及指导为患者补充外源性胰岛素以防止β细胞耗竭的工具。本研究调查了与胰岛制备过程相关的因素以及供体和受体特征，并评估了它们与移植后PIR和GFI的关联。目标是确定影响移植后胰岛移植功能的最相关因素。我们研究了供体和受体特征以及胰岛处理因素对移植后PIR和GFI的影响。使用患者的基线胰岛素摄入量、移植后餐后2小时血糖以及胰高血糖素刺激的C肽计算3个月时的PIR和GFI。选择了13例移植病例进行研究，这些病例在移植后的最初几周内患者每周平均胰岛素摄入量呈逐渐下降趋势（假设血糖水平恒定）且有可用的3个月PIR和GFI数据。进行单因素分析以评估供体和受体特征以及胰岛处理因素对以PIR和GFI反映的胰岛移植功能的影响。在单独的线性回归模型中，将PIR和GFI视为连续反应变量。分离的供体胰岛消化时间较短与移植后较低的PIR（P = 0.014）和较高的GFI（P = 0.027）相关。与消化酶暴露相关的胰岛损伤会影响移植后使用PIR和GFI评估的胰岛功能。
