5 research outputs found
The demise of islet allotransplantation in the United States: A call for an urgent regulatory update
Get PDFIslet allotransplantation in the United States (US) is facing an imminent demise. Despite nearly three decades of progress in the field, an archaic regulatory framework has stymied US clinical practice. Current regulations do not reflect the state-of-the-art in clinical or technical practices. In the US, islets are considered biologic drugs and “more than minimally manipulated” human cell and tissue products (HCT/Ps). In contrast, across the world, human islets are appropriately defined as “minimally manipulated tissue” and not regulated as a drug, which has led to islet allotransplantation (allo-ITx) becoming a standard-of-care procedure for selected patients with type 1 diabetes mellitus. This regulatory distinction impedes patient access to islets for transplantation in the US. As a result only 11 patients underwent allo-ITx in the US between 2016 and 2019, and all as investigational procedures in the settings of a clinical trials. Herein, we describe the current regulations pertaining to islet transplantation in the United States. We explore the progress which has been made in the field and demonstrate why the regulatory framework must be updated to both better reflect our current clinical practice and to deal with upcoming challenges. We propose specific updates to current regulations which are required for the renaissance of ethical, safe, effective, and affordable allo-ITx in the United States
Simple measures to monitor \u3b2-cell mass and assess islet graft dysfunction
No full textThe aim of this study was to develop a simple test for the assessment of islet graft dysfunction based on measures involving fasting C-peptide. Calculations were made to account for the dependence of C-peptide secretion on glucose concentration (C-peptide/glucose ratio [CP/G]) and adjusted for renal function by calculating the C-peptide/glucose-creatinine ratio (CP/GCr). Values from 22 recipients were analyzed at different times post-last islet infusion. Receiver operating characteristic curves were used to determine which of these measures best predicts high 90-minute glucose (90 min-Glc; >10 mmol/L) after a Mixed Meal Tolerance Test (MMTT). In this initial analysis, CP/G was found to be superior predicting high 90 min-Glc with a larger area under the ROC curve than C-peptide (p = 0.01) and CP/GCr (p = 0.06). We then correlated C-peptide and CP/G with islet equivalents--IEQ/kg infused, 90 min-Glc after MMTT and clinical outcome (beta-score). C-peptide and CP/G in the first 3 months post-last islet infusion correlated with IEQ/kg infused. CP/G correlated with 90 min-Glc and beta-score. C-peptide and CP/G are good indicators of islet mass transplanted. CP/G is more indicative of graft dysfunction and clinical outcome than C-peptide alone. The ease of calculation and the good correlation with other tests makes this ratio a practical tool when monitoring and managing islet transplant recipients
