Predictive Value of C-Peptide Measures for Clinical Outcomes of β-Cell Replacement Therapy in Type 1 Diabetes: Report From the Collaborative Islet Transplant Registry (CITR)

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

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)

   OBJECTIVE To determine C-peptide measures and levels associated with positive glycemic control outcomes following islet transplantation (ITx) in type 1 diabetes. RESEARCH DESIGN AND METHODS We evaluated Collaborative Islet Transplant Registry (CITR) Islet-Alone recipients with pre-transplant C-peptide 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. 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. CONCLUSION 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. </p

‘A picture is worth a thousand words’—A photovoice study exploring health professionals’ experiences during the COVID‐19 pandemic

AIM: To elicit the experiences and perspectives of health professionals working on the frontline in the COVID‐19 pandemic. BACKGROUND: Although some qualitative studies have been carried out in health professionals during COVID‐19 pandemic, to our knowledge, no study has used the Photovoice method. DESIGN: A qualitative descriptive study using Photovoice was carried out between March and June 2020. METHODS: A total of 20 health professionals were recruited from public and private healthcare services. The participants were invited to share photographs about their experiences while working during COVID‐19 pandemic. Following the Photovoice method, audio‐recorded interviews were conducted. The data were analysed using the ‘SHOWED’ mnemonic, with five questions answered about each photograph. The EQUATOR checklist has been used. RESULTS/FINDINGS: Three themes emerged: (1) Personal attitudes of health professionals; (2) Support from the community; and (3) Management of institutional resources. Despite the fact that health professionals in this study were exposed to major risks while caring for patients with COVID‐19’ they felt a strong sense of responsibility towards the community. In order to handle these stressful situations, they used coping mechanisms, good humour and leisure, but also received support from the population, who saw them as highly skilled health professionals. CONCLUSION: These findings highlight the essential role of health professionals in the COVID‐19 pandemic and the tireless work they are carrying out to provided highly skilled care. RELEVANCE TO CLINICAL PRACTICE: These findings could contribute to raise awareness on the needs of health professionals during the pandemic, allowing managers to plan strategies to ensure the safety, and well‐being of these professionals, as well as adopting similar strategies in their practice to create a space for critical reflection through participatory approaches

Islets Transplantation at a Crossroads - Need for Urgent Regulatory Update in the United States: Perspective Presented During the Scientific Sessions 2021 at the American Diabetes Association Congress

Clinical islet allotransplantation has been successfully regulated as tissue/organ for transplantation in number of countries and is recognized as a safe and efficacious therapy for selected patients with type 1 diabetes mellitus. However, in the United States, the FDA considers pancreatic islets as a biologic drug, and islet transplantation has not yet shifted from the experimental to the clinical arena for last 20 years. In order to transplant islets, the FDA requires a valid Biological License Application (BLA) in place. The BLA process is costly and lengthy. However, despite the application of drug manufacturing technology and regulations, the final islet product sterility and potency cannot be confirmed, even when islets meet all the predetermined release criteria. Therefore, further regulation of islets as drugs is obsolete and will continue to hinder clinical application of islet transplantation in the US. The Organ Procurement and Transplantation Network together with the United Network for Organ Sharing have developed separately from the FDA and BLA regulatory framework for human organs under the Human Resources & Services Administration to assure safety and efficacy of transplantation. Based on similar biologic characteristics of islets and human organs, we propose inclusion of islets into the existing regulatory framework for organs for transplantation, along with continued FDA oversight for islet processing, as it is for other cell/tissue products exempt from BLA. This approach would reassure islet quality, efficacy and access for Americans with diabetes to this effective procedure