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Background: A closed-loop bedside-type artificial pancreas for perioperative glucose control has previously been introduced. However, artificial pancreas therapy was often interrupted due to continuous blood sampling failure. We developed an interprofessional work manual to reduce the interruption time of artificial pancreatic therapy for perioperative blood glucose control due to continuous blood sampling failure. This study aimed to investigate the usefulness of this manual., Methods: The manual consisted of the following sections: (1) the roles of the professionals in the preparation and management of the artificial pancreas, (2) how to address continuous blood sampling failure, and (3) checkpoints for interprofessional transfer of the artificial pancreas. We compared the results before the introduction of the manual and 2 years after the introduction of the manual., Results: There were 35 and 37 patients in the Before and After groups, respectively. There were no significant differences in patient backgrounds between the two groups, although there was significantly less blood loss in the After group (1164 vs. 366 mL; p < 0.001). The mean artificial pancreas therapy and artificial pancreas therapy interruption times were 847 min and 20 min, respectively. Artificial pancreas therapy interruption time (34 vs. 8 min; p = 0.078) and time per interruption (24 vs. 4 min; p < 0.001) were significantly shorter in the After group than in the Before group., Conclusions: The interprofessional working manual was useful in reducing the artificial pancreatic therapy interruption time for perioperative glucose control., (© 2024 The Author(s). Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Patients with type 1 diabetes and concurrent subcutaneous insulin resistance present unique diagnostic and therapeutic challenges for clinicians. The standard therapeutic approach is the administration of intravenous insulin. Pancreatic transplantation should be considered at an appropriate time, particularly in the event of life-threatening ketoacidosis, hyperglycemia, hypoglycemia, catheter-associated thrombosis, and infections. We present the case of a 24-year-old woman with type 1 diabetes since early childhood and increasingly uncontrollable subcutaneous and intramuscular insulin resistance. Furthermore, we present the diagnostic pathway and therapeutic interventions performed, culminating in pancreatic transplantation as a curative approach. Immediate graft function resulted in optimal glycemic control., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Islet transplantation is a promising approach for treating patients with unstable T1DM. However, it is confronted with numerous obstacles throughout the various stages of the transplantation procedure. Significant progress has been made over the last 25 years in understanding the mechanisms behind the loss of functional islet mass and in developing protective strategies. Nevertheless, at present, two to three pancreases are still needed to treat a single patient, which limits the maximal number of patients who can benefit from islet transplantation. Thus, this publication provides an overview of recent scientific findings on the various issues affecting islet transplantation. Specifically, we will focus on the understanding of the mechanisms involved and the strategies developed to alleviate these problems from the isolation stage to the post-transplantation phase. Finally, we hope that this review will highlight new avenues of action, enabling us to propose pancreatic islet transplantation to a maximum number of patients with T1DM.

This opinion paper evaluates the potential of porcine islets as a promising alternative in beta cell replacement therapy for Type 1 Diabetes (T1D), juxtaposed with the current limitations of human donor islets. It analyzes the compatibility of pig islets with human glucose metabolism, their prospects as a limitless and high-quality source of beta cells, and the unique immunogenic challenges they present in xenotransplantation. Additionally, the paper discusses the regulatory and ethical considerations pertinent to the use of porcine islets. By synthesizing current research and expert perspectives, the paper highlights both the opportunities and significant barriers that need addressing to advance pig islets as a viable therapeutic option. The findings advocate for a balanced and forward-looking approach to the integration of pig islets in T1D treatment, underscoring the need for continued research and dialogue in this evolving field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Piemonti, Citro, Tomajer, Partelli and Caldara.)

Background: Islet transplantation has been associated with better metabolic control and quality of life than insulin treatment alone, but direct evidence of its effect on hard clinical endpoints is scarce. We aimed to assess the effect of islet transplantation on patient-graft survival in kidney transplant recipients with type 1 diabetes., Methods: In this retrospective cohort study, we enrolled all patients with type 1 diabetes who received a kidney graft in France during the study period, identified from the CRISTAL nationwide registry. Non-inclusion criteria included recipients from transplant centres that never proposed islet transplantation during the study period, recipients with a functional pancreas throughout the follow-up duration, recipients with more than two kidney transplants, HLA-sensitised recipients, recipients with less than 1 year of follow-up after kidney transplantation, misclassified recipients with type 2 diabetes, recipients aged over 65 years, recipients of kidney grafts from Donation after Circulatory Death donors, recipient with HIV or hepatitis, recipients with cancer, and recipients of combined liver-kidney transplants. Patients who also received islet-after-kidney (IAK) transplantation were compared with controls who received kidney transplantation alone according to a 1:2 matching method based on time-dependent propensity scores, ensuring patients comparability at the time of islet transplantation. The primary outcome was patient-graft survival, a composite outcome defined by death, re-transplantation, or return to dialysis., Findings: Between Jan 1, 2000, and Dec 31, 2017, 2391 patients with type 1 diabetes were identified as having received a kidney transplant, 47 patients of whom also received an islet transplantation. 2002 patients were not eligible for islet transplantation and 62 were excluded due to missing data. 327 eligible recipients from 15 centres were included in the study dataset for the target trial emulation. 40 patients who received IAK transplantation were successfully matched to 80 patients who received kidney transplantation alone. 13 (33%) of 40 patients in the IAK transplantation group returned to dialysis or died, compared with 36 (45%) of 80 patients in the kidney transplantation alone group. We found a significant benefit of islet transplantation compared with kidney transplantation alone on patient-graft survival, with a hazard ratio (HR) of 0·44 (95% CI 0·23-0·88; p=0·022), mainly explained by a protective effect on the risk of death (HR 0·41, 0·13-0·91; p=0·042). There was no meaningful association between IAK and death-censored graft survival (0·73, 0·30-1·89; p=0·36)., Interpretation: In kidney transplant recipients with type 1 diabetes, IAK transplantation was associated with a significantly better patient-graft survival compared with kidney transplantation alone, mainly due to a protective effect on the risk of death. These results potentially serve as compelling grounds for advocating wider access to islet transplantation in patients with type 1 diabetes undergoing kidney transplant, as reimbursement of islet transplantation is provided in few countries worldwide., Funding: Programme Hospitalier de la Recherche Clinique, Fondation pour la Recherche Medicale, and Fonds de Dotation Line Renaud-Loulou Gasté., Competing Interests: Declaration of interests MM, RL, YF, FB, GB, CA, LK, MLQ, DA, MB, AB-S, LF, PM, SL, LB, LE, MC, AH, JK-C, TB, M-CV, MH, and FP declare no competing interests. SC declares support for attending meetings or travel from Astra Zeneca, Alexion, Sanofi, and Pierre Fabre and participation on a data safety monitoring board or advisory board from Astra Zeneca, Alexion, Chiesi, Pierre Fabre, Pfizer, and Samsung Bioepis. OV declares payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Sanofi-Aventis, Eli-Lilly, and Novo-Nordisk and support for attending meetings or travel from Sanofi-Aventis., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Competing Interests: SF reports grants from the Novo Nordisk Islet Stem Cell Programme, Breakthrough T1D International, the Steve Morgan Foundation/Diabetes UK, Helmsley Charitable Foundation, British Heart Foundation, Medical Research Council, EastBio, and the Chief Scientist Office; consulting fees from the Novo Nordisk Stem Cell therapy Programme; patents (GB2313199.8, August, 2023); is a member of the Breakthrough T1D UK Scientific Committee; is on the Novo Nordisk UK Research Foundation Board of Trustees; is a board member of the Danish Diabetes and Endocrinology Academy on Strategic Partnerships; is a member of the International Pancreas and Islet Transplantation Association Education Group; is part of the Type 1 Diabetes Immunotherapy Consortium; is a member of Breakthrough T1D International; and was previously a member of the Diabetes UK, Clinical Studies Group, Lead Metabolic and Obesity Networks, Society for Endocrinology, and Council of Health Care Professionals. TWHK reports no competing interests.

Whole-organ pancreas, pancreatic-kidney and islet transplantation are surgical therapeutic options for the treatment of type 1 diabetes. They can enable effective glycemic control, improve quality of life and delay/reduce the secondary complications of type 1 diabetes mellitus. Radiologists are integral members of the multidisciplinary transplantation team involved in these procedures, with multimodality imaging serving as the mainstay for early recognition and management of transplant related complications. This review highlights the transplantation procedures available for patients with type 1 Diabetes Mellitus with a focus on the imaging appearance of transplantation-related complications., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Given the increasing frequency of simultaneous pancreas-kidney transplants performed in recipients with Type II diabetes and CKD, we sought to evaluate possible differences in the rates of allograft rejection, infection, and surgical complications in 298 Type I (T1D) versus 47 Type II (T2D) diabetic recipients of simultaneous pancreas-kidney transplants between 2006-2017. There were no significant differences in patient or graft survival. The risk of biopsy-proven rejection of both grafts was not significantly different between T2D and T1D recipients (HR pancreas = 1.04, p = 0.93; HR kidney = 0.96; p = 0.93). Rejection-free survival in both grafts were also not different between the two diabetes types (p pancreas = 0.57; p kidney = 0.41). T2D had a significantly lower incidence of de novo DSA at 1 year (21% vs. 39%, p = 0.02). There was no difference in T2D vs. T1D recipients regarding readmissions (HR = 0.77, p = 0.25), infections (HR = 0.77, p = 0.18), major surgical complications (HR = 0.89, p = 0.79) and thrombosis (HR = 0.92, p = 0.90). In conclusion, rejection, infections, and surgical complications after simultaneous pancreas-kidney transplant are not statistically significantly different in T2D compared to T1D recipients., Competing Interests: The authors of this manuscript have conflicts of interest to disclose as described by the Transplant International. JO is co-founder of, has equity interest in and serves as Chair of the Scientific Advisory Board of Regenerative Medical Solutions, Inc. He receives clinical trial support from Veloxis Pharmaceuticals, CareDx Transplant Management, Inc., Natera, Inc. and Vertex Pharmaceuticals, Inc. DK reports serving as a scientific advisor for, or member of, eGenesis, and receiving research funding from Medeor Pharma and the National Institutes of Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martinez, Pham, Wang, Stalter, Welch, Leverson, Marka, Al-Qaoud, Mandelbrot, Parajuli, Sollinger, Kaufman, Redfield and Odorico.)

BACKGROUND Obesity is suggested to impair the outcome after simultaneous pancreas-kidney transplantation, which affects survival, but the quantity and distribution of adipose tissue is not yet considered in obesity assessment. We aimed to evaluate the impact of body composition on outcome after simultaneous pancreas-kidney transplantation. MATERIAL AND METHODS We retrospectively analyzed data from 40 patients who underwent simultaneous pancreas-kidney transplantation due to type 1 diabetes mellitus with consecutive end-stage renal disease. Uni- and multivariate analyses, including donor's characteristics, were performed. RESULTS Only 6 (15%) recipients were obese. The incidence of postoperative complications was correlated with lower body fat proportion (p=0.03). This correlation remained significant in the multivariate analysis (p=0.015). Nevertheless, obesity was significantly associated with worse overall survival (p<0.001). Visceral tissue proportion was correlated with a higher level of glycated hemoglobin in long-term follow-up (p=0.003). CONCLUSIONS Fat quantity and distribution should be included in the assessment of obesity. A protective effect of adipose tissue was detected on outcome after simultaneous pancreas-kidney transplantation in normosthenic recipients, but obesity still appears to have a negative effect on outcome after transplantation. Visceral fat distribution can promote de novo diabetes mellitus.

Introduction: Simultaneous pancreas-kidney transplantation (SPK) is the preferred treatment for individuals with type-1 diabetes and end-stage renal disease. However, a limited supply of "Ideal Pancreas Donors" contributed to a growing disparity between available organs and recipients. Even though SPK outcomes from pediatric donors match those from adult donors, unclear guidelines on minimum age and weight criteria for extra small pediatric pancreas donors lead to hesitancy among several transplant centers to utilize these grafts due to concerns about inadequate islet mass, technical challenges, and increased risk of allograft thrombosis., Methods: This report details the successful outcomes of SPK transplantations performed at the study center between December 2021 and January 2024, using four extra small pediatric brain-dead donors (ESPDs). Each donor was aged ≤5 years and weighed <20 kg., Results: All SPK recipients achieved immediate posttransplant euglycemia without requiring insulin. None of the recipients experienced graft pancreatitis, graft thrombosis, allograft rejection, or required re-exploration. During a 5-27-month follow-up period, all ESPD recipients maintained optimal graft function, as evidenced by normal glucose tolerance tests and HbA1c (4.9%-5.2%), with 100% graft and patient survival., Conclusion: This report examines the usage of ESPDs in SPK transplantation, highlighting their potential to expand the donor pool and reduce wait times in areas with scarce deceased organ donations, thereby increasing the number of available organs for transplantation with acceptable outcomes. Revising donor selection guidelines to reflect the diverse risk-benefit profiles of waitlisted individuals is crucial to addressing geographical disparities and reducing organ discard rates., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Type 1 diabetes mellitus is characterized by absolute insulin deficiency, which requires life-long insulin replacement. Exogenous multiple-daily insulin injections are most commonly prescribed for patients with type 1 diabetes mellitus. However, exogenous insulin supply often fails to cope with real-time changing life-log variables, such as activity, diet and stress, which results in recurrent hypo- and hyperglycemia in patients with type 1 diabetes mellitus. Islet transplantation is an ideal method to treat patients with type 1 diabetes mellitus, as it can restore the endogenous capacity of glucose-stimulated insulin secretion. However, due to donor scarcity and technical barriers, only a limited number of islet transplantations have been carried out in Asia, including South Korea. Since 2013, our center has carried out two allogenic islet transplantations, with one case leading to near total insulin independence after one-to-one islet transplantation. Although the other patient failed to restore endogenous insulin production, there was a remarkable improvement in hypoglycemia. We speculate that islet transplantation remains an important and ideal treatment option for patients with type 1 diabetes mellitus who suffer from recurrent severe hypoglycemia., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims/hypothesis: Stem cell-derived islets (SC-islets) are being used as cell replacement therapy for insulin-dependent diabetes. Non-invasive long-term monitoring methods for SC-islet grafts, which are needed to detect misguided differentiation in vivo and to optimise their therapeutic effectiveness, are lacking. Positron emission tomography (PET) has been used to monitor transplanted primary islets. We therefore aimed to apply PET as a non-invasive monitoring method for SC-islet grafts., Methods: We implanted different doses of human SC-islets, SC-islets derived using an older protocol or a state-of-the-art protocol and SC-islets genetically rendered hyper- or hypoactive into mouse calf muscle to yield different kinds of grafts. We followed the grafts with PET using two tracers, glucagon-like peptide 1 receptor-binding [ 18 F]F-dibenzocyclooctyne-exendin-4 ([ 18 F]exendin) and the dopamine precursor 6-[ 18 F]fluoro-L-3,4-dihydroxyphenylalanine ([ 18 F]FDOPA), for 5 months, followed by histological assessment of graft size and composition. Additionally, we implanted a kidney subcapsular cohort with different SC-islet doses to assess the connection between C-peptide and stem cell-derived beta cell (SC-beta cell) mass., Results: Small but pure and large but impure grafts were derived from SC-islets. PET imaging allowed detection of SC-islet grafts even <1 mm 3 in size, [ 18 F]exendin having a better detection rate than [ 18 F]FDOPA (69% vs 44%, <1 mm 3 ; 96% vs 85%, >1 mm 3 ). Graft volume quantified with [ 18 F]exendin (r 2 =0.91) and [ 18 F]FDOPA (r 2 =0.86) strongly correlated with actual graft volume. [ 18 F]exendin PET delineated large cystic structures and its uptake correlated with graft SC-beta cell proportion (r 2 =0.68). The performance of neither tracer was affected by SC-islet graft hyper- or hypoactivity. C-peptide measurements under fasted or glucose-stimulated conditions did not correlate with SC-islet graft volume or SC-beta cell mass, with C-peptide under hypoglycaemia having a weak correlation with SC-beta cell mass (r 2 =0.52)., Conclusions/interpretation: [ 18 F]exendin and [ 18 F]FDOPA PET enable non-invasive assessment of SC-islet graft size and aspects of graft composition. These methods could be leveraged for optimising SC-islet cell replacement therapy in diabetes., (© 2024. The Author(s).)

Background: Islet or β-cell transplantation is a therapeutical approach to substitute the insulin-producing cells which are abolished in type 1 diabetes mellitus. The shortage of human islets as well as the complicated and costly isolation process limit the application of these techniques in daily clinical practice. EndoC-βH is a human β-cell line that readily forms aggregates termed pseudoislets, providing an alternative to primary human islets or β-cells., Methods: EndoC-βH3 cells were seeded and incubated to form pseudoislets. Their insulin secretion was analyzed by ELISA and compared with cell monolayers. Pseudoislets were transplanted into streptozotocin-treated NMRi nu/nu mice. Blood glucose was monitored before and after transplantation and compared with wild types. Grafts were analyzed by immunohistology., Results: This study shows that EndoC-βH cells are able to form pseudoislets by aggregation, leading to an enhanced glucose stimulated insulin secretion in vitro. These pseudoislets were then successfully transplanted into the livers of diabetic mice and produced insulin in vitro. Blood glucose levels of the streptozocin-treated recipient mice were significantly decreased when compared to pre-transplantation and matched the levels found in control mice., Conclusion: We suggest pseudoislets aggregated from EndoC-βH cells as a valuable and promising model for islet transplantation research.

Metabolic and Bariatric Surgery (MBS) is effective in improving metabolic outcomes and reducing weight in patients with obesity and diabetes, with less explored benefits in type 1 diabetes (T1D). This study aimed to evaluate the impact of MBS on weight loss and insulin requirements in T1D patients compared to insulin-treated type 2 diabetes (T2D) patients over a 5-year period. This retrospective analysis included patients who underwent primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) with a confirmed preoperative diagnosis of either T1D or insulin-treated T2D. Primary endpoints focusing on weight loss and secondary outcomes assessing changes in insulin dosage and glycemic control. After 5 years, weight loss was similar across groups, with total weight loss at 14.2% for T1D and 17.6% for insulin-treated T2D in SG, and 22.6% for T1D vs. 26.8% for insulin-treated T2D in RYGB. Additionally, there was a significant reduction in median daily insulin doses from 140.5 units at baseline to 77.5 units at 1 year postoperatively, sustained at 90 units at 5 years. The differential impact of MBS procedure was also highlighted, where RYGB patients showed a more pronounced and enduring decrease in insulin requirements compared to SG., (© 2024 World Obesity Federation.)

Background: Islet transplantation is a promising treatment for type 1 diabetes that aims to restore insulin production and improve glucose control, but long-term graft survival remains a challenge due to immune rejection., Methods: ScRNA-seq data from syngeneic and allogeneic islet transplantation grafts were obtained from GSE198865. Seurat was used for filtering and clustering, and UMAP was used for dimension reduction. Differentially expressed genes were analyzed between syngeneic and allogeneic islet transplantation grafts. Gene set variation analysis (GSVA) was performed on the HALLMARK gene sets from MSigDB. Monocle 2 was used to reconstruct differentiation trajectories, and cytokine signature enrichment analysis was used to compare cytokine responses between syngeneic and allogeneic grafts., Results: Three distinct macrophage clusters (Mø-C1, Mø-C2, and Mø-C3) were identified, revealing complex interactions and regulatory mechanisms within macrophage populations. The significant activation of macrophages in allogeneic transplants was marked by the upregulation of allograft rejection-related genes and pathways involved in inflammatory and interferon responses. GSVA revealed eight pathways significantly upregulated in the Mø-C2 cluster. Trajectory analysis revealed that Mø-C3 serves as a common progenitor, branching into Mø-C1 and Mø-C2. Cytokine signature enrichment analysis revealed significant differences in cytokine responses, highlighting the distinct immunological environments created by syngeneic and allogeneic grafts., Conclusion: This study significantly advances the understanding of macrophage roles within the context of islet transplantation by revealing the interactions between immune pathways and cellular fate processes. The findings highlight potential therapeutic targets for enhancing graft survival and function, emphasizing the importance of understanding the immunological aspects of transplant acceptance and longevity., Competing Interests: Author ZC was employed by company BGI Medical Group. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pu, Chen, Lu, Wu, Cai and Mou.)

In the United States, potential transplant candidates with insulin-dependent diabetes mellitus are inconsistently offered pancreas transplantation (PTx), contributing to a dramatic decline in pancreas allograft utilization over the past 2 decades. The American Society of Transplantation organized a workshop to identify barriers inhibiting PTx and to develop strategies for a national comeback. The 2-day workshop focused on 4 main topics: (1) referral/candidate selection, (2) organ recovery/utilization, (3) program performance/patient outcomes, and (4) enhanced education/research. Topics were explored through expert presentations, patient testimonials, breakout sessions, and strategic planning, including the identification of tasks for immediate focus. Additionally, a modified-Delphi survey was conducted among workshop members to develop and rate the importance of barriers, and the impact and feasibility of workgroup-identified improvement strategies. The panelists identified 16 barriers to progress and 44 strategies for consideration. The steps for a national comeback in PTx involve greater emphasis on efficient referral and candidate selection, better donor pancreas utilization practices, eliminating financial barriers to procurement and transplant, improving collaboration between transplant and diabetes societies and professionals, and increasing focus on PTx training, education, and research. Partnership between national societies, patient advocacy groups, and professionals will be essential to realizing this critical agenda., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. Krista L. Lentine is supported by the Mid-America Transplant/Jane A. Beckman Endowed Chair in Transplantation and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01DK120518. Krista L. Lentine and David A. Axelrod are senior staff of the SRTR. Unrelated to this work: Krista L. Lentine receives consulting fees from CareDx and speaker honoraria from Sanofi; David A. Axelrod receives consulting fees from CareDx. Workshop participant Joseph Scalea is co-founder and CMO of MediGO., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Allogeneic intraportal islet transplantation (ITx) has become an established treatment for patients with poorly controlled type 1 diabetes. However, the loss of viable beta-cell mass after transplantation remains a major challenge. Therefore, noninvasive imaging methods for long-term monitoring of the transplant fate are required. In this study, [ 68 Ga]Ga-DOTA-exendin-4 positron emission tomography/computed tomography (PET/CT) was used for repeated monitoring of allogeneic neonatal porcine islets (NPI) after intraportal transplantation into immunosuppressed genetically diabetic pigs. NPI transplantation (3320-15,000 islet equivalents per kg body weight) led to a reduced need for exogenous insulin therapy and finally normalization of blood glucose levels in 3 out of 4 animals after 5 to 10 weeks. Longitudinal PET/CT measurements revealed a significant increase in standard uptake values in graft-bearing livers. Histologic analysis confirmed the presence of well-engrafted, mature islet clusters in the transplanted livers. Our study presents a novel large animal model for allogeneic intraportal ITx. A relatively small dose of NPIs was sufficient to normalize blood glucose levels in a clinically relevant diabetic pig model. [ 68 Ga]Ga-DOTA-exendin-4 PET/CT proved to be efficacious for longitudinal monitoring of islet transplants. Thus, it could play a crucial role in optimizing ITx as a curative therapy for type 1 diabetes., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: It is unclear whether kidney/pancreas (KP) transplantation will prevent the progression of peripheral arterial disease (PAD) in patients with insulin dependent diabetes (IDDM) and end-stage renal disease. We sought to determine the pre- and posttransplant prevalence of symptomatic PAD and changes in carotid artery intima-media thickness (IMT) in KP recipients., Methods: In this single center study, outcomes were compared between KP recipients with and without a history of PAD. A subset of recipients underwent pre- and posttransplant IMT measurements., Results: Among the study group (N = 107), 18 (17%) recipients admitted to a pretransplant history of symptomatic PAD, comprised 11 foot infections and 7 amputations (5 minor and 2 major). Baseline characteristics of age, gender, race, years of diabetes, dialysis history, smoking history, years of hypertension, and history of coronary artery disease (CAD) were equivalent between PAD and non-PAD cohorts. At a median follow-up of 60 months (IQR: 28, 110), 16 (15%) KP recipients had suffered a PAD event. In multivariate analysis, a pretransplant history of PAD (hazard ratio [HR] 9.66, p < 0.001) and CAD (HR 3.33, p = 0.04) were independent predictors of posttransplant PAD events. Among a subset of 20 recipients (3 with PAD), mean IMT measurements pretransplant and at a median of 24 (range 18-24) months posttransplant, showed no evidence of disease progression., Conclusion: Based on IMT measurements and clinical results, KP transplantation stabilized PAD in most patients, but did not alter outcomes of symptomatic PAD recipients. A pretransplant history of PAD and CAD was an independent predictor of posttransplant PAD events., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diabetes is a prevalent chronic disease that traditionally requires severe reliance on medication for treatment. Oral medication and exogenous insulin can only temporarily maintain blood glucose levels and do not cure the disease. Most patients need life-long injections of exogenous insulin. In recent years, advances in islet transplantation have significantly advanced the treatment of diabetes, allowing patients to discontinue exogenous insulin and avoid complications.Long-term follow-up results from recent reports on islet transplantation suggest that they provide significant therapeutic benefit although patients still require immunotherapy, suggesting the importance of future transplantation strategies. Although organ shortage remains the primary obstacle for the development of islet transplantation, new sources of islet cells, such as stem cells and porcine islet cells, have been proposed, and are gradually being incorporated into clinical research. Further research on new transplantation sites, such as the subcutaneous space and mesenteric fat, may eventually replace the traditional portal vein intra-islet cell infusion. Additionally, the immunological rejection reaction in islet transplantation will be resolved through the combined application of immunosuppressant agents, islet encapsulation technology, and the most promising mesenchymal stem cells/regulatory T cell and islet cell combined transplantation cell therapy. This review summarizes the progress achieved in islet transplantation, and discusses the research progress and potential solutions to the challenges faced., Competing Interests: YS was employed by MSD China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Huang, Liu, Zhao, Sun, Mao and Li.)

Islets experience enormous stress during the isolation process, leading to suboptimal endocrine function after total pancreatectomy with islet autotransplantation (TPIAT). Our investigation focused on inducing isolation stress in islets ex vivo, where proinflammatory cytokines and hypoxia prompted the release of stress exosomes (exo S ) sized between 50 and 200 nm. Mass spectrometry analysis revealed 3 distinct subgroups of immunogenic proteins within these exo S : damage-associated molecular patterns (DAMPs), chaperones, and autoantigens. The involvement of endosomal-sorting complex required for transport proteins including ras-associated binding proteins7A, ras-associated binding protein GGTA, vacuolar protein sorting associated protein 45, vacuolar protein sorting associated protein 26B, and the tetraspanins CD9 and CD63, in exo S biogenesis was confirmed through immunoblotting. Next, we isolated similar exo S from the islet infusion bags of TPIAT recipients (N = 20). The exosomes from infusion bags exhibited higher DAMP (heat shock protein family A [Hsp70] member 1B and histone H2B) levels, particularly in the insulin-dependent TPIAT group. Additionally, elevated DAMP protein levels in islet infusion bag exosomes correlated with increased insulin requirements (P = .010) and higher hemoglobin A1c levels 1-year posttransplant. A deeper exploration into exo S functionality revealed their potential to activate monocytes via the toll-like receptor 3/7: DAMP axis. This stimulation resulted in the induction of inflammatory phenotypes marked by increased levels of CD68, CD80, inducible nitric oxide synthase, and cyclooxygenase-2. This activation mechanism may impact the successful engraftment of transplanted islets., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Islet transplantation (ITx) is an established and safe alternative to pancreas transplantation for type 1 diabetes mellitus (T1DM) patients. However, most ITx recipients lose insulin independence by 3 years after ITx due to early graft loss, such that multiple donors are required to achieve insulin independence. In the present study, we investigated whether skeletal myoblast cells could be beneficial for promoting angiogenesis and maintaining the differentiated phenotypes of islets. In vitro experiments showed that the myoblast cells secreted angiogenesis-related cytokines (vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and stromal-derived factor-1 α (SDF-1 α )), contributed to maintenance of differentiated islet phenotypes, and enhanced islet cell insulin secretion capacity. To verify these findings in vivo, we transplanted islets alone or with myoblast cells under the kidney capsule of streptozotocin-induced diabetic mice. Compared with islets alone, the group bearing islets with myoblast cells had a significantly lower average blood glucose level. Histological examination revealed that transplants with islets plus myoblast cells were associated with a significantly larger insulin-positive area and significantly higher number of CD31-positive microvessels compared to islets alone. Furthermore, islets cotransplanted with myoblast cells showed JAK-STAT signaling activation. Our results suggest two possible mechanisms underlying enhancement of islet graft function with myoblast cells cotransplantation: "indirect effects" mediated by angiogenesis and "direct effects" of myoblast cells on islets via the JAK-STAT cascade. Overall, these findings suggest that skeletal myoblast cells enhance the function of transplanted islets, implying clinical potential for a novel ITx procedure involving myoblast cells for patients with diabetes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Takeshi Kado et al.)

Allogeneic islet transplantation has become a standard therapy for unstable type 1 diabetes. However, considering the large number of type 1 diabetic patients, the shortage of donors is a serious issue. To address this issue, clinical islet xenotransplantation is conducted. The first clinical islet xenotransplantation was performed by a Swedish team using fetal pancreatic tissue. Thereafter, clinical trials of islet xenotransplantation were conducted in New Zealand, Russia, Mexico, Argentina, and China using neonatal pig islets. In clinical trials, fetal or neonatal pancreata are used because of the established reliable islet isolation methods. These trials demonstrate the method's safety and efficacy. Currently, the limited number of source animal facilities is a problem in terms of promoting islet xenotransplantation. This limitation is due to the high cost of source animal facilities and the uncertain future of xenotransplantation. In the United States, the first xenogeneic heart transplantation has been performed, which could promote xenotransplantation. In Japan, to enhance xenotransplantation, the 'Medical Porcine Development Association' has been established. We hope that xenogeneic transplantation will become a clinical reality, serving to address the shortage of donors.

Carpal tunnel syndrome (CTS) occurs more often among individuals with diabetes. The aim of this retrospective observational registry study was to examine whether individuals with diabetes and CTS are treated surgically to the same extent as individuals with CTS but without diabetes. Data on CTS diagnosis and surgery were collected from the Skåne Healthcare Register (SHR). A total of 35,105 individuals (age ≥ 18 years) diagnosed with CTS from 2004-2019 were included. Data were matched to the Swedish National Diabetes Register (NDR. Cox regression models were used to calculate the risk of the use of surgical treatment. Of the 35,105 included individuals with a CTS diagnosis, 17,662 (50%) were treated surgically, and 4,966 (14%) had diabetes. A higher number of individuals with diabetes were treated surgically (2,935/4,966, 59%) than individuals without diabetes (14,727/30,139, 49%). In the Cox regression model, diabetes remained a significant risk factor for surgical treatment (PR 1.14 (95% CI 1.11-1.17)). Individuals with type 1 diabetes were more frequently treated surgically (490/757, 65%) than individuals with type 2 diabetes (2,445/4,209, 58%). There was no difference between the sexes and their treatment. The duration of diabetes was also a risk factor for surgical treatment in diabetes type 2, but high HbA1c levels were not. Individuals with diabetes are more likely to be treated surgically for CTS than individuals without diabetes. Individuals with type 1 diabetes are more likely to be treated surgically for CTS than individuals with type 2 diabetes., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MZ has been a consultant for Ansell Medical on hand problems in dentistry., (Copyright: © 2024 Svensson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Simultaneous pancreas-kidney transplantation (SPKT) is the best treatment for selected individuals with type 1 diabetes mellitus and end-stage renal disease. Despite advances in surgical techniques, donor and recipient selection, and immunosuppressive therapies, SPKT remains a complex procedure with associated surgical complications and adverse consequences. We conducted a retrospective study that included 263 SPKT procedures performed between May 2000, and December 2022. A total of 65 patients (25%) required at least one relaparotomy, resulting in an all-cause relaparotomy rate of 2.04 events per 100 in-hospital days. Lower donor body mass index was identified as an independent factor associated with reoperation (OR .815; 95% CI:  .725-.917, p = .001). Technical failure (TF) occurred in 9.9% of cases, primarily attributed to pancreas graft thrombosis, intra-abdominal infections, bleeding, and anastomotic leaks. Independent predictors of TF at 90 days included donor age above 36 years (HR 2.513; 95% CI 1.162-5.434), previous peritoneal dialysis (HR 2.503; 95% CI 1.149-5.451), and specific pancreas graft reinterventions. The findings highlight the importance of carefully considering donor and recipient factors in SPKT. The incidence of TF in our study population aligns with the recent series. Continuous efforts should focus on identifying and mitigating potential risk factors to enhance SPKT outcomes, thereby reducing post-transplant complications., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified for double organ liver-pancreas transplantation beyond typical indications. The respiratory symptoms of cystic fibrosis were moderate and well-treated. The patient was endangered mainly by liver insufficiency and recurrent hypoglycemia, which was due to the treatment of diabetes with high doses of insulin. Computed tomography showed mild bronchiectasis, cirrhotic liver, splenomegaly, and atrophy of the pancreas. Pseudomonas aeruginosa colonized the upper respiratory tract. Gastrointestinal complications were sufficient for the patient to be qualified for combined liver-pancreas transplantation., Methods: First, a standard hepatectomy was performed. The liver was transplanted orthotopically. Subsequently, the team performed pancreas transplantation through a separate incision. The donor's duodenum was anastomosed to the recipient's jejunum, close to the ligament of Treitz., Results: No serious complications were noted during the postoperative period. Transplanted organs started functioning without delay. The patient was discharged after 6 weeks in general good condition. Twenty months later, the patient felt well, and the grafts kept functioning properly., Conclusion: Combined liver-pancreas transplantation in patients with CF restores exocrine and endocrine pancreatic function and minimizes the risk of life-threatening complications associated with liver insufficiency. Improvement of life quality coincides with the possibility of discontinuing insulin and pancreatic enzyme supplementation. The combination of liver and pancreas transplantation may prevent advanced pulmonary complications, extend the prognosis of survival, and improve the long-term life quality., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Long-lasting diabetes mellitus type 1 and end-stage renal disease induce severe metabolic and immunologic deterioration. Pretransplant C-reactive protein (CRP) and albumin (ALB) levels impact kidney transplantation. We evaluated the effects of preoperative CRP, ALB, neutrophils (NEU), and platelet (PLT) counts on 1- and 5-year recipient survival after simultaneous pancreas and kidney transplantation (SPK)., Methods: Among 103 SPK recipients, the parameters were as follows: CRP (mean: 4.5 ± 4.97 mg/L); NEU (mean: 5.12 ± 2.13 × 10 3 /mm 3 ); PLT (mean: 244 ± 84 × 10 3 /mm 3 ); ALB (mean 4.5 ± 0.75 g/dL) were obtained before transplantation. Cox regression, uni-, multivariate analysis for 1- and 5-year survivals were performed with 95% CIs, and the area under the receiver operating characteristic (ROC) curve (AUC) was assessed., Results: In Cox regression, ALB <3.65 g/dL significantly affected 1- and 5-year survivors with hazard ratios of 8 (95% CI, 1.5-38.28; P < .05) and 3.13 (95% CI, 1.45-6.73; P < .05), respectively. In univariate analysis, we found significantly decreased 1-year survival when PLT <180×10 3 /mm 3 , ALB <3.65 g/dL, NEU >5.8×10 3 /mm 3 and CRP >2.25 mg/L with odds ratios (OR) of 6.75 (95% CI, 2.12-21.15); 4.05 (95% CI, 1.3-12.09); 2.97 (95% CI, 1.02-8.64) and 5.51 (95% CI, 1.67-18.19), respectively. Independent factors for 5-year survival were CRP, ALB, and PLT with OR of 4.72 (95% CI, 1.67-13.29), 3.31 (95% CI, 1.18-9.25), and 4.2 (95% CI, 1.39-12.68), respectively. In multivariate analysis, we built 2 models for 1-year survival. Model 1 (ALB+PLT) with ORs of 3.12 (95% CI, 0.97-10.07) and 5.55 (95% CI, 1.67-18.4); and model 2 (CRP+PLT) with ORs of 5.51 (95% CI, 1.5-17.3) and 4.3 (95% CI, 1.2-15.06), respectively. The AUC for models 1 and 2 were 0.74 and 0.759, respectively., Conclusions: NEU, PLT, ALB, and CRP levels assessed before transplantation are independent factors for 1- and 5-year SPK recipient survival., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Type-1 Diabetes Mellitus (T1DM) manifests due to pancreatic beta cell destruction, causing insulin deficiency and hyperglycaemia. Current therapies are inadequate for brittle diabetics, necessitating pancreatic islet transplants, which however, introduces its own set of challenges such as paucity of donors, rigorous immunosuppression and autoimmune rejection. Organoid technology represents a significant stride in the field of regenerative medicine and bypasses donor-based approaches. Hence this article focuses on strategies enhancing the in vivo engraftment of islet organoids (IOs), namely vascularization, encapsulation, immune evasion, alternative extra-hepatic transplant sites and 3D bioprinting. Hypoxia-induced necrosis and delayed revascularization attenuate organoid viability and functional capacity, alleviated by the integration of diverse cell types e.g., human amniotic epithelial cells (hAECs) and human umbilical vein endothelial cells (HUVECs) to boost vascularization. Encapsulation with biocompatible materials and genetic modifications counters immune damage, while extra-hepatic sites avoid surgical complications and immediate blood-mediated inflammatory reactions (IBMIR). Customizable 3D bioprinting may help augment the viability and functionality of IOs. While the clinical translation of IOs faces hurdles, preliminary results show promise. This article underscores the importance of addressing challenges in IO transplantation to advance their use in treating type 1 diabetes effectively., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events., Methods: This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015)., Results: Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047)., Conclusion: In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Insular allograft for unstable type 1 diabetes and autograft in pancreatectomy patients are nowadays considered established procedures with precise indications and predictable outcomes. The clinical outcome of islet transplantation is similar to that of pancreas transplantation, avoiding the complications associated with organ transplantation., Objective: We hypothesised that transplantation of islets of Langerhans within an endocrine organ could better promote their engraftment and function. This could help to resolve or ameliorate known pathological conditions such as unstable type 1 diabetes and complicated type 2 diabetes., Rationale: Pancreatic islet transplantation is currently performed almost exclusively in the liver. The liver provides a sufficiently favourable environment, although not entirely. The hepatic parenchyma has a lower oxygen tension than the pancreatic parenchyma and the vascular structure of the liver is not typical of an exclusively endocrine organ. Moreover, islet transplantation into the liver is not without complications, including hematoma or portal vein thrombosis., Proposed Project: The thyroid gland is the endocrine gland proposed as a 'container'. In fact, it has all the characteristics of 'physio-compatibility' which can address the objectives assumed. It is indeed an ideal site because it is an easily accessible anatomical site that allows islets to be implanted using ultrasound-guided transcutaneous inoculation technique. Moreover, it has physiological and anatomical endocrine affinities with pancreatic islets and, if necessary, it can be removed, using hormone supplementation or replacement therapy., Conclusions: The thyroid gland may be proposed as an ideal site for islet implantation due to its anatomical and physiocompatibility characteristics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Obesity in patients with type 1 diabetes (T1D) may worsen their prognosis. Bariatric surgery in these patients can be associated with complications such as diabetic ketoacidosis and severe hypoglycemic episodes. Closed-loop insulin delivery could be a solution to avoid them. Case Report: A 45-year-old woman with T1D and obesity (body mass index of 38.4 kg/m 2 ) was included in our preoperative course of bariatric surgery. Three months before surgery, a closed-loop insulin delivery was instituted due to one prior severe hypoglycemia. Patient did not have immediate or late postoperative hypoglycemia despite consuming a weak amount of carbohydrate. Three months after surgery glycemic control was on target with 86% of time in range 70-180 mg/dL and no time below 70 mg/dL. Conclusion: This case report shows that the use of a closed-loop insulin delivery made it possible to perform bariatric surgery in complete safety for our patient.

A public health emergency such as the COVID-19 pandemic has behavioral, mental and physical implications in patients with type 1 diabetes (T1D). To what extent the presence of a transplant further increases this burden is not known. Therefore, we compared T1D patients with an islet or pancreas transplant (β-cell Tx; n = 51) to control T1D patients ( n = 272). Fear of coronavirus infection was higher in those with β-cell Tx than without (Visual Analogue Scale 5.0 (3.0-7.0) vs. 3.0 (2.0-5.0), p = 0.004) and social isolation behavior was more stringent (45.8% vs. 14.0% reported not leaving the house, p < 0.001). A previous β-cell Tx was the most important predictor of at-home isolation. Glycemic control worsened in patients with β-cell Tx, but improved in control patients (ΔHbA1c +1.67 ± 8.74 vs. -1.72 ± 6.15 mmol/mol, p = 0.006; ΔTime-In-Range during continuous glucose monitoring -4.5% (-6.0%-1.5%) vs. +3.0% (-2.0%-6.0%), p = 0.038). Fewer patients with β-cell Tx reported easier glycemic control during lockdown (10.4% vs. 22.6%, p = 0.015). All T1D patients, regardless of transplantation status, experienced stress (33.4%), anxiety (27.9%), decreased physical activity (42.0%), weight gain (40.5%), and increased insulin requirements (29.7%). In conclusion, T1D patients with β-cell Tx are increasingly affected by a viral pandemic lockdown with higher fear of infection, more stringent social isolation behavior and deterioration of glycemic control. This trial has been registered in the clinicaltrials.gov registry under identifying number NCT05977205 (URL: https://clinicaltrials.gov/study/NCT05977205)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Landstra, Ruissen, Regeer, Nijhoff, Ballieux, van der Boog, de Vries, Huisman and de Koning.)

Diabetes is a chronic and progressive disease that affects an increasing number of patients. The prevalence of associated psychological comorbidities is high and often requires the implementation of targeted psychological interventions. Pancreas or islet transplantation remains a therapeutic option to consider, for a part of patients with type 1 diabetes unstable disease or established complications. From the clinical indication to the waiting period for a transplantation, then to the postoperative and long-term care, the diabetic patient is found to experience perpetual changes that may test his adaptability. In this article, the psychological aspects of the pancreas or islet transplantation, as well as the role of a liaison psychiatrist in a transplantation unit will be discussed., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Islet transplantation holds significant promise as a curative approach for type 1 diabetes (T1D). However, the transition of islet transplantation from the experimental phase to widespread clinical implementation has not occurred yet. One major hurdle in this field is the challenge of insufficient vascularization and subsequent early loss of transplanted islets, especially in non-intraportal transplantation sites. The establishment of a fully functional vascular system following transplantation is crucial for the survival and secretion function of islet grafts. This vascular network not only ensures the delivery of oxygen and nutrients, but also plays a critical role in insulin release and the timely removal of metabolic waste from the grafts. This review summarizes recent advances in effective strategies to improve graft revascularization and enhance islet survival. These advancements include the local release and regulation of angiogenic factors ( e.g. , vascular endothelial growth factor, VEGF), co-transplantation of vascular fragments, and pre-vascularization of the graft site. These innovative approaches pave the way for the development of effective islet transplantation therapies for individuals with T1D.

Aims: Pancreatic islet allotransplantation is an effective therapy for type 1 diabetes mellitus, restoring glycaemic control and hypoglycaemic awareness in patients with recurrent severe hypoglycaemia. Insulin independence following transplant is being increasingly reported; however, this is not a primary endpoint in the UK. Having surpassed 10 years of islet transplantation in Scotland, we aimed to evaluate the impact of insulin independence following transplant on metabolic outcomes and graft survival., Methods: We conducted a retrospective analysis on data collected prospectively between 2011 and 2022. Patients who underwent islet transplantation in Scotland up to the 31st January 2020 were included. Primary endpoint was graft survival (stimulated C-peptide >50 pmol/L). Secondary endpoints included GOLD score, HbA1c, C-peptide and insulin requirement. Outcomes were compared between patients who achieved insulin independence at any point following transplant versus those who did not., Results: 60 patients were included. 74.5% experienced >50 severe hypoglycaemic episodes in the year preceding transplant. There was a 55.0% decrease in insulin requirement following transplant and 30.0% achieved insulin independence. Mean graft survival time was 9.0 years (95% CI 7.2-10.9) in patients who achieved insulin independence versus 4.4 years (95% CI 3.4-5.3) in patients who did not. Insulin independence was associated with significantly improved graft function, glycaemic control and hypoglycaemic awareness at 1 year., Conclusions: This is the largest UK single-centre study on islet transplant to date. Our findings demonstrate significantly improved outcomes in patients who achieved insulin independence following islet transplantation., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Pancreas transplant (PTx) is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes types 1 and 2. The paper aims to review and analyze graft survival, patient survival, and the impact on diabetic complications. We describe that the graft survival was 82-98% at 1 year, 90% at 5 years, and 75-54% at 10 years for simultaneous pancreas-kidney recipient; 71% pancreas after kidney (PAK), and 62% PTx alone at 1 year. Patient survival: At 1 year for recipients was 96.9% simultaneous pancreas-kidney transplantation (SPK); for PAK transplantation recipients, 96.3%; and for PTx alone recipients, 98.3%. In general, the pancreas transplantation improves and reverses diabetic complications. Finally, the pancreatic transplant is a morbid procedure and emerges as a significant alternative in diabetes management, directly competing with conventional insulin therapies. Results so far suggest that the most effective transplant model is the SPK. While more patients could benefit from this procedure, surgical complications and the need for immunosuppression pose significant challenges., (Copyright: © 2024 Permanyer.)

Objectives: Our goal was to determine levels of sex hormones in men with type 1 diabetes mellitus and type 2 diabetes mellitus after autologous mesenchymal stem cell transplant., Materials and Methods: We examined 10 male patients (32-56 years old) with type 1 diabetes mellitus and type 2 diabetes mellitus, whom we subsequently divided into 2 groups and examined. Group 1 comprised 5 male patients who received autologous mesenchymal stem cell transplant (cells were obtained from patient's iliac crest and cultured for 3-4 weeks) by intravenous infusion. Group 2 comprised 5 male patients (control group) who were on hypoglycemic tablet therapy or insulin therapy. The quantity of autologous mesenchymal stem cells infused was 95 × 106 to 97 × 106 cells. We analyzed levels of testosterone, luteinizing hormone, estradiol, and glycated hemoglobin in patients both before and 3 months after the autologous mesenchymal stem cell transplant procedure., Results: In men with type 1 diabetes mellitus and type 2 diabetes mellitus, autologous mesenchymal stem cell transplant led to an increase in testosterone levels from 5.31 ± 2.12 to 6.33 ± 2.12 ng/mL (P = .82), a decrease in luteinizing hormone from 8.43 ± 1.25 to 5.94 ± 1.57 mIU/mL (P = .04), and a decrease in glycated hemoglobin from 9.45 ± 1.24% to 8.53 ± 1.08% (P = .25) after 3 months. The increase in testosterone in men with autologous mesenchymal stem cell transplant group of 6.33 ± 2.12 ng/mL was significant compared with men in the control group (3.9 ± 1.18 ng/mL; P = .01)., Conclusions: Testosterone level increased and luteinizing hormone level decreased within 3 months after autologous mesenchymal stem cell transplant in men with diabetes mellitus.

Pancreas transplantation alone (PTA) is a β cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m 2 , and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10-year eGFR (mL/min/1.73 m 2 ) were 76.3 (58.1-100.8) and 51.3 (35.3-65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post-transplant, 38 eGFR < 30 mL/min/1.73 m 2 and 49 requiring KT. KF declined most significantly within 6 months post-PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death-censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In islet transplantation (ITx), primary graft function (PGF) or beta cell function measured early after last infusion is closely associated with long term clinical outcomes. We investigated the association between PGF and 5 year insulin independence rate in ITx and pancreas transplantation (PTx) recipients. This retrospective multicenter study included type 1 diabetes patients who underwent ITx in Lille and PTx in Nantes from 2000 to 2022. PGF was assessed using the validated Beta2-score and compared to normoglycemic control subjects. Subsequently, the 5 year insulin independence rates, as predicted by a validated PGF-based model, were compared to the actual rates observed in ITx and PTx patients. The study enrolled 39 ITx (23 ITA, 16 IAK), 209 PTx recipients (23 PTA, 14 PAK, 172 SPK), and 56 normoglycemic controls. Mean[SD] PGF was lower after ITx (ITA 22.3[5.2], IAK 24.8[6.4], than after PTx (PTA 38.9[15.3], PAK 36.8[9.0], SPK 38.7[10.5]), and lower than mean beta-cell function measured in normoglycemic control: 36.6[4.3]. The insulin independence rates observed at 5 years after PTA and PAK aligned with PGF predictions, and was higher after SPK. Our results indicate a similar relation between PGF and 5 year insulin independence in ITx and solitary PTx, shedding new light on long-term transplantation outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chetboun, Masset, Maanaoui, Defrance, Gmyr, Raverdy, Hubert, Bonner, Supiot, Kerleau, Blancho, Branchereau, Karam, Chelghaf, Houzet, Giral, Garandeau, Dantal, Le Mapihan, Jannin, Hazzan, Caiazzo, Kerr-Conte, Vantyghem, Cantarovich and Pattou.)

Pancreatic transplantation is considered by the American Diabetes Association and the European Association for the Study of Diabetes an acceptable surgical procedure in patients with type 1 diabetes also undergoing kidney transplantation in pre-final or end-stage renal disease if no contraindications are present. Pancreatic transplantation, however, is a complex surgical procedure and may lead to a range of postoperative complications that can significantly impact graft function and patient outcomes. Postoperative computed tomography (CT) is often adopted to evaluate perfusion of the transplanted pancreas, identify complications and as a guide for interventional radiology procedures. CT assessment after pancreatic transplantation should start with the evaluation of the arterial Y-graft, the venous anastomosis and the duodenojejunostomy. With regard to complications, CT allows for the identification of vascular complications, such as thrombosis or stenosis of blood vessels supplying the graft, the detection of pancreatic fluid collections, including pseudocysts, abscesses, or leaks, the assessment of bowel complications (anastomotic leaks, ileus or obstruction), and the identification of bleeding. The aim of this pictorial review is to illustrate CT findings of surgical-related complications after pancreatic transplantation. The knowledge of surgical techniques is of key importance to understand postoperative anatomic changes and imaging evaluation. Therefore, we first provide a short summary of the main techniques of pancreatic transplantation. Then, we provide a practical imaging approach to pancreatic transplantation and its complications providing tips and tricks for the prompt imaging diagnosis on CT., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: The role of the common channel length in duodenal switch (DS) on remission of type II diabetes mellitus (DM), when stratifying patients based on diabetes severity, is not well understood., Methods: We retrospectively reviewed 341 consecutive patients with DM undergoing DS with one of three different common channel (CC) lengths (100 cm, 150 cm, and 200 cm), each with a fixed 300 cm alimentary limb (AL). Patients were stratified by insulin dependence (IDDM) versus non-insulin dependent diabetes (NIDDM). Data was collected at one year and at the last available follow-up., Results: The NIDDM group had a similar average HbA1c at last follow-up for each of the CC lengths. However, the IDDM group had lower average HbA1c with shorter CC lengths (100 cm = 5.4%, 150 cm = 6%, 200 cm = 6.4%, p < 0.05). Shorter CC lengths resulted in a greater proportion of patients achieving remission in the IDDM group (66%, 50%, 32% in the 100 cm, 150 cm, and 200 cm CC, respectively, p < 0.01). Improvements in HbA1c were independent of weight loss and average DiaRem scores were similar between CC lengths. Rates of nutritional deficiencies were higher in shorter common channel lengths. Revision for malnutrition was similar between common channel lengths (100 cm group: 3.7%; 150 cm group: 1.8%; 200 cm group: 0%, p = NS)., Conclusions: When the AL is fixed, shortening CC lengths results in improved glycemic control and remission of DM in patients with the need for insulin preoperatively. Milder forms of DM are treated well with any of the CC lengths., (© 2023. The Author(s).)

Simultaneous pancreas-kidney transplantation is an effective treatment option for end-stage renal disease with diabetes mellitus. Successful simultaneous pancreas-kidney transplantation allows achieving euglycemia, stabilizing existing microvascular complications and slowing their progression, improving the patient's quality of life, lipid and calcium-phosphorus metabolism, reducing the risks of cardiovascular events. Therefore, in view of the patient's severe general condition due to prolonged intoxication, hyperglycemia and other complications of chronic kidney disease, the earliest possible surgical treatment with minimization of the patient's stay on dialysis therapy is crucial to improve the outcome of transplantation.

Background: While prior studies have confirmed the protective effect of diabetes on abdominal aortic aneurysm (AAA) development, much less is known about the effect of diabetes, and in particular insulin dependence, on outcomes following AAA repair. In this study, we aim to evaluate the role of insulin-dependent diabetes on short-term and long-term outcomes following open and endovascular AAA repair., Methods: The Vascular Implant Surveillance and Interventional Outcomes Network (VISION), a registry linking the Vascular Quality Initiative (VQI) data with Medicare claims, was queried for patients who underwent open or endovascular AAA repair from 2011 to the present. Exclusion criteria were unknown diabetes status, prior aortic intervention, maximum aneurysm diameter <45 mm at presentation, and Medicare Advantage coverage due to inconsistent follow-up. Patients were stratified based on diabetes status (no diabetes versus diabetes) and insulin dependence (no diabetes or non-insulin-dependent diabetes versus insulin-dependent diabetes)., Results: Of the 38,437 cases in the VISION endovascular aortic aneurysm (EVAR) and open aortic aneurysm repair (OAR) databases, 21,943 met inclusion criteria. Perioperative outcomes after OAR were comparable between diabetic and nondiabetic patients. However, diabetic patients undergoing EVAR were significantly more likely to have a postoperative myocardial infarction (1.0% vs 0.6%, P = 0.04) and have a 30-day readmission (10.9% vs 8.8%, P < 0.001). Insulin-dependent diabetic patients were more likely to require a 30-day readmission after OAR (24.5% vs 13.5%, P = 0.02) and EVAR (15.1% vs 9.0%, P < 0.001); however, only insulin-dependent diabetes mellitus (IDDM) patients undergoing EVAR experienced higher rates of postoperative myocardial infarction (1.9% vs 0.7%, P < 0.01). After propensity score matching, patients with IDDM undergoing EVAR were additionally at increased risk of mortality at 1-year, 3-year, and 5-year follow-up with the highest risk occurring at the 1-year mark (hazard ratio 1.79, P < 0.0001), while IDDM patients undergoing OAR were only at a significantly increased risk of mortality at 5-year follow-up (hazard ratio 1.90, P = 0.01)., Conclusions: Patients with insulin-dependent diabetes have greater than 14% one-year mortality following open or endovascular aneurysm repair, compared to 8% for all others. Our findings raise questions about whether insulin-dependent diabetics should have a higher size threshold for prophylactic repair, although further studies are needed to address this question and consider the influence of glycemic control on these outcomes., (Copyright © 2023. Published by Elsevier Inc.)

Diabetes mellitus is a chronic metabolic disease, characterized by high blood sugar levels; it affects more than 500 million individuals worldwide. Type 1 diabetes mellitus (T1DM) is results from insufficient insulin secretion by islets; its treatment requires lifelong use of insulin injections, which leads to a large economic burden on patients. Islet transplantation may be a promising effective treatment for T1DM. Clinically, this process currently involves directly infusing islet cells into the hepatic portal vein; however, transplantation at this site often elicits immediate blood-mediated inflammatory and acute immune responses. Subcutaneous islet transplantation is an attractive alternative to islet transplantation because it is simpler, demonstrates lower surgical complication risks, and enables graft monitoring and removal. In this article, we review the current methods of subcutaneous device-free islet transplantation. Recent subcutaneous islet transplantation techniques with high success rate have involved the use of bioengineering technology and biomaterial cotransplantation-including cell and cell growth factor co-transplantation and hydrogel- or simulated extracellular matrix-wrapped subcutaneous co-transplantation. In general, current subcutaneous device-free islet transplantation modalities can simplify the surgical process and improve the posttransplantation graft survival rate, thus aiding effective T1DM management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Xu, You, Yang, Feng, Yang, Li, Chen and Gao.)

Historically, only patients with brittle diabetes or severe recurrent hypoglycemia have been considered for islet transplantation (ITx). This population has been selected to optimize the risk-benefit profile, considering risks of long-term immunosuppression and limited organ supply. However, with the advent of stem cell (SC)-derived ITx and the potential for immunosuppression-free ITx, consideration of a broader recipient cohort may soon be justified. Simultaneously, the classical categorization of diabetes is being challenged by growing evidence in support of a clustering of disease subtypes that can be better categorized by the All New Diabetics in Scania (ANDIS) classification system. Using the ANDIS classification, 5 subtypes of diabetes have been described, each with unique causes and consequences. We evaluate consideration for ITx in the context of this broader patient population and the new classification of diabetes subtypes. In this review, we evaluate considerations for ITx based on novel diabetes subtypes, including their limitations, and we elaborate on unique transplant features that should now be considered to enable ITx in these "unconventional" patient cohorts. Based on evidence from those receiving whole pancreas transplant and our more than 20-year experience with ITx, we offer recommendations and potential research avenues to justify implementation of SC-derived ITx in broader populations of patients with all types of diabetes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Islet delivery devices (IDDs) offer potential benefits for islet transplantation and stem cell-based replacement in type 1 diabetes. Little is known about patient preferences regarding islet delivery device characteristics and implantation strategies. Patient preferences for IDDs and implantation strategies remain understudied. We invited patients, parents and caregivers to fill in an online questionnaire regarding IDDs. An online survey gathered responses from 809 type 1 diabetes patients and 47 caregivers. We also assessed diabetes distress in a subgroup of 412 patients. A significant majority (97%) expressed willingness to receive an IDD. Preferred IDD attributes included a 3.5 cm diameter for 37.7% of respondents, while when provided with all options, 30.4% found dimensions unimportant. Respondents were open to approximately 4 implants, each with a 5 cm incision. Many favored a device functioning for 12 months (33.4%) or 24 months (24.8%). Younger participants (16-30) were more inclined to accept a 6 months functional duration ( p < 0.001). Functional duration outweighed implant quantity and size ( p < 0.001) in device importance. This emphasizes patients' willingness to accommodate burdens related to IDD features and implantation methods, crucial for designing future beta cell replacement strategies., Competing Interests: AvA is founder and shareholder of Lighthouse Biomedical BV a start-up company aiming to commercialize beta cell delivery devices in the future. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tol, de Bont, Boon, de Koning and van Apeldoorn.)

Islet transplantation improves metabolic control in patients with unstable type 1 diabetes. Clinical outcomes have been improving over the last decade, and the widely used beta-score allows the evaluation of transplantation results. However, predictive pre-transplantation criteria of islet quality for clinical outcomes are lacking. In this proof-of-concept study, we examined whether characterization of the electrical activity of donor islets could provide a criterion. Aliquots of 8 human donor islets from the STABILOT study, sampled from islet preparations before transplantation, were characterized for purity and split for glucose-induced insulin secretion and electrical activity using multi-electrode-arrays. The latter tests glucose concentration dependencies, biphasic activity, hormones, and drug effects (adrenalin, GLP-1, glibenclamide) and provides a ranking of CHIP-scores from 1 to 6 (best) based on electrical islet activity. The analysis was performed online in real time using a dedicated board or offline. Grouping of beta-scores and CHIP-scores with high, intermediate, and low values was observed. Further analysis indicated correlation between CHIP-score and beta-score, although significance was not attained (R = 0.51, p = 0.1). This novel approach is easily implantable in islet isolation units and might provide means for the prediction of clinical outcomes. We acknowledge the small cohort size as the limitation of this pilot study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Raoux, Lablanche, Jaffredo, Pirog, Benhamou, Lebreton, Wojtusciszyn, Bosco, Berney, Renaud, Lang and Catargi.)

Current guidelines support the use of continuous glucose monitoring devices and insulin pumps in minor surgical procedures for pediatric patients with type 1 diabetes mellitus. However, there are few reported cases of using hybrid closed loop technology in the perioperative period. This retrospective case series presents seven pediatric patients with type 1 diabetes who underwent eight surgical procedures with maintenance of hybrid closed loop systems. This paper also provides considerations for future use of hybrid closed loop systems perioperatively., (© 2023 John Wiley & Sons Ltd.)