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We report the 1-year results from one patient as the preliminary analysis of a first-in-human phase I clinical trial (ChiCTR2300072200) assessing the feasibility of autologous transplantation of chemically induced pluripotent stem-cell-derived islets (CiPSC islets) beneath the abdominal anterior rectus sheath for type 1 diabetes treatment. The patient achieved sustained insulin independence starting 75 days post-transplantation. The patient's time-in-target glycemic range increased from a baseline value of 43.18% to 96.21% by month 4 post-transplantation, accompanied by a decrease in glycated hemoglobin, an indicator of long-term systemic glucose levels at a non-diabetic level. Thereafter, the patient presented a state of stable glycemic control, with time-in-target glycemic range at >98% and glycated hemoglobin at around 5%. At 1 year, the clinical data met all study endpoints with no indication of transplant-related abnormalities. Promising results from this patient suggest that further clinical studies assessing CiPSC-islet transplantation in type 1 diabetes are warranted. [Display omitted] • Patient-derived islets were generated with chemically induced pluripotent stem cells • Transplantation of these islets to an abdominal site led to engraftment in one patient • Exogenous insulin-independent glycemic control was restored in the patient • All safety and efficacy clinical endpoints were met at 1-year follow-up of the patient Chemically induced stem-cell-derived islets were transplanted beneath the abdominal anterior rectus sheath in one patient with type 1 diabetes, resulting in tolerable safety and promising restoration of exogenous-insulin-independent glycemic control at 1-year follow-up. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this work was to describe the phenotype of adults presenting with a first episode of diabetic ketoacidosis (DKA) in Cape Town, South Africa, and identify predictors of insulin independence at 12 and 60 months after presentation. Methods: A prospective, descriptive cohort study of all individuals, 18 years or older, presenting for the first time with DKA to four public-sector hospitals of the Groote Schuur Academic Health Complex was performed. Clinical, biochemical and laboratory data including GAD antibody and C-peptide status were collected at baseline. Insulin was systematically weaned and stopped in individuals who achieved normoglycaemia within the months after DKA. Individuals were followed for 12 months and then annually until 5 years after initial presentation with ketoacidosis. Results: Eighty-eight individuals newly diagnosed with diabetes when presenting with DKA were included and followed for 5 years. The mean ± SD age was 35±10 years and the median (IQR) BMI at diagnosis was 28.5 (23.3–33.4) kg/m2. Overall, 46% were insulin independent 12 months after diagnosis and 26% remained insulin independent 5 years after presentation. Forty-one participants (47%) tested negative for anti-GAD and anti-IA-2 antibodies and had C-peptide levels >0.3 nmol/l; in this group, 68% were insulin independent at 12 months and 37% at 5 years after diagnosis. The presence of acanthosis nigricans was strongly associated with insulin independence (OR 27.1 [95% CI 7.2, 102.2]; p<0.001); a positive antibody status was associated with a lower likelihood of insulin independence at 12 months (OR 0.10 [95% CI 0.03, 0.36]; p<0.001). On multivariable analysis only acanthosis (OR 11.5 [95% CI 2.5, 53.2]; p=0.004) was predictive of insulin independence 5 years after diagnosis. Conclusions/interpretation: The predominant phenotype of adults presenting with a first episode of DKA in Cape Town, South Africa, was that of ketosis-prone type 2 diabetes. These individuals presented with obesity, acanthosis nigricans, negative antibodies and normal C-peptide and could potentially be weaned off insulin at follow-up. Classic type 1 diabetes (lower weight, antibody positivity, low or unrecordable C-peptide levels and long-term insulin dependence) was less common. The simple clinical sign of acanthosis nigricans is a strong predictor of insulin independence at 12 months and 5 years after initial presentation. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Recovering functional beta cell mass is a promising approach for future diabetes therapies. The aim of the present study is to investigate the effects of adjudin, a small molecule identified in a beta cell screen using zebrafish, on pancreatic beta cells and diabetes conditions in mice and human spheroids. Methods: In zebrafish, insulin expression was examined by bioluminescence and quantitative real-time PCR (qPCR), glucose levels were examined by direct measurements and distribution using a fluorescent glucose analogue, and calcium activity in beta cells was analysed by in vivo live imaging. Pancreatic islets of wild-type postnatal day 0 (P0) and 3-month-old (adult) mice, as well as adult db/db mice (i.e. BKS(D)-Leprdb/JOrlRj), were cultured in vitro and analysed by qPCR, glucose stimulated insulin secretion and whole mount staining. RNA-seq was performed for islets of P0 and db/db mice. For in vivo assessment, db/db mice were treated with adjudin and subjected to analysis of metabolic variables and islet cells. Glucose consumption was examined in primary human hepatocyte spheroids. Results: Adjudin treatment increased insulin expression and calcium response to glucose in beta cells and decreased glucose levels after beta cell ablation in zebrafish. Adjudin led to improved beta cell function, decreased beta cell proliferation and glucose responsive insulin secretion by decreasing basal insulin secretion in in vitro cultured newborn mouse islets. RNA-seq of P0 islets indicated that adjudin treatment resulted in increased glucose metabolism and mitochondrial function, as well as downstream signalling pathways involved in insulin secretion. In islets from db/db mice cultured in vitro, adjudin treatment strengthened beta cell identity and insulin secretion. RNA-seq of db/db islets indicated adjudin-upregulated genes associated with insulin secretion, membrane ion channel activity and exocytosis. Moreover, adjudin promoted glucose uptake in the liver of zebrafish in an insulin-independent manner, and similarly promoted glucose consumption in primary human hepatocyte spheroids with insulin resistance. In vivo studies using db/db mice revealed reduced nonfasting blood glucose, improved glucose tolerance and strengthened beta cell identity after adjudin treatment. Conclusions/interpretation: Adjudin promoted functional maturation of immature islets, improved function of dysfunctional islets, stimulated glucose uptake in liver and improved glucose homeostasis in db/db mice. Thus, the multifunctional drug adjudin, previously studied in various contexts and conditions, also shows promise in the management of diabetic states. Data availability: Raw and processed RNA-seq data for this study have been deposited in the Gene Expression Omnibus under accession number GSE235398 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE235398). [ABSTRACT FROM AUTHOR]

Long-term success in beta-cell replacement remains limited by the toxic effects of calcineurin inhibitors (CNI) on beta-cells and renal function. We report a multi-modal approach including islet and pancreas-after-islet (PAI) transplant utilizing calcineurin-sparing immunosuppression. Ten consecutive non-uremic patients with Type 1 diabetes underwent islet transplant with immunosuppression based on belatacept (BELA; n = 5) or efalizumab (EFA; n = 5). Following islet failure, patients were considered for repeat islet infusion and/or PAI transplant. 70% of patients (four EFA, three BELA) maintained insulin independence at 10 years post-islet transplant, including four patients receiving a single islet infusion and three patients undergoing PAI transplant. 60% remain insulin independent at mean follow-up of 13.3 ± 1.1 years, including one patient 9 years after discontinuing all immunosuppression for adverse events, suggesting operational tolerance. All patients who underwent repeat islet transplant experienced graft failure. Overall, patients demonstrated preserved renal function, with a mild decrease in GFR from 76.5 ± 23.1 mL/min to 50.2 ± 27.1 mL/min (p = 0.192). Patients undergoing PAI showed the greatest degree of renal impairment following initiation of CNI (56% ± 18.7% decrease in GFR). In our series, repeat islet transplant is ineffective at maintaining long-term insulin independence. PAI results in durable insulin independence but is associated with impaired renal function secondary to CNI dependence. [ABSTRACT FROM AUTHOR]

Introduction: In pancreatic islet transplantation, the exact contribution of human leukocyte antigen (HLA) matching to graft survival remains unclear. Islets may be exposed to allogenic rejection but also the recurrence of type 1 diabetes (T1D). We evaluated the HLA-DR matching, including the impact of diabetogenic HLADR3 or HLA-DR4 matches. Methods: We retrospectively examined the HLA profile in 965 transplant recipients and 2327 islet donors. The study population was obtained from patients enrolled in the Collaborative Islet Transplant Registry. We then identified 87 recipients who received a single-islet infusion. Islet-kidney recipients, 2nd islet infusion, and patients with missing data were excluded from the analysis (n=878). Results: HLA-DR3 and HLA-DR4 were present in 29.7% and 32.6% of T1D recipients and 11.6% and 15.8% of the donors, respectively. We identified 52 T1D islet recipients mismatched for HLA-DR (group A), 11 with 1 or 2 HLA-DRmatches but excluding HLA-DR3 and HLA- DR4 (group B), and 24 matched for HLA-DR3 or HLA-DR4 (group C). Insulin-independence was maintained in a significantly higher percentage of group B recipients from year one through five post-transplantation (p<0.01). At five-year post-transplantation, 78% of group B was insulin-independent compared to 24% (group A) and 35% (group C). Insulinindependence correlated with significantly better glycemic control (HbA1c <7%), fasting blood glucose, and reduced severe hypoglycemic events. Matching HLAA-B-DR (≥3) independently of HLA- DR3 or HLA-DR4 matching did not improve graft survival. Conclusion: This study suggests that matching HLA-DR but excluding the diabetogenic HLA-DR3 and/or 4 is a significant predictor for long-term islet survival. [ABSTRACT FROM AUTHOR]

IntroductionIn pancreatic islet transplantation, the exact contribution of human leukocyte antigen (HLA) matching to graft survival remains unclear. Islets may be exposed to allogenic rejection but also the recurrence of type 1 diabetes (T1D). We evaluated the HLA-DR matching, including the impact of diabetogenic HLA-DR3 or HLA-DR4 matches.MethodsWe retrospectively examined the HLA profile in 965 transplant recipients and 2327 islet donors. The study population was obtained from patients enrolled in the Collaborative Islet Transplant Registry. We then identified 87 recipients who received a single-islet infusion. Islet-kidney recipients, 2nd islet infusion, and patients with missing data were excluded from the analysis (n=878).ResultsHLA-DR3 and HLA-DR4 were present in 29.7% and 32.6% of T1D recipients and 11.6% and 15.8% of the donors, respectively. We identified 52 T1D islet recipients mismatched for HLA-DR (group A), 11 with 1 or 2 HLA-DR-matches but excluding HLA-DR3 and HLA- DR4 (group B), and 24 matched for HLA-DR3 or HLA-DR4 (group C). Insulin-independence was maintained in a significantly higher percentage of group B recipients from year one through five post-transplantation (p

In this Commentary, we echo the conclusions of a recent review titled " The promise of stem cell-derived islet replacement therapy," which highlighted recent advances in producing glucose responsive "islets" from stem cells and the benefits of their use in islet transplant therapy in type 1 diabetes (T1D). The review also outlined the status of clinical islet transplantation and the challenges that have prevented it from reaching its full therapeutic promise. We agree with the conclusions of the review and suggest that the identified challenges may be overcome by using the eye anterior chamber as an islet transplant site. We anticipate that the combination of stem cell-derived islets and intraocular transplant could help this promising T1D therapy reach full fruition. [ABSTRACT FROM AUTHOR]

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas that causes pain and gastrointestinal problems in patients. Robot‐assisted total pancreatectomy with autologous islet cell transplantation (TPAIT) is a surgical procedure for treating patients with CP that has been unresponsive to other treatments. After performing a total pancreatectomy, the surgical team isolates islet cells and then infuses them into the patient's liver. To provide the best possible care for patients undergoing TPAIT, perioperative nurses should understand the physiological functions of the pancreas, the etiology of and treatment options for CP, and their role in coordinating care for this patient population. This article discusses the disease process for CP, reasons for choosing the robotic approach to TPAIT, preparation of the OR for the procedure, the role of the RN circulator during a robot‐assisted TPAIT, and nursing management of the patient during the postoperative phase of care. [ABSTRACT FROM AUTHOR]

Pancreatic islet transplantation is a minimally invasive procedure that can restore normoglycemia and insulin independence in Type 1 diabetics without the surgical complications associated with vascularized pancreas transplantation. The advances made in this field over the past decade have dramatically improved patient outcomes, and the procedure is now transitioning from an experimental treatment to a clinical reality. Nonetheless, a number of important issues continue to hamper the success of islet transplantation and must be addressed before there is widespread clinical acceptance. These include the relative inefficiency of the islet isolation process, the progressive loss of islet function over time and the need for multiple donors to achieve insulin independence. Here, we discuss the current status of islet transplantation and examine its future as a treatment for Type 1 diabetes. [ABSTRACT FROM AUTHOR]

This report summarizes a 5-year phase 1/2 allogeneic islet transplantation clinical trial conducted at the University of Illinois at Chicago (UIC). Ten patients were enrolled in this single center, open label, and prospective trial in which patients received 1-3 transplants. The first four subjects underwent islet transplantation with the Edmonton immunosuppressive regimen and the remaining six subjects received the UIC immunosuppressive protocol (Edmonton plus etanercept and exenatide). All 10 patients achieved insulin independence after 1-3 transplants. At 5 years of follow-up, 6 of the initial 10 patients were free of exogenous insulin. During the follow-up period, 7 of the 10 patients maintained positive C-peptide levels and a composite hypoglycemic score of 0. Most patients maintained HbA1c levels <6.0 % (42.1 mmol/mol) and a significantly improved β-score. In conclusion, this study demonstrated long-term islet graft function without using T cell depleting induction, with an encouraging outcome that includes 60 % of patients remaining insulin independent after 5 years of initial transplantation. [ABSTRACT FROM AUTHOR]

Pancreas transplantation consistently induces insulin-independence in beta-cell-penic diabetic patients, but at the cost of major surgery and life-long immunosuppression. One year after grafting, patient survival rate now exceeds 95 % across recipient categories, while insulin independence is maintained in some 85 % of simultaneous pancreas and kidney recipients and in nearly 80 % of solitary pancreas transplant recipients. The half-life of the pancreas graft currently averages 16.7 years, being the longest among extrarenal grafts, and substantially matching the one of renal grafts from deceased donors. The difference between expected (100 %) and actual insulin-independence rate is mostly explained by technical failure in the postoperative phase, and rejection in the long-term period. Death with a functioning graft remains a further major issue, especially in uremic patients who have undergone prolonged periods of dialysis. Refinements in graft preservation, surgical techniques, immunosuppression, and prophylactic treatments are expected to further improve the results of pancreas transplantation. [ABSTRACT FROM AUTHOR]

Diabetes has become a major public health problem in China nowadays. There are almost 97 million diabetic patients nationwide. Latent autoimmune diabetes in adults (LADA) is a subtype of autoimmune diabetes. Although it has been reported for about 20 years, the diagnostic criteria of this disease remain controversial. The discussion mainly focused on serum autoantibodies, period of insulin need and age of diagnosis. Besides, β cell function, metabolic parameters, genetic factors and cell immunity may also contribute to the formulation of the criteria. Here, we aim to review and discuss the diagnostic criteria of latent autoimmune diabetes in adults. [ABSTRACT FROM AUTHOR]

Living-donor pancreas transplants (LDPs) were introduced at Chiba-East National Hospital in 2004, and 12 LDPs have been performed at this institution to date. Based on the outcome of these 12 LDPs, the efficacy and safety of LDPs are herein discussed. Twelve diabetic patients underwent LDPs; ten had simultaneous pancreas and kidney transplants from living donors, one had pancreas transplant after a kidney transplant from a living donor, and one had a pancreas transplant alone from a living donor. The donors were parents or brothers and the ABO blood types were incompatible in three LDPs. The procedures for the donor and recipient operations were performed according to the technique established by the University of Minnesota. Bladder drainage was used in 11 recipients and enteric drainage was used in one patient. Tacrolimus, basiliximab, mycophenolate mofetil, and prednisone were used for induction and immunosuppressive treatment. A splenectomy, double-filtered plasmapheresis, and plasma exchange were added in the ABO-incompatible LDPs. No complications were observed in the donors during hospitalization. The 1-year survivals of the patients, kidney grafts, and pancreas grafts were 100, 100, and 100%, respectively. The 3-year survivals were 91.7, 90, and 91.7%, respectively. Three patients developed leakage of pancreatic juice and one patient required a surgical procedure. Cytomegalovirus antigenemia was detected in five patients (42%). Based on the excellent outcome of the LDPs at this institution, LDPs is therefore expected to become a promising option for the treatment of patients with severe diabetes. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the long-term outcomes—in terms of glucose control, renal function and procedure-related complications—of simultaneous islet–kidney (SIK) transplantation with those of simultaneous pancreas–kidney (SPK) transplantation in patients with type 1 diabetes mellitus. HbA1c, need for insulin, GFR and complication rate were compared between 13 recipients of SIK and 25 recipients of SPK transplants at the same institution. The mean follow-up was 41 months. Two primary organ non-functions occurred in the SIK group. HbA1c did not differ at any time point during follow-up in the SIK group compared with the SPK group (mean during follow-up 6.3 vs 5.9%). Similarly, kidney function over time was not different between the two groups. A higher rate of insulin independence following SPK transplantation (after 1 year 96 vs 31% in the SIK group) was counterbalanced by a higher rate of serious adverse events (40% relaparotomies vs 0% in the SIK group). The endogenous insulin production achieved by islet transplantation, combined with optimal insulin therapy, was sufficient for maintaining near-normal glucose levels. In terms of glucose control, islet transplantation provides results comparable to those achieved with pancreas transplantation. However, SPK results in a higher rate of insulin independence, albeit at the cost of more surgical complications. These results have led to a new paradigm in islet transplantation at our institution, where the primary goal is not insulin independence, but good glucose control and avoidance of severe hypoglycaemia. [ABSTRACT FROM AUTHOR]

Stresses encountered during human islet isolation lead to unavoidable β-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, β-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less β-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.

In patients with chronic pancreatitis (CP), autologous islet transplantation (AIT) is often coupled with total pancreatectomy (TP) in aims to preserve patients' insulin secretory function. Despite a third of patients achieving insulin independence post-total pancreatectomy and autologous islet transplantation (TPAIT), many will require the addition of insulin therapy for maintenance of glycemic control overtime. We aimed through this study to investigate the early metabolic profile signature of insulin independent subjects post-TPAIT, specifically exploring markers of beta cell stress in this cohort. In a prospective study design, we identified 37 subjects who underwent TPAIT between 2008 and 2017. Metabolic parameters were assessed using mixed meal tolerance test data (MMTT), and the insulin-to-proinsulin index ratio, a marker of beta cell stress. Assessments between metabolic variables were evaluated using the Wilcoxon signed rank test. A significance level of 0.05 was assumed for all comparisons. At a mean (±standard deviation) follow up duration of 37.7±17 months post-TPAIT, 11 patients (30%) were insulin independent with a mean HbA1C of 5.85±0.42%. Despite adequate glycemic control in the latter cohort, we observed significantly higher median peak glucose (180.5 versus 115.0 mg/dL; p=0.031), and lower median fasting C-peptide (0.95 versus 1.5 ng/mL; p=0.008) on post-TPAIT MMTT compared to pre-TPAIT MMTT. Additionally, significantly lower insulin-to-proinsulin index AUC ratio was seen post-TPAIT compared to pre-TPAIT (p=0.022). A decline in the proinsulin processing capacity, expressed by a lower insulin-to-proinsulin index ratio was seen in insulin independent subjects post-TPAIT. Further studies exploring the pathophysiology underlying these findings should be attained.

Milestones in the history of diabetes therapy include the discovery of insulin and successful methods of beta cell replacement including whole pancreas and islet cell transplantation options. While pancreas transplantation remains the gold standard for patients who have difficulty controlling their symptoms with exogenous insulin, islet allotransplantation is now able to provide similar results with some advantages that make it an attractive potential alternative. The Edmonton Protocol, which incorporated a large dose of islets from multiple donors with steroid-free immunosuppression helped to establish the modern era of islet transplantation almost 20 years ago. While islet allotransplantation is recognized around the world as a powerful clinical therapy for type 1 diabetes it is not yet recognized by the Federal Drug Administration of the United States. Large-scale clinical trials administered by the Clinical Islet Transplantation Consortium have recently demonstrated that the well-regulated manufacture of a human islet product transplanted into patients with difficult to control type 1 diabetes and with a history of severe hyperglycemic episodes can safely and efficaciously maintain glycemic balance and eliminate the most severe complications associated with diabetes. The results of these clinical trials have established a strong basis for licensure of clinical islet allotransplantation in the US. Recognition by the Federal Drug Administration would likely lead to third party reimbursement for islet allotransplantation as a therapeutic option in the United States and would make the treatment available to many more patients. The high costs of rampant diabetes justify the expense of the treatment, which is in-line with the costs of clinical pancreas transplantation. While much enthusiasm and hope is raised toward the development and optimization of stem cell therapy, the islet transplantation community should push toward licensure, if that means broader access of this procedure to patients who may benefit from it. Even as we prepare to take the first steps in that direction, we must acknowledge the new challenges that a shift from the experimental to clinical will bring. Clinical islet allotransplantation in the United States would be a game-changing event in the treatment of type 1 diabetes and also generate enthusiasm for continued research.

Islet cell transplantation is a promising functional cure for type 1 diabetes; however, maintaining long-term islet graft function and insulin independence is difficult to achieve. In this short report we present a patient with situs inversus, who at the time of islet transplantation had a 26-year history of type 1 diabetes, complicated by hypoglycemic unawareness and severe hypoglycemic events. After a single allogeneic islet transplant of a low islet mass, and despite developing de novo anti-insulin and anti-GAD65 autoantibodies, the patient has remarkably maintained insulin independence with tight glycemic control and normal metabolic profiles for 10 years, after receiving prolonged non-T-cell depleting immunosuppression.

Islet transplantation is considered an advanced therapy in the treatment of type-1 diabetes, with a progressive improvement of clinical results as seen in the Collaborative Islet Transplant Registry (CITR) report. It is an accepted method for the stabilization of frequent hypoglycemia, or severe glycemic lability, in patients with hypoglycemic unawareness, poor diabetic control, or a resistance to intensive insulin-based therapies. Worldwide data confirm a positive trend in this field, with the integrated management of pivotal factors: adequate islet mass, immunosuppressive protocols, additional anti-inflammatory therapy, and pre-transplant allo-immunity assessment. Insulin independence has been observed in several clinical trials with different rate, ranging 100-65% of patients; the maintenance of this condition during the follow-up progressively decreased, actually arranged on 44% 3 years after the last infusion, according to data reported from the CITR. Successful duration is progressively increasing, with ≥13 years being the longest reported insulin-free condition on record. The immediate results of functioning islet transplantation are an improvement in hypoglycemic awareness and a reduction in the glycated hemoglobin level. Furthermore, many studies have shown its influence on the chronic complications of diabetes, such as peripheral neuropathy, retinopathy, and macroangiopathy. Pre-transplant nephropathy remains an exclusion criterion as immunosuppressive therapy can exacerbate kidney-function deterioration. The problems linked to immunosuppression following islet transplantation for the treatment of type-1 diabetes need to be considered in order to achieve the correct risk/benefit ratio for each patient., (Copyright © 2015. Published by Elsevier Ltd.)