Diabetes mellitus is not associated with worse short term outcome in patients older than 65 years old post-liver transplantation

BACKGROUND Non-alcoholic fatty liver disease is a global health care challenge and a leading indication of liver transplantation(LT).Hence,more patients with diabetes mellitus(DM)are undergoing LT,especially,above the age of 65.AIM To evaluate the impact of DM on short-term outcomes post-LT in patients over the age of 65.METHODS We collected data of patients who underwent LT from January 2001 until December 2019 using our electronic medical record.We assessed the impact of DM on short-term outcomes,one-year,post-LT based on the following variables:Survival at one year;acute cellular rejection(ACR)rates;intensive care unit(ICU)and hospital length of stay;and readmissions.RESULTS Total of 148 patients who are 65 year or older underwent LT during the study period.The mean age is 68.5±3.3 years and 67.6%were male.The median Model for End-stage Liver Disease score at time of transplantation was 22(6-39),39%of patients had hepatocellular carcinoma and 77.7%underwent living donor LT.The one-year survival was similar between DM patients and others,91%.ACR occurred in 13.5%of patients(P=0.902).The median ICU stay is 4.5-day P=0.023.The rates of ICU and 90-d readmission were similar(P=0.821)and(P=0.194),respectively.CONCLUSION The short-term outcome of elderly diabetic patients undergoing LT is similar to others.The presence of DM in elderly LT candidates should not discourage physicians from transplant consideration in this cohort of patients.

Simultaneous pancreas-kidney transplantation for end-stage renal failure in type 1 diabetes mellitus: Current perspectives

Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challenges for clinicians across the world,especially when associated with CKD and ESRF.Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM.Simultaneous pancreas-kidney transplant(SPK)is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications.However,limited availability of the organs for transplantation,the need for long-term immunosuppression to prevent rejection,peri-and post-operative complications of SPK,lack of resources and the expertise for the procedure in many centers,and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe.This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.

Risk factors for new onset diabetes mellitus after liver transplantation: A meta-analysis

AIM: To determine the risk factors for new-onset diabetes mellitus(NODM) after liver transplantation by conducting a systematic review and meta-analysis.METHODS: We electronically searched the databases of MEDLINE, EMBASE and the Cochrane Library from January 1980 to December 2013 to identify relevant studies reporting risk factors for NODM after liver transplantation. Two authors independently assessed the trials for inclusion and extracted the data. Discrepancies were resolved in consultation with a third reviewer. All statistical analyses were performed with the Rev Man5.0 software(The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios(OR) or weighted mean differences(WMD) with 95% confidence intervals(CIs) were calculated using either a fixed effects or a random effects model, based on the presence(I2 < 50%) or absence(I2 > 50%) of significant heterogeneity. RESULTS: Twenty studies with 4580 patients were included in the meta-analysis, all of which were retrospective. The meta-analysis identified the following significant risk factors: hepatitis C virus(HCV) infection(OR = 2.68; 95%CI: 1.92-3.72); a family history of diabetes(OR = 1.69, 95%CI: 1.09-2.63, P < 0.00001); male gender(OR = 1.53; 95%CI: 1.24-1.90; P < 0.0001); impaired fasting glucose(IFG; OR = 3.27; 95%CI: 1.84-5.81; P < 0.0001); a family history of diabetes(OR = 1.69; 95%CI: 1.09-2.63; P = 0.02); use of tacrolimus(OR = 1.34; 95%CI: 1.03-1.76; P = 0.03) and body mass index(BMI)(WMD = 1.19, 95%CI: 0.69-1.68, P < 0.00001). Other factors, such as hepatitis B virus infection and alcoholism, were not found to be associated with the incidence of NODM.CONCLUSION: The study showed that HCV infection, IFG, a family history of diabetes, male gender, tacrolimus and BMI are risk factors for NODM after liver transplantation.

Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation

AbstractAIM： To investigate the impact of minimum tacrolimus（TAC） on new-onset diabetes mellitus （NODM） afterliver transplantation （LT）.METHODS： We retrospectively analyzed the data of973 liver transplant recipients between March 1999and September 2014 in West China Hospital LiverTransplantation Center. Following the exclusion ofineligible recipients, 528 recipients with a TAC-dominantregimen were included in our study. We calculatedand determined the mean trough concentration ofTAC （cTAC） in the year of diabetes diagnosis in NODMrecipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value forpredicting NODM 6 mo after LT was identified usinga receptor operating characteristic curve. TAC-relatedcomplications after LT was evaluated by χ^2 test, andthe overall and allograft survival was evaluated usingthe Kaplan-Meier method. Risk factors for NODM afterLT were examined by univariate and multivariate Cox regression.RESULTS： Of the 528 transplant recipients, 131（24.8%） developed NODM after 6 mo after LT, andthe cumulative incidence of NODM progressivelyincreased. The mean cTAC of NODM group recipientswas significantly higher than that of recipients in thenon-NODM group （7.66 ± 3.41 ng/mL vs 4.47 ± 2.22ng/mL, P 〈 0.05）. Furthermore, NODM group recipientshad lower 1-, 5-, 10-year overall survival rates （86.7%,71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P 〈0.05） and allograft survival rates （92.8%, 84.6%, and75.7% vs 96.1%, 91%, and 86.1%, P 〈 0.05） thanthe others. The best cutoff of mean cTAC for predictingNODM was 5.89 ng/mL after 6 mo after LT. Multivariateanalysis showed that old age at the time of LT （〉 50years）, hypertension pre-LT, and high mean cTAC （≥5.89 ng/mL） after 6 mo after LT were independent riskfactors for developing NODM. Concurrently, recipientswith a low cTAC （〈 5.89 ng/mL） were less likely tobecome obese （21.3% vs 30.2%, P 〈 0.05） or todevelop dyslipidemia （27.5% vs 44.8%, P 〈0.05）,chronic kidney dysfunction （14.6% vs 22.7%, P 〈 0.05）,and moderate to severe infection （24.7% vs 33.1%, P〈 0.05） after LT than recipients in the high mean cTACgroup. However, the two groups showed no significantdifference in the incidence of acute and chronicrejection, hypertension, cardiovascular events and newonsetmalignancy.CONCLUSION： A minimal TAC regimen can decreasethe risk of long-term NODM after LT. Maintaining a cTACvalue below 5.89 ng/mL after LT is safe and beneficial.

Post-transplant diabetes mellitus in liver transplantation:Hangzhou experience

BACKGROUND: Diabetes mellitus (DM) is a frequent and serious complication in patients with liver diseases. We aimed to assess the prevalence and consequences of post-transplant DM (PTDM) in Chinese patients with HBV-related liver diseases and to determine the possible risk factors. METHODS: Altogether 165 patients with HBV infection and undergoing cadaveric related liver transplantation (LT) were enrolled. The clinical data of patients with (PTDM group) and without PTDM (non-PTDM group) were compared. RESULTS: Of the 165 patients, 28 had DM and 12 had impaired fasting glucose (IFG) before LT. Patients with pre-transplant DM or IFG had a survival rate similar to that of the others. Forty patients (24.2%) developed PTDM with a mean time of 36 17 days (range 2-300 days) after LT. Of those, 32 developed PTDM within 3 months post-LT and 29 needed insulin treatment. Pre-transplant hepatic encephalopathy and tacrolimus application were found more frequently in the PTDM group than in the non-PTDM group. The plasma tacrolimus levels were notably higher at I and 3 months post-LT in the PTDM group than those in the non-PTDM group. Compared to the non-PTDM group, the PTDM group showed remarkably poorer survival and tumor-free survival in patients with hepatocellular carcinoma, and significantly higher incidence of sepsis, fungal infection, chronic kidney diseases and biliary complications after LT. CONCLUSIONS: Pre-transplant DM did not affect the patient survival after LT. Since PTDM is common, it has a negative impact on outcome and may contribute to tumor recurrence. Pre-transplant hepatic encephalopathy, a tacrolimus-based regimen, and high levels of tacrolimus are clearly associated with the occurrence of PTDM.

Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation

BACKGROUND:New-onset diabetes after transplantation(NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation(LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients.METHODS:A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom Mass ARRAY. Modified clinical models in predicting NODAT were established and evaluated.RESULTS:The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients(56% vs 39%, P=0.014). Dominant model(GG vs GT+TT, P=0.030) and recessive model(GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age(OR=1.048, P=0.004), BMI(OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT(OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT(AUROC=0.743, P<0.001).CONCLUSION:ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.

Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation

AIM to determine whether diabetes mellitus(DM) affects prognosis/recurrence after liver transplantation(Lt) for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC). METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent Lt with antiviral prophylaxis. Patient data were obtained from the China Liver transplant Registry(https://www.cltr.org/). to compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis. RESULTS Univariate analysis of 1631 patients who underwent Lt found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after Lt between the two groups were significant(P = 0.041), but recurrence-free survival rates were not(P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years(P = 0.002), the presence of vascular invasion(P = 0.096), tumors ≤ 3 cm(P = 0.047), two to three tumor nodules(P = 0.007), Child-Pugh grade B(P = 0.018), and preLt alanine aminotransferase levels between 40 and 80 IU/L(P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/m L(P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM(P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after Lt. CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor Lt outcomes. Prevention strategies for HCC patients with DM are recommended.

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus

Simultaneous liver,pancreas-duodenum,and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis,renal failure,and insulin dependent diabetes mellitus(IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus,mycophenolate mofetil,and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation,and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

Pancreas transplantation in type Ⅱ diabetes mellitus

Although the diagnosis of type 2 diabetes mellitus was once considered a contraindication to simultaneous pancreas-kidney transplantation, a growing body of evidence has revealed that similar graft and patient survival can be achieved when compared to type 1 diabetes mellitus recipients. A cautious strategy regarding candidate selection may limit appropriate candidates from additional benefits in terms of quality of life and potential amelioration of secondary side effects of the disease process. Although our current understanding of the disease has changed, uniform listing characteristics to better define and study this population have limited available data and must be established.

Recent advances in new-onset diabetes mellitus after kidney transplantation

A common challenge in managing kidney transplant recipients(KTR)is posttransplant diabetes mellitus(PTDM)or diabetes mellitus(DM)newly diagnosed after transplantation,in addition to known pre-existing DM.PTDM is an important risk factor for post-transplant cardiovascular(CV)disease,which adversely affects patient survival and quality of life.CV disease in KTR may manifest as ischemic heart disease,heart failure,and/or left ventricular hypertrophy.Available therapies for PTDM include most agents currently used to treat type 2 diabetes.More recently,the use of sodium glucose co-transporter 2 inhibitors(SGLT2i),glucagon-like peptide-1 receptor agonists(GLP-1 RA),and dipeptidyl peptidase 4 inhibitors(DPP4i)has cautiously extended to KTR with PTDM,even though KTR are typically excluded from large general population clinical trials.Initial evidence from observational studies seems to indicate that SGLT2i,GLP-1 RA,and DPP4i may be safe and effective for glycemic control in KTR,but their benefit in reducing CV events in this otherwise high-risk population remains unproven.These newer drugs must still be used with care due to the increased propensity of KTR for intravascular volume depletion and acute kidney injury due to diarrhea and their single-kidney status,pre-existing burden of peripheral vascular disease,urinary tract infections due to immunosuppression and a surgically altered urinary tract,erythrocytosis from calcineurin inhibitors,and reduced kidney function from acute or chronic rejection.

Xenotransplantation of embryonic pig pancreas for treatment of diabetes mellitus in non-human primates

Transplantation therapy for diabetes in humans is limited by the low availability of human donor whole pancreas or islets. Outcomes are complicated by immunosuppressive drug toxicity. Xenotransplantation is a strategy to overcome supply problems. Implantation of tissue obtained early during embryogenesis is a way to reduce transplant immunogenicity. Pig insulin is biologically active in humans. In that regard the pig is an appropriate xenogeneic organ donor. Insulin-producing cells originating from embryonic pig pancreas obtained very early following pancreatic primordium formation [embryonic day 28 (E28)] engraft long-term in rhesus macaques. Endocrine cells originating from embryonic pig pancreas transplanted in host mesentery migrate to mesenteric lymph nodes, engraft, differentiate and improve glucose tolerance in rhesus macaques without the need for immune suppression. Transplantation of embryonic pig pancreas is a novel approach towards beta cell replacement therapy that could be applicable to humans.

Safety evaluation of human umbilical cord-mesenchymal stem cells in type 2 diabetes mellitus treatment:A phase 2 clinical trial

BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were observed on chest X-ray.CONCLUSION Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM.It can improve human immunity and inhibit lymphocytes.Coagulation function should be monitored vigilantly for abnormalities.

Modified upper abdominal cluster transplantation in patients with end-stage liver diseases associated with insulin dependent type 2 diabetes mellitus

Objective Modified upper abdominal cluster transplantation ( MCT) ,which was inspired by classical cluster transplant technique,has been proven more effective and feasible in the treatment of patients with end stage liver diseases associated with insulin - dependent

Post-transplant diabetes mellitus and preexisting liver disease-a bidirectional relationship affecting treatment and management

Liver cirrhosis and diabetes mellitus(DM)are both common conditions with significant socioeconomic burden and impact on morbidity and mortality.A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications.Type 2 DM(T2DM)is a wellrecognized risk factor for chronic liver disease and vice-versa,DM may develop as a complication of cirrhosis,irrespective of its etiology.Liver transplantation(LT)represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease(NAFLD),which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM.The metabolic risk factors including immunosuppressive drugs,can contribute to persistent or de novo development of DM and NAFLD after LT.T2DM,obesity,cardiovascular morbidities and renal impairment,frequently associated with metabolic syndrome and NAFLD,may have negative impact on short and long-term outcomes following LT.The treatment of DM in the context of chronic liver disease and post-transplant is challenging,but new emerging therapies such as glucagon-like peptide-1 receptor agonists(GLP-1RAs)and sodium–glucose cotransporter 2 inhibitors(SGLT2i)targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.

Impact of immunosuppression on incidence of post-transplant diabetes mellitus in solid organ transplant recipients:Systematic review and meta-analysis

BACKGROUND Solid organ transplantation is a life-saving intervention for end-stage organ disease.Post-transplant diabetes mellitus(PTDM)is a common complication in solid organ transplant recipients,and significantly compromises long-term survival beyond a year.AIM To perform a systematic review and meta-analysis to estimate incidence of PTDM and compare the effects of the 3 major immunosuppressants on incidence of PTDM.METHODS Two hundred and six eligible studies identified 75595 patients on Tacrolimus,51242 on Cyclosporine and 3020 on Sirolimus.Random effects meta-analyses was used to calculate incidence.RESULTS Network meta-analysis estimated the overall risk of developing PTDM was higher with tacrolimus(OR=1.495%CI:1.0–2.0)and sirolimus(OR=1.8;95%CI:1.5–2.2)than with Cyclosporine.The overall incidence of PTDM at years 2-3 was 17%for kidney,19%for liver and 22%for heart.The risk factors for PTDM most frequently identified in the primary studies were age,body mass index,hepatitis C,and African American descent.CONCLUSION Tacrolimus tends to exhibit higher diabetogenicity in the short-term(2-3 years post-transplant),whereas sirolimus exhibits higher diabetogenicity in the longterm(5-10 years post-transplant).This study will aid clinicians in recognition of risk factors for PTDM and encourage careful evaluation of the risk/benefit of different immunosuppressant regimens in transplant recipients.

Understanding host-graft crosstalk for predicting the outcome of stem cell transplantation

Mesenchymal stromal cells(MSCs)hold great promise for tissue regeneration in debilitating disorders.Despite reported improvements,the short-term outcomes of MSC transplantation,which is possibly linked to poor cell survival,demand extensive investigation.Disease-associated stress microenvironments further complicate outcomes.This debate underscores the need for a deeper understanding of the phenotypes of transplanted MSCs and their environment-induced fluctuations.Additionally,questions arise about how to predict,track,and comprehend cell fate post-transplantation.In vivo cellular imaging has emerged as a critical requirement for both short-and long-term safety and efficacy studies.However,translating preclinical imaging methods to clinical settings remains challenging.The fate and function of transplanted cells within the host environment present intricate challenges,including MSC engraftment,variability,and inconsistencies between preclinical and clinical data.The study explored the impact of high glucose concentrations on MSC survival in diabetic environments,emphasizing mitochondrial factors.Preserving these factors may enhance MSC survival,suggesting potential strategies involving genetic modification,biomaterials,and nanoparticles.Understanding stressors in diabetic patients is crucial for predicting the effects of MSC-based therapies.These multifaceted challenges call for a holistic approach involving the incorporation of large-scale data,computational disease modeling,and possibly artificial intelligence to enable deterministic insights.

Don´t give up on mitochondria as a target for the treatment of diabetes and its complications

In this editorial,we discuss an article by Wang et al,focusing on the role of mitochondria in peripheral insulin resistance and insulin secretion.Despite numerous in vitro and pre-clinical studies supporting the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of diabetes and its complications,efforts to target mitochondria for glycemic control in diabetes using mitochondria-targeted antioxidants have produced inconsistent results.The intricate functionality of mitochondria is summarized to underscore the challenges it poses as a therapeutic target.While mitochondria-targeted antioxidants have demonstrated improvement in mitochondrial function and oxidative stress in pre-clinical diabetes models,the results regarding glycemic control have been mixed,and no studies have evaluated their hypoglycemic effects in diabetic patients.Nonetheless,pre-clinical trials have shown promising outcomes in ameliorating diabetes-related complications.Here,we review some reasons why mitochondria-targeted antioxidants may not function effectively in the context of mitochondrial dysfunction.We also highlight several alternative approaches under development that may enhance the targeting of mitochondria for diabetes treatment.

Transplantation for the treatment of type 1 diabetes

Transplantation of pancreatic tissue, as either the intact whole pancreas or isolated pancreatic islets has become a clinical option to be considered in the treatment of patients with type 1 insulin-dependant diabetes mellitus. A successful whole pancreas or islet transplant offers the advantages of attaining normal or near normal blood glucose control and normal hemoglobin Alc levels without the risks of severe hypoglycemia associate with intensive insulin therapy. Both forms of transplants are also effective at eliminating the occurrence of significant hypoglycemic events （even with only partial islet function evident）. Whereas whole pancreas transplantation has also been shown to be very effective at maintaining a euglycemic state over a sustained period of time, thus providing an opportunity for a recipient to benefit from improvement of their blood glucose control, it is associated with a significant risk of surgical and post-operative complications. Islet transplantation is attractive as a less invasive alternative to whole pancreas transplant and offers the future promise of immunosuppression-free transplantation through pretransplant culture. Islet transplantation however, may not always achieve the sustained level of tight glucose control necessary for reducing the risk of secondary diabetic complications and exposes the patient to the adverse effects of immunosuppression. Although recent advances have led to an increased rate of obtaining insulin-independence following islet transplantation, further developments are needed to improve the longterm viability and function of the graft to maintain improved glucose control over time.

Diabetes mellitus and cellular replacement therapy: Expected clinical potential and perspectives

Diabetes mellitus(DM) is the most prevailing disease with progressive incidence worldwide. Despite contemporary treatment type one DM and type two DM are frequently associated with long-term major microvascular and macrovascular complications. Currently restoration of failing β-cell function, regulation of metabolic processes with stem cell transplantation is discussed as complements to contemporary DM therapy regimens. The present review is considered paradigm of the regenerative care and the possibly effects of cell therapy in DM. Reprogramming stem cells, bone marrowderived mononuclear cells; lineage-specified progenitor cells are considered for regenerative strategy in DM. Finally, perspective component of stem cell replacement in DM is discussed.

Surgical complications after pancreatic transplantation:A computed tomography imaging pictorial review

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.