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Objective: Telomere shortening and DNA oxidation are associated with premature vascular aging, which may be involved in lower-extremity amputation (LEA). We sought to investigate whether leukocyte telomere length (LTL) and plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation, were associated with LEA in subjects with type 1 diabetes at high vascular risk., Research Design and Methods: LTL (quantitative PCR) and plasma 8-OHdG concentrations (immunoassay method) were assessed at baseline in the GENEDIAB (Génétique de la Néphropathie Diabétique) type 1 diabetes cohort. Logistic and Cox proportional hazards regression models were fitted to estimate odds ratio (OR) (at baseline) and hazard ratio (HR) (during follow-up), with related 95% CI, by increasing biomarker tertiles (T1, T2, T3)., Results: Among 478 participants (56% male, mean ± SD age 45 ± 12 years and diabetes duration 29 ± 10 years), 84 patients had LEA at baseline. Baseline history of LEA was associated with shorter LTL (OR for T2 vs. T1 0.62 [95% CI 0.32-1.22] and for T3 vs. T1 0.41 [0.20-0.84]) but not with plasma 8-OHdG (1.16 [0.56-2.39] and 1.24 [0.61-2.55], respectively). New cases of LEA occurred in 34 (12.3%) participants during the 10-year follow-up. LTL were shorter (HR T2 vs. T1 0.25 [95% CI 0.08-0.67] and T3 vs. T1 0.29 [0.10-0.77]) and plasma 8-OHdG higher (2.20 [0.76-7.35] and 3.11 [1.07-10.32]) in participants who developed LEA during follow-up compared with others. No significant interaction was observed between biomarkers on their association with LEA., Conclusions: We report the first independent association between LTL shortening and excess risk of LEA in type 1 diabetes. High plasma 8-OHdG was also associated with incident LEA but partly dependent on cofounding variables., (© 2020 by the American Diabetes Association.)

The psychological burden experienced by people with diabetes prior to islet transplantation is recognized but has not been studied comprehensively, especially in relation to glycemia. Therefore, we conducted a rigorous pre-operative psychosocial profile of UK islet transplant recipients, and compared groups with higher/lower HbA1 c to test the null hypothesis that pre-transplant hypoglycemia awareness and psychosocial burden would not be related to baseline HbA1 c in this high-risk cohort. Pre-transplant, recipients (n = 44) completed validated hypoglycemia awareness questionnaires and generic/diabetes-specific measures of psychological traits and states. Scores were compared in groups, dichotomized by HbA1 c (≤8% versus >8%). Participants were aged (mean±SD) 53 ± 10 years; 64% were women; with HbA1 c 8.3 ± 1.7%. Median rate of severe hypoglycemia over the preceding 12 months was 13 events/person-year and 90% had impaired awareness of hypoglycemia (Gold/Clarke score ≥4). Participants had elevated fear of hypoglycemia (HFS-II Worry), impaired diabetes-specific quality of life (DQoL) and low generic health status (SF-36; EQ-5D). One quarter reported scores indicating likely anxiety/depression (HAD). Dispositional optimism (LOT-R) and generalized self-efficacy (GSE) were within published 'norms.' Despite negative perceptions of diabetes (including low personal control), participants were confident that islet transplantation would help (BIPQ). Hypoglycemia awareness and psychosocial profile were comparable in lower (n = 24) and higher (n = 20) HbA1 c groups. Islet transplant candidates report sub-optimal generic psychological states (anxiety/depressive symptoms), health status and diabetes-specific psychological states (fear of hypoglycemia, diabetes-specific quality of life). While their generic psychological traits (optimism, self-efficacy) are comparable with the general population, they are highly optimistic about forthcoming transplant. HbA1 c is not a proxy measure of psychosocial burden, which requires the use of validated questionnaires to systematically identify those who may benefit most from psychological assessment and support.

Background: The 2014 pancreas allocation system (PAS) intended to decrease geographic variability in listing practices for simultaneous pancreas and kidney (SPK) transplant and define eligibility criteria for those with type 2 diabetes mellitus (T2DM). Our primary aims were to evaluate geographic disparities in access to SPK and assess T2DM SPK listings in the pre- and post-PAS eras., Methods: Adult listings for SPK and kidney transplant (pre-PAS, January 2010 to October 29, 2014; post-PAS, October 30, 2014, to June 2, 2017) were identified in the Scientific Registry of Transplant Recipients. Multivariable logistic regression models tested associations of geography and/or diabetes mellitus type on the likelihood of SPK versus kidney transplant listing pre- and post-PAS. Competing risk models tested the likelihood of SPK transplantation within 2 years of listing for SPK., Results: Among 41 205 listings (27 393 pre-PAS; 24 439 T2DM), univariate analysis showed reduced percentages for SPK post-PAS (22.1%-20.8%; P = 0.003). After adjusting for patient and center characteristics, geographic disparities declined slightly but persisted post-PAS (era by region interaction P < 0.001). The era by type of diabetes mellitus interaction effect was statistically significant (P = 0.039), reflecting that the proportions of SPK listings for T2DM increased in the post-PAS era (3.4%-3.9%; univariate P = 0.038), while those for type 1 diabetes mellitus remained statistically stable (47.9%-48.4%; univariate P = 0.571). Among people listed for SPK, geographic disparities in the cumulative incidence of transplantation within 2 years declined and the overall likelihood of transplantation increased in the post-PAS era (both P < 0.001)., Conclusions: Geographic disparities in access to SPK declined slightly but persisted post-PAS. With new allocation change proposals and elimination of listing criteria for T2DM, further monitoring is warranted.

Objective: Improvement in insulin alternatives is leading to a delayed presentation of microvascular and macrovascular complications of diabetes. The objective of this study was to evaluate the long-term outcomes of older (≥50 years) diabetic patients who receive a pancreas transplantation (PT)., Research Design and Methods: We retrospectively evaluated all 338 PTs performed at our center between 2000 and 2016 (mean follow-up 9.4±4.9 years). Recipient and graft survivals were estimated for up to 10 years after PT. Major adverse cardiovascular events (MACEs) before and after PT were included in the analysis., Results: Thirty-nine patients (12%) were ≥50 years old (52.7±2.3 years) at the day of PT, of which 29 received a simultaneous pancreas-kidney transplantation (SPK) and 10 a pancreas after kidney transplantation (PAK). SPK recipients were first transplants, whereas in the PAK up to 50% were pancreas re-transplantations. Recipient and pancreas graft survivals at 10 years were similar between the group <50 years old and the older group for both SPK and PAK (log-rank p>0.05). The prevalence of MACE prior to PT was similar between both groups (31% vs 29%). Following PT, older recipients presented inferior post-transplant MACE-free survival. In a multivariate regression model, diabetes vintage (HR 1.054, p=0.03) and pre-transplantation MACE (HR 1.98, p=0.011), but not recipient age (HR 1.45, p=0.339), were associated with post-transplant MACE., Conclusions: Long-term survival of older pancreas transplant recipients are similar to younger counterparts. Diabetes vintage, but not age, increased the risk of post-transplantation MACE. These results suggest pancreas transplantation is a valuable treatment alternative to older diabetic patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Simultaneous pancreas-kidney transplantation (SPKT) aimed at increasing the life expectancy for diabetic patients with end-stage kidney disease (ESKD). However, the risks of surgery complications and immunosuppression therapy make it unclear if the SPKT positively impacts patient's quality of life (QoL). Using the Kidney Disease Quality of Life-Short-Form Health Survey (KDQOL-SF36) and Problems Areas in Diabetes (PAID) measurement tools, we compared the QoL of 57 patients on the pretransplant waiting list with that of 103 patients who had undergone SPKT. Posttransplantation patients were assessed within different time intervals (<1, 1-3, and >3 years). Mean KDQOL-SF36 scores were better among posttransplantation patients in the SF36 and KDQOL domains. It was also observed patients' stress reduction in PAID mean score (P = 0.011) after SPKT. We concluded that patients receiving SPKT had a better perception of QoL than did patients on the waiting list, and this positive perception remained almost entirely comparable over the three different intervals of the posttransplantation time. These positive results showed better outcomes when excluding patients that lost pancreas graft function. Further research is needed to compare diabetic patients with kidney transplant alone using specific measurement tools to evaluate patient's QoL., (© 2019 Steunstichting ESOT.)

Background: The concept of organ transplantation as treatment for complex genetic conditions, including Wolcott-Rallison syndrome (WRS), continues to show promise. Liver transplantation is essential for survival of patients with WRS, and pancreas transplantation cures their type I diabetes mellitus., Methods: The recipient, a 3-year-old girl weighing 14 kg at the time of transplantation, suffered from major complications of WRS, including repetitive liver failure episodes and poorly controlled diabetes. The patient underwent a nonacute, combined, simultaneous liver and pancreas transplantation from a pediatric donor without using the en bloc technique., Results: Well-preserved graft functions at 2-year follow-up with normal liver and pancreas function., Conclusions: This is the first case report of simultaneous liver and pancreas transplantation as treatment of WRS in a small child in Europe. Two-year follow-up demonstrates that organ transplantation can halt life-threating recurrent liver failure episodes and cure type 1 diabetes.

Aims/introduction: To investigate the long-term efficacy and safety of islet transplantation (ITx) compared with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII)., Materials and Methods: Among 619 patients diagnosed as insulin-dependent diabetes mellitus or type 1 diabetes at Kyoto University, Kyoto, Japan, seven patients were selected as the ITx group and 26 age-matched patients with no endogenous insulin secretion were selected as the MDI/CSII group. Hemoglobin A1c, aspartate aminotransferase/alanine aminotransferase (AST/ALT) and creatinine were assessed retrospectively at 1, 2, 5 and 10 years for both groups; serum C-peptide immunoreactivity was assessed for the ITx group. Major clinical events were also assessed., Results: Hemoglobin A1c improvement in ITx was significant at 1 year (8.4% [7.8-9.9%] at baseline to 7.1% [6.3-7.4%] in ITx vs 8.2% [7.4-9.8%] at baseline to 8.1% [7.3-9.5%] in MDI/CSII, P < 0.01 between groups), and was maintained at 2 years (7.4% [6.3-8.2%] vs 8.4% [7.4-9.6%], P = 0.11). The increase of stimulated C-peptide immunoreactivity was significant at 1 year (0.57 ng/mL [0.26-0.99 ng/mL], P < 0.05 from baseline) and 2 years (0.43 ng/mL [0.19-0.67 ng/mL], P < 0.05), although it became insignificant thereafter. There was no significant difference in AST/ALT or creatinine at 10 years, although a transient AST/ALT elevation was observed in ITx. In regard to clinical events, the occurrence of severe hypoglycemia was 14% vs 31% (relative risk 0.46, P = 0.64), that of infectious disease was 43% vs 12% (relative risk 3.71, P = 0.09) and digestive symptoms was 43% vs 7.7% (relative risk 5.57, P = 0.05) in ITx vs MDI/CSII, respectively. No patient died in either group., Conclusions: The present findings showed that ITx was considered to contribute to the reduction of hypoglycemia and better glycemic control with tolerable, but attention-requiring, risks over a period of 10 years compared with MDI/CSII., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

This study aimed to evaluate whether the BETA-2 score is a reliable early predictor of graft decline and loss of insulin independence after islet allotransplantation. Islet transplant procedures were stratified into 3 groups according to clinical outcome: long-term insulin independence without islet graft decline (group 1, N = 9), initial insulin independence with subsequent islet graft decline and loss of insulin independence (group 2, N = 13), and no insulin independence (group 3, N = 13). BETA-2 was calculated on day 75 and multiple times afterwards for up to 145 months posttransplantation. A BETA-2 score cut-off of 17.4 on day 75 posttransplantation was discerned between group 1 and groups 2 and 3 (area under the receiver operating characteristic 0.769, P = .005) with a sensitivity and negative predictive value of 100%. Additionally, BETA-2 ≥ 17.4 at any timepoint during follow-up reflected islet function required for long-term insulin independence. While BETA-2 did not decline below 17.4 for each of the 9 cases from group 1, the score decreased below 17.4 for all transplants from group 2 with subsequent loss of insulin independence. The reduction of BETA-2 below 17.4 predicted 9 (1.5-21) months in advance subsequent islet graft decline and loss of insulin independence (P = .03). This finding has important implications for posttransplant monitoring and patient care., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: In contrast to insulin-dependent type 1 diabetes mellitus (T1DM), the indication for Simultaneous pancreas-kidney transplantation (SPK) in patients with type 2 diabetes mellitus (T2DM) is still ambiguous and wisely Eurotransplant (ET) only granted transplant-permission in a selected group of patients. However, with regard to improvement of metabolic conditions SPK might still be a considerable treatment option for lean insulin dependent type 2 diabetics suffering from renal disease., Methods: Medical data (2001-2013) from all consecutive T1DM and T2DM patients who received a SPK or kidney transplant alone (KTA) at the University Hospital of Leipzig were analyzed. Donor, recipients and long-term endocrine, metabolic and graft outcomes were investigated for T1DM and T2DM-SPK recipients (transplanted upon a special request allocation by ET) and T2DM patients who received a KTA during the same period., Results: Eighty nine T1DM and 12 T2DM patients received a SPK and 26 T2DM patients received a KTA. Patient survival at 1 and 5 years was 89.9 and 88.8% for the T1DM group, 91.7 and 83.3% for the T2DM group, and 92.3 and 69.2% for the T2DM KTA group, respectively (p < 0.01). Actuarial pancreas graft survival for SPK recipients at 1 and 5 years was 83.1 and 78.7% for the T1DM group and 91.7 and 83.3% for the T2DM group, respectively (p = 0.71). Kidney allograft survival at 5 years was 79.8% for T1DM, 83.3% for T2DM, and 65.4% for T2DM KTA (p < 0.01). Delayed graft function (DGF) rate was significantly higher in type 2 diabetics received a KTA. Surgical, immunological and infectious complications showed similar results for T1DM and T2DM recipients after SPK transplant and KTA, respectively. With regard to the lipid profile, the mean high-density lipoprotein (HDL)- cholesterol levels were significantly higher in T1DM recipients compared to T2DM patients before transplantation (p = 0.02) and remained significantly during follow up period., Conclusion: Our data demonstrate that with regard to metabolic function a selected group of patients with T2DM benefit from SPK transplantation. Consensus guidelines and further studies for SPK transplant indications in T2DM patients are still warranted.

Pancreas transplantation is considered the curative treatment for severe type 1 diabetes mellitus in selected cases. Since the first procedure in 1966, surgical techniques have been improved. The current trend among most medical centers, as well as at our Institution, is enteric drainage and systemic venous or portal anastomosis. The aim of this pictorial essay is to describe the main imaging features of pancreatic transplantation with duodenoduodenostomy drainage.

Background: The safety and efficacy of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) to treat obesity and associated comorbidities, including diabetes mellitus, is well established. As diabetes may add risk to the perioperative period, we sought to characterize perioperative outcomes of these surgical procedures in diabetic patients., Methods: Using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database, we identified patients who underwent LSG and LRYGB between 2015 and 2017, grouping by non-diabetics (NDM), non-insulin-dependent diabetics (NIDDM), and insulin-dependent diabetics (IDDM). Primary outcomes included serious adverse events, 30-day readmission, 30-day reoperation, and 30-day mortality. Univariate and multivariable analyses were used to evaluate the outcome in each diabetic cohort., Results: Multivariable analysis of patients who underwent LSG (with NDM patients as reference) showed higher 30-day mortality (NIDDM AOR = 1.52, p = 0.043; IDDM AOR = 1.91, p = 0.007) and risk of serious adverse events (NIDDM AOR = 1.15, p < 0.001; IDDM AOR = 1.58, p < 0.001) in the diabetic versus NDM groups. Multivariable analysis of patients who underwent LRYGB (with NDM patients as reference) showed higher risk of serious adverse events (NIDDM AOR = 1.09, p = 0.014; IDDM AOR = 1.43, p < 0.001) in the diabetic versus NDM groups., Conclusions: Diabetics who underwent LSG and LRYGB had higher rates of several perioperative complications compared with non-diabetics. IDDM had a stronger association with several perioperative complications compared with NIDDM. This increase in morbidity and mortality is modest and should be weighed against the real benefits of bariatric surgery in patient with obesity and diabetes mellitus.

Background. Nutrition education is one of the most important factors determining the effectiveness of treatment and maintaining an adequate quality of life (QoL) in children and adolescents with type 1 diabetes., Material and Methods. A randomized single-blind study was conducted between October 2017 and April 2019 at the Children's Clinical Hospital in Warsaw. The study included 170 patients (aged 8-17) with at least 1-year history of type 1 diabetes, treated with insulin pumps. The participants were randomly divided into two groups: a control group (C) - traditional/ informative education methods, and an experimental group (E) - modern/interactive methods. PedsQL Diabetes Module 3.0 questionnaire was used in the assessment of the QoL. Total PedsQL score was the primary outcome. The secondary outcomes included the results obtained in five subscales of the questionnaire. The relationships between selected variables and changes in scores were also verified., Results. Data obtained from 136 patients were analyzed. In both groups no significant changes regarding total PedsQL were noted 6 months after the intervention. However, a significant reduction occurred as regards the scores of 'Communication' subscale in group C. Analyzing other determinants of the QoL, significant dependencies were observed between: the level of physical activity and a change in 'Diabetes symptoms' subscale, and the level of parents' education and a change in 'Treatment barriers' subscale., Conclusions. Both methods of nutrition education exerted a comparable influence on the total QoL. However, modern methods were more effective in terms of the improvement in the aspect of communication. Additionally, moderate physical activity and parents' tertiary education constituted valid determinants of various aspects of the QoL in children and adolescents with type 1 diabetes., Competing Interests: The authors have nothing to declare, (© Copyright by the National Institute of Public Health - National Institute of Hygiene.)

Background: In simultaneous pancreas-kidney (SPK) transplant recipients, the majority of complications described in the literature, are early postoperative complications. However, there is growing attention for late complications associated with SPK transplantation., Methods: In this case series, we present 3 cases, 2 enterically and 1 bladder-derived SPK transplant patients, with anastomotic hemorrhage of the donor duodenum as a very late complication, >10 years after transplantation (11, 22, and 18 y later, respectively)., Results: In our center, 122 SPK transplantations have been performed between January 1992 and June 2018. The 3 cases reported here are the only patients in our cohort presenting with delayed anastomotic hemorrhage of the donor duodenum (2.5%). In the first 2 patients, reintervention with reconstruction of the anastomosis was performed. A congestive and friable mucosa was seen, and the resection specimen showed enlarged and congestive submucosal veins in both patients. There was no recurrence of bleeding after reintervention. In the third patient, enteric derivation was not possible because of the extremely fragile intestinal tissue perioperatively, and a conservative approach was taken. As possible precipitating factors are concerned, all 3 of our patients were taking low-dose aspirin and/or clopidogrel as secondary cardiovascular prevention., Conclusions: Bleeding of the transplanted donor duodenum can present as a late complication, several years after SPK transplantation. The development of enlarged, congestive submucosal veins could play a role in these late bleedings, and antiplatelet therapy could be a precipitating factor. Further research is necessary to investigate the pathophysiology, the prevalence, optimal treatment, and the consequent influence on mortality, morbidity, and graft loss after SPK transplantation.

Pancreas transplantation (PTx) has been performed worldwide for patients with type 1 diabetes accompanied with end-stage renal disease or uncontrollable glycemic fluctuation. Nevertheless, risk factors of posttransplant glucose intolerance, which is responsible for progress of diabetic complications, remains unclear, especially in cases without pancreatic graft function loss. Therefore, this study was conducted to search for predictive factors of future glucose tolerance in PTx recipients without pancreatic graft function loss. Subjects were selected from among 41 Japanese patients with type 1 diabetes who received PTx between 2000 and 2016 in Osaka University Hospital, and 24 subjects free from rejections and thromboses were analyzed. Several examinations to evaluate insulin secretion and insulin sensitivity within 6 months after transplantation (initial examination) were performed. Glucose tolerance was evaluated by 120-minute post-load plasma glucose level during 75-g oral glucose tolerance tests (OGTT), referred to as PG OGTT 120, at the initial examination and between 1 year and 2 years posttransplantation (maintenance period). The initial examination factors that were correlated with PG OGTT 120 in the maintenance period were PG OGTT 120 [r = 0.52 (p = 0.01)], insulinogenic index [r = -0.65 (p < 0.01)], and the ratio of incremental area under the curve of insulin to that of plasma glucose (iAUCR) calculated from data of OGTT [r = -0.65 (p < 0.01)]. Insulinogenic index [β = -0.28 (p = 0.02)] and iAUCR [β = -0.29 (p = 0.02)] were still significantly correlated with PG OGTT 120 in the maintenance period after adjustment for PG OGTT 120 at the initial examination. In conclusion, insulinogenic index and iAUCR from OGTT performed in the early posttransplantation period were predictive factors of future glucose intolerance.

Background: Total pancreatectomy for chronic pancreatitis leads to brittle diabetes and challenging glycemic control with half of all patients experiencing severe hypoglycemia, many requiring medical intervention or hospitalization. Pancreas transplantation has the potential to manage both the endocrine and the exocrine insufficiency in this patient population., Methods: Between June 1, 2005, and July 1, 2016, 8 patients with brittle diabetes following total pancreatectomy underwent pancreas transplantation. All grafts had systemic venous and enteric exocrine drainage. Data included demographics, graft and patient survival, pre- and post-transplant supplementation with pancreatic enzymes, and narcotic usage., Results: Patient survival rate at 1 and 3 years was 88%. Pancreas graft survival rate of those alive at 1 year was 100% and 86%, respectively. About 75% of these patients remained insulin-free until their time of death, loss of follow-up, or present day. Of the patients with maintained graft function at 3 years, none required further hospitalization for glycemic control. About 75% of these patients have also maintained exocrine function without pancreatic enzyme supplementation., Conclusions: Pancreas transplant can treat both exocrine and endocrine insufficiency and give long-term insulin-free survival and should be considered as a viable treatment option for patients who have undergone total pancreatectomy for chronic pancreatitis., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1-year graft survival for both organs was not different. At last follow-up, uncensored and death-censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: There are no multicenter studies on the influence of diabetes duration on pancreatic transplant outcomes. Our study aimed to determine how type 1 diabetes duration influenced survival of pancreatic grafts., Methods: The data of 8,139 patients who received pancreas transplants during 2006-2015 were extracted from the Scientific Registry of Transplant Recipients database. Patients were separated into two groups according to duration of diabetes: S group (diabetes ≤20 years) and L group (>20 years)., Results: Compared to S group, L group were older and prone to be male, to have higher body mass index, to receive pancreas after kidney transplantation (PAK), and to be White. Patient survival was not significantly different between the two groups, but pancreatic survival was better in the L group (hazard ratio 0.88; P = 0.012). Pancreatic survival of L group was better than S group in pancreas transplant alone and simultaneous pancreas-kidney transplantation (SPK). Graft survival was not significant different between the two groups in PAK. Diabetes duration was an independent predictor of graft survival in SPK patients (hazard ratio 0.86; P = 0.012)., Conclusions: Diabetes duration has no influence on patient survival. However, long duration of type 1 diabetes mellitus appears to be protective against pancreatic graft loss., (© 2019 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objective: Diabetes is the leading cause of nontraumatic lower-extremity amputations (LEAs). Identification of patients with foot ulcers at risk for amputation remains clinically challenging. Plasma copeptin, a surrogate marker of vasopressin, is associated with the risk of cardiovascular and renal complications in diabetes., Research Design and Methods: We assessed the association between baseline plasma copeptin and risk of LEA during follow-up in four cohorts of people with type 1 (GENESIS, n = 503, and GENEDIAB, n = 207) or type 2 diabetes (DIABHYCAR, n = 3,101, and SURDIAGENE, n = 1,452) with a median duration of follow-up between 5 and 10 years. Copeptin concentration was measured in baseline plasma samples by an immunoluminometric assay., Results: In the pooled cohorts with type 1 diabetes ( n = 710), the cumulative incidence of LEA during follow-up by increasing tertiles (tertile 1 [TER1], TER2, and TER3) of baseline plasma copeptin was 3.9% (TER1), 3.3% (TER2), and 10.0% (TER3) ( P = 0.002). Cox regression analyses confirmed the association of copeptin with LEA: hazard ratio (HR) for 1 SD increment of log[copeptin] was 1.89 (95% CI 1.28-2.82), P = 0.002. In the pooled cohorts of type 2 diabetes ( n = 4,553), the cumulative incidence of LEA was 1.1% (TER1), 2.9% (TER2), and 3.6% (TER3) ( P < 0.0001). In Cox regression analyses, baseline plasma copeptin was significantly associated with LEA: HR for 1 SD increment of log[copeptin] was 1.42 (1.15-1.74), P = 0.001. Similar results were observed in the cohort with type 2 diabetes for lower-limb revascularization (HR 1.20 [95% CI 1.03-1.39], P = 0.02)., Conclusions: Baseline plasma copeptin is associated with cumulative incidence of LEA in cohorts of people with both type 1 and type 2 diabetes and may help to identify patients at risk for LEA., (© 2019 by the American Diabetes Association.)

Objectives: Pancreas transplant improves quality of life and survival of patients irrespective of pretransplant C-peptide levels. Our objectives were to examine complications and outcomes in patients without measureable C-peptide (insulin-dependent type 1 diabetes mellitus) and carefully selected patients with measurable C-peptide (insulin-dependent type 2 diabetes mellitus) after pancreas transplant., Materials and Methods: We conducted a retrospective analysis to examine the demographic, transplant factors, complications, and outcomes in patients with nondetectable pretransplant C-peptide (insulin-dependent type 1 diabetes mellitus) and patients with detectable pretransplant C-peptide (insulin-dependent type 2 diabetes mellitus)., Results: Of 214 consecutive pancreas transplant procedures over a 12-year period, 112 had pretransplant C-peptide level testing (63 patients with type 1 and 49 with type 2 diabetes mellitus). Patients with type 1 disease were more likely to be female (P = .048), and patients with type 2 disease were more likely to be African American (P < .001) and have undergone previous pancreas transplant (P = .042). We observed no differences in donor factors or posttransplant factors (C-peptide after year 2, glucose, and hemoglobin A1C, except that patients with type 2 disease had more pancreatitis) (P = .036). There were no differences in posttransplant complications; however, patients with type 2 disease had significantly higher BK virus nephropathy (P = .006). There were no differences in outcomes between cohorts (rejection, graft loss, or death; P = not significant)., Conclusions: Pancreas transplant can be performed with excellent and equivalent outcomes in patients with type 1 and carefully selected type 2 diabetes mellitus. Patients with type 2 disease are more likely to have posttransplant pancreatitis and BK virus nephropathy, affecting the net benefit for transplant.

BACKGROUND Pancreas transplantation can be a viable treatment option for patients with type 1 diabetes mellitus (T1DM), especially for those who are candidates for kidney transplantation. T1DM may rarely recur after pancreas transplantation, causing the loss of pancreatic graft. The aim of this study was to describe the prevalence of T1DM recurrence after pancreas transplantation in our series. MATERIAL AND METHODS Eighty-one patients transplanted from 2002 to 2015 were included. Autoantibody testing (GADA and IA-2) was performed before pancreas transplantation and during the follow-up. RESULTS The series includes 48 males and 33 females, mean age 37.4±5.7 years and mean duration of diabetes 25.5±6.5 years. Patients received simultaneous pancreas kidney (SPK) transplantation. After SPK transplantation, 56 patients retained pancreatic graft, 8 patients died, and 17 patients lost their pancreatic graft. T1DM recurrence occurred in 2 of the 81 transplanted patients, yielding a prevalence of 2.5%, with an average time of appearance of 3.3 years after transplant. Pancreatic enzymes were normal in the 2 patients, ruling out pancreatic rejection. T1DM recurrence was confirmed histologically, showing selective lymphoid infiltration of the pancreatic islets. CONCLUSIONS T1DM recurrence after pancreas transplantation is infrequent; however, it is one of the causes of pancreatic graft loss that should always be ruled out. Negative autoimmunity prior to transplantation does not ensure that T1DM does not recur.

Purpose of Review: Beta-cell replacement is the best therapeutic option for patients with type 1 diabetes. Because of donor scarcity, more extended criteria donors are used for transplantation. Donation after circulatory death donors (DCD) are not commonly used for pancreas transplantation, because of the supposed higher risk of complications. This review gives an overview on the pathophysiology, risk factors, and outcome in DCD transplantation and discusses different preservation methods., Recent Findings: Studies on outcomes of DCD pancreata show similar results compared with those of donation after brain death (DBD), when accumulation of other risk factors is avoided. Hypothermic machine perfusion is shown to be a safe method to improve graft viability in experimental settings. DCD should not be the sole reason to decline a pancreas for transplantation. Adequate donor selection and improved preservation techniques can lead to enhanced pancreas utilization and outcome.

The prevalence of obesity within the diabetic population is on the rise. This development poses unique challenges for pancreas transplantation candidates as obese individuals are often denied access to transplant. The introduction of robotic approach to transplant has been shown to improve outcomes in obese patients. A single center retrospective review of pancreas transplant cases over a 4-year period ending December 2018 was performed. Patients undergoing robotic surgery were compared to their counterparts undergoing open transplant. 49 patients (10 robot, 39 open) received pancreas transplants over the study period. Mean age was 43.1 ± 7.5 vs. 42.8 ± 9.7 years. There were no significant differences in demographics except body mass index (33.7 ± 5.2 vs. 27.1 ± 6.6, P = 0.005). Operative duration (7.6 ± 1.6 vs. 5.3 ± 1.4, P < 0.001), and warm ischemia times [45.5 (IQR: 13.7) vs. 33 (7), P < 0.001] were longer in the robotic arm. There were no wound complications in the robotic approach patients. Graft (100% vs. 88%, P = 0.37) and patient survival (100% vs. 100%, P = 0.72) after 1 year were similar. Our findings suggest that robotic pancreas is both safe and effective in obese diabetic patients, without added risk of wound complications. Wide adoption of the technique is encouraged while long term follow-up of our recipients is awaited., (© 2019 Steunstichting ESOT.)

Objective: The long-term outcome of allogenic islet transplantation is unknown. The aim of this study was to evaluate the 10-year outcome of islet transplantation in patients with type 1 diabetes and hypoglycemia unawareness and/or a functioning kidney graft., Research Design and Methods: We enrolled in this prospective parallel-arm cohort study 28 subjects with type 1 diabetes who received islet transplantation either alone (ITA) or after a kidney graft (IAK). Islet transplantation consisted of two or three intraportal infusions of allogenic islets administered within (median [interquartile range]) 68 days (43-92). Immunosuppression was induced with interleukin-2 receptor antibodies and maintained with sirolimus and tacrolimus. The primary outcome was insulin independence with A1C ≤6.5% (48 mmol/mol). Secondary outcomes were patient and graft survival, severe hypoglycemic events (SHEs), metabolic control, and renal function., Results: The primary outcome was met by (Kaplan-Meier estimates [95% CI]) 39% (22-57) and 28% (13-45) of patients 5 and 10 years after islet transplantation, respectively. Graft function persisted in 82% (62-92) and 78% (57-89) of case subjects after 5 and 10 years, respectively, and was associated with improved glucose control, reduced need for exogenous insulin, and a marked decrease of SHEs. ITA and IAK had similar outcomes. Primary graft function, evaluated 1 month after the last islet infusion, was significantly associated with the duration of graft function and insulin independence., Conclusions: Islet transplantation with the Edmonton protocol can provide 10-year markedly improved metabolic control without SHEs in three-quarters of patients with type 1 diabetes, kidney transplanted or not., (© 2019 by the American Diabetes Association.)

Type 1 diabetes mellitus (T1DM) is characterized by hyperglycemia, owing to the loss of pancreatic β cells in response to an autoimmune reaction leading to a state of absolute insulin deficiency. T1DM treatment is shifting from exogenous insulin replacement therapy toward pancreatic β-cell replacement, to restore physiologically responsive insulin secretion to variations in blood glucose levels. β-cell replacement strategies include human whole pancreas transplantation, islet transplantation with cell encapsulation and bioengineered pancreas. Interventional radiology and imaging modalities including positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, ultrasonography, and molecular imaging are imperative to enable successful β-cell replacement. Herein, the role of radiological modalities in the treatment of T1DM and its prospective use for noninvasive post-transplantation graft monitoring is discussed., (Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The main goal of treatment for type 1 diabetes is to control glycaemia with insulin therapy to reduce disease complications. For some patients, technological approaches to insulin delivery are inadequate, and allogeneic islet transplantation is a safe alternative for those patients who have had severe hypoglycaemia complicated by impaired hypoglycaemia awareness or glycaemic lability, or who already receive immunosuppressive drugs for a kidney transplant. Since 2000, intrahepatic islet transplantation has proven efficacious in alleviating the burden of labile diabetes and preventing complications related to diabetes, whether or not a previous kidney transplant is present. Age, body-mass index, renal status, and cardiopulmonary status affect the choice between pancreas or islet transplantation. Access to transplantation is limited by the number of deceased donors and the necessity of immunosuppression. Future approaches might include alternative sources of islets (eg, xenogeneic tissue or human stem cells), extrahepatic sites of implantation (eg, omental, subcutaneous, or intramuscular), and induction of immune tolerance or encapsulation of islets., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Most life-threatening diabetes-related complications involve the kidneys, eyes, cardiovascular system, and autonomic nervous system. Clinical islet transplantation (CITx) may be a therapeutic option for some patients. In this study, we analyzed the progression of diabetic complications after CITx and in patients waiting for islet transplantation., Methods: From 2008 to 2015, 67 patients were listed for pancreatic or islet transplantation. We compared beta scores, islet scores, and secondary complications between patients who underwent islet allotransplantation (CITx group, n = 6) and the patients awaiting islet transplantation (wait group, n = 19) at baseline and during the 1-year follow-up., Results: In the CITx group, good islet function was observed in 80% of patients 1 month post-transplantation and 40% of patients 1 year post-transplantation; however, no patient achieved insulin independence. One patient who underwent simultaneous islet-kidney transplantation died on day 8 because of severe bleeding in the retroperitoneal space. In 1 case, islet primary nonfunction was observed. Mean islet score in the CITx group 1 year post-transplantation was significantly higher than the pretransplant score and wait group scores at enrollment and 1 year later (P < .01). Increased albuminuria was observed in 3 of 11 (27%) patients in the wait group and 0 patients in the CITx group (P = .08). One patient (9%) in the wait group developed chronic renal failure requiring hemodialysis. Ophthalmologic procedures were required by 47% of patients in the wait group and 0 patients in the CITx group in the first year after transplantation (P < .01)., Conclusion: Successful islet transplantation slows the progression of diabetic complications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Current therapy for Type 1 diabetes (T1D) is characterized by significant glucose variability (GV). Pancreas transplantation (PT) is performed in certain T1D patients with and without end-stage renal disease. To date, GV has been examined to a limited extent after PT., Methods: We investigated GV using continuous glucose monitoring (CGM) 3-6 weeks after PT., Results: Eleven patients had simultaneous kidney pancreas transplantation (SPK), nine pancreas after kidney (PAK), and six pancreas transplantation alone (PTA). Mean CGM showed no difference between SPK, 126.5 ± 13.9, PAK 119.9 ± 12.8, and PTA 131.1 ± 29 mg/dL (P value .6). Percentage of time in range (TIR, 70-180 mg/dL) was 92% for SPK, 93.4% in PAK, and 88.5% in PTA with only 0.3%, 1.5%, and 0.3% of time <70 mg/dL. Percentage >180 mg/dL was 7.9% for SPK, 4.9% PAK, and 11% in PTA. Other measures of GV were similar in the three cohorts. In six patients, CGM was performed before and after PT and improved significantly. GV was also better compared with a matched cohort of T1D patients., Conclusions: All 3 types of PT resulted in excellent glucose control 3-6 weeks post-procedure. CGM outcomes represent an important objective outcome after PT., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Simultaneous pancreas-kidney transplant is the ultimate therapy for patients who have uncontrolled and complicated type 1 diabetes mellitus with end-stage renal disease. The combined pancreas transplant provides a euglycemic milieu for the kidney and protects it from recurrence of diabetic complications. Our patient, a 41-year-old woman with end-stage diabetic nephropathy and history of multiple abdominal surgeries (ovarian cyst fenestration, adnexal extirpation, abdominal wall reconstruction), including urinary diversion (Bricker loop, above double J stent), underwent simultaneous pancreas-kidney transplant. After reperfusion, the kidney had immediate function and creatinine levels dropped to normal levels during the early postoperative period (creatinine of 102 μmol/L, estimated glomerular filtration rate of 52 mL/min/1.73 m2) and remained stable during follow-up. Serum glucose levels dropped to within normal ranges postoperatively and remained so during follow-up. The postoperative course was complicated by hydronephrosis due to transient edema of the anastomosis of the ureter to the Bricker loop, after early incidental removal of the double J catheter. This was successfully treated with a temporary percutaneous nephrostomy. Multiple previous surgeries, including a Bricker deviation, may not be a definitive contraindication for simultaneous pancreas-kidney transplant. In selected cases, special considerations may lead to a successful procedure providing better quality of life and life expectancy, even for patients with multiple comorbidities.

Background: Diabetes mellitus (DM) is associated with increased post-operative complications in various surgeries. Little data exist regarding the impact of long-standing DM (>25 years) on outcomes in pancreas transplantation (PTX). The objectives of our study were to determine if long-standing pre-transplant DM (>25 years) was associated with inferior outcomes following PTX., Methods: Using a 13-year (April, 2000-May, 2012) retrospective analysis, we examined demographic and transplant factors, complications, and outcomes in patients without (Group A) and with (Group B) long-standing (>25 years) pre-PTX DM., Results: Mean follow-up was 4.2 years. Of 214 consecutive PTX performed, 137 (105 simultaneous PTX (SPK), 25 PTX after kidney (PAK), 7 PTX alone (PTA)) had pre-PTX duration of DM recorded, including 65 in Group A and 72 in Group B. There were no differences between cohorts with respect to demographics. There were no differences in post-PTX surgical/medical complications. There were no differences in outcomes between cohorts (ie, rejection, graft loss or death)., Conclusions: This large-scale analysis demonstrated that PTX can be performed in patients with long-standing DM with excellent patient and graft outcomes. Long-standing DM did not lead to an increased post-PTX infections or complications. Our study suggests that duration of DM should not impact PTX candidacy., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Painful chronic pancreatitis (CP) is the main indication for analgesic pancreatectomy with simultaneous islet autotransplantation to prevent postoperative diabetes mellitus (DM). However, advanced CP may lead to insulin secretion disorders and DM. There are doubts as to whether islet autotransplantation in such cases is an appropriate procedure. The aim of this study was to analyze the results of islet autotransplantation in patients with CP with already diagnosed with DM., Method: Between 2008 and 2015, at the Department of General and Transplantation Surgery, patients with CP and unsatisfying pain treatment with positive fasting C-peptide ( > 0.3 ng/mL) level were qualified for simultaneous pancreatectomy and islet autotransplantation. Eight procedures were performed. In 5 cases patients had DM diagnosed prior to the procedure (DM group n = 5). Three patients without DM diagnosed prior to surgery were the control group (n = 3)., Result: There were no cases of procedure-related deaths in either group. Pain relief without analgesics was reported by all patients. Good islet function was observed in 80% (4/5) of the DM group vs 100% (3/3) in the control group (P = ns). Brittle diabetes was diagnosed in 1 patient in the DM group as a result of islet primary non-function., Conclusion: Patients with CP-related severe pain and DM patients with positive C-peptides should be considered for pancreatectomy and islet autotransplantation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Diabetes is an autoimmunologic disease that may have a different background. The aim of our study was to show that type 1 diabetes is accompanied by changes in gene expression in peripheral blood mononuclear cells. We analyzed the genes characteristic of pancreatic islet cells and genes playing a big part in autoimmune diseases and cancer., Design: The study included 21 patients and was performed to examine the expression of 9 genes. The patients were divided into 3 research groups: people with type 1 diabetes, people with diabetes after pancreas transplant, and a control group of healthy patients. To assess the level of expression, RNA material was obtained from peripheral blood collected from individuals qualified for the study., Results: The results of the study showed many interesting changes in the expression level of the analyzed genes. It was demonstrated that CASR gene expression was significantly higher in transplant patients than in diabetic patients. Differences in the level of activity are also noted in genes that take part in autoimmune diseases., Proposal: Profiling gene expression in peripheral blood samples may be a useful and noninvasive diagnostic tool that allows early detection of changes leading to the onset or resumption of diabetes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Charcot neuropathic osteoarthropathy (CNO) is one of the most devastating complications of neuropathy in patients with diabetes. Establishing diagnosis of CNO is difficult, due to the lack of clear clinical and radiological diagnostic criteria. Diagnosis is even more difficult when there is atypical and bilateral clinical presentation. Since CNO may lead to foot deformity, lower-extremity amputation and significant decrements in quality of life, it must be detected and treated without delay. Treatment focuses mainly on interruption of the inflammatory process and relief from pain using feet offloading devices. In more severe cases, surgical intervention may be needed. Additionally, the use of custom-made insoles and custom-made orthopaedic shoes is mandatory., Case Presentation: We report a case of a young diabetic patient who presented to our clinic with bilateral and atypical presentation of Charcot foot disease. Patient was treated successfully upon diagnosis with bilateral aircast offloading. Unfortunately, due to depression and non-compliance, the disease progressed to severe and permanent lesions later on., Conclusion: Despite the rareness of this disease, clinicians must include CNO into differential diagnosis of diabetic foot oedema, inflammation and deformity.

Background: Patients with diabetes and kidney disease are at risk of diabetes-related foot ulcers (DFU). Whether this risk is modified post simultaneous pancreas-kidney (SPK) or kidney only (KO) transplant is unknown., Methods: We evaluated the incidence of new onset DFU post SPK and KO transplant in 235 patients with diabetic kidney disease and diabetic neuropathy. In total 90 (51% male) SPK patients and 145 KO (66% male, 26% Type 1 DM) were evaluated in a single centre retrospective study. Median (range) follow up was 6 (3 to 13) years for both cohorts., Results: We observed that 16 (17%) of SPK and 22 (15%) KO patients respectively developed a DFU during follow up. In both cohorts a history of peripheral arterial disease [37.5% vs. 4%] and pre-transplant history of DFU were associated with post transplant DFU (p ≪ 0.05). In KO cohort, patients who developed a DFU were more likely to have T1DM than T2DM (29% vs. 10%), p ≪ 0.05. There was no impact of DFU on SPK transplant failure. In contrast patients with DFU post KO transplant had more than five fold increased hazard ratio (HR) of transplant failure as compared to those without DFU independent of other risk factors [HR 5.19 95% CI (2.05 to 13.18) p = 0.001]., Conclusion: Nearly 1 in 7 patients develop a new onset DFU post KO or SPK transplantation and DFU also significantly increases risk of failure of the transplanted kidney. Our results highlight the need for greater awareness of regular foot examination, DFU prevention and risk evaluation in post-transplant patients., Research in Context: Evidence before this study Patients with diabetes and kidney disease are at enhanced risk of diabetic foot ulcers (DFU). Whether this risk is modified post successful kidney only (KO) or simultaneous pancreas and kidney (SPK) transplantation is unknown. Small case series and studies with short term follow up report varied rates of incidence and are from historical cohorts before the use of modern anti-transplant medications and treatments. Short term studies also suggest that post SPK the resultant normoglycaemia may reverse some features and risk markers of DFU. There are no long term studies on the incidence and impact of diabetic foot ulcers in patients with diabetic kidney disease post SPK or KO transplantation. Added value of this study We report the long term follow up results on DFU incidence, clinical features and related impact on transplant viability in 235 patients with diabetic kidney disease and neuropathy post successful SPK and KO transplant at a single centre. We observed that nearly 1 in 7 patients developed a DFU during follow up and that in patients who received KO transplant onset of DFU was associated with more than 5 fold increase of transplant failure. Implications of all the available evidence Our results highlight the need for greater awareness of regular foot examination, DFU prevention and risk evaluation in post-transplant patients. Despite normoglycaemia post SPK there is a residual burden and risk of DFU. Our work establishes a clinical rationale for further research to explore putative mechanisms that could explain the association between DFU and renal transplant dysfunction., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Type 1 diabetes impacts 1.3 million people in the USA with a total direct lifetime medical cost of $133.7 billion. Management requires a mix of daily exogenous insulin administration and frequent glucose monitoring. Decision-making by the individual can be burdensome., Recent Findings: Beta-cell replacement, which involves devices protecting cells from autoimmunity and allo-rejection, aims at restoring physiological glucose regulation and improving clinical outcomes in patients. Given the significant burden of T1D in the healthcare systems, cost-effectiveness analyses can drive innovation and policymaking in the area. This review presents the health economics analyses performed for donor-derived islet transplantation and the possible outcomes of stem cell-derived beta cells. Long-term cost-effectiveness of islet transplantation depends on the engraftment of these transplants, and the expenses and thresholds assumed by healthcare systems in different countries. Early health technology assessment analyses for stem cell-derived beta-cell replacement suggest manufacturing optimization is necessary to reduce upfront costs.

Introduction: The number of pancreas transplants (PTX) in patients with Type 2 diabetes (T2DM) has increased in response to excellent outcomes in appropriately selected patients. Not all pancreas transplant centers share an enthusiasm for performing PTX for T2DM out of concern for increased complication rates. This study aims to clarify the characteristics of T2DM recipients with successful outcomes to clarify which candidates are more suitable for PTX as means of maximizing access to this highly effective therapy for Type 2 patients., Methods & Results: At MedStar Georgetown Transplant Institute, 50 patients underwent pancreas transplant between 2013 and 2016. Based on patient characteristics, 38 (78%) were categorized as T1DM, and 11 (22%) were considered T2DM. One case was excluded due to early graft loss. The estimated age of diabetes onset was significantly different between T1DM and T2DM cohorts (13 years vs. 29 years, P < .001). T2DM patients had significantly higher preoperative C-peptide levels (4.11 vs. 0.05, P < .001). Preoperative HbA1c, preoperative Body Mass Index (BMI), number of diabetic complications, and hemodialysis status were similar between both groups. At 2-year follow-up, there was no statistical difference in glycemic control between the two groups (T1DM vs. T2DM). Infectious complications and readmission rates were similar. Other trends that did not meet statistical significance included T1DM group with a slightly higher mortality and re-intervention rate. The T2DM group demonstrated higher BMI, higher rejection rates, and higher short-term postoperative insulin requirements. Graft survival was 95% and 82% for T1 and T2DM at 2 years post-transplant, respectively., Conclusion: Successful PTX in T1DM and T2DM recipient groups resulted in comparable glycemic control at 2-year post-transplant follow-up. T2DM group had a trend toward higher BMI as well as higher rates of rejection, temporary insulin requirement and graft failure, although none of these trends reached statistical significance. These results suggest that strict classification of T1 and T2DM by itself may not be relevant to achieving excellent outcomes in pancreas transplantation and, therefore, patient selection for PTX should not be based primarily on this classification., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims/hypothesis: The study aimed to assess the impact on neuropathy of simultaneous pancreas and kidney transplantation (SPK) in individuals with type 1 diabetes., Methods: This longitudinal observational study examined neuropathic symptoms, deficits, quantitative sensory testing, neurophysiology, corneal confocal microscopy and skin biopsy results in 32 healthy (non-diabetic) control participants, 29 individuals with type 1 diabetes and severe diabetic peripheral neuropathy [DPN] and 36 individuals with type 1 diabetes after SPK., Results: Following SPK, HbA 1c , eGFR, triacylglycerols and HDL improved significantly (all p < 0.05). Compared with the DPN group, which remained unchanged over the 36 month study period, corneal confocal microscopy assessments improved over 36 months following SPK, with increasing corneal nerve fibre density of 5/mm 2 (95% CI 1.8, 8.2; p = 0.003) and corneal nerve fibre length of 3.2 mm/mm 2 (95% CI 0.9, 5.5; p = 0.006). The Neuropathy Symptom Profile and peroneal nerve conduction velocity also improved significantly by 36 months compared with DPN (2.5; 95% CI 0.7, 4.3; p = 0.008 and 4.7 m/s; 95% CI 2.2, 7.4; p = 0.0004, respectively), but with a temporal delay compared with the corneal confocal microscopy assessments. Intraepidermal nerve fibre density did not change following SPK; however, mean dendritic length improved significantly at 12 (p = 0.020) and 36 (p = 0.019) months. In contrast, there were no changes in the Neuropathy Disability Score, quantitative sensory testing or cardiac autonomic function assessments. Except for a small decrease in corneal nerve fibre density in the healthy control group, there were no changes in any other neuropathy measure in the healthy control or DPN groups over 36 months., Conclusions/interpretation: SPK is associated with early and maintained small nerve fibre regeneration in the cornea and skin, followed by an improvement in neuropathic symptoms and peroneal nerve conduction velocity.

Pancreas transplantation is currently the most effective and curative treatment for complicated type 1 diabetes mellitus, providing durable and physiological insulin-independent euglycemia, preventing worsening or ameliorating of diabetic complications, and improving quality of life. Currently, more than 31 000 pancreas transplantation procedures have been performed, mainly in the United States. Pancreas transplantation is still an uncommon procedure in Asia, mainly performed in Korea, Taiwan, and Japan. The first pancreas (simultaneous pancreas and kidney transplantation) transplantation was successfully initiated at Taipei Veterans General Hospital on September 19, 2003, and we are the first team to be qualified to perform human pancreas procurement and transplantation by Taiwan Department of Health on August 31, 2007. The technique success rate in our pancreas transplantation is 97%, with 1-year pancreas graft survival rate of 95.8%, 5-year pancreas graft survival rate of 89.9%, and 10-year pancreas graft survival rate of 65.9%.

Aims/hypothesis: Autoimmune attack against the insulin-producing beta cells in the pancreatic islets results in type 1 diabetes. However, despite considerable research, details of the type 1 diabetes immunopathology in situ are not fully understood mainly because of difficult access to the pancreatic islets in vivo., Methods: Here, we used direct non-invasive confocal imaging of islets transplanted in the anterior chamber of the eye (ACE) to investigate the anti-islet autoimmunity in NOD mice before, during and after diabetes onset. ACE-transplanted islets allowed longitudinal studies of the autoimmune attack against islets and revealed the infiltration kinetics and in situ motility dynamics of fluorescence-labelled autoreactive T cells during diabetes development. Ex vivo immunostaining was also used to compare immune cell infiltrations into islet grafts in the eye and kidney as well as in pancreatic islets of the same diabetic NOD mice., Results: We found similar immune infiltration in native pancreatic and ACE-transplanted islets, which established the ACE-transplanted islets as reliable reporters of the autoimmune response. Longitudinal studies in ACE-transplanted islets identified in vivo hallmarks of islet inflammation that concurred with early immune infiltration of the islets and preceded their collapse and hyperglycaemia onset. A model incorporating data on ACE-transplanted islet degranulation and swelling allowed early prediction of the autoimmune attack in the pancreas and prompted treatments to intercept type 1 diabetes., Conclusions/interpretation: The current findings highlight the value of ACE-transplanted islets in studying early type 1 diabetes pathogenesis in vivo and underscore the need for timely intervention to halt disease progression.

The limited availability of human islets has led to the examination of porcine islets as a source of clinically suitable tissue for transplantation in patients with diabetes mellitus. Islets from porcine donors are commonly used in both in vitro and in vivo experiments studying diabetes mellitus. However, there are significant differences in quality and quantity of islet yield depending on donor pig age, as well as substantial differences in the costs of pancreas procurement in adult versus neonatal and juvenile pigs. In this study, we compared the total cost per islet of juvenile pig pancreata with that of neonatal and adult pigs. Although adult porcine pancreata yield, on average, more than five times the amount of islets than do juvenile and neonatal pancreata, we found that the high price of adult pigs led to the cost per islet being more than twice that of juvenile and neonatal islets (US $0.09 vs $0.04 and $0.02, respectively). In addition, neonatal and juvenile islets are advantageous in their scalability and retention of viability after culture. Our findings indicate that isolating neonatal and juvenile porcine islets is more cost-effective and scalable than isolating adult porcine islets.

Pancreas transplant achieves consistent long-term euglycemia in type 1 diabetes. Allograft thrombosis (AT) causes the majority of early graft failure. We compared outcomes of four anticoagulation regimens administered to 95 simultaneous kidney-pancreas or isolated pancreas transplanted between 1/1/2015 and 11/20/2018. Early postoperative anticoagulation regimens included the following: none, subcutaneous heparin/aspirin, with or without dextran, and heparin infusion. The regimens were empirically selected based on each surgeon's assessment of hemostasis of the operative field and personal preference. A sonographic-based global scoring system of AT is presented. The 47-month recipients and graft survival were 95% and 86%, respectively. Recipients with or without AT had similar survival. Five and four grafts were lost due to death and AT, respectively. Outcomes of prophylaxis regimens correlated with intensity of anticoagulation. Compared with no anticoagulation, an increase in hemorrhagic complications occurred exclusively with iv heparin. The higher arterial AT score found in regimens lacking antiplatelet therapy highlights the importance of early antiaggregants therapy. Abnormal fibrinolysis was associated with an increase in AT score. Platelet dysfunction, warm ischemia time, and enteric drainage were predictive of AT and, along with other known risk factors, were incorporated into an algorithm that matches intensity of early postoperative anticoagulation to the thrombotic risk., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Type 1 diabetes is characterised by insulin deficiency caused by autoimmune destruction of the pancreatic beta cells. The treatment of type 1 diabetes is exogenous insulin in the form of multiple daily injections or continuous subcutaneous insulin infusion. Advances in diabetes technology have been exponential in the past few decades, culminating in studies to develop an automated artificial pancreas, also known as the closed-loop system. This has recently led to a commercially available, hybrid artificial pancreas in the USA and Europe. This review article aims to provide an overview of the rationale for an artificial pancreas system and an update of the current state of artificial pancreas development. We explore the different types of artificial pancreas systems being studied, including the use of adjunctive therapy, and the use of these systems in different groups of users. In addition, we discuss the potential psychosocial impact and the challenges and limitations of implementing artificial pancreas use into clinical practice.

Aim: Islet autotransplantation (IAT) is considered a 'non-immune' model of islet transplant, with no risk for autoimmune-mediated beta cell loss, but we have previously observed de novo type 1 diabetes in one total pancreatectomy with islet autotransplantation (TPIAT) recipient. We aimed to investigate the clinical significance of glutamic acid decarboxylase antibodies (GADA), as a sensitive marker for autoimmune diabetes mellitus (DM), in patients with chronic pancreatitis undergoing TPIAT., Methods: We identified 9 patients undergoing TPIAT with elevated GADA pre-TPIAT (8 non-diabetic and 1 with C-peptide positive DM), otherwise demographically similar to GADA negative TPIAT recipients (n=341). Metabolic and clinical measures related to islet cell function were recorded both before and after TPIAT., Results: None of the 9 TPIAT patients achieved insulin independence after surgery, vs. 33% of GADA negative patients (n=318 with 1-yr follow-up). The two patients with the highest titters of GADA (>250 IU/mL) both experienced islet graft failure, despite normoglycaemia pre-TPIAT and high islet mass transplanted (5276 and 9378 IEQ per kg), with elevated HbA1c levels post-TPIAT (8.3%, 9.6%). The remaining 7 seven were insulin dependent with partial graft function and HbA1c levels <7%., Conclusion: Insulin dependence was more frequent in 9 patients with elevated GADA prior to TPIAT than in GADA negative TPIAT recipients, with graft failure in 2 cases. We speculate that beta-cell autoimmunity may occur in a small subset of TPIAT recipients and that beta cell antibody testing prior to TPIAT may be warranted to identify individuals at higher risk for insulin dependence., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: Continuous intravenous (IV) insulin infusion therapy minimizes blood glucose (BG) fluctuations and prevents metabolic deterioration in pediatric patients with type 1 diabetes (T1D) during intercurrent illness and surgery. However, data on the adequate fluid and insulin substitution in this situation is rare. We evaluated the effectiveness and safety of IV insulin therapy according to our local protocol., Methods: Retrospective study of 124 cases of hospitalization with IV insulin therapy because of intercurrent illness (n = 78) or minor surgery (n = 46) in 62 patients with T1D (mean age: 9.6 ± 5.4 years). The patients received a glucose-electrolyte infusion and short-acting insulin (normal insulin). Infusion rate was adapted according to the BG measured hourly. Glycemic control was analyzed in subgroups subdivided by age, glycated hemoglobin (HbA1c) and reason for hospitalization., Results: Mean infusion time was 22 hours (range 1.5-147 hours). In 65% of the infusion time, patients' BG was within the target range (4-8 mmol/L). Critical events (BG <3 or > 15 mmol/L) were found in 6% of the infusion time. Comparison of glycemic control in subgroups for HbA1c and the reason for hospitalization revealed no significant differences. However, patients aged <12 years exhibited significant more critical events, primarily hypoglycemia compared to adolescents (hypoglycemia/case 2.4 ± 2.7 vs 0.9 ± 2.0; P < 0.001)., Conclusions: Our protocol for IV insulin therapy proved to be appropriate for adequate glycemic control in pediatric patients with T1D during intercurrent illness and surgery. However, the regime seems to be more suitable in adolescents. We adapted our protocol in younger patients with reduction of the insulin dose., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report., (Copyright © 2018. Published by Elsevier Masson SAS.)

Islet cell transplantation is curative therapy for patients with complicated autoimmune type 1 diabetes (T1D). We report the diagnostic potential of circulating transplant islet-specific exosomes to noninvasively distinguish pancreatic β cell injury secondary to recurrent autoimmunity vs immunologic rejection. A T1D patient with hypoglycemic unawareness underwent islet transplantation and maintained normoglycemia until posttransplant day 1098 before requiring exogenous insulin. Plasma analysis showed decreased donor islet exosome quantities on day 1001, before hyperglycemia onset. This drop in islet exosome quantity signified islet injury, but did not distinguish injury type. However, analysis of purified transplant islet exosome cargoes showed decrease in insulin-containing exosomes, but not glucagon-containing exosomes, indicating selective destruction of transplanted β cells secondary to recurrent T1D autoimmunity. Furthermore, donor islet exosome cargo analysis showed time-specific increase in islet autoantigen, glutamic acid decarboxylase 65 (GAD65), implicated in T1D autoimmunity. Time-matched analysis of plasma transplant islet exosomes in 3 control subjects undergoing islet cell transplantation failed to show changes in islet exosome quantities or intraexosomal cargo expression of insulin, glucagon, and GAD65. This is the first report of noninvasive diagnosis of recurrent autoimmunity after islet cell transplantation, suggesting that transplant tissue exosome platform may serve as a biomarker in islet transplant diagnostics., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: The aim of this study is to evaluate how treatment with total contact cast (TCC) affects the balance of proteases in diabetic foot ulcers (DFUs) as they heal., Materials and Methods: This was a prospective observational study of 22 eligible patients with neuropathic plantar DFUs in a hospital-based wound care center. All patients treated with TCC had adequate arterial circulation (ankle-brachial index > 0.75), no sign of infection, and all DFUs were grade 1A according to the University of Texas Diabetic Wound Classification System. Patients had weekly follow-up visits for wound evaluation and reapplication of the TCC. Wound tissues were obtained at baseline (week 0 prior to initial treatment), week 3, week 6, and week 12. Tissue homogenates were analyzed for matrix metalloprotease (MMP) 2, MMP-9, tissue inhibitor matrix metalloproteinase (TIMP) 1, and TIMP-2. Wound measurements were obtained at weekly follow-up visits, and healing rates were calculated by photodigital planimetry., Results: Treatment with TCC for 3 weeks resulted in a 20% decrease in MMP-2 (P = .031) and 44% decrease in MMP-9 (P = .018). By week 6, MMP-2 and MMP-9 levels were reduced by 37% and 55%, respectively. Tissue inhibitor matrix metalloproteinase 1 increased by 42% (P = .033) and TIMP-2 by 44% (P = .04) after 6 weeks of therapy with TCC., Conclusions: This significant and rapid drop of both MMP-2 and MMP-9 strongly suggests a decline of the inflammatory phase and initiation of the proliferation phase.