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Query: UMLS:C0011854 (type 1 diabetes)
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Although intensified insulin therapy regimens enable normalization of blood glucose levels and related metabolic parameters, these regimens are associated with an increased incidence of hypoglycemic episodes. Pancreas transplantation has achieved the goal of providing insulin independence with stable and continuous normoglycemia. But because of the associated morbidity and mortality and the need for life-long immunosuppression after transplant, it is difficult to justify pancreas transplantation in diabetic patients at a pre-uremic stage. Pancreas transplantation is therefore performed in conjugation with renal transplantation. The majority of renal transplant centers, however, have been reluctant to perform simultaneous kidney-pancreas transplantation in insulin-dependent uremic patients because of the additional risks associated with pancreas transplantation. More recently, refinements in surgical technique, introduction of new immunosuppressive agents, and better selection of transplant candidates have contributed to improved survival. Today, combined pancreas-kidney transplantation is an accepted treatment for carefully selected patients with insulin dependent diabetes and end-stage renal disease and in a small group of patients with uncontrolled severe metabolic problems. The effect of a euglycemic state after pancreas transplantation on the progression of micro- and macroangiopathy remains to be proved, although recently there is evidence to suggest that some end-organ lesions may be halted or even ameliorated. Further improvement in anti-rejection strategies may achieve better long-term graft survival and provide the incentive to perform pancreas transplantation at an earlier stage, before severe secondary complications of diabetes develop.
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PMID:Pancreas transplantation. 1039 43

In patients with type I diabetes mellitus, adequate blood glucose control prevents the development or aggravation of late complications. Apart from administration of insulin, transplantation of insulin-producing tissue is also a possibility. Transplantation of Langerhans islets which contain the insulin-producing beta cells is still in its initial phase. Transplantation of the entire pancreas received a boost in the mid-eighties when it became possible to drain the secretion of the exocrine part of the pancreas to the bladder using the duodenum. Other important steps forward were prevention and treatment of rejection and improvement of the preservation fluid. Because pancreas transplantation makes lifelong immunosuppression necessary, it is performed mainly in patients subjected to kidney transplantation because of terminal renal failure. The one-year survival of the patients after simultaneous pancreas and kidney transplantation increased to over 90%, that of the grafted pancreas to 82% and that of the grafted kidney to 86-90%. The one-year survival after transplantation of the pancreas alone increased to 62%. A successful pancreas transplantation leads to independence from insulin treatment and to normal glucose and HbA1c values. Pancreas transplantation also reduces diabetes nephropathy and progression of coronary sclerosis.
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PMID:[Gastrointestinal surgery and gastroenterology. II. Transplantation of pancreas]. 1052 12

Pancreas transplantation is being performed with increasing frequency and increasing technical success. The availability of new immunosuppressant agents has been associated with a reduction in the previously high rates of allograft rejection in recipients of simultaneous pancreas-kidney transplants. These lower rejection rates have, in turn, led to changes in surgical techniques and a resurgence of interest in isolated pancreas transplantation--either in nonuremic patients or, more commonly, in patients who have already received a prior kidney transplant. Pancreas transplantation has emerged as an important option for the management of patients with type I diabetes mellitus and diabetic nephropathy.
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PMID:Kidney-pancreas transplantation for diabetic nephropathy. 1074 60

Type 1 diabetes mellitus in nonobese diabetic (NOD) mice, a well-known model of human type 1 diabetes, has been considered to be caused by the destruction of insulin-producing beta cells in the islets of the pancreas by self-reactive T cells. Antigen-presenting cells like dendritic cells (DCs) and macrophages are expected to be involved in the processes from their role in generating regulatory or effector T cells. These immunohistochemical studies revealed that CD11c-positive DCs already appeared in the islets of NOD mice as early as 4 weeks old when lymphocytes were not yet infiltrated in the islet, and thus insulitis was not developed. DCs were first observed to locate around swollen parainsular vessels. From age 7 weeks onward to age 13 weeks, more DCs were present in parainsular areas where lymphocytes had also accumulated, and the number of DCs in the islets as well as lymphocytes increased. However, at the end stage of insulitis from age approximately 17 weeks onward, the number of DCs in the islets decreased. In contrast, accumulation of DCs in the para- and periislets was not observed in 7- and 17-week-old ICR female mice that do not develop type 1 diabetes. Double-staining studies using confocal laser scanning microscopy showed that the CD11c-positive DCs coexpress both major histocompatibility (MHC) class II and costimulatory molecules, CD80 and CD86. Electron-microscopy studies further demonstrated that cell bodies and processes of the DCs make close contact with lymphocytes. These results suggest that DCs infiltrated into the pancreatic islets are capable of stimulating T cells by the MHC class II-antigenic peptide complex, together with costimulatory molecules, which eventually lead to the beta-cell destruction in NOD mice.
Pancreas 2000 Apr
PMID:In situ characterization of dendritic cells occurring in the islets of nonobese diabetic mice during the development of insulitis. 1076 56

Pancreas transplantation can improve quality of life for patients with type 1 diabetes by eliminating hypoglycemic and hyperglycemic episodes, the need for insulin injections, frequent self-monitoring of blood glucose levels, and dietary restrictions. Increasing evidence suggests that it may slow the progression of long-term diabetic complications. On the other hand, patients risk the adverse effects of lifelong immunosuppression.
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PMID:Pancreas transplantation in type 1 diabetes: hope vs reality. 1078 Jan

Patients with alcohol-related chronic pancreatitis (ARCP) often have peripheral neuropathy, but no data on the occurrence of autonomic neuropathy (AN) are available for this condition. To assess the autonomic function and the significance of its abnormalities for the prognosis of ARCP, 18 patients with ARCP and associated diabetes mellitus (P-DM group), 10 with ARCP without evidence of diabetes mellitus (P group), 17 patients with insulin-dependent diabetes mellitus (IDDM group), and 18 healthy controls answered a structured questionnaire and underwent three standardized cardiovascular (CV) tests that yielded six different parameters for autonomic nerve function. Patients with at least one symptom plus two abnormal results on CV tests were regarded as having AN. ARCP patients were followed up for 48 months and mortality rates were recorded. The proportions of patients with AN were 66.6% in the P-DM group, 30.0% in the P group, and 29.4% in IDDM patients. Seven of 15 ARCP patients with AN died during follow-up, compared with one of 13 of those without AN (p < 0.037). In conclusion, AN is commonly found in ARCP patients and carries an ominous prognosis.
Pancreas 2000 May
PMID:Autonomic nervous function in alcohol-related chronic pancreatitis. 1082 89

Pancreas transplantation in patients with type 1 diabetes presents allogeneic beta-cell autoantigens to the immune system long after the initial beta-cell destruction that leads to diabetes has occurred. The aims of this study were to determine whether re-exposure to beta-cell autoantigen through transplantation affect the humoral autoimmune response and whether its modulation correlates with graft outcome. Antibodies to the major autoantigens GAD (GADA) and protein tyrosine phosphatase IA-2 (IA-2A) were measured before and after transplantation in patients with type 1 diabetes who received pancreas and kidney allografts. In the 110 cases studied, pancreas graft survival was not significantly associated with the presence of GADA or IA-2A before transplantation. In the 75 patients with sequential follow-up samples up to 11.2 years after transplantation, autoantibodies were persistently undetectable in 44 cases (59%) and remained at stable detectable levels in 13 cases (17%). Substantial changes in antibody levels were found in 18 cases (24%), of which 13 cases (17%) had declining levels and 5 cases (7%) had marked increments after transplantation. Rising GADA and IA-2A levels in these five patients were predominantly of the IgG1 subclass, with progressive spreading of epitope reactivity. Pancreas graft function was lost 0.7-2.3 years after rising autoantibody levels in four of these five patients, and a significantly lower pancreas graft survival was found in patients with major rises in either GADA or IA-2A levels (P < 0.0001 vs. the remainder) and in patients having persistently high levels of IA-2A (P = 0.002 vs. stable antibody-negative patients). Kidney graft survival was not associated with islet autoantibody status. In conclusion, a minority of patients receiving pancreas allografts under generalized immunosuppression show a stimulation of islet autoantibody reactivity characteristic of that found in preclinical type 1 diabetes, which is almost invariably followed by graft function failure and resumption of insulin therapy.
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PMID:Modulation of humoral islet autoimmunity by pancreas allotransplantation influences allograft outcome in patients with type 1 diabetes. 1086 38

Diabetes mellitus is the most devastating chronic disease of all time. This review discusses the current therapies for type 1 diabetes that are predicated on the restoration of insulin secretion by transplantation. Recent developments in vascularized pancreas transplantation have led to a dramatic increase in the number of these procedures performed worldwide, with over 10,000 cases reported currently to the International Pancreas Transplant Registry. Although the procedure contributes to a significant improvement in quality of life, compared with traditional insulin therapy, it still suffers from a number of shortcomings, including a persistently high postoperative morbidity rate and the requirement of long-term immunosuppression. Islet transplantation is therefore being pursued actively as an equally efficient means of restoring normoglycemia, but without the attendant morbidity of the whole-organ procedure, and hopefully with a significantly reduced need for immunosuppression.
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PMID:Pancreatic and islet transplantation. 1098 Oct 19

Diabetes mellitus, a common complication of chronic pancreatitis, can disturb the metabolism of zinc, copper, and selenium. We analyzed the effects of hyperglycemia, malabsorption, and dietary intake on these factors in 35 men with alcohol-induced chronic pancreatitis complicated by insulin-treated diabetes mellitus (CP-D), 12 men with chronic pancreatitis but no diabetes (nondiabetic CP), 25 men with type 1 diabetes mellitus (type 1 DM), and 20 control subjects. Diabetes due to chronic pancreatitis was associated with decreased plasma zinc and selenium concentrations and with increased urinary copper excretion. Of the chronic pancreatitis patients, 17% had low plasma zinc, and 41% of them had low plasma selenium. None of the type 1 diabetic patients had low plasma concentrations of zinc, but 12% of them had a low selenium concentration. Hyperglycemia, as assessed by fasting plasma glucose and by plasma HbAlc, was responsible for the increased zinc excretion and the decreased superoxide dismutase activity. The perturbations of the copper, selenium, and zinc metabolism were particularly pronounced in subjects with chronic pancreatitis plus diabetes mellitus. We have yet to determine whether the differences in trace-element status contribute to the clinical expression of the disease.
Pancreas 2001 Apr
PMID:Evidence that diabetes mellitus favors impaired metabolism of zinc, copper, and selenium in chronic pancreatitis. 1129 33

Pancreas transplantation is the only treatment for type I diabetes mellitus that can induce an insulin-independent normoglycemic state. Because of the need for immunosuppression, it has been most widely applied in uremic diabetic recipients of kidney transplant with a high success rate, particularly when done as a simultaneous (SPK) procedure (insulin independence > 80% at 1 year) with patient and kidney graft survival rates equivalent to or higher than in those who receive a kidney transplant alone. The results of solitary pancreas transplants (PAK in nephropathic diabetic recipients or PTA in nonuremic recipients) have also dramatically improved; 1-year graft survival rates are more than 80% and 70%, respectively, with the new immunosuppressants tacrolimus and mycophenolate mofetil. Multiple factors are important for successful application of pancreas transplantation, as summarized in this review.
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PMID:Pancreas transplantation for treatment of diabetes mellitus. 1134 3


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