The place of pancreas transplantation in therapy]

Insulin dependent diabetes mellitus is one of the most ravaging diseases of the civilised world mainly because of its secondary complications. Even the most careful exogenous insulin administration can neither maintain an entirely physiological glucose metabolism nor prevent the development of the late complications. Today pancreatic transplantation is the only therapy leading to total normalisation of glucose and lipid metabolism in type I diabetic patients. Beside the improvement of the life quality resulted by the independence of the insulin administration and of the dietary restrictions, secondary complications as nephropathy, retinopathy and neuropathy are positively influenced. Best results can be obtained with the simultaneous procedure, grafting kidney and pancreas from the same donor. In this case the grafted pancreas can also increase the patient survival rate and the kidney graft function rate comparing with the results of the kidney transplantation alone. In conclusion simultaneous pancreatic-kidney transplantation is clearly indicated for the treatment of type I diabetic patients with end-stage kidney disease.     

The first case of single pancreas transplantation in Hungary

Simultaneous pancreas kidney (SPK) transplantation is the only routinely used therapeutic option which can provide insulin independence, euglycemia and good renal replacement for type I diabetes mellitus patients with end stage renal disease. Several patients have some complications of diabetes without renal failure. For these patients pancreas transplantation alone is a therapeutic option. The first pancreas transplantation alone was performed 6 years after the launch of our pancreas transplant program. The patient was a 40-years-old man. Enteric drainage was used with portal venous drainage. Anti IL-2. R antibody, daclizumab was given as prolonged induction therapy. In spite of the technical and immunological difficulties there were neither technical failures nor acute rejection. 3 years after the transplantation the patient has a good quality of life without insulin therapy with excellent renal function. Conclusion: PTA transplant is a routinely used therapeutic option with good survival rate and good quality of life for type I diabetes mellitus patients without end stage renal disease.     

Allogeneic whole pancreas transplantation in insulin-dependent diabetes mellitus

A clinical whole organ pancreas transplantation program for patients with insulin-dependent diabetes mellitus complicated by end-stage renal disease was initiated at Henry Ford Hospital in 1987. Five patients have received pancreatic allografts after a previous kidney transplant (phase 1), and six patients had simultaneous pancreas-kidney transplants (phase 2). Ten patients had functioning pancreatic grafts after surgery, and all of them had normal carbohydrate tolerance with appropriate plasma free insulin responses to an oral glucose tolerance test three months after transplantation. As long as 28 months postsurgery six patients remained free of insulin requirements; however, one patient rejected the pancreatic allograft, and three patients died because of cytomegalovirus pneumonia. Two of the latter patients had functioning pancreatic allografts at the time of their demise. These results compare favorably with those of the International Pancreas Transplant Registry which reflects the world experience. Pancreas transplantation is a unique experimental treatment with the potential of restoring euglycemia and improving the prognosis of insulin-dependent diabetic patients.     

Pancreatic islet cell transplantation: update and new developments.

Pancreatic islet cell transplantation is a treatment alternative for patients with type 1 diabetes who experience hypoglycemic unawareness despite maximal care. The good results obtained by the group from Edmonton and other centers, with 80% insulin independence at 1 year posttransplant, are not sustainable over time, with 5-year insulin independence achieved in only 10% of patients. However, persistent graft function, even without insulin independence, results in improved glucose control and avoidance of hypoglycemic events. Changes in organ preservation, islet processing technique, and immunosuppression regimens can result in improvement of results in the future. Islet autotransplantation is an option for patients who undergo total pancreatectomy for chronic pancreatitis with debilitating pain, in which reinfusion of the islets from the resected pancreas can result in avoidance of postsurgical diabetes or enhanced glucose control.     

Advances in pancreas transplantation

The potential to reverse diabetes has to be balanced against the morbidity of long-term immunosuppression associated with transplantation. For a patient with renal failure, the treatment of choice is often a simultaneous transplant of the pancreas and kidney or pancreas after kidney. For a patient with glycaemic instability, choices between a solid organ or islet transplant have to be weighed against benefits and risks of remaining on insulin. Results of simultaneous transplant of the pancreas and kidney transplantation are comparable to other solid-organ transplants, and there is evidence of improved quality of life and life expectancy. There is some evidence of benefit with respect to the progression of secondary diabetic complications in patients with functioning transplants for several years.     

Immunology in medical practice. XXX. Organ transplantation: indications and results

During the past 30 years, solid organ transplantation has developed into a routine medical procedure. Currently, one-year transplant survival rates for kidney, heart, liver and pancreas are between 80 and 90%; for most organs, the long-term results are fair with 5-year survival rates of 60%. Inclusion criteria for potential recipients have become less stringent. These days, potential recipients are rarely excluded on the basis of their calendar age alone. The development of more and stronger immunosuppressive drugs has facilitated transplantation across wider immunological differences between donor and recipient with good results. While the number of patients on the waiting lists for organ transplantation increased, the number of organs offered for donation decreased. This has resulted in waiting times of several years for most organ transplantations. While the short-term outcome has improved significantly over the past decades, the long-term outcome has not. Most renal transplants, for example, are lost due to chronic rejection. The challenge for the future will be to improve the long-term outcome of organ transplantation and to decrease the morbidity associated with chronic immunosuppressive therapy.     

Simultaneous pancreas-kidney transplantation--an alternative option for the treatment of type 1 diabetes mellitus with renal failure

INTRODUCTION: Simultaneous pancreas kidney (SPK) transplantation is the only routinely used therapeutic option which can provide insulin independence, euglycemia and good renal replacement. AIMS: Analysis of the five years' experience of the first Hungarian SPK transplants. MATERIAL: From 29 October 1998. through 31 December 2003. 32 SPK transplants were performed from 53 type 1 diabetes mellitus patients with ESRD on the waiting list. Enteric drainage was performed in all transplanted patients in 20 combined with systemic venous drainage, whereas in 12 patients portal venous drainage was used. In 18 patients only maintenance immunosuppression was administered without ATG induction therapy. Anti IL-2R antibody, daclizumab was given as induction therapy in 14 patients. RESULTS: 24 patients out of 32 transplanted are insulin independent with excellent renal function. 2 patients were lost in the perioperative period due to septic complication. 2 patients died 5 months after transplantation. 1 patient became insulin dependent in 7 month following the SPK transplant, while preserving a marginal renal function. One patient became insulin dependent 2 years after the SPK transplant and was returned to chronic hemodialysis treatment one more year later. 2 patients are insulin independent but lost his renal graft due to therapy resistant rejection. CONCLUSION: SPK transplant is a routinely used therapeutic option with good survival rate and good quality of life for type I diabetes mellitus patients with ESRD.     

Pancreatic islet and stem cell transplantation: new strategies in cell therapy of diabetes mellitus

Long-term studies strongly suggest that tight control of blood glucose can prevent the development and retard the progression of chronic complications of type 1 diabetes mellitus. In contrast to conventional insulin treatment, replacement of a patient's islets of Langerhans either by pancreas organ transplantation of by isolated islet transplantation is the only treatment to achieve a constant normoglycemic state and avoiding hypoglycemic episodes, a typical adverse event of multiple daily insulin injections. However, the expense of this benefit is still the need for immunosuppressive treatment of the recipient with all its potential risks. Islet cell transplantation offers the advantage of being performed as a minimally invasive procedure, in which islets can be perfused percutaneously into the liver via the portal vein. As of June 2003, 705 pancreatic islet transplants worldwide have been reported to the International Islet Transplant Registry (ITR) at our Third Medical Department, University of Giessen/Germany. Data analysis shows at 1 year after adult islet transplantation a patient survival rate of 97%, a functioning islet graft in 54% of the cases, whereas insulin independence was meanwhile achieved in 20% of the cases. However, using a novel protocol established by the Edmonton Center/Canada, the insulin independence rates have improved significantly reaching meanwhile a 50-80% level. Finally, the concept of islet cell or stem cell transplantation is most attractive since it offers many perspectives: islet cell availability could become unlimited and islet or stem cells my be transplanted without life-long immunosuppressive treatment of the recipient, just to mention 2 of them.     

Diabetes following kidney transplantation. Report of 35 cases

Post-transplant diabetes mellitus (PTDM) is a frequent complication of renal transplantation. It has a prevalence rate ranging from 3 to 46%. We undertook a retrospective study of 175 nondiabetic renal transplant recipients to determine the prevalence rate, clinical characteristics, and risk factors of PTDM in kidney transplant recipients in our region. Thirty five patients (20%) developed PTDM, 50% were diagnosed by 3 months post transplantation. Eight patients (22.8%) were insulin recurrent. PTDM was independent of kidney source, family history of diabetes, age, sex, incidence of acute rejection, body weight gain, steroid or cyclosporine dose, use of beta-blockers and cytomegalovirus infection. Acturial 5 years survival was 79.4% in the diabetic compared to 80.5% in the control group. Patient survival was similar in the two groups. We conclude that PTDM is frequent in our patients. No significant risk factors of PTDM were identified in this study.     

Fructan Improves Survival and Function of Cryopreserved Rat Islets

Cryopreservation of pancreatic islets enables their long-term storage and subsequent transplantation; however, post-cryopreservation, islets viability, and functions are reduced to a significant extent. Islet is composed of five cells (α cell, β cell, δ cell, ε cell, and PP cell), and blood vessels that carry the nutrition. Freezing technology of the organization has not developed a good method. This paper is studied using a fructan which has been found to effectively freeze protect a material of the cell. Islet transplantation has been established as an effective means of treating patients with type 1 diabetes. In this study, we demonstrated the effectiveness of using a fructan on the cryopreserved islets by showing valid results for diabetes. Isolated rat islets were cryopreserved using phosphate-buffered saline (PBS) supplemented with different concentrations of fructan and/or dimethyl sulfoxide (DMSO) in FBS. The survival rates of the islets were estimated at different time intervals, and insulin secretion function was tested in vitro. Furthermore, the in vivo function was tested by syngeneic transplantation into streptozotocin-induced diabetic rats, and the grafts were analyzed histologically and immunohistochemically. Fructan significantly increased islet survival; 30% fructan led to survival rates of more than 90% on day 3, which was significantly higher than those of the DMSO groups (p < 0.05). For both fructan and DMSO, the survival showed dose dependence, with the highest rates observed for 30% fructan and 10% DMSO, respectively (p < 0.05). The fructan groups showed a significantly increased insulin secretion volume in comparison to the DMSO groups (p < 0.05). Furthermore, cell clusters of pancreatic islets were well maintained in the fructan group, whereas margin collapse and vacuolation were observed in the DMSO group. Three days after transplantation of pancreatic islets preserved with 30% fructan, the blood glucose levels of diabetic rats were restored to the normal range, and removal of transplanted pancreatic islets from the kidney led to a profound increase in blood glucose levels. Together, these results show that a fructan is effective at cryopreserving rat pancreatic islets for subsequent transplantation.     

Pancreatic transplantation.

In the last few years there has been considerable improvement in results with pancreatic transplantation. Several centers now report a 1-year graft survival rate of 50%-60%. Patients with well-functioning grafts become insulin independent and have normal or near normal fasting ans post-prandial glucose levels and normal glycosylated hemoglobin values. The glucose tolerance as measured by oral and intravenous glucose tolerance tests is normal in 50%-80% of the patients but subnormal in the others. One important reason for subnormal glucose tolerance is medication with cyclosporin and prednisolone. In most cases an improvement in neuropathy is found and retinopathy seems to be stabilized. Preliminary data indicate that the provision of a pancreatic graft prevents the occurrence of diabetic nephropathy in a simultaneously or previously transplanted kidney.     

Transplantation of the islets of Langerhans in patients with diabetes mellitus type 1

Since 1921 and until recently, insulin by injection has been the only treatment for patients with diabetes mellitus type 1. After pancreas transplantation, which became possible in 1977, the next logical step to cure patients with diabetes mellitus type 1 is the transplantation of the islets of Langerhans. In the last few years, the results of islet transplantation are markedly improved thanks to developments in the isolation technique and better immunosuppressive protocols. Ongoing problems in islet transplantation are allo-immunity, auto-immunity and the growing shortage of donor pancreases. Alternatives to pancreas donation, be it post-mortem or from a living donor, could be: sources for islets are xenotransplantation with the aid of pig islets and beta-cell neogenesis from embryonic stem cells or pancreatic duct cells.     

Treatment of reactive hypoglycemia with buformin.

The therapeutic effect of short-term buformin (l-butylbiguanide) treatment was investigated in 12 patients with reactive hypoglycemia. Eleven of them were classified as having idiopathic reactive hypoglycemia, nine obese and two nonobese. None of these patients had a degree of hyperglycemia during glucose tolerance tests which would indicate diabetes mellitus. In one patient reactive hypoglycemia was related to chemical diabetes. The diagnosis of reactive hypoglycemia was established on the basis of patient's hypoglycemic reaction and low blood glucose levels during 6-hour oral glucose tolerance tests. The patient's received 200 mg of buformin daily for 7 days and its therapeutic effectiveness was assessed by repeat testing. Buformin treatment resulted in significant increase of blood glucose values between 180 and 360 min after oral glucose challenge and in considerable improvement of hypoglycemia in nine obese patients with idiopathic reactive hypoglycemia and in the patient with chemical diabetes. Buformin also significantly reduced maximal insulin response and incremental insulin areas. In two nonobese patients hypoglycemic reaction was deteriorated after buformin therapy.     

Catabolic response and parenteral nutrition after simultaneous kidney-pancreas transplantation.

The aim of the study was to quantify the catabolism rate induced by simultaneous kidney-pancreas transplantation and to evaluate the impact of parenteral nutrition (PN) on recovery of graft function. Twenty-six diabetic uremic patients were studied. The average urea nitrogen production (UNP) was 5.2 +/- 1.7 g during the first 24 h after transplantation, while patients did not receive energy and nitrogen support. Energy (30 kcal.kg-1.day-1) and nitrogen (0.15 g.kg-1.day-1) intake started 24 h after surgery. In 14 patients, a mixed regimen was adopted (70% carbohydrates, 30% lipids), and 12 patients received only hypertonic glycidic solutions. The recovery of kidney function was immediate in all cases, with a prompt decrease in blood urea nitrogen and serum creatinine levels. C-peptide levels rose immediately after the revascularization of the pancreas graft and remained within the normal range during the PN period. No significant difference was observed in UNP or glucose tolerance between the mixed-regimen and glycidic groups. However, on average 6.6, and 1.5 hyperglycemic episodes occurred during the 1st wk of PN in the glycidic and mixed-regimen groups, respectively. The posttransplantation catabolism rate was similar to that induced by an elective major surgical procedure. Eucaloric PN did not affect the recovery of kidney and pancreas graft function. A mixed energy regimen seems to be most suitable for kidney-pancreas transplant patients because it prevents hyperglycemia which might be misdiagnosed as rejection.     

肾移植术后早期糖尿病的原因分析及护理观察

肾移植术后早期,患者处于应激状态和药物副作用的影响,要求密切监测的生命体征指标很多,其中肾移植术后对患者血糖的监护是必不可少的一项,特别是患者术前有糖尿病痛史.肾移植术后糖尿病(PTDM)是影响肾移植患者术后存活的重要并发症之一,其发病率达2.5％～20.0％.血糖维持在正常范围,是保证患者顺利恢复的重要内容之一.我们选取解放军第309医院器官移植中心泌尿二科于2009年1月至2011年5月共开展同种异体肾移植手术的286患者,回顾性分析并结合肾移植术后糖尿病的发病原因进行讨论,总结护理观察要点.     

提高糖尿病住院患者围手术期血糖控制达标率

运用品管圈方法,组建多学科协作小组,针对提高围手术期使用胰岛素泵治疗糖尿病患者血糖控制达标率进行改进,包括完善资料、修订流程、落实培训与考核等。改善后,胰岛素泵操作规范率由32.7%提升至96.0%,非内分泌科胰岛素泵资料完善率由30.2%提升至95.0%,胰岛素泵操作正确率由35.0%提升至83.0%,患者及家属糖尿病知识知晓率由35.0%提升至83.0%,护士对专科知识知晓率由51.8%提升至96.0%,围手术期血糖控制达标率由45.0% 提升至76.5%。品管圈活动开展可有效提高糖尿病住院患者围手术期血糖控制达标率,使全院围手术期糖尿病患者胰岛素泵治疗血糖护理标准同质化,提高了患者满意度。     

Incidence, timing and site of infections among pancreas transplant recipients

The incidence, timing and site of infections among the different categories of pancreas transplant recipients were investigated. Patients were divided into three groups: pancreas transplant alone (PTA), pancreas after kidney transplant (PAK), or simultaneous pancreas and kidney (SPK) transplants. Length of follow-up, time to death, pancreas graft survival, incidence, timing and site of bacterial infections were noted. Our study showed that at least 75% of pancreas transplant recipients experienced at least one infection (range from 77.8% in the PTA group to 86.7% in the PAK group). The SPK group presented the highest rate of infections with 35.1 infections per 1000/patient-days. Symptomatic urinary tract infections were the most common cause of infection in all patients. The incidence of infections was higher during the first month after transplantation, except for the SPK transplant group, where infections occurred over a longer time period.     

胰岛素泵与皮下注射胰岛素强化治疗初发2型糖尿病的疗效对比

目的:临床研究胰岛素泵与皮下注射胰岛素强化治疗初发2型糖尿病的疗效.方法:选取2016年7月~2018年7月在本院治疗的2型糖尿病患者91例为研究对象进行回顾性分析.将患者归类为胰岛素泵组(观察组):46例患者,采用胰岛素泵方案治疗;间断胰岛素皮下注射组(对照组):45例患者,采取间断胰岛素皮下注射方案治疗.分析组间相关指标变化意义.结果:①经过治疗后发现胰岛素泵组血糖及β细胞功能各项指标对比间断胰岛素皮下注射组具有明显优势,P<0.05.②经过治疗后发现胰岛素泵组血糖达标时间及低血糖情况对比间断胰岛素皮下注射组具有明显优势,P<0.05.结论:新诊断的2型糖尿病患者使用胰岛素泵强化治疗不仅有助于恢复胰岛β细胞功能,降低患者血糖,而且与间歇性胰岛素皮下注射相比,还可降低平均血糖顺应时间和低血糖.     

镉对大鼠胰脏的毒作用

目的探讨镉对内分泌和外分泌功能的影响。方法将96只SD大鼠分为4组,分别为对照组和50、100、200mg/LCdCl2染毒组,饮水染毒30、60、90d。测定不同染毒时间大鼠血糖、尿糖、血胰岛素、淀粉酶的改变及血液中金属含量的改变;测定尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG);并测定了胰脏组织中金属的含量以及胰脏金属硫蛋白基因、胰岛素基因和淀粉酶基因的表达情况。结果染毒组大鼠血糖水平在染毒90d的中、高剂量组有明显增加,差异有统计学意义(P<0.05),中剂量组血糖平均值为5.83mmol/L,高剂量组为6.46mmol/L;发现尿糖水平的增高先于尿NAG的增高。各剂量组大鼠血液和胰脏中镉的含量明显增加。在染毒90d中、高剂量组血锌含量降低。在染毒30d的中、高剂量组血液中胰岛素水平明显降低,而血淀粉酶改变不明显。在染毒90d的中、高剂量组胰脏组织中锌的含量明显增加。胰脏中金属硫蛋白基因表达均有不同程度的增加;胰岛素基因的表达除染毒60d中剂量组明显降低外,其他各组差异均无统计学意义(P>0.05)。而胰淀粉酶的基因表达在染毒60d和90d的中、高剂量组均明显增高。结论镉可以在胰脏组织蓄积,引起组织中必需元素锌水平的改变,导致基因和蛋白表达的改变,进一步引起胰脏内、外分泌功能的改变。