[Use of vildagliptin from an internal disease specialists point of view]. / Vyuzití vildagliptinu z pohledu interního lékare.

Dipeptidyl peptidase 4 inhibitors (DPP 4) are used as an oral hypoglycaemic agent in Type- 2 diabetic patients. From a clinical point of view the most important advantages of this preparation are improved diabetes compensation, significant reduction of hypoglycaemia risk compared with sulfonylurea derivatives, neutral weight profile and good GIT tolerance. Vildagliptin is a molecule from the group of DPP 4 inhibitors which is recently used in internal outpatient care.

Similar early complication rate in simultaneous pancreas and kidney recipients on tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus immunosuppressive regimens.

INTRODUCTION: We compared the incidence of severe complications among 123 consecutive simultaneous pancreas and kidney (SPK) recipients randomized for treatment either with tacrolimus plus mycophenolate mofetil (MMF) or tacrolimus plus sirolimus during their initial postoperative hospital stay. METHODS: Patients with type 1 diabetes mellitus (T1DM) and renal failure with no age limit who underwent SPK were randomly assigned to tacrolimus/sirolimus or tacrolimus/MMF immunosuppressive protocols. We analyzed the rate of adverse events that led to death, graft loss, operative revision, or prolonged hospital stay. RESULTS: From 2002 to 2009, 62 recipients were included in the MMF and 61 in the Rapamycin (Rapa) groups. More than 2/3 of recipients suffered from at least 1 complication: 74% MMF and 77 % Rapa group (P > .05). No patient died in the MMF and 3 in the Rapa group (P = .11). Pancreas graftectomy was performed in 13% of the MMF group and in 5% of the Rapa group (P = .20). Ten of 62 recipients in the MMF and 13/61 in the Rapa group required operative treatment of wound infections (P = .49). There were no differences in the rates of gastrointestinal bleeding (11% and 8%), kidney lymphocele (6% and 5%), ileus (1.6% both), pancreatic leak (1.6% both), or ureteral leak (0 and 3%) between the groups. CONCLUSION: We did not observe a difference in the rate of severe postoperative complications between groups. With the use of extraperitoneal placement of the pancreatic graft, fluid collections and wound infections remain the most frequent albeit curable postoperative complications.

Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

Metabolic effect of sirolimus versus mycophenolate mofetil on pancreatic graft function in the early posttransplant period.

Metabolic effects of immunosuppressive agents are of great importance in pancreas or islet transplantation. The aim of our study was to compare effects of tacrolimus-based immunosuppression in conjunction with sirolimus (RAPA) versus mycophenolate mofetil (MMF) on glucose metabolism in type 1 diabetic recipients following a simultaneous pancreas and kidney transplantation (SPK). We examined 30 insulin-independent patients after SPK with venous systemic drainage of the pancreatic graft. All recipients had good kidney graft function. Fasting glycemia, insulin levels, glycosylated hemoglobin (HbA(lc)), standard intravenous glucose tolerance test (IVGTT), and trough RAPA levels were assessed in pancreas recipients before elective steroid withdrawal. Insulin sensitivity was evaluated using the homeostasis model assessment (HOMA-IR). The groups did not differ in age, BMI, posttransplant period, steroid daily dose, HbA(lc), and fasting glycemia. We did not find any significant difference in the IVGTT response. Area under the curve of insulin levels during IVGTT and HOMA-IR were significantly lower in the RAPA group. Trough levels of RAPA had no significant impact on any of the examined parameters. Glucose tolerance measured with the use of IVGTT was similar in patients treated with RAPA and MMF. However, recipients on sirolimus treatment had significantly lower insulinemia during the test and consequently more favorable indices of insulin action as assessed by HOMA-IR.

A prospective comparison of bladder versus enteric drainage in vascularized pancreas transplantation.

In previous years, the number of pancreas transplants has increased significantly. Debate continues over the optimum technique for exocrine drainage. Enteric drainage (ED) has recently been increasingly popular owing to the long-term complications of bladder drainage (BD). We prospectively evaluated 40 consecutive pancreas transplant recipients undergoing either bladder (n = 20) or enteric (n = 20) drainage. After simultaneous kidney-pancreas transplantation 1-year patient, kidney, and pancreas graft survival rates were 95%, 95%, 85% for the BD group, and 90%, 85%, 85%, for the ED group. Surgical complications were not significantly different between the two groups. The incidence of acute rejection, major infections and cytomegalovirus disease were also similar. The length of the initial hospital stay was likewise comparable. However, the BD group was characterized by a slight increase in the number of urologic complications, metabolic acidosis, and dehydration. Our results suggest excellent patient and graft survival irrespective of the drainage technique.

A prospective comparison of bladder versus enteric drainage in vascularized pancreas transplantation.

Although the number of pancreas transplants has increased significantly in previous years, debate continues concerning the optimum technique for exocrine pancreas drainage. Enteric drainage (ED) has recently been increasingly popular due to the long-term complications with bladder drainage (BD). We prospectively assigned 40 consecutive pancreas transplant recipients to either bladder (n = 20) or enteric (n = 20) drainage. Patient, kidney, and pancreas graft survival rates at 1 year after simultaneous kidney-pancreas transplantation were 95%, 95%, 85%, for BD group and 90%, 85%, 85% for ED group, respectively. Surgical complications were not significantly different between the two groups. The incidence of acute rejection, major infections, and CMV disease were similar between groups. The length of the initial hospital stay was likewise comparable. However, the BD group showed a slight increase in the number of urologic complications, metabolic acidosis, and dehydration. Based on the results of our study, patient and graft survivals were excellent irrespective of technique.

Modulating amylase and lipase secretion in the pancreatic graft by somatostatin administration: preliminary results of a prospective, randomized trial.

Pancreas transplantation is a routine method for the treatment of diabetes mellitus. One of the main challenges of a transplant with extraperitoneal placement of the pancreatic graft is impaired wound healing due to massive amylase and lipase secretion by the pancreatic graft, evoking edemtous fluid. From February 2002 through January 2003, we performed pancreatic transplant procedures in 21 patients who were prospectively and randomly assigned to two groups: 8 organ donors and the recipients were administered somatostatin by continuous infusion. Thirteen grafts were harvested and transplanted without somatostatin infusion. The two groups did not show significantly differences in mean donor or recipient ages, weights, of serum amylase and lipase content values or drain output until day 6. There was a significantly lower lipase in the drain output of transplant recipients given somatostatin (12.5 and 54.2 micromol/L, respectively; P <.05). Neither the post-pancreatic transplant wound healing nor the number of rejection episodes were affected by somatostatin administration.

[Vascular complications after pancreatic transplantation]. / Cévní komplikace po transplantaci pankreatu.

Transplantation of pancreas is presently the only way of treating diabetes of the 1st type, capable to secure a long-term normoglycemia. In spite of the fact that the surgical technique and tactics of the whole intervention has been standardized over the last years, surgical complications and more specifically vascular complications still pose a certain risk of the graft loss. The thrombosis of vessels of the transplanted pancreas occurred in our group in 4.1 per cent of cases. The other rare complications included a false aneurysm of the supplying artery and stenosis of the out-coming vein from the pancreatic graft. Both these complications were successfully treated by a radio-invasive approach. A refinement of the surgical technique and the introduction of new immunosuppressive drugs manifests favorably in decreasing occurrence of vascular complications after the transplantation of pancreas.

Spectral analysis of heart rate variation following simultaneous pancreas and kidney transplantation.

Only marginally improved results have been observed in standard autonomic function tests (AFT) in follow-up studies after simultaneous pancreas and kidney transplantation (SPK). We therefore used power spectral analysis (PSA) of heart rate variability (HRV) to assess the effect of SPK on autonomic neuropathy in patients with type I diabetes mellitus (DM I). We evaluated 82 patients with DM I who were insulin and dialysis free following SPK. Both pre- and posttransplant (at [mean +/- SD], 25 +/- 15 months post-SPK) examinations were performed in 29 patients. Posttransplant evolution was examined in another 60 patients with two serial examinations at 20 +/- 20 and 43 +/- 27 months after SPK. Comparisons included 32 age-matched healthy controls and 13 patients with kidney transplant alone (KTA) matched for age and duration of DM I at a comparable time point posttransplant. Short-term time (modified Ewing battery) and frequency domain (PSA of HRV: LF-low, HF-high frequency, and TP-total spectral power) analysis was performed with a telemetric, on-line, computer-aided system. Significantly worse results in all standard AFT and PSA indexes were obtained for SPK patients compared with controls at all time points. No significant improvement was seen in SPK patients in the posttransplant period and no differences were found compared with KTA patients. Thus the results of a power spectral analysis of HRV failed to show improvement following SPK. This examination adds little positive information to that obtained from standard autonomic function tests.

[Diagnostic value of determination of autoantibodies in gluten-sensitive enteropathy]. / Diagnostický prínos stanovení autoprotilátek u gluten-senzitivní enteropatie.

The study is focused on the immunopathological mechanisms of development of gluten-sensitive enteropathy (coeliac disease). It describes environmental factors and the role of autoantibodies and autoaggressive cells in the bowel inflammation. Attention is paid to the autoantibodies used in routine laboratory diagnosis of coeliac disease. The objective is a summary of rational diagnostic algorithms used in screening, diagnostics, treatment and dispensary care of patients with coeliac disease, especially with latent forms associated with other organ-specific immunopathological diseases. Exploration of anti-gliadin and anti-endomysial antibodies in diabetes mellitus type I were submitted. Furthermore, indications of these tests in the routine laboratory practice was analyzed.

[Treatment of diabetes with the insulin pump]. / Lécba diabetiku inzulinovou pumpou.

Diabetes control by subcutaneous insulin infusion (CSII) by an insulin pump becomes the therapeutic option, which most closely mimics the physiologic insulin secretion pattern. It may bring glycemia close to normal levels even in cases where the standard injection insulin therapy fails. After CSII installation the mean daily dose of insulin can be reduced and the compensation of diabetes improves (decreases). CSII is usually installed in diabetic patients where the disease cannot be sufficiently controlled, namely in patients with "dawn phenomenon", severe hypoglycemia, and progression of diabetic complications. Results of long-term follow-up study of CSII-treated diabetic patients at our department (IKEM) confirmed the high efficacy of this method and the minimal incidence of therapy-related complications (severe hypoglycemia, ketoacidosis, body weight increase, technical complications).

Beneficial effect of pancreas and kidney transplantation on advanced diabetic retinopathy.

In pancreas recipients with advanced diabetic eye disease, conflicting ophthalmologic results over different follow-up periods have been reported. In the present prospective study we performed ophthalmologic evaluation groups of type I diabetic patients: 1) normoglycemic recipients of pancreas and kidney grafts (group SPK, n = 43, follow-up 44.9 +/- 35.1 months), 2) pancreas and kidney graft recipients with nonfunctioning pancreatic graft, and recipients of isolated kidney graft (group K, n = 45, follow-up 60.3 +/- 34.2 months). The examinations were performed before transplantation, at the end of follow-up (at least 1 year), and in 63 recipients also at 3 years posttransplant. Visual acuity results at baseline and at the end of follow-up were 0.48 +/- 0.39 vs. 0.50 +/- 0.39 in the SPK group, and 0.46 +/- 0.38 vs. 0.40 +/- 0.39 in the K group. While intragroup changes were not significant, the changes were significantly different between the groups (p < 0.05). Fundoscopic findings at the end of follow-up were improved, stabilized, or deteriorated in the SPK group in 21.3%, 61.7%, and 17.0%, respectively. The respective figures for the K group were 6.1%, 48.8%, and 45.1% (p < 0.001). Similar results were obtained when evaluating findings at 3 years posttransplant. Before transplantation, 78% of the SPK group and 81% of the K group had been treated by laser. The need for additional posttransplant laser therapy was significantly lower in the SPK (31%) than in the K group (58%; p < 0.001). In conclusion, pancreas transplant exerts a beneficial effect on the course of diabetic retinopathy even in its late stage.

[Metabolic sequelae of pancreatic transplantation using two different surgical techniques]. / Metabolické dusledky transplantace pankreatu pri pouzití dvou ruzných chirurgických technik.

BACKGROUND: By transplantation of the pancreas in diabetics type 1 long-term-term independence on exogenous insulin can be achieved. The extent of normalization of the carbohydrate metabolism can depend on the applied surgical technique. The objective of the submitted work was to compare indicators of compensation of diabetes one year after combined transplantation of the kidney and pancreas, using the method of transplantation of a segment of the pancreas with obliteration of the pancreatic duct by a polymer and the method of transplantation of the whole pancreas with drainage of the pancreatic duct into the urinary bladder. METHODS AND RESULTS: The authors examined two groups of recipients, 13 subjects each with full function of the pancreatic graft one year after transplantation where a combined transplantation of the kidney and pancreatic segment (group SP) had been performed or of the kidney and whole pancreas (group CP). The authors investigated the blood sugar level, glycated haemoglobin, intravenous glucose tolerance test, free insulin level and C-peptide as well as some indicators of the lipid metabolism and acid base balance. In both groups normal blood sugar levels were achieved, though the mean values in the course of the day were higher in group SP than in group CP (mean +/- SE 5.48 +/- 0.11 as compared with 4.98 +/- 0.09; p < 0.01). Glycated haemoglobin declined in group SP from the pretransplantation value of 9.31 +/- 0.09 to 6.40 +/- 0.10% and in group CP from 9.49 +/- 0.15 to 4.92 +/- 0.08%. In group CP the glycated haemoglobin after transplantation was significantly lower (p < 0.01), similarly as the coefficient of glucose assimilation (1.83 +/- 0.03 as compared with 1.25 +/- 0.15; p < 0.05). Indicators of the acid base balance did not differ. Recipients in group CP were however permanently treated with bicarbonate. CONCLUSIONS: With both transplantation method it is possible to achieve compensation of diabetes close to normal. The carbohydrate tolerance is however better after transplantation of the whole pancreas.

[Risk factors for diabetic foot in recipients of renal and pancreatic transplants]. / Rizika diabetické nohy pro príjemce renálních a pankreatických transplantátu.

BACKGROUND: The risk of tissue damage of the foot in diabetic subjects is due to a combination of arterial insufficiency and peripheral neuropathy. The probable development of diabetic foot with possible subsequent amputation is greater in uraemic diabetics. The objective of the presented work was to assess the incidence and risk of diabetic foot in diabetic patients where on account of renal failure transplantation of the kidney was performed. METHODS AND RESULTS: In a retrospective study in 1983-1992 for a period of 6 months to 7 years a group of 64 diabetics was investigated (37 men and 27 women), mean age 42.8 years, range 29-58 years where on account of diabetic nephropathy renal (n = 49, 76.6%) or renal and pancreatic transplantation (n = 15, 23.4%) was performed. At the time of transplantation 53 patients (82.8%) suffered from peripheral neuropathy, 24 (37.5%) from angiopathy of the lower extremities. During the follow up period 22 patients (34.4%) developed ulcerations of the skin of the lower extremities, incl. 15 patients (23.4%) with a local and 4 (6.3%) with a phlegmonous infection. In 10 patients (15.6%) amputation had to be performed. CONCLUSIONS: Ulceration of the foot in diabetics cannot be prevented by transplantation of the kidney or transplantation of the kidney and pancreas. Ulceration of the foot is at present an important contraindication for transplantation.

[Long-term treatment of diabetes with transplantation of a pancreatic segment]. / Dlouhodobá lécba diabetu transplantací segmentu pankreatu.

BACKGROUND: Successful transplantation of the pancreas is at present the only way how to ensure on a long-term basis an almost physiological regulation of the carbohydrate metabolism in type 1 diabetics. So far it is, however, indicated mainly in patients with already advanced microangiopathy where at the same time also renal transplantation is planned and long-term experience is so far limited. The objective of the submitted paper is to report on the development of metabolic compensation and its impact on the development of microangiopathic changes in type 1 diabetics where the complete function of both grafts persisted more han five years. METHODS AND RESULTS: From a group of 34 combined transplantations of a pancreatic segment with an obliterated duct and a kidney, implemented in 1983-1988 in the Institute of Clinical and Experimental Medicine, a group of nine type 1 diabetics was followed up where the independence on exogenous insulin and haemodialyzation treatment persisted for or still persists for 5-8 years. After annual intervals the blood sugar level was examined, the intravenous glucose to tolerance test, free insulin levels, glycosylated haemoglobin, an ophthalmological and neurological examination was made, incl. the peripheral and autonomous system, and by means of a standard questionnaire the quality of life before and after transplantation was assessed. In all examined subjects normal blood sugar levels were recorded. The fasting insulin levels in transplant recipients were higher than in healthy subjects (22 vs. 10.2 microU/ml, p < 0.01) while in the course of the blood sugar curve corresponding levels were recorded. Glycosylated haemoglobin remained after 5 years quite or almost normal (4.2-7.2%). The coefficient of glucose assimilation after 5 years varied in the range from 0.7 to 1.9% min. Hypoglycaemic states were not recorded. In none of the recipients in the course of the investigation deterioration of the ophthalmological finding was observed and in three patients improvement was recorded. Symptoms of somatic polyneuropathy improved in all patients but signs of vegetative neuropathy remained unchanged. In all recipients psychic, physical and social rehabilitation as well as the general quality of life improved markedly. CONCLUSIONS: Although the group of investigated patients is so far small, the authors provided evidence that combined transplantation of the pancreas and kidney can influence in a very favourable way the quality of life and development of microangiopathic complications. As the success rate of transplantations of the pancreas in increasing and the risk of surgical complications is declining due to improving surgical techniques, the authors conclude that combined transplantation of the pancreas and kidney is at present the optimal therapeutic procedure in type 1 diabetics with chronic renal insufficiency and that indication for transplantation of the pancreas could be moved to earlier stages of diabetes when it would be possible to influence the development of diabetic microangiopathy more favourably.