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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of atherosclerotic cardiovascular complications is a common and serious problem for the long-term survivors of organ transplantation. Cyclosporine A plus steroid-based immuno-suppression regimens in these patients are associated with the development of hypertension, hyperlipidemia, obesity, and diabetes mellitus. Whether the new immunosuppressive agent tacrolimus (FK506) confers any advantage in terms of these cardiovascular risk factors has been less well studied. We compared serial changes in blood pressure, lipids, body weight, and glucose levels during the first 12 months after liver transplantation in patients using either cyclosporine A (n = 39) or tacrolimus (n = 24)-based immunosuppression. By 12 months, the prevalence of hypertension, hypercholesterolemia, and obesity was increased in the cyclosporine A group compared to tacrolimus: 82% versus 33%, 33% versus 0%, and 46% versus 29%, respectively (all p < .05). Triglyceride and total cholesterol levels were 196 +/- 23 versus 125 +/- 13 mg/dL and 225 +/- 9 versus 159 +/- 7 mg/dL for the cyclosporine A versus tacrolimus groups, respectively (p < .05). Cumulative posttransplant steroid dose was not related to the observed lipid changes in either group, although the increase in triglycerides was positively correlated to weight gain and diuretic use in the cyclosporine A group. The incidence of diabetes mellitus was not increased from baseline in either group. These results indicate that tacrolimus, compared to cyclosporine A, is associated with a less adverse cardiovascular risk profile in the first year after liver transplantation. Whether these differences persist and become clinically relevant to a liver transplant recipient population that is increasingly older and has more preexisting cardiovascular disease remains to be determined.
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PMID:Evolution of cardiovascular risk after liver transplantation: a comparison of cyclosporine A and tacrolimus (FK506). 937 52

Pancreas transplantation for the better treatment of diabetes mellitus is becoming an important part of the service offered to diabetic patients requiring renal transplantation. Improvements in surgical technique make this a useful option. A major problem, limiting more extensive use of pancreas transplantation to other diabetic patients, remains the inadequacies of present immunosuppressive regimens. A relatively new agent, FK506 or tacrolimus, is being used increasingly because of perceived benefits over older therapeutic agents. There are concerns about the diabetogenic effect of tacrolimus. These may be dose-related, and low-dose tacrolimus regimens, by allowing reduction in dosage of other diabetogenic immunosuppressive agents, have produced encouraging results in pancreas transplantation in many centres. Further improvements in immunosuppressive regimens may widen the clinical implications for pancreas transplantation but identifying the patient group who will most benefit remains a priority.
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PMID:Update of tacrolimus in pancreas transplantation. 940 Sep 14

Tacrolimus (FK 506) has been evaluated as immunosuppressive therapy in patients with a variety of solid organ and other transplants. Extensive data have now confirmed its efficacy as primary or rescue therapy in renal and hepatic transplantation. In prospective and historically controlled studies of primary therapy, tacrolimus generally demonstrated greater efficacy than the conventional formulation of cyclosporin for preventing episodes of acute rejection and allowed reduction of corticosteroid use. Chronic rejection rates were also significantly lower with tacrolimus in a large randomised liver transplantation trial. However, patient and graft survival rates were similar in both treatment groups (although numerically larger in adults with liver transplants). In children, rejection rates and corticosteroid requirements were usually lower with tacrolimus and patient and graft survival were generally similar with the 2 immunosuppressants. The finding of reduced corticosteroid requirements with tacrolimus may be of particular benefit in prepubertal children, who are still growing. A small amount of evidence has also accumulated regarding the use of tacrolimus as primary therapy in patients who have undergone bone marrow or heart and/or lung transplantation. Data are not conclusive, particularly in children, but tacrolimus appears to be useful for treating patients who have undergone these organ transplantations and may be associated with a lower incidence of obliterative bronchiolitis than cyclosporin in the latter group. Potential efficacy has also been shown in a limited number of patients with pancreas or pancreas-kidney, pancreatic islet and intestinal or multivisceral transplants, and in children who have undergone heart or heart-lung transplantation. Tacrolimus also has a use as rescue therapy in bone marrow, heart, lung and pancreatic transplantation, but data are currently insufficient for conclusions to be made. However, these results support the need for further study in these populations. Adverse effects occurring during tacrolimus therapy are generally of the type common to all immunosuppressive regimens. However, diabetes mellitus, neurotoxicity and nephrotoxicity are more common in tacrolimus than cyclosporin recipients. Hyperlipidaemia, hypertension, hirsutism and gingival hyperplasia are more common with cyclosporin. In 2 large multicentre clinical trials (US liver and European renal), tacrolimus was discontinued more frequently during the first year because of adverse events. However, the tolerability of tacrolimus appears related to dosage, improving as the dose is reduced. Tacrolimus should be considered an effective primary immunosuppressant in renal and hepatic transplantation. The drug is also a useful agent for rescue therapy in patients experiencing rejection or poor tolerability to cyclosporin. Thus, tacrolimus provides the clinician with an effective option for patients requiring immunosuppression and, with a different tolerability and efficacy profile to cyclosporin, it will better allow the tailoring of therapy to meet the needs of individual patients.
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PMID:Tacrolimus. An update of its pharmacology and clinical efficacy in the management of organ transplantation. 942 97

Tacrolimus (FK 506) is a new macrocyclic lactone immunosuppressant which possesses similar but more potent immunosuppressive properties compared with cyclosporin. It is able to inhibit T cell proliferation and the production of interleukine 2 (and other growth promoting cytokines). A major interest of tacrolimus is that it can be used as a rescue therapy since clinical trials have demonstrated its ability to be effective in some patients who develop rejection episodes refractory to current regimens, including corticosteroids. Tacrolimus is highly bound to erythrocytes and is largely metabolized, primarily in the liver, by Cyt P450 3A4. Its excretion pathway concerns the bile almost exclusively. Like cyclosporin, the drug is associated with a range of adverse effects including nephrotoxicity, neurotoxicity and diabetes. Tacrolimus also exhibits a large inter- and intra-individual variability of its pharmacokinetics. Because of this variability and the narrow therapeutic index of tacrolimus, monitoring of tacrolimus blood concentrations would be useful for optimization of therapy. However, even if we know that by maintaining the residual blood concentration under 15 micrograms/l it is possible to reduce dramatically the occurrence of adverse effects, we still have not determined the threshold value of clinical efficacy. This will be important for current and future clinical pharmacology investigations with tacrolimus.
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PMID:[Clinical pharmacokinetics and therapeutic monitoring of tacrolimus]. 943 90

In order to avoid the side effects of tacrolimus (FK506), a lowdose FK506-based regimen was started from 1 June 1991. The dose was adjusted to maintain the FK506 whole blood trough level at 15-20 ng/ml for 7 days postoperatively, at 10-15 ng/ml for 2 months, and under 10 ng/ml thereafter. The graft survival rates at 3 years and 5 years were 87.8 and 82.3% (FK506) vs 86.8 and 86.8% [cyclosporine (CyA)]. The incidence of acute rejection within the first 90 days was 31.6% in the FK506 group which was lower than the 57.1% of the CyA group (P = 0.0585). Grades of acute rejection episodes over IIA in the FK506 group were 20%, which was lower than the 37% in the CyA group. The mean oral dosages of FK506 were 0.061 and 0.04 mg/kg per day at 3 and 5 years, respectively. The incidence of new onset diabetes was 27.8% in the FK506 group and 17.1% in the CyA group. However, insulin therapy was withdrawn in all patients of the FK506 group within 5 months. The percentage of patients who required an antihypertensive agent was 28.6% and 40% in the FK506 group and 73.2% and 88% in the CyA group at 1 and 3 years, respectively (P < 0.05). Nephrotoxicity was seen in 20% of the FK506 group and 14.3% of the CyA group. Hypercholesterolemia was less frequent in the FK506 group than the CyA group. The FK506-based regimen described here is a protocol with the potential to reduce its adverse effects. The Whole blood concentration of FK506 should be monitored and blood levels maintained in the range of 5-10 ng/ml after 90 postoperative days for optimal efficacy and minimal toxicity.
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PMID:Low-dose tacrolimus (FK506)-based immunosuppressive protocol in living donor renal transplantation. 966 45

A 54-year-old man undergoing hemodialysis because of end-stage renal failure was transplanted with a cadaver kidney in November 1997. He had no history of diabetes. Tacrolimus was used as the primary immunosuppressant. Three weeks after transplantation, he developed insulin-requiring diabetes mellitus. Anti-glutamic acid decarboxylase antibody was not detected on the third post-operative day, but appeared 4 weeks after transplantation. The recipient had DNA haplotypes that indicated susceptibility to Type 1 diabetes in Japanese subjects. Immunosuppressive therapy was changed from tacrolimus to cyclosporin. Thereafter, titer of anti-glutamic acid decarboxylase antibody disappeared and the patient's insulin requirement was notably reduced. The mechanism underlying the development of diabetes in this case appears to be, in part, direct beta-cell toxicity due to tacrolimus therapy, resulting in secondary beta-cell autoimmunity. This case suggests that tacrolimus therapy after transplantation should be used with caution in patients with genetic susceptibility to Type 1 diabetes.
Diabetes Res Clin Pract 1998 Nov
PMID:Post-transplant diabetes with anti-glutamic acid decarboxylase antibody during tacrolimus therapy. 988 44

The results of pancreas transplantation have improved in the ciclosporin A era. Success rates are now similar to those in other types of organ transplantation, and the number of cases has increased concomitantly. As of December 1997, 10,283 pancreas transplantation procedures had been reported to the International Pancreas Transplant Registry. Since 1995, over 1,000 have been reported annually, 75% of which have been performed in the USA. The majority (88%) of those carried out in the USA consist of simultaneous pancreas and kidney (SPK) transplantations, followed by pancreas transplantation after kidney transplantation (10%) and pancreas transplantation alone (PTA) (2%). From 1994 to 1997, the overall one-year patient survival rate was 94%. The graft survival rate for SPK was the highest, with one- and three-year graft survival rates of 82% and nearly 80%, respectively. The administration of FK506 and mycophenolate mofetil has improved the results in patients undergoing pancreas transplantation. Althought the technical failure rate has decreased, graft thrombosis remains the most frequent cause of technical failure (5.5% for SPK with exocrine bladder drainage and 11% for SPK with enteric drainage). The standard surgical procedure has included pancreas-exocrine bladder drainage, but the current trend is to perform physiological enteric drainage. It has been reported that the portal venous and enteric exocrine drainage methods are safe, with outcomes similar to those of the standard technique. It appears that these will become the standard methods in the near future. The primary objective of improved quality of life is achieved in patients with functioning pancreas grafts, and transplantation results in modest reductions in secondary diabetes mellitus complications. However, it must still be confirmed whether the long-term quality-of-life benefits outweigh the potential risks. The secondary objective of pancreas transplantation is to prevent complications of diabetes mellitus. It is necessary to develop methods for the early detection of rejection, which will lead to significant improvements in the results of PTA. Although 15 pancreas transplantation surgeries have been carried out in Japan, they ceased after 1994. Currently, social debate to determine the rules governing such procedures is ongoing.
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PMID:[Current status and future of pancreas transplantation]. 1002 97

Tacrolimus is a T cell-specific immunosuppressive agent that has been used in a relatively small number of pediatric kidney transplant recipients. It has been used as a primary immunosuppressive agent, with patient survival rates of over 95%, and graft survival rates of over 90%. In the largest series reported, some two-thirds of the successfully transplanted recipients have been taken off steroids, with substantial catch-up growth, and over 80% have been taken off antihypertensive medications. Important complications have included EBV-related post-transplant lymphoproliferative disorder and post-transplant diabetes mellitus, both reversible. Tacrolimus has also been used to rescue patients with refractory acute rejection, with a success rate of 70%-75%. This review summarizes the current world experience with tacrolimus in pediatric renal transplantation, and describes the details of tacrolimus dosing and the treatment of tacrolimus-related complications. On balance, tacrolimus is an effective immunosuppressive agent and offers important advantages in the management of pediatric renal transplant recipients.
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PMID:Tacrolimus in pediatric renal transplantation: a review. 1008 28

As of November 1997, 9,891 pancreas transplantation were reported to the International Pancreas Transplant Registry. In the United States, for all 1994-97, SPK, PAK, and PTA transplants, one-year graft survival rates were 82%, 71%, and 62%, respectively. The 1994-97 pancreas survival rates in all categories were higher than in previous eras. The improvement in graft survival rates has been associated with the introduction of FK506 and MMF, but excellent results are seen with cyclosporine, so the improvement may in part be due to the increasing experience that centers now have with pancreas transplantation. Although the standard surgical procedure remains pancreas-exocrine bladder drainage, the number of enteric drainage cases is increasing. It has been reported that the portal venous and enteric drainages are safe, with outcomes similar to those of standard technique. It appears that these will become the standard methods in the near future. Although 15 pancreas transplantations have been carried out in Japan, they ceased after 1994. Currently, social debate to determine the rules governing such procedures is ongoing. As of December 1995, 306 adult islet allotransplantation were reported to the Islet Transplant Registry. One-year islet survival rates were 27% in cases for 1990-94. Islet transplantation has the potential to be the most physiological advantage for the treatment of diabetes mellitus. However, the endocrine function provided by these transplants has been far from optimal.
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PMID:[Current status and future prospect of pancreas and islet transplantation]. 1019 60

Tacrolimus is a very potent drug for preventing all types of acute rejection after renal transplantation. The decrease of vascular rejection may have important long-term implications. This is demonstrated in the 3-year data of the U.S. multicentre trial, where a significant decrease of graft loss was observed in the tacrolimus patients compared to cyclosporine patients. Safety profiles of both drugs are the same, but there are some major differences in side effects. Hyperglycemia is more common during tacrolimus, but generally the induction of hyperglycemia is a dose-dependent reversible process, which leads generally to diabetes mellitus during high systemic exposure, in certain races and prediabetics. Gum hyperplasia and hirsutism are not seen during tacrolimus therapy and there is a more favorable cardiovascular risk profile during tacrolimus as compared to cyclosporine based immunosuppression.
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PMID:Use of tacrolimus in renal transplantation. 1061 83


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