Metabolic Effect of Sirolimus Versus Mycophenolate Mofetil on Pancreatic Graft Function in the Early Posttransplant Period

Havrdova, Tereza; Saudek, F; Bouc̆ek, P; Adamec, M; Koznarová, R; Jedináková, T; Karasová, L; Skibová, J

doi:10.1016/j.transproceed.2005.09.056

Cited by 8 publications

(4 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This demonstrated significantly lower HbA 1c levels in the mycophenalate group, while 6% of patients on rapamycin developed NODAT compared with 3% in the mycophenalate group (20). A further nonrandomized comparison of rapamycin with mycophenalate in pancreas transplant recipients also receiving tacrolimus demonstrated significantly lower plasma insulin levels during an intravenous glucose tolerance test with rapamycin (21). …”

Section: Clinical Evidence Of Rapamycin β-Cell Toxicitymentioning

confidence: 99%

Evidence for Rapamycin Toxicity in Pancreatic β-Cells and a Review of the Underlying Molecular Mechanisms

2013

View full text Add to dashboard Cite

Rapamycin is used frequently in both transplantation and oncology. Although historically thought to have little diabetogenic effect, there is growing evidence of β-cell toxicity. This Review draws evidence for rapamycin toxicity from clinical studies of islet and renal transplantation, and of rapamycin as an anticancer agent, as well as from experimental studies. Together, these studies provide evidence that rapamycin has significant detrimental effects on β-cell function and survival and peripheral insulin resistance. The mechanism of action of rapamycin is via inhibition of mammalian target of rapamycin (mTOR). This Review describes the complex mTOR signaling pathways, which control vital cellular functions including mRNA translation, cell proliferation, cell growth, differentiation, angiogenesis, and apoptosis, and examines molecular mechanisms for rapamycin toxicity in β-cells. These mechanisms include reductions in β-cell size, mass, proliferation and insulin secretion alongside increases in apoptosis, autophagy, and peripheral insulin resistance. These data bring into question the use of rapamycin as an immunosuppressant in islet transplantation and as a second-line agent in other transplant recipients developing new-onset diabetes after transplantation with calcineurin inhibitors. It also highlights the importance of close monitoring of blood glucose levels in patients taking rapamycin as an anticancer treatment, particularly those with preexisting glucose intolerance.

show abstract

Section: Clinical Evidence Of Rapamycin β-Cell Toxicitymentioning

confidence: 99%

Evidence for Rapamycin Toxicity in Pancreatic β-Cells and a Review of the Underlying Molecular Mechanisms

2013

View full text Add to dashboard Cite

show abstract

“…However, this was not observed in our series, since kidney function over time proved to be very stable. With regard to glucose control, a prospective study did not reveal any different effects of mycophenolate mofetil and sirolimus in SPK recipients [29].…”

Section: Discussionmentioning

confidence: 89%

Simultaneous islet–kidney vs pancreas–kidney transplantation in type 1 diabetes mellitus: a 5 year single centre follow-up

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis The aim of this study was to compare the long-term outcomes-in terms of glucose control, renal function and procedure-related complications-of simultaneous islet-kidney (SIK) transplantation with those of simultaneous pancreas-kidney (SPK) transplantation in patients with type 1 diabetes mellitus. Methods HbA 1c , need for insulin, GFR and complication rate were compared between 13 recipients of SIK and 25 recipients of SPK transplants at the same institution. The mean follow-up was 41 months.Results Two primary organ non-functions occurred in the SIK group. HbA 1c did not differ at any time point during follow-up in the SIK group compared with the SPK group (mean during follow-up 6.3 vs 5.9%). Similarly, kidney function over time was not different between the two groups. A higher rate of insulin independence following SPK transplantation (after 1 year 96 vs 31% in the SIK group) was counterbalanced by a higher rate of serious adverse events (40% relaparotomies vs 0% in the SIK group). Conclusions/interpretation The endogenous insulin production achieved by islet transplantation, combined with optimal insulin therapy, was sufficient for maintaining near-normal glucose levels. In terms of glucose control, islet transplantation provides results comparable to those achieved with pancreas transplantation. However, SPK results in a higher rate of insulin independence, albeit at the cost of more surgical complications. These results have led to a new paradigm in islet transplantation at our institution, where the primary goal is not insulin independence, but good glucose control and avoidance of severe hypoglycaemia.

show abstract

“…Data on mycophenolate mofetil are scarce. In animal models, impaired insulin secretion was observed [ 39 ]; in simultaneous kidney-pancreas recipients, evidence exists of insulin resistance in comparison with use of sirolimus alone [ 40 ].…”

Section: Alternative Infusion Sitementioning

confidence: 99%

Current challenges in islet transplantation

Leitão

Cure²,

Tharavanij³

et al. 2008

Curr Diab Rep

View full text Add to dashboard Cite

Allogeneic islet transplantation is becoming a treatment option for patients with unstable type 1 diabetes mellitus (T1DM). Around 80% of the islet recipients achieve insulin independence after one or two islet infusions under "Edmonton-like" immunosuppressive protocol, but only 10% will remain insulin independent over the long term. Islet transplantation leads to glucose stabilization, and severe hypoglycemia is prevented even in patients back on insulin injections. Thus, islet transplantation has achieved the proposed targets in patients with unstable T1DM: normalizing blood glucose and hemoglobin A(1c), preventing severe hypoglycemic episodes, and improving quality of life. The current aims of islet transplantation programs are to maintain the success achieved and to overcome remaining obstacles and limitations.

show abstract

Metabolic Effect of Sirolimus Versus Mycophenolate Mofetil on Pancreatic Graft Function in the Early Posttransplant Period

Cited by 8 publications

References 4 publications

Evidence for Rapamycin Toxicity in Pancreatic β-Cells and a Review of the Underlying Molecular Mechanisms

Evidence for Rapamycin Toxicity in Pancreatic β-Cells and a Review of the Underlying Molecular Mechanisms

Simultaneous islet–kidney vs pancreas–kidney transplantation in type 1 diabetes mellitus: a 5 year single centre follow-up

Current challenges in islet transplantation

Contact Info

Product

Resources

About