Immunosuppression and Post-transplant Hyperglycemia

Curr Diabetes Rev. 2015;11(3):144-54. doi: 10.2174/1573399811666150331160846.

Abstract

Background: Post-transplant diabetes mellitus is a significant risk factor for cardiovascular disease in solid organ transplantation. The main underlying pathophysiological mechanism of PTDM is pancreatic beta cell dysfunction in the context of insulin resistance, but the relative importance of each of these important components of glycemic metabolism is under intense debate.

Methods: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials to January 15, 2015. We selected systematic reviews and meta-analyses and randomized clinical trials. When no such reports were found for a given topic or drug, observational studies were included in the assessment.

Results: There are agents with known diabetogenic effects: corticosteroids, calcineurin inhibitors including tacrolimus and cyclosporine, as well as the mammalian target of rapamycin inhibitors (sirolimus and everolimus). The association between the use of induction agents and PTDM is very scarce. No diabetogenic effects have been found with the use of azathioprine, mycophenolate mofetil and its derivatives.

Conclusion: Immunosuppression is the major modifiable risk factor for development of PTDM but risk versus benefit analysis is required to balance risk of developing PTDM versus rejection. Caution is advisable in immunosuppressant adjustments in the event that PTDM develops based on current evidence. Physicians should choose and use immunosuppression regimens shown to have the best outcome for patient and graft survival, irrespective of PTDM risk.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Cortex Hormones / adverse effects
  • Azathioprine / therapeutic use
  • Calcineurin Inhibitors / adverse effects
  • Cyclosporine / adverse effects
  • Diabetes Mellitus / chemically induced*
  • Diabetes Mellitus / metabolism
  • Everolimus / adverse effects
  • Graft Rejection / prevention & control*
  • Humans
  • Hyperglycemia / chemically induced*
  • Hyperglycemia / metabolism
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / therapeutic use
  • Postoperative Complications / chemically induced*
  • Postoperative Complications / metabolism
  • Sirolimus / adverse effects
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Tacrolimus / adverse effects
  • Transplantation / methods*

Substances

  • Adrenal Cortex Hormones
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Cyclosporine
  • Everolimus
  • TOR Serine-Threonine Kinases
  • Mycophenolic Acid
  • Azathioprine
  • Sirolimus
  • Tacrolimus