Several terms are used in the literature to describe the presence of diabetes following organ transplantation. “New-onset diabetes after transplantation” (NODAT) is one such designation that describes individuals who develop new-onset diabetes following transplant. NODAT excludes patients with pretransplant diabetes that was undiagnosed as well as posttransplant hyperglycemia that resolves by the time of discharge (103). Another term, “posttransplantation diabetes mellitus” (PTDM) (103,104), describes the presence of diabetes in the posttransplant setting irrespective of the timing of diabetes onset.
Hyperglycemia is very common during the early posttransplant period, with ˜90% of kidney allograft recipients exhibiting hyperglycemia in the first few weeks following transplant (103-106). In most cases, such stress- or steroidinduced hyperglycemia resolves by the time of discharge (106,107). Although the use of immunosuppressive therapies is a major contributor to the development of PTDM, the risks of transplant rejection outweigh the risks of PTDM and the role of the diabetes care provider is to treat hyperglycemia appropriately regardless of the type of immunosuppression (103). Risk factors for PTDM include both general diabetes risks (such as age, family history of diabetes, etc.) as well as transplant-specific factors, such as use of immunosuppressant agents (108). Whereas posttransplantation hyperglycemia is an important risk factor for subsequent PTDM, a formal diagnosis of PTDM is optimally made once the patient is stable on maintenance immunosuppression and in the absence of acute infection (106-108). The OGTT is considered the gold standard test for the diagnosis of PTDM (103,104,109,110). However, screening patients using fasting glucose and/or A1C can identify high-risk patients requiring further assessment and may reduce the number of overall OGTTs required.
Few randomized controlled studies have reported on the short- and long-term use of antihyperglycemic agents in the setting of PTDM (108,111,112). Most studies have reported that transplant patients with hyperglycemia and PTDM after transplantation have higher rates of rejection, infection, and rehospitalization (106,108,113).
Insulin therapy is the agent of choice for the management of hyperglycemia and diabetes in the hospital setting. After discharge, patients with preexisting diabetes could go back on their pretransplant regimen if they were in good control before transplantation. Those with previously poor control or with persistent hyperglycemia should continue insulin with frequent home self-monitoring of blood glucose to determine when insulin dose reductions may be needed and when it may be appropriate to switch to noninsulin agents.
No studies to date have established which noninsulin agents are safest or most efficacious in PTDM. The choice of agent is usually made based on the side effect profile of the medication and possible interactions with the patient’s immunosuppression regimen (108). Drug dose adjustments may be required because of decreases in the glomerular filtration rate, a relatively common complication in transplant patients. A small short-term pilot study reported that metformin was safe to use in renal transplant recipients (114), but its safety has not been determined in other types of organ transplant. Thiazolidinediones have been used successfully in patients with liver and kidney transplants, but side effects include fluid retention, heart failure, and osteopenia (115,116). Dipeptidyl peptidase 4 inhibitors do not interact with immunosuppressant drugs and have demonstrated safety in small clinical trials (117,118). Well-designed intervention trials examining the efficacy and safety of these and other antihyperglycemic agents in patients with PTDM are needed.