MD Conference Express ADA 2011 - (Page 9)

of transplantations, and the longer survival of both grafts and recipients. Post-transplant diabetes mellitus (PTDM) is particularly common after kidney transplant, but recognition of diabetes after liver and heart transplants is increasing, as more of these procedures are done. PTDM has “clear-cut consequences,” said Jennifer Larsen, MD, University of Nebraska Medical Center, Omaha, Nebraska, USA, with diabetes decreasing graft and patient survival after kidney transplant and increasing the risk of infection (Figure 2). Figure 2. Impact of Diabetes on Patient Survival After Kidney Transplant. No DM 100% 90% DM PTDM risk for diabetes compared with those who receive a living donor graft. Risk varies with cause of renal failure, with those having hypertensive kidney disease and polycystic kidney disease at higher risk. There are several other candidate genes for risk after kidney transplant, including vitamin D receptor polymorphisms. A steatotic liver graft and a history of hepatitis or cirrhosis also increases risk after liver transplant. Finally, and most importantly, many of the immunosuppressant medications that are used for transplant also contribute to risk. High-dose corticosteroids are associated with the highest risk for post-transplant diabetes. Other immunosuppressant agents also contribute to risk. The calcineurin inhibitors, tacrolimus more than cyclosporine, decrease insulin secretion and increase β-cell apoptosis. Sirolimus causes insulin resistance and later β-cell apoptosis as well. “However, the immunosuppression regimen should not be chosen with the hopes of avoiding diabetes. The primary goal of immunosuppression is to prevent rejection, because rejection [of the graft] has an even great impact,” Dr. Larsen said. In PTDM, the diabetes goal is an HbA1C <7%. However, the approach to treatment is complex because of greater insulin resistance, changing glomerular filtration rate (GFR), frequent interruptions in eating, and drug-drug interactions. Metformin is contraindicated in most patients because of low GFR, frequent infections, and need for frequent contrast procedures. Sulfonylureas should be used only when the GFR is adequate because of the risk of hypoglycemia (>40 mL/min). Thiazolidinediones should be avoided after heart or liver transplantation. Exenatide should be avoided, because nausea can be more severe with renal insufficiency, and its impact on immunosuppressant drug absorption has not been well studied. In the end, most patients with PTDM will require insulin. As many transplant recipients have a lower GFR, their risk for hypoglycemia is higher; therefore short-acting insulins are preferable. Insulin should be tailored to the patient’s eating pattern, and requirements can change rapidly. Dr. Larsen emphasized the need for clinicians to evaluate the patient’s feet, as neuropathy may not completely resolve and infections can develop much faster in the setting of immunosuppression. For this reason, patients should also be educated about the importance of foot care. Regular eye care is still important, because corticosteroids increase the risk of cataracts, and immunosuppression can increase the risk for eye infections as well. Early recognition of PTDM leads to better control of HbA1C. Ideally, screening for diabetes should begin at the transplant evaluation and continue at least annually after transplant with fasting glucose and HbA1C. Dr. Larsen stressed the need for team management of PTDM. 9 Patient Survival 80% 70% 60% 50% 40% 2 4 6 8 10 12 14 16 Years after transplantation Reproduced with permission from J. Larsen, MD. International consensus guidelines for new-onset diabetes after kidney transplant were published in 2003 [Davidson J et al. Transplantation 2003]. The guidelines note criteria for PTDM that are the same as those established by the American Diabetes Association for diabetes in the general population; that is, a fasting blood sugar level of 126 mg/dL on two occasions, a random blood sugar level of 200 mg/ dL or more with symptoms, and a 2-hour glucose level of 200 mg/dL or more during oral glucose tolerance testing. The 2003 guidelines, however, have limitations. Because there is no standard for diabetes screening before transplantation, some patients who are identified with PTDM may have had undiagnosed diabetes before transplant. The criteria do not take into consideration the setting or timing of the hyperglycemia. Using these criteria, individuals who have just received high-dose corticosteroids could be identified as having PTDM, even if hyperglycemia resolves after the hospitalization. Likewise, individuals who develop diabetes 20 years after transplant could also be classified as having PTDM; yet, the implications are likely quite different. Perhaps the greatest limitation is that the guidelines have not been widely adopted across all transplant programs and groups. There are many risk factors for PTDM. Many have preexisting risks, such as family history and obesity. History of hepatitis C infection also greatly increases risk after all types of organ transplant. After kidney transplant, individuals who receive a deceased donor graft are at higher Peer-Reviewed Highlights from the American Diabetes Association 71st Annual Scientific Sessions  http://www.mdconferencexpress.com

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