New-Onset Posttransplantation Diabetes Mellitus: Insulin Resistance or Insulinopenia? Impact of Immunosuppressive Drugs, Cytomegalovirus and Hepatitis C Virus Infection

Restoration of renal function may ameliorate uremia induced insulin resistance. Therefore it seems a paradox that new-onset posttransplantation diabetes mellitus (PTDM) is a frequently observed complication after renal transplantation. The incidence varies between 2 and 50% depending on the population under study, criteria for the diagnosis of diabetes and the time of follow up. This review addresses recent findings on transplant specific risk factors and pathogenesis of PTDM after solid organ transplantation, and we focus on the following issues: 1. The relative impact of insulin resistance and insulinopenia in the pathogenesis of PTDM. 2. The role of immunosuppressive drugs with special emphasis on calcineurin inhibitors (cyclosporine A, tacrolimus) and steroids. 3. The possible roles of cytomegalovirus and hepatitis C infections. Conclusions: New-onset PTDM is characterized by a variety of clinical manifestations, ranging from predominantly insulin resistance which can be handled with lifestyle intervention, to beta-cell failure requiring insulin treatment. The etiology is multi-factorial, but diabetogenic immunosuppressive drugs are of major importance. Future studies should therefore address the effects of different immunosuppressive regimens on the incidence of PTDM. In addition, the impact of cytomegalovirus infection and hepatitis C on PTDM needs further evaluation.