Diabetes Tacrolimus-Associated Posttransplant Diabetes Mellitus in Renal Transplant Recipients: Role of Hepatitis C Infection S. Baid, N. Tolkoff-Rubin, M.L. Farrell, F.L. Delmonico, W.W. Williams, D. Hayden, D. Ko, A.B. Cosimi, and M. Pascual R ECENT STUDIES SUGGEST an association be- tween hepatitis C virus (HCV) infection and diabetes mellitus both in the nontransplant setting as well as after liver transplantation. 1–6 Posttransplant diabetes mellitus (PTDM) is a common complication after organ transplan- tation, and its overall incidence has been reported to vary between 5% to and 30% in renal recipients. 7 In addition to the usual risk factors for diabetes mellitus in the general population such as age, body mass index (BMI), race, and a family history of diabetes, immunosuppressive agents, par- ticularly steroids and calcineurin inhibitors (cyclosporine or tacrolimus), are important risk factors for the development of PTDM in allograft recipients. 7,8 Tacrolimus (TAC) has been shown to be slightly more diabetogenic than cyclo- sporine (CsA), particularly in the initial clinical trials. 7,9,10 TAC-induced PTDM has been associated with steroid use, TAC level, and the recipient race. 7,10 However, the role of HCV infection in the development of PTDM after renal transplantation remains unclear. In this study, we assessed the incidence of TAC-associated PTDM and analyzed possible risk factors including HCV infection in patients receiving TAC for three different clinical indications. METHODS Between July 1994 and July 2000, 138 adult renal allograft recipi- ents received TAC at our institution. We excluded 24 patients who had diabetes either before transplantation or before the initiation of TAC (n = 114). Charts of the remaining 114 evaluable patients were reviewed in detail for demographics such as age, gender, race, body mass index at the time of transplant and at 1, 3, and 6 months posttransplant, number of transplants, clinical course, indication for TAC use, dose and levels of TAC at 7 days, 1, 3, and 6 months, cumulative steroid doses from 1 week before to 1 month after start of TAC, number of methylprednisolone boluses and antilympho- cyte antibody treatment used within the first year posttransplanta- tion, incidence of new onset of PTDM within 1 year after the initiation of TAC (TAC-associated PTDM), and prevalence of hepatitis C (HCV) infection. PTDM was defined as new onset of persistent posttransplant hyperglycemia (fasting blood glucose  150 mg/dL or random blood glucose  200 mg/dL on at least three occasions) and/or requirement of treatment with oral hypoglycemic agents  insulin. Our baseline immunosuppressive regimen con- sisted of CsA-prednisone-azathioprine before June 1997 and of CsA-prednisone-mycophenolate mofetil after that period. TAC was used only for special indications as divided into the following three groups one prophylactic (P group): for immunologically mediated glomerular disease, highly sensitized patients, and recip- ients on repeat transplants (target levels: 10 to 12 ng/mL), (2) rescue group (R group): as rescue treatment for steroid-resistant rejection requiring antilymphocyte antibody therapy (target levels: 10 to 15 ng/mL), and (3) conversion (C group): conversion in stable patients greater than 3 months posttransplant for hirsutism, gingi- val hyperplasia, or hyperlipidemia (target levels: 6 to 8 ng/mL). All results are expressed as mean  standard deviation. Com- parisons between groups were done using Fisher’s exact or chi- square test for categorical variables, and unpaired t test or Wil- coxon rank-sum test for continuous variables. A multivariate analysis using the Cox proportional-hazards model was also per- From the Renal and Transplantation Units and Department of Biostatistics, Massachusetts General Hospital, Boston, Massa- chusetts, USA. Address reprint requests to Seema Baid, MD Renal Unit, Massachusetts General Hospital, 100, Charles River Plaza, 5th Floor, Boston, MA 02114. E-mail: sbaid1@partners.org © 2002 by Elsevier Science Inc. 0041-1345/02/$–see front matter 655 Avenue of the Americas, New York, NY 10010 PII S0041-1345(02)03060-9 Transplantation Proceedings, 34, 1771–1773 (2002) 1771