Glucose Metabolism in Heart Transplant Recipients Treated With FK506 or Cyclosporine G. Sahar, M. Berman, T. Ben-Gal, E. Sahar, A. Kogan, R. Michowitch, M. Saute, M. Kramer, A. Sagie, Y. Shapira, D. Aravot, and B.A. Vidne P OSTTRANSPLANT diabetes mellitus (PTDM) has gained widespread attention due to the micro- and macrovascular complications that increase the morbidity and mortality rates of patients receiving solid organs. A higher incidence of PTDM has been associated with immu- nosuppressive therapy. This study compares glucose metab- olism in heart transplant recipients receiving either FK506 or cyclosporine. METHODS Two groups of heart transplant recipients, differing in their immu- nosuppressive regimen—FK506 or cyclosporin—were followed for periods up to 6 years. Blood levels of glucose and of the respective immunosuppressive agent were measured regularly, and, if needed, anti-hyperglycemic treatment prescribed. The concomitant therapy with low-dose steroids and azathioprine was the same for both cohorts. T-test were performed to compare with the mean values of the two groups. RESULTS Thirty patients were followed up for a mean period of 25.6  5.6 months. Every patient served as a “self” control subject. Fourteen patients were treated with FK506 and 16 with CsA; one patient was converted to FK506 due to gum hypertrophy and bleeding attributed to CsA. The mean CsA level was 238.78 ng/mL, and mean FK506 level was 9.78 ng/mL. The glucose levels were similar between the two groups namely, 133.33  12.5 mg/dL and 118  15.7 mg/dL for FK506 and CsA, respectively (P = .08). Similar values were obtained in repeated measures over different periods. Two of 14 patients in the FK506 group and 3 of 16 in CsA group were treated with insulin; one patient received an oral antiglycemic. DISCUSSION Tacrolimus and CsA have been shown to contribute to the development of PTDM after orthotopic liver grafting. 4 Several studies indicate that pancreatic cells are the primary targets for the diabetogenic effects of CsA and tacrolimus. Andersson et al. 1 reported that CsA impairs pancreatic islet DNA synthesis, proinsulin biosynthesis, and insulin release from cultured mouse islets. CsA suppresses glucose induced first- and second-phase insulin responses. 2 Animal and clinical studies indicate that tacrolimus has same diabeto- genic potency by causing cell dysfunction after liver trans- plantation. 3 The pathogenesis of posttransplant hyperglyce- mia is multifactorial; factors other than immunosuppressive therapy may also contribute to the impairment of glucose tolerance post-heart transplantation, such as a family his- tory of diabetes or occurrence of rejection episodes, with a higher cumulative steroid medication. The diabetogenic impact of tacrolimus and CsA in kidney transplantation is controversial. 5 Our experience suggests that heart transplant recipients show no significant difference in glucose metabolism, al- though a few sporadic cases in both groups needed antig- lycemic treatment, indicating that the long-term use of either tacrolimus or CsA probably does not cause chronic, cumulative pancreas toxicity. REFERENCES 1. Andersson A, Borg H, Hallberg A, et al: Diabetologia 27:66, 1984 2. Gillison SL, Bartlett ST, Curry DL, et al: Diabetes 38:465, 1989 3. Tabasco-Minguillan J, Mieles L, Carrol P, et al: Transplanta- tion 58:862, 1993 4. Konrad T, Steinmuller T, Vicini P, et al: Transplantation 69:2072, 2000 5. van Duijnhoven EM, Christiaans MH, Boots JM, et al: J Am Soc Nephrol 13:213, 2002 From the Department of Cardiothoracic Surgery, Heart-Lung Transplant Unit (G.S., M.B., E.S., A.K.R.M., M.S., D.A., B.A.V.), the Department of Cardiology (T.B.-G., A.S., Y.S.), and the Pulmonary Institute (M.K.) Rabin Medical Center, Beilinson Cam- pus, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Address reprint requests to Dr Marius Berman, Department of Cardiothoracic Surgery, Rabin Medical Center, Campus Beilin- son, Petah Tikva 49100, Israel. E-mail: mariusby@yahoo.com 0041-1345/03/$–see front matter © 2003 by Elsevier Science Inc. doi:10.1016/S0041-1345(03)00095-2 360 Park Avenue South, New York, NY 10010-1710 678 Transplantation Proceedings, 35, 678 (2003)