INSULIN REQUIREMENTS AFTER LIVER-TRANSPLANTATION AND FK-506 IMMUNOSUPPRESSION

Hyperglycemia and new-onset diabetes mellitus is a well-recognized com plication of solid organ transplantation. With the advent of FK-506 as a new immunosuppressive drug used in orthotopic liver transplantation (OLT), much attention has been paid to its diabetogenic effects. Curr ently, there are no data on the long term effects of FK-506 in glucose metabolism after OLT. In the present study, we determined the need fo r outpatient insulin in 52 American veterans who received 58 liver tra nsplants using primary immunosuppression with FK-506 and PRED, with a mean follow-up of 467 days (range 17-952 days). We also analyzed their plasma glucose and FK-506 levels as well as the doses of PRED and FK- 506 that they received at various intervals post-OLT. There were 7/52 (13.6%) patients who required insulin for the first time after OLT. Of these, the number of patients on insulin at 3, 6, and 12 months post- OLT was 5/47 (10.6%), 6/44 (13.6%), and 1/26 (3.8%), with none requiri ng insulin de novo at 18, 24, and 30 months post-OLT. Three patients r equired insulin temporarily but subsequently became normoglycemic with out additional therapy. The need for insulin was not related to the do se of FK-506 administered nor the plasma level. Patients who required outpatient insulin were receiving higher doses of PRED than those not requiring insulin. The need for insulin did not affect the long-term g raft or patient survival. In conclusion, the need for insulin with FK- 506 compares favorably to that of previous immunosuppressive regimens, and FK-506 may have a reversible diabetogenic effect that is not dose dependent.