POST-TRANSPLANT DIABETES MELLITUS IN PEDIATRIC THORACIC ORGAN RECIPIENTS RECEIVING TACROLIMUS-BASED IMMUNOSUPPRESSION

Abstract

894 Background: Post-transplant diabetes mellitus (PTDM) is a well-known complication of tacrolimus-based immunosuppression in both adult and pediatric solid organ recipients. However, the 'natural history' of diabetes in the pediatric thoracic transplant population has not yet been described. Methods: We identified all pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression who developed PTDM. Diabetes was defined as glucose intolerance requiring insulin therapy or oral hypoglycemic agents more than 30 days after transplantation for a minimum duration of 30 days. Medical records were reviewed, with a particular focus on the clinical course of PTDM and its relationship to drug weaning. Results: Diabetes developed in 22 of 139 (16%) thirty day survivors of heart (11/93, 12%) and heart-lung / lung (11/46, 24%) recipients receiving tacrolimus-based immunosuppression since October 1989. Three patients had cystic fibrosis. In 14 (64%) patients, the immunosuppressive regimen at the onset of PTDM also included maintenance corticosteroids. Fifteen (68%) patients had demonstrated glucose intolerance on at least one occasion outside the early postoperative period prior to the onset of diabetes. Eight patients (36%) developed diabetes during pulsed corticosteroid therapy. Median time of onset after transplantation was 9.0 months (range 1 to 62). Two patients were ketotic at presentation. Initial therapy consisted of subcutaneous insulin in 20 (91%) patients. One patient was begun on an oral hypoglycemic agent, and in one patient, dietary intervention was first attempted. Both of these patients required the addition of insulin to their regimen. The median follow-up after development of PTDM was 39.1 months (range 1-76). There was a significant decrease in the mean tacrolimus dosage from onset of PTDM to most recent follow-up (0.26 to 0.16 mg/kg/day, p < 0.01). This was associated with a decrease in mean whole blood tacrolimus level from 16.4 to 12.8 ng/ml. There was also a significant decrease in daily maintenance corticosteroid requirements over the same period (0.21 to 0.13 mg/kg/day, p < 0.04). Despite this significant reduction in immunosuppression, only 3/22 (14%) patients were able to be weaned off insulin, at 5, 14, and 36 months from onset. These 3 patients comprised 2 of 5 weaned off corticosteroids, and one of 9 who required continued maintenance corticosteroids. Two additional patients were changed from tacrolimus to cyclosporine, one for intractable headaches, and one for pancytopenia. Diabetes persisted in both patients after the switch. Conclusions: Diabetes mellitus is a common complication in pediatric thoracic transplant patients receiving tacrolimus-based immunosuppression. Insulin dependence in our population rarely resolved, even after lowering tacrolimus and steroid doses. Discontinuation of steroids does not guarantee resolution of diabetes. The value of switching to cyclosporine has not been fully explored.