FK 506-associated diabetes mellitus in the pediatric transplant population is a rare complication.

F K 506 is a powerful new investigational immunosup-. pressant that has been used successfully first as an organ rescue agent and then as a primary antirejection agent. FK 506 has been shown to have a favorable profile on pancreatic islets in vitro'; however, the agent does decrease glucose-induced insulin release at high concentrations from bo~ rodent 2 • 3 and human islets. 2 This agent also prolongs the clearance of glucose and decreases insulin release from transplanted dog islets in vivo. 4 and is diabetogenic in some species of animals s and more importantly in adult humans. 6 The aim of this study was to the magnitude of the diabetogenic effect of FK 506 in pediatric patients undergoing organ transplantation. METHODS Patients who developed insulin-requiring diabetes were identified using a variety of methods including outpatient chart reviews. review of endocrine consults for diabetes management. information from transplant physicians and nurse coordinators. and contact with referring physicians to identify problems that occurred after hospital discharge. FK 506 for the following indications: 108 primary liver transplants, 44liver "rescues." 1 liver/kidney transplant. 3 liver/small bowel transplants. 22 primary kidneys, 9 kidney "rescues." 16 primary hearts. and 3 heart "rescues." Patients who had diabetes mellitus prior to the transplant and patients who underwent upper abdominal exenteration including pancreatectomy and pancreatic islet transplanta-tion were excluded from the analysis. Only three pediatric patients developed insulin-requiring diabetes while on FK 506 as a single agent. AU patients had been off steroids at least 1 week at the time that diabetes developed. The three patients who developed diabetes were adolescents with liver disease who were switched to FK 506 in an attempt to rescue a previously transplanted liver with chronic rejection despite maximal standard immunosup-pressive drugs. All patients were treated with cyclosporine (CyA) and steroids prior to the switch. CyA was stopped and FK 506 treatment was immediately instituted. Rejection was successfully managed in all patients initially; however. one patient required retransplantation for recurrence of autoimmune hepatitis 17 months after the switch (Table 1). Only one patient had a high plasma FK level at any time prior to developing diabetes (15 nglmL, patient 3. Table 1). All patients have returned to full activities. Diabetes in the setting of organ rescue developed late (from 17 to 27 days). All patients were symptomatic from hyperglycemia and plasma glucose levels ranged from 326 mgldL to > 1.000 mgldL. No patient …