CLINICAL DETERMINANTS OF GLUCOSE-HOMEOSTASIS AFTER PANCREAS TRANSPLANTATION

Although successful simultaneous pancreas and kidney transplantation ( SPK) achieves normoglycemia in the majority of diabetic recipients wit h end-stage renal disease, little is known about the factors that infl uence long-term endocrine function, In this prospective study of 48 bl adder-drained SPK patients, 209 oral glucose tolerance tests were perf ormed between 3 months and 6 years after transplantation. Normal fasti ng glucose levels and systemic hyperinsulinemia were stable for up to 6 years after SPK, Multivariate analysis revealed that increased area- under-curve (AUG) levels of C-peptide 3 months after transplantation w ere predicted by short surgical pancreas anastomosis time, greater rec ipient body weight, and total HLA mismatch score. Episodes of acute pa ncreas rejection were not associated with reduced allograft insulin ou tput in the long term, Insulin output, stimulated by oral glucose tole rance tests and assessed by the ratio of AUC insulin to AUC glucose, f ell gradually after transplantation and was decreased by an elevated s erum calcium level and high cyclosporine dose, The ratio of fasting in sulin to glucose, which acts as a marker of peripheral insulin resista nce, fell with time after transplantation and was increased by greater body weight, higher prednisolone dose, and lower cyclosporine dose, T he inhibitory effect of cyclosporine on both fasting and postprandial insulin output was, however, minor when quantified by multivariate ana lysis, Endocrine function of the transplanted pancreas was not correla ted with its exocrine function measured by urinary amylase excretion, nor was there a correlation with change in renal function measured by isotopic glomerular filtration rate, In summary, simultaneous pancreas and kidney transplantation leads to excellent long-term glucose homeo stasis maintained at the expense of systemic hyperinsulinemia, The key factors adversely affecting peripheral resistance in SPK were cortico steroid therapy, body weight, and time after transplantation. The susc eptibility of islets to ischemia-reperfusion injury, as quantitated by surgical anastomosis time, may have implications for islet transplant ation programs, as may the relative resistance of islets to allograft rejection, Glucose homeostasis after SPK, while remaining abnormal, ma y be used as the standard against which islet transplantation must be measured.