Effect of pancreas transplantation on free fatty acid metabolism in uremic IDDM patients

To assess the effect of pancreas transplantation on free fatty acid (FFA) and glucose metabolism, we studied seven uremic IDDM patients (HbA1c 9.1%), nine IDDM patients after combined kidney-pancreas transplantation (HbA1c 5.8%), seven patients with chronic uveitis (HbA1c 5.6%), and nine normal control subjects (HbA1c 5.5%) by means of the [3-3H]glucose and [1-14C]palmitate infusion techniques combined with indirect calorimetry and euglycemic insulin clamp. In the postabsorptive state, pancreas-transplant patients had similar plasma glucose and FFA concentrations and non-statistically different rates of hepatic glucose production (HGP) and FFA turnover, while demonstrating a reduced rate of FFA oxidation (42 ± 5 vs. 73 ± 10 μmicromol · m−2 · min−1; P < 0.05) compared with control subjects. After 180 min of tracer equilibration, all subjects underwent a low-dose (100 min, 8 mU · m−2 · min−1) followed by a high-dose (100 min, 40 mU · m−2 · min−1) euglycemic insulin infusion. During insulin infusion, pancreas-transplant patients showed a greater inhibition of FFA concentration (609 ± 76 to 58 ± 15 micromol/l) compared with healthy subjects (681 ± 90 to 187 ± 25 micromol/l; P < 0.01 vs. pancreas-transplant patients). FFA turnover and oxidation rates during both low-dose and high-dose insulin infusions were lower in pancreas-transplant patients compared with healthy subjects (P < 0.03 and P < 0.01, for turnover and oxidation, respectively). Uremic IDDM patients demonstration altered basal and insulin-mediated glucose metabolism. Pancreas transplantation normalized only insulin-mediated glucose oxidation, leaving the stimulation of non-oxidative glucose disposal still markedly defective. In conclusion, patients after pancreas transplantation have normal basal FFA turnover and reduced basal FFA oxidation rates. During hyperinsulinemia, pancreas-transplant patients show a normal inhibition of FFA turnover and FFA oxidation. Insulin-mediated glucose metabolism remained abnormal after pancreas transplantation. Our findings may be related to the effect of chronic immunosuppressive therapy on glucose and FFA metabolism.