Insulin regulation of free fatty acid kinetics in adult cystic fibrosis patients with impaired glucose tolerance

Abstract

Cystic fibrosis (CF) patients are insulin-resistant with regards to suppression of hepatic glucose production and proteolysis, but the effect of insulin on adipose free fatty acid (FFA) release has not been studied. [9,10-(3)H]palmitate kinetics were measured in 11 stable adult CF patients with impaired glucose tolerance (IGT) and 9 normal control subjects. Baseline plasma palmitate concentrations [CF = 99 +/- 13 (median 74, range 65 to 187); control = 88 +/- 9 (88, 46 to 138) micromol/L, P = .9] and palmitate flux [CF = 114 +/- 11 (100, 72 to 171); control = 105 +/- 12 (106, 54 to 182) micromol/min, P = 0.9] were not different between CF patients and controls. During a euglycemic clamp with infusion of insulin to physiologic postprandial levels, however, palmitate concentrations tended to be higher in CF patients: CF = 18 +/- 3 (13, 10 to 47), control = 12 +/- 1 (11, 8 to 18) micromol/L, P = 0.08. The higher palmitate concentrations during hyperinsulinemia appeared to be due to reduced suppression of adipose tissue palmitate release, because mean palmitate flux was 33% greater in CF subjects [32 +/- 5 (26, 17 to 66) micromol/min] than controls: [24 +/- 2 (23, 17 to 34) micromol/min], P = .20. There was considerably greater heterogeneity in insulin-induced suppression of plasma palmitate concentration and flux in CF patients compared to normal control subjects. In summary, a defect in insulin suppression of lipolysis was seen in clinically stable CF patients with IGT, similar to what has been described in CF for amino acid and glucose metabolism. This quantitative difference in lipolysis may account for inadequate insulin-induced suppression of hepatic glucose production in CF, and may be a metabolic adaptation to increased energy needs.