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PEDIATRICS Vol. 101 No. 3 March 1998, pp. 433-437

Proteolysis Associated With Insulin Resistance in Cystic Fibrosis

Received Aug 1, 1997; accepted Oct 15, 1997.

Dana S. Hardin*, §, Adrian LeBlancDagger , Sheila Lukenbaugh§, Laurie Para§, and Dan K. Seilheimer§

From the * Department of Pediatrics, University of Texas Health Science Center, Houston, Texas; the Dagger  Department of Medicine, Baylor College of Medicine, Houston, Texas; and the § Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas.

Objective.  We hypothesized that patients with cystic fibrosis (CF) have higher rates of protein breakdown than normal volunteers and that the infusion of insulin would result in less suppression of proteolysis.

Methods.  Using [1-13C]leucine and a three-step hyperinsulinemic euglycemic clamp, we measured rates of leucine appearance in 29 adult CF patients and 18 matched-control volunteers. The CF patients were characterized by oral glucose tolerance testing and clinical status scoring.

Results.  The CF patients had significantly increased proteolysis when compared with that of controls (CF, 123 ± 28 µmol/kg/h; controls, 71 ± 15 µmol/kg/h) and rates of proteolysis were significantly different between CF patients with impaired glucose tolerance and diabetes and those CF patients with normal glucose tolerance. Suppression of proteolysis by insulin was less in all CF subgroups than in the controls at peripheral insulin levels of 16 and 29 µU/mL. At peripheral insulin levels of 100 µU/mL, there was no difference in insulin suppression of proteolysis between CF patients and controls. Importantly, basal rates of proteolysis had an inverse relationship with clinical status in CF patients (r = -.76).

Conclusions.  Our findings indicate that proteolysis is higher in adult CF patients than in controls and that CF patients exhibit resistance to the anabolic effects of insulin on proteolysis. Most significantly, our findings indicate that basal rates of proteolysis inversely correlate with clinical status in CF.

Key words: proteolysis, insulin resistance, cystic fibrosis.




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