A. Moran et al., Protein metabolism in clinically stable adult cystic fibrosis patients with abnormal glucose tolerance, DIABETES, 50(6), 2001, pp. 1336-1343
Cystic fibrosis (CF) patients are reported to experience chronic protein ca
tabolism. Since diabetes or impaired glucose tolerance (IGT) is common in C
F, me hypothesized that their protein catabolic state is related to reduced
insulin secretion or reduced insulin action. A total of 12 clinically stab
le adult CF patients with abnormal glucose tolerance and 12 age-, sex-, and
lean body mass-matched healthy control subjects underwent protein turnover
studies using L-[l-C-13]leucine, L-[N-15] phenylalanine, and L-[H-2(4)]tyr
osine, with and without exogenous insulin infusion. In the baseline fasting
state, protein metabolism was entirely normal in CF patients, with no evid
ence of increased protein catabolism. In contrast, striking abnormalities m
ere seen in CF patients when insulin was infused, since they did not experi
ence normal suppression of the appearance rates of leucine, phenylalanine,
or tyrosine (indexes of protein breakdown). At an insulin concentration of
45 +/- 2 muU/ml, normal control subjects suppressed the leucine appearance
rate by 19 +/- 5% (P < 0.01), ketoisocaproate appearance rate by 10 <plus/m
inus> 3% (P = 0.03), tyrosine appearance rate by 11 +/- 2% (P = 0.03), and
phenylalanine appearance rate by 6 +/- 3% (P = 0.07). Phenylalanine convers
ion to tyrosine decreased by 22 +/- 7% (P = 0.03). At a similar insulin con
centration of 44 +/- 3 muU/ml, normal suppression of amino acid appearance
did not occur in CF. The leucine appearance rate decreased by 4 +/- 2% (P =
0.65), ketoisocaproate appearance rate by 1 +/- 2% (P = 0.94), tyrosine ap
pearance rate by 0 +/- 6% (P = 0.56), phenylalanine appearance rate by 5 +/
- 6% (P = 0.34), and phenylalanine conversion to tyrosine by 5 +/- 6% (P =
0.95). poor suppression of the amino acid appearance rate in CF was not rel
ated to previously documented glucose tolerance status (IGT or CF-related d
iabetes without fasting hyperglycemia), fasting insulin levels, the acute i
nsulin response, insulin sensitivity, cytokine or counterregulatory hormone
levels, resting energy expenditure, caloric intake, pulmonary function, or
clinical status. Protein synthesis was not significantly affected by insul
in infusion in either normal control subjects or CF patients. In conclusion
, clinically stable adult CF patients have normal indexes of protein breakd
own and synthesis in the fasting state. In contrast, elevation of plasma in
sulin to physiological postprandial levels fails to normally suppress index
es of protein breakdown. It is therefore likely that inability to spare pro
tein during the postprandial state is the cause of protein catabolism in th
ese patients.