Changes in response to insulin and the effects of varying glucose tolerance on whole-body protein metabolism in patients with cystic fibrosis.
BACKGROUND
Diabetes mellitus has been reported to increase whole-body protein breakdown and thus loss of lean body mass. Cystic fibrosis-related diabetes (CFRD) is associated with undernutrition and increased mortality.


OBJECTIVE
We hypothesized that CFRD is associated with increased whole-body protein breakdown, which results in negative protein balance, and that correction of the glucose intolerance with insulin therapy would normalize whole-body protein metabolism.


METHODS
Rates of whole-body protein turnover and protein balance were measured in 28 adults with cystic fibrosis (17 M, 11 F). Subjects were assessed with a modified oral-glucose-tolerance test and categorized as having normal glucose tolerance, impaired glucose tolerance, or CFRD with and without fasting hyperglycemia; then they were compared with previously diagnosed CFRD adults already receiving insulin therapy. Indexes of protein turnover were calculated from [15N]glycine and 15N in urinary urea.


RESULTS
Analysis of variance for the 28 subjects showed that whole-body protein breakdown was highest (P<0.05) in patients with CFRD. Whole-body protein synthesis was not significantly affected by impaired glucose tolerance. Significant (P<0.05) improvement in net protein synthesis occurred in the CFRD group 3 mo after insulin therapy was administered. Follow-up studies of 3 subjects with CFRD showed significant improvement in net protein synthesis after insulin therapy. Monitoring of the protein homeostasis of the impaired glucose tolerance group gave clues to the progression of their metabolic homeostasis.


CONCLUSIONS
CFRD has an adverse effect on protein homeostasis by increasing net protein synthesis.
Rafii
Mahroukh
M
Department of Nutritional Sciences, University of Toronto, Toronto, Canada.
Chapman
Karen
K
Stewart
Cynthia
C
Kelly
Erin
E
Hanna
Amir
A
Wilson
David C
DC
Tullis
Elizabeth
E
Pencharz
Paul B
PB
D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D009587:Nitrogen Isotopes / Q000652:urine; D009752:Nutritional Status; D011506:Proteins / Q000378:metabolism*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D009587:Nitrogen Isotopes; D011506:Proteins