Protein Metabolism in Clinically Stable Adult Cystic Fibrosis Patients With Abnormal Glucose Tolerance

Abstract

In contrast, striking abnormalities were seen in CF patients when insulin was infused, since they did not experience normal suppression of the appearance rates of leucine, phenylalanine, or tyrosine (indexes of protein breakdown). At an insulin concentration of 45 ؎ 2 U/ml, normal control subjects suppressed the leucine appearance rate by 19 ؎ 5% (P < 0.01), ketoisocaproate appearance rate by 10 ؎ 3% (P ‫؍‬ 0.03), tyrosine appearance rate by 11 ؎ 2% (P ‫؍‬ 0.03), and phenylalanine appearance rate by 6 ؎ 3% (P ‫؍‬ 0.07). Phenylalanine conversion to tyrosine decreased by 22 ؎ 7% (P ‫؍‬ 0.03). At a similar insulin concentration of 44 ؎ 3 U/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 appearance 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 related to previously documented glucose tolerance status (IGT or CF-related diabetes without fasting hyperglycemia), fasting insulin levels, the acute insulin 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 insulin infusion in either normal control subjects or CF patients. In conclusion, clinically stable adult CF patients have normal indexes of protein breakdown and synthesis in the fasting state. In contrast, elevation of plasma insulin to physiological postprandial levels fails to normally suppress indexes of protein breakdown. It is therefore likely that inability to spare protein during the postprandial state is the cause of protein catabolism in these patients. Diabetes

Diabetes Is Associated With Dramatically Decreased Survival in Female but Not Male Subjects With Cystic Fibrosis

“…We have hypothesized that this chronic decline in clinical status, which begins long before the appearance of overt diabetes, is related to excessive breakdown of protein and lipid stores (25,26). An alternative explanation is that the development of frank diabetes is a marker for some other biological difference that is not immediately apparent.…”

“…In the current study, BMI was similar between female subjects with CFRD and the other study groups, suggesting comparable nutritional status, but lean body mass was not specifically measured. Insulin is a potent anabolic hormone, and insulin deficiency may contribute to morbidity and mortality in CF by promoting an overall catabolic state (25). Androgens are effective anabolic agents that may help maintain muscle mass in male subjects with CF, even in the presence of insulin deficiency.…”

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

“…Studies performed with these techniques have shown variable results, with both normal insulin sensitivity (24)(25)(26)(27) and insulin resistance for glucose (28)(29)(30), protein (31,32), and lipid metabolism (33). These may be related to increased glucose production and gluconeogenesis during fasting (34,35).…”

Insulin-secretion abnormalities and clinical deterioration related to impaired glucose tolerance in cystic fibrosis

“…This document states that nutritional and metabolic consequences of IGT in CF patients are still unknown and thus no specific guidelines for management are given, except for a close follow up to detect the onset of CFRD. However, recent studies pointed towards mild glucose metabolism alterations as a cause of clinical deterioration in patients with CF (23,24).…”