Evaluation of factors controlling glucose tolerance in patients with HCV infection before and after 4 months therapy with interferon-alpha.
BACKGROUND
Epidemiological data suggest that chronic hepatitis C virus (HCV) infection may contribute to the development of diabetes mellitus. Therapy of HCV infection with recombinant interferon-alpha (r-IFN-alpha) can also impair of glucose metabolism.


METHODS
To investigate the impact of HCV infection and the therapy with r-IFN-alpha on glucose metabolism we measured insulin sensitivity, glucose effectiveness, and first and second phase insulin secretion, using the minimal modelling analysis of frequently sampled intravenous glucose tolerance tests in 13 nondiabetic patients with HCV-induced liver disease before and after therapy with r-INF-alpha (6 x 106 U, subcutaneously, three times a week over 4 months). Liver biopsy was performed to evaluate and score liver fibrosis as a marker of HCV-induced cell injury.


RESULTS
Insulin sensitivity (r = - 0.59, P < 0.05) and first phase insulin secretion (r = - 0.66, P < 0.03) were negatively related to the fibrosis score. Insulin sensitivity rose from 1.96 (SEM 0.37, n = 8) to 5.69 (SEM 0.99, n = 8) 10-4 min-1 per microU mL-1 (P < 0.01) in responders and from 2.51 (SEM 0.61, n = 5) to 6.95 (SEM 1.99, n = 5) in nonresponders after 4 months r-INF-alpha therapy. Fasting free fatty acids decreased significantly to about 50% (P < 0.01) in patients with and without therapy response after 4 months, whereas first phase insulin secretion did not change.


CONCLUSIONS
HCV-induced liver injury is related to the deterioration of insulin sensitivity and first phase insulin response, thus impairing glucose homeostasis in these HCV-infected patients. The administration of r-INF-alpha three times a week over 4 months is not associated with an impairment of glucose homeostasis.
Konrad
T
T
J.W. Goethe-University, Frankfurt, Germany.
Zeuzem
S
S
Vicini
P
P
Toffolo
G
G
Briem
D
D
Lormann
J
J
Herrmann
G
G
Berger
A
A
Kusterer
K
K
Teuber
G
G
Cobelli
C
C
Usadel
K H
KH
D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000209:etiology; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis; D008297:Male; D012044:Regression Analysis
D001786:Blood Glucose; D007328:Insulin; D016898:Interferon-alpha