Severity of HCV-induced liver damage alters glucose homeostasis in noncirrhotic patients with chronic HCV infection.
OBJECTIVE
To investigate the link between hepatitis C infection and glucose intolerance, we measured insulin sensitivity, glucose effectiveness and beta-cell secretion in noncirrhotic HCV-infected patients with normal glucose tolerance according to WHO criteria as assessed by oral glucose tolerance tests.


METHODS
Glucose, insulin and C-peptide data from frequently sampled intravenous glucose tolerance tests were analyzed using the minimal modeling technique for glucose and C-peptide to determine insulin sensitivity, glucose effectiveness, first and second phase insulin secretion in noncirrhotic HCV-infected patients (n = 10) and in healthy control subjects (n = 10). Histological activity index (HAI) as well as the extent of fibrosis were evaluated by scoring liver biopsies.


RESULTS
Insulin sensitivity (2.72 +/- 1.63 vs. 6.84 +/- 1. 20 10(-4) min(-1) per microU/ml, p < 0.01) and glucose effectiveness (2.29 +/- 0.45 vs. 2.89 +/- 0.39 10(-2) min(-1), p < 0.05) ere significantly lower in patients with HCV-induced liver disease. Insulin sensitivity was negatively related to serum alanine aminotransferase (r = -0.47, p < 0.05) and aspartate aminotransferase concentrations (r = -0.65, p < 0.05). Multiple linear regression analysis revealed a strong relation of insulin sensitivity with fibrosis score and HAI (r = -0.82, p < 0.02 for both). Second phase insulin secretion was significantly enhanced in HCV-infected patients (14.30 +/- 2.04 vs. 8.29 +/- 1.65 min(-1), p < 0.05).


CONCLUSIONS
HCV-infected patients with normal glucose tolerance are insulin and glucose resistant. The impairment of glucose tolerance appears to be closely related with the severity of HCV-induced liver damage.
Konrad
T
T
Department of Internal Medicine &ndash I, Research Group for Clinical Physiology and Transplantation Physiology, J.W. Goethe University, Frankfurt a.M., Germany. konrad-frankfurt@t-online.de
Zeuzem
S
S
Toffolo
G
G
Vicini
P
P
Teuber
G
G
Briem
D
D
Lormann
J
J
Lenz
T
T
Herrmann
G
G
Berger
A
A
Cobelli
C
C
Usadel
K
K
D000328:Adult; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology*; D005951:Glucose Tolerance Test; D019698:Hepatitis C, Chronic / Q000150:complications*; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012720:Severity of Illness Index