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Abstract
Patients with hepatic cirrhosis often have demonstrable glucose intolerance. We studied
21 patients with cirrhosis of the liver. Oral glucose tolerance tests (OGTT), intravenous
arginine stimulation tests (IVAST), and intravenous insulin tolerance tests (IVITT)
were performed, and timed blood samples were obtained for the assay of glucose immunoreactive
insulin (IRI), C-peptide (C-P), and immunoreactive glucagon (IRG). The 125I-insulin binding to circulating monocytes was studied in some of the patients. All
results were compared to those of similar studies performed on healthy controls. During
OGTT significant glucose intolerance was demonstrable in the patients with cirrhosis
(2 hr plasma glucose 198.8 ± 14.3 mg/dl in cirrhosis and 116.4 ± 4.2 in controls;
p < 0.001). Two-hour plasma IRI, C-P, and IRG were significantly higher in the cirrhotic
patients than in controls (p < 0.001; < 0.001; < 0.025). In response to IVAST, the
patients with cirrhosis showed a greater first-phase insulin secretion and controls
had a slightly better second-phase insulin release. Plasma IRG rose from a basal value
of 446 pg/ml to 1100 in the patients with cirrhosis and from 171 pg/ml to 494 in controls.
After intravenous insulin administration, there was only a 40% decline in plasma glucose
concentration from basal values in the patients with cirrhosis whereas the controls
showed a 60% decline, demonstrating that the patients with cirrhosis had significant
insulin resistance. Moreover, the half-life of insulin was prolonged in the patients
with cirrhosis (![Math Eq]()
in cirrhosis and 10.3 in controls; p < 0.001); and the ratio of C-P to insulin during
OGTT was also reduced, indicating that the patients with cirrhosis have reduced hepatic
clearance of insulin. The specific binding of 125I-insulin to circulating monocytes was 2.7% in cirrhosis, 2% in obese controls, and
4% in lean controls. There was a significant negative correlation between the fasting
plasma insulin values and the specific binding of insulin. In conclusion, patients
with hepatic cirrhosis have significant glucose intolerance characterized by hyperinsulinemia,
hyperglucagonemia, insulin resistance, and down-regulation of insulin receptors. Although
hyperinsulinemia is probably caused by reduced hepatic clearance of insulin, hyperglucagonemia
is primarily due to increased pancreatic secretion.
in cirrhosis and 10.3 in controls; p < 0.001); and the ratio of C-P to insulin during
OGTT was also reduced, indicating that the patients with cirrhosis have reduced hepatic
clearance of insulin. The specific binding of 125I-insulin to circulating monocytes was 2.7% in cirrhosis, 2% in obese controls, and
4% in lean controls. There was a significant negative correlation between the fasting
plasma insulin values and the specific binding of insulin. In conclusion, patients
with hepatic cirrhosis have significant glucose intolerance characterized by hyperinsulinemia,
hyperglucagonemia, insulin resistance, and down-regulation of insulin receptors. Although
hyperinsulinemia is probably caused by reduced hepatic clearance of insulin, hyperglucagonemia
is primarily due to increased pancreatic secretion.Abbreviations:
Oral glucose tolerance test ((OGTT)), intravenous insulin tolerance test ((IVITT)), intravenous arginine stimulations test ((IVAST)), immunoreactive insulin ((IRI)), immunoreactive glucagon ((IRG)), C-peptide ((C-P)), bovine serum albumin ((BSA))To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
May 24,
1983
Received:
November 23,
1982
Footnotes
☆This work was supported by grants from the Veterans Administration (S. S. S., W. C. D.) and National Institute of Health 01A,29008; ∗National Institute of Health Training Grant(s) AM0708803 and NIH Short term Student Training Grant 1-T-35AM-07405-02.
☆☆Presented in part at the Southern Meeting, American Federation for Clinical Research, New Orleans, La., January 1982, and at the 64th Annual meeting of the Endocrine Society at San Francisco, June 1982.
Identification
Copyright
© 1983 Published by Elsevier Inc.
