Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis
Article first published online: 6 DEC 2005
Copyright © 1991 American Association for the Study of Liver Diseases
Volume 14, Issue 1, pages 103–111, July 1991
How to Cite
Kruszynska, Y. T., Home, P. D. and McIntyre, N. (1991), Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis. Hepatology, 14: 103–111. doi: 10.1002/hep.1840140117
- Issue published online: 6 DEC 2005
- Article first published online: 6 DEC 2005
- Manuscript Accepted: 21 FEB 1991
- Manuscript Received: 16 AUG 1990
Hepatic insulin extraction is difficult to measure in humans; as a result, the interrelationship between defective insulin secretion and insulin insensitivity in the pathogenesis of glucose intolerance in cirrhosis remains unclear. To reassess this we used recombinant human C-peptide to measure C-peptide clearance in cirrhotic patients and controls and thus derive C-peptide and insulin secretion rates after a 75-gm oral glucose load and during a 10 mmol/L hyperglycemic clamp. Cirrhotic patients were confirmed as insulin-insensitive during a euglycemic clamp (glucose requirement: 4.1 ± 0.1 mg/kg/min vs. 8.1 ± 0.5 mg/kg/min; p < 0.001), which also demonstrated a low insulin metabolic clearance rate (p < 0.001). Although intolerant after oral glucose, the cirrhotic patients had glucose requirements identical to those of controls during the hyperglycemic clamp (cirrhotic patients: 6.1 ± 1.0 mg/kg/min; controls: 6.3 ± 0.7 mg/kg/min), suggesting normal intravenous glucose tolerance.
C-peptide MCR was identical in cirrhotic patients (2.93 ± 0.16 ml/min/kg) and controls (2.96 ± 0.24 ml/min/kg). Insulin secretion was higher in cirrhotic patients, both fasting (2.13 ± 0.26 U/hr vs. 1.09 ± 0.10 U/hr; p < 0.001) and from min 30 to 90 of the hyperglycemic clamp (5.22 ± 0.70 U/hr vs. 2.85 ± 0.22 U/hr; p < 0.001). However, with oral glucose the rise in serum C-peptide concentration was relatively delayed, and the insulin secretion index (secretion/area under 3-hr glucose curve) was not elevated. Hepatic insulin extraction was reduced both in fasting and during the hyperglycemic clamp (p < 0.001).
Thus hypersecretion and decreased insulin clearance contribute to the four- to sixfold increased insulin levels in cirrhotic patients (fasting and after oral or intravenous glucose). In response to intravenous glucose, this hyperinsulinemia compensates for peripheral-tissue insulin insensitivity, accounting for normal rates of glucose disposal. In response to oral glucose, compensation is only partial, glucose intolerance being most marked in those cirrhotic patients with a lower insulin secretory response (r = −0.76, p < 0.02). (HEPATOLOGY 1991;14:103–111.)