[en] To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test (0.3 g glucose/kg BW) in nine compensated cirrhotic patients and nine healthy volunteers well matched for age, sex, and body weight. The insulin secretion rate was derived by the deconvolution of plasma C-peptide levels, insulin sensitivity was calculated using Bergman's minimal model method, and insulin clearance was estimated by dividing the 0-180 min area under the curve of insulin secretion rate by that of peripheral plasma insulin levels. The cirrhotic patients were characterized during the frequently sampled i.v. glucose tolerance test by a 60% greater insulin secretion rate (P < 0.05), a markedly reduced insulin sensitivity index (SI; 2.82 +/- 0.75 vs. 5.86 +/- 0.68 x 10(-4) min/mU.L; P < 0.01) and a 40% reduced insulin clearance (725 +/- 169 vs. 1165 +/- 99 mL/min.m-2; P < 0.05). The reduction of insulin clearance was significantly correlated with the amplitude of the portosystemic shunt, measured using an isotopic method (r = 0.75; P < 0.02). In conclusion, cirrhosis is characterized by an important peripheral hyperinsulinism, resulting from both a higher insulin secretion rate and a reduced insulin hepatic clearance; the severe insulin resistance explains the glucose metabolism alterations.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Letiexhe, Michel ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Gerard, Pascale ; Centre Hospitalier Universitaire de Liège - CHU > Neurologie CHR
Bastens, B. H.
Pirotte, Jeannine ; Université de Liège - ULiège > Département des sciences cliniques > Médecine générale
Belaiche, Jacques ; Centre Hospitalier Universitaire de Liège - CHU > Gastro-Entérologie-Hépatologie
Lefebvre, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Language :
English
Title :
Insulin secretion, clearance, and action on glucose metabolism in cirrhotic patients.
Publication date :
1993
Journal title :
Journal of Clinical Endocrinology and Metabolism
ISSN :
0021-972X
eISSN :
1945-7197
Publisher :
Endocrine Society, Chevy Chase, United States - Maryland
Schölmerich J, Holstege A. 1990 Aetiology and pathophysiology of chronic liver disorders. Drugs. 40:3-22.
Huet PM, Villeneuve JP, Pomier-Layrargues G, Maarleau D. 1985 Hepatic circulation in cirrhosis. Clin Gastroenterol. 14:155-168.
Petrides AS, DeFronzo RA. 1989 Glucose metabolism in cirrhosis: a review with some perspectives for the future. Diabetes Metab Rev. 5:691-709.
Shmueli E, Record CO, Alberti KGMM. 1992 Liver disease, carbohydrate metabolism and diabetes. Baillieres Clin Endocrinol Metab. 6:719-743.
Johnston DG, Alberti KG, Binder C, Faber OK, Wright R, Orskov H. 1982 Hormonal and metabolic changes in hepatic cirrhosis. Horm Metab Res. 14:34-39.
Iwasaki Y, Sato H, Ohkubo A, et al. 1980 Effect of spontaneous portal-systemic shunting on plasma insulin and amino acid concentration. Gastroenterology. 78:677-683.
Petrides AS, Groop LC, Riely CA, DeFronzo RA. 1991 Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis. J Clin Invest. 88:561-570.
Muller MJ, Willmann O, Rieger A, Fenk A, Selberg O, Lautz HU. 1992 Mechanism of insulin resistance associated with liver cirrhosis. Gastroenterology. 102:2033-2041.
Kruszynska YT, Harry DS, Bergman RN, McIntyre N. 1993 Insulin sensitivity, insulin secretion and glucose effectiveness in diabetic and non-diabetic cirrhotic patients. Diabetologia. 36:121-128.
Marchesini G, Pacini G, Bianchi G, Patrono D, Cobelli C. 1990 Glucose disposal, β-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment. Gastroenterology. 99:1715-1722.
Field JB, Rojdmark S, Harding P et al. 1980 Role of liver in insulin physiology. Diabetes Care. 3:255-260.
Ferrannini E, Cobelli C. 1987 The kinetics of insulin in man. Diabetes Metab Rev. 3:335-397.
Proietto J, Dudley FJ, Aitken P, Alford FP. 1984 Hyperinsulinemia and insulin resistance of cirrhosis: the importance of insulin hypersecretion. Clin Endocrinol (Oxf). 21:657-665.
Andersen BN, Hagen C, Faber OK, Lindholm J, Boisen P, Worn-ing H. 1983 Glucose tolerance and B cell function in chronic alcoholism: its relation to hepatic histology and exocrine pancreatic function. Metabolism. 32:1029-1032.
Iwasaki Y, Ohkubo A, Kajinuma H, Akanuma Y, Kosaka K. 1978 Degradation and secretion of insulin in hepatic cirrhosis. J Clin Endocrinol Metab. 47:774-779.
Johnston D, Alberti K Faber O, Binder C. 1977 Hyperinsulinism of hepatic cirrhosis: diminished degradation or hypersecretion? Lancet. 1:10-13.
Polonsky KS, Rubenstein AH. 1984 C-peptide as a measure of the secretion and hepatic extraction of insulin. Pitfalls and limitations. Diabetes. 33:486-494.
Vannini P, Forlani G, Marchesini G, Ciavarella A, Zoli M, Pisi E. 1984 The euglycemic clamp technique in patients with liver cirrhosis. Horm Metab Res. 16:341-343.
Cavallo-Perin P, Bruno A, Nuccio P, Goria M, Pagano G, Lenti G. 1986 Feedback inhibition of insulin secretion is altered in cirrhosis. J Clin Endocrinol Metab. 63:1023-1027.
Kruszynska YT, Home PD, McIntyre N. 1991 Relationship between insulin sensitivity, insulin secretion and glucose tolerance in cirrhosis. Hepatology. 14:103-111.
Magnusson J, Tranberg KG. 1987 Impaired early insulin response to intravenous glucose in alcoholic liver cirrhosis. Scand J Gastroenterol. 22:301-307.
Kruszynska YT, Munro J, Home PD, McIntyre N. 1992 Twenty-four hour C-peptide and insulin secretion rates and diurnal profiles of glucose, lipids and intermediary metabolites in cirrhosis. Clin Sei. 83:597-605.
Pacini G Cobelli. 1990 Estimation of d-cell secretion and insulin hepatic extraction by the minimal modeling technique. Comp Methods Progr Biomed. 32:241-248.
Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. 1973 Transection of oesophagus for bleeding oesophageal varices. Br J Surg. 60:646-649.
Pauwels S. Geubel AP, Dive C, Beckers C. 1982 Breath14C02 after intravenous administration on [14C] aminopyrine in liver diseases. Dig Sei. 27:49-56.
Shiomi S, Kuroki T, Kurai O et al. 1988 Portal circulation by technetium 99m pertechnetate per rectal portal scintigraphy. J Nucl Med. 29:460-465.
Pirotte J, Lambinet N, Dereze C, Etienne M, Rigo P, Belaiche J. 1992 Portal systemic shunting in patients with alcoholic liver disease. Relationships with portal pressure, histological lesions and liver function. Eur J Gastroenterol Hepatol. 4:183-187.
Bergman RN, Phillips LS, Cobelli C. 1981 Physiologic evaluation of factors controlling glucose tolerance in man. Measurement of insulin sensitivity and B-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest. 68:1456-1467.
Scheen AJ, Lefèbvre PJ. 1992 Assessment of insulin resistance in vivo: application to the study of type 2 diabetes. Horm Res. 38:19-27.
Hales CN, Randle PJ. 1963 Immunoassay of insulin with insulin-antibody precipitate. BiochemJ. 88:137-146.
Heding LG. 1975 Radioimmunological determination of human C-peptide in serum. Diabetologia. 11:541-548.
Polonsky KS, Licinio-Paixao J, Given BD, et al. 1986 Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest. 77:98-105.
Van Cauter E, Mestrez F, Sturis J, Polonsky KS. 1992 Estimation of insulin secretion rate from C-peptide levels. Diabetes. 41:368-377.
Shapiro ET, Tillil H, Miller MA, et al. 1987 Insulin secretion and clearance: comparison after oral and intravenous glucose. Diabetes. 36:1365-1371.
Conard V. 1955 Mesure de l'assimilation du glucose. Bases théo-riques et applications cliniques. PhD thesis, Université Libre de Bruxelles, Brussels, Belgium. 1-139.
Zerbe GO. 1979 Randomization analysis of the completely randomized design extended to growth and response curves. J Am Stat Assoc. 74:215-221.
Proietto J, Alford F, Dudley F. 1980 The mechanism of carbohydrate intolerance of cirrhosis. J Clin Endocrinol Metab. 51:1030-1036.
Cavallo-Perin P, Cassader M, Bozzo C, et al. 1985 Mechanism of insulin resistance in human liver cirrhosis. Evidence of a combined receptor and postreceptor defect. J Clin Invest. 75:1659-1665.
Iversen J, Vilstrup H, Tygstrup N. 1984 Kinetics of glucose metabolism in relation to insulin concentrations in patients with alcoholic cirrhosis and in healthy persons. Gastroenterology. 87:1138-1143.
Marchesini G, Melli A, Checchia GA, et al. 1985 Pancreatic βcell function in cirrhotic patients with and without overt diabetes. C-Peptide response to glucagon and to meal. Metabolism. 34:695-701.
Pelkonen R, Kallio H, Suoranta H, Karonen SL. 1981 Plasma insulin, C-peptide, and blood glucose in portal, hepatic and peripheral veins in liver cirrhosis. Effect of intravenous tolbutamide. Acta Endocrinol (Copenh). 97:496-502.
Greco A, Crucitti F, Ghirlanda G, et al. 1979 Insulin and glucagon concentration in portal and peripheral veins in patients with hepatic cirrhosis. Diabetologia. 17:23-28.
Nygren A, Adner N, Sundblad L, Wiechel KL. 1985 Insulin uptake by the human alcoholic cirrhotic liver. Metabolism. 34:48-52.
Bosch J, Gomis R, Kravetz D, et al. 1984 Role of spontaneous portal-systemic shunting in hyperinsulinism of cirrhosis. Am J Physiol. 247:G206-G212.
Ohnishi K, Mishima, Takashi M, et al. 1983 Effects of intra- and extrahepatic portal systemic shunts on insulin metabolism. Dig Dis. 28:201-206.
Holst J, Burcharth F, Kühl C. 1980 Pancreatic glucoregulatory hormones in cirrhosis of the liver: portal vein concentrations during intravenous glucose tolerance test and in response to a meal. Diabetes Metab. 6:117-127.
Smith-Laing G, Sherlock S, Faber OK. 1979 Effects of spontaneous portal-systemic shunting on insulin metabolism. Gastroenterology. 76:685-690.
Cavallo-Perin P, Bruno A, Nuccio P, et al. 1986 Insulin resistance in human liver cirrhosis is not modified by porto-systemic surgical shunt. Acta Endocrinol (Copenh). 112:377-382.
Sirinek KR, O'Dorisio TM, Levine BA. 1991 Glucose intolerance and hyperinsulinemia of cirrhosis are not results of spontaneous or surgical portosystemic shunting. Am J Surg 161:149-153.
