Measurement of the whole body clearance of infused glycerol as a test of liver function after major hepatectomy
Summary Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells...
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| Published in | Clinical physiology and functional imaging Vol. 22; no. 4; pp. 266 - 270 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Science, Ltd
01.07.2002
Blackwell Science |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1475-0961 1475-097X |
| DOI | 10.1046/j.1475-097X.2002.00429.x |
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| Abstract | Summary
Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells, may be suitable as a simple test of liver function. Seven patients after major hepatectomy, six patients after colectomy and 12 healthy subjects were studied. Patients were investigated on the first day after surgery. All participants were studied during a 150‐min basal period followed by a 120‐min infusion of 16 μmol kg−1 min−1 13C‐labelled glycerol. Whole body glycerol clearance was calculated from the change in plasma glycerol concentration. Whole body glucose production was measured with 6,6 2H2 glucose infused as a tracer in the basal state and during glycerol infusion. In addition, 13C glucose synthesis was monitored to quantitate gluconeogenesis from glycerol. Patients after liver resection had higher plasma glycerol concentrations and lower whole body glycerol clearance than healthy subjects and patients after colectomy. They also had higher plasma glucagon concentrations. Their fasting glucose production was mildly elevated in the fasting state and did not change after glycerol infusion, indicating a normal hepatic autoregulation of glucose production. These results indicate that whole body glycerol clearance can be simply determined from plasma glycerol concentrations during exogenous glycerol infusion. It is significantly reduced in patients after major hepatectomy, suggesting that it constitutes a sensitive test of hepatic function. Its use as a preoperative testing procedure remains to be evaluated. |
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| AbstractList | Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells, may be suitable as a simple test of liver function. Seven patients after major hepatectomy, six patients after colectomy and 12 healthy subjects were studied. Patients were investigated on the first day after surgery. All participants were studied during a 150-min basal period followed by a 120-min infusion of 16 mumol kg-1 min-1 13C-labelled glycerol. Whole body glycerol clearance was calculated from the change in plasma glycerol concentration. Whole body glucose production was measured with 6,6 2H2 glucose infused as a tracer in the basal state and during glycerol infusion. In addition, 13C glucose synthesis was monitored to quantitate gluconeogenesis from glycerol. Patients after liver resection had higher plasma glycerol concentrations and lower whole body glycerol clearance than healthy subjects and patients after colectomy. They also had higher plasma glucagon concentrations. Their fasting glucose production was mildly elevated in the fasting state and did not change after glycerol infusion, indicating a normal hepatic autoregulation of glucose production. These results indicate that whole body glycerol clearance can be simply determined from plasma glycerol concentrations during exogenous glycerol infusion. It is significantly reduced in patients after major hepatectomy, suggesting that it constitutes a sensitive test of hepatic function. Its use as a preoperative testing procedure remains to be evaluated. Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells, may be suitable as a simple test of liver function. Seven patients after major hepatectomy, six patients after colectomy and 12 healthy subjects were studied. Patients were investigated on the first day after surgery. All participants were studied during a 150‐min basal period followed by a 120‐min infusion of 16 μmol kg −1 min −1 13 C‐labelled glycerol. Whole body glycerol clearance was calculated from the change in plasma glycerol concentration. Whole body glucose production was measured with 6,6 2 H 2 glucose infused as a tracer in the basal state and during glycerol infusion. In addition, 13 C glucose synthesis was monitored to quantitate gluconeogenesis from glycerol. Patients after liver resection had higher plasma glycerol concentrations and lower whole body glycerol clearance than healthy subjects and patients after colectomy. They also had higher plasma glucagon concentrations. Their fasting glucose production was mildly elevated in the fasting state and did not change after glycerol infusion, indicating a normal hepatic autoregulation of glucose production. These results indicate that whole body glycerol clearance can be simply determined from plasma glycerol concentrations during exogenous glycerol infusion. It is significantly reduced in patients after major hepatectomy, suggesting that it constitutes a sensitive test of hepatic function. Its use as a preoperative testing procedure remains to be evaluated. Summary Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells, may be suitable as a simple test of liver function. Seven patients after major hepatectomy, six patients after colectomy and 12 healthy subjects were studied. Patients were investigated on the first day after surgery. All participants were studied during a 150‐min basal period followed by a 120‐min infusion of 16 μmol kg−1 min−1 13C‐labelled glycerol. Whole body glycerol clearance was calculated from the change in plasma glycerol concentration. Whole body glucose production was measured with 6,6 2H2 glucose infused as a tracer in the basal state and during glycerol infusion. In addition, 13C glucose synthesis was monitored to quantitate gluconeogenesis from glycerol. Patients after liver resection had higher plasma glycerol concentrations and lower whole body glycerol clearance than healthy subjects and patients after colectomy. They also had higher plasma glucagon concentrations. Their fasting glucose production was mildly elevated in the fasting state and did not change after glycerol infusion, indicating a normal hepatic autoregulation of glucose production. These results indicate that whole body glycerol clearance can be simply determined from plasma glycerol concentrations during exogenous glycerol infusion. It is significantly reduced in patients after major hepatectomy, suggesting that it constitutes a sensitive test of hepatic function. Its use as a preoperative testing procedure remains to be evaluated. Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells, may be suitable as a simple test of liver function. Seven patients after major hepatectomy, six patients after colectomy and 12 healthy subjects were studied. Patients were investigated on the first day after surgery. All participants were studied during a 150-min basal period followed by a 120-min infusion of 16 mumol kg-1 min-1 13C-labelled glycerol. Whole body glycerol clearance was calculated from the change in plasma glycerol concentration. Whole body glucose production was measured with 6,6 2H2 glucose infused as a tracer in the basal state and during glycerol infusion. In addition, 13C glucose synthesis was monitored to quantitate gluconeogenesis from glycerol. Patients after liver resection had higher plasma glycerol concentrations and lower whole body glycerol clearance than healthy subjects and patients after colectomy. They also had higher plasma glucagon concentrations. Their fasting glucose production was mildly elevated in the fasting state and did not change after glycerol infusion, indicating a normal hepatic autoregulation of glucose production. These results indicate that whole body glycerol clearance can be simply determined from plasma glycerol concentrations during exogenous glycerol infusion. It is significantly reduced in patients after major hepatectomy, suggesting that it constitutes a sensitive test of hepatic function. Its use as a preoperative testing procedure remains to be evaluated.Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells, may be suitable as a simple test of liver function. Seven patients after major hepatectomy, six patients after colectomy and 12 healthy subjects were studied. Patients were investigated on the first day after surgery. All participants were studied during a 150-min basal period followed by a 120-min infusion of 16 mumol kg-1 min-1 13C-labelled glycerol. Whole body glycerol clearance was calculated from the change in plasma glycerol concentration. Whole body glucose production was measured with 6,6 2H2 glucose infused as a tracer in the basal state and during glycerol infusion. In addition, 13C glucose synthesis was monitored to quantitate gluconeogenesis from glycerol. Patients after liver resection had higher plasma glycerol concentrations and lower whole body glycerol clearance than healthy subjects and patients after colectomy. They also had higher plasma glucagon concentrations. Their fasting glucose production was mildly elevated in the fasting state and did not change after glycerol infusion, indicating a normal hepatic autoregulation of glucose production. These results indicate that whole body glycerol clearance can be simply determined from plasma glycerol concentrations during exogenous glycerol infusion. It is significantly reduced in patients after major hepatectomy, suggesting that it constitutes a sensitive test of hepatic function. Its use as a preoperative testing procedure remains to be evaluated. |
| Author | Tappy, Luc Revelly, Jean-Pierre Cayeux, Marie-Christine Berger, Mette Vallet, Cedric Matter, Maurice Gillet, Michel Chioléro, René Koestinger, Armin |
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| Cites_doi | 10.1152/ajpendo.1995.268.4.E630 10.1152/ajpendo.1996.271.6.E1110 10.1053/bega.1999.0048 10.1152/ajpendo.1990.258.2.E288 10.1097/00000658-199904000-00009 10.1159/000129474 10.1002/cpt1972132159 10.1111/j.1600-0676.1986.tb00293.x 10.1002/lt.500050201 10.1152/ajpgi.2000.278.6.G967 10.1210/jcem-54-5-961 10.1152/ajplegacy.1970.219.2.497 10.1152/ajpendo.1987.252.1.E77 10.2337/diabetes.46.2.204 10.1097/00075197-199903000-00012 10.1046/j.1365-2281.1998.00136.x 10.1155/1995/47538 10.1097/00007890-200005270-00045 |
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| Keywords | Human Digestive system Liver Glycerol Hepatic disease Clearance Glucose Metabolism Hepatectomy Surgery Digestive diseases Tumor Quantitative analysis Gluconeogenesis |
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| References | Chiolero R, Tappy L, Gillet M et al. Effect of a major hepatectomy on glucose and lactate metabolism. Ann Surg (1999); 229: 505-513. Newsholme EA, Leech AR. Biochemistry for the Medical Sciences (1983). John Wiley & Sons, Chichester. Kaiho T, Miyazaki M, Ito H et al. Reduced hepatic functional reserve in cirrhosis and obstructive jaundice with special reference to histological morphometric analysis and galactose elimination capacity. Eur Surg Res (1996); 28: 333-340. Winkler B, Rathgeb I, Steele R, Altszuler N. Conversion of glycerol to glucose in the normal dog. Am J Physiol (1970); 219: 497-502. Landau BR, Wahren J, Previs SF, Ekberg K, Chandramouli V, Brunengraber H. Glycerol production and utilization in humans: sites and quantitation. Am J Physiol (1996); 271: E1110-E1117. Proietto J, Rohner-Jeanrenaud F, Ionescu E, Terrettaz J, Sauter JF, Jeanrenaud B. Non-steady-state measurement of glucose turnover in rats by using a one-compartment model. Am J Physiol (1987); 252: E77-E84. Zoedler T, Ebener C, Becker H, Roeher HD. Evaluation of liver function tests to predict operative risk in liver surgery. HPB Surg (1995); 9: 13-18. DeBodo R, Steele R, Altszuler N, Dunn A, Bishop J. On the hormonal regulation of carbohydrate metabolism: studies with 14C-glucose. Recent Prog Horm Res (1963); 19: 445-488. Tourtellotte WW, Reinglass JL, Newkirk TA. Cerebral dehydration action of glycerol. I. Historical aspects with emphasis on the toxicity and intravenous administration. Clin Pharmacol Ther (1972); 13: 159-171. Jahoor F, Peters EJ, Wolfe RR. The relationship between gluconeogenic substrate supply and glucose production in humans. Am J Physiol (1990); 258: E288-E296. Keller U, Sonnenberg GE, Burckhardt D, Perruchoud A. Evidence for an augmented glucagon dependence of hepatic glucose production in cirrhosis of the liver. J Clin Endocrinol Metab (1982); 54: 961-968. Houben KW, McCall JL. Liver transplantation for hepatocellular carcinoma in patients without underlying liver disease: a systematic review. Liver Transplant Surg (1999); 5: 91-95. Tappy L, Chiolero R, Berger M. Autoregulation of glucose production in health and disease. Curr Opin Clin Nutr Metab Care (1999); 2: 161-164. Zoli M, Marchesini G, Melli A, Viti G, Marra A, Marrano D, Pisi E. Evaluation of liver Volume and liver function following hepatic resection in man. Liver (1986); 6: 286-291. Henry S, Trueb L, Sartori C, Scherrer U, Jequier E, Tappy L. Effects of a sympathetic activation by lower body negative pressure on glucose and lipid metabolism. Clin Physiol (1998); 18: 562-569. Tappy L, Cayeux M-C, Schneiter P et al. Effects of lactate on glucose metabolism in healthy subjects and in severely injured hyperglycemic patients. Am J Physiol (1995); 268: E630-E635. DeMatteo RP, Fong Y, Blumgart LH. Surgical treatment of malignant liver tumours. Best Prac Res Clin Gastroenterol (1999); 13: 557-574. Koestinger A, Gillet M, Chiolero R, Mosimann F, Tappy L. Effect of liver transplantation on hepatic glucose metabolism in a patient with type 1 glycogen storage disease. Transplantation (2000); 69: 2205-2207. Shangraw RE, Jahoor F. Lipolysis and lipid oxidation in cirrhosis and after liver transplantation. Am J Physiol (2000); 278: G967-G973. Tappy L, Dussoix P, Iynedjian P et al. Abnormal regulation of hepatic glucose output in Maturity onset diabetes of the young caused by a specific mutation of the glucokinase gene. Diabetes (1997); 46: 204-208. 1987; 252 1995; 9 1998; 18 1996; 28 1990; 258 2000; 69 2000; 278 1982; 54 1997; 46 1986; 6 1999; 13 1996; 271 1983 1995; 268 1999; 2 1972; 13 1999; 5 1999; 229 1963; 19 1970; 219 Newsholme EA (e_1_2_6_12_1) 1983 Winkler B (e_1_2_6_19_1) 1970; 219 e_1_2_6_21_1 e_1_2_6_10_1 e_1_2_6_20_1 DeBodo R (e_1_2_6_3_1) 1963; 19 e_1_2_6_9_1 e_1_2_6_8_1 e_1_2_6_5_1 e_1_2_6_4_1 e_1_2_6_7_1 e_1_2_6_6_1 e_1_2_6_13_1 e_1_2_6_14_1 e_1_2_6_11_1 e_1_2_6_2_1 e_1_2_6_17_1 e_1_2_6_18_1 e_1_2_6_15_1 e_1_2_6_16_1 |
| References_xml | – reference: Jahoor F, Peters EJ, Wolfe RR. The relationship between gluconeogenic substrate supply and glucose production in humans. Am J Physiol (1990); 258: E288-E296. – reference: Winkler B, Rathgeb I, Steele R, Altszuler N. Conversion of glycerol to glucose in the normal dog. Am J Physiol (1970); 219: 497-502. – reference: Keller U, Sonnenberg GE, Burckhardt D, Perruchoud A. Evidence for an augmented glucagon dependence of hepatic glucose production in cirrhosis of the liver. J Clin Endocrinol Metab (1982); 54: 961-968. – reference: Landau BR, Wahren J, Previs SF, Ekberg K, Chandramouli V, Brunengraber H. Glycerol production and utilization in humans: sites and quantitation. Am J Physiol (1996); 271: E1110-E1117. – reference: Shangraw RE, Jahoor F. Lipolysis and lipid oxidation in cirrhosis and after liver transplantation. Am J Physiol (2000); 278: G967-G973. – reference: Tappy L, Chiolero R, Berger M. Autoregulation of glucose production in health and disease. Curr Opin Clin Nutr Metab Care (1999); 2: 161-164. – reference: Chiolero R, Tappy L, Gillet M et al. Effect of a major hepatectomy on glucose and lactate metabolism. Ann Surg (1999); 229: 505-513. – reference: Kaiho T, Miyazaki M, Ito H et al. Reduced hepatic functional reserve in cirrhosis and obstructive jaundice with special reference to histological morphometric analysis and galactose elimination capacity. Eur Surg Res (1996); 28: 333-340. – reference: Zoedler T, Ebener C, Becker H, Roeher HD. Evaluation of liver function tests to predict operative risk in liver surgery. HPB Surg (1995); 9: 13-18. – reference: Zoli M, Marchesini G, Melli A, Viti G, Marra A, Marrano D, Pisi E. Evaluation of liver Volume and liver function following hepatic resection in man. Liver (1986); 6: 286-291. – reference: DeBodo R, Steele R, Altszuler N, Dunn A, Bishop J. On the hormonal regulation of carbohydrate metabolism: studies with 14C-glucose. Recent Prog Horm Res (1963); 19: 445-488. – reference: Henry S, Trueb L, Sartori C, Scherrer U, Jequier E, Tappy L. Effects of a sympathetic activation by lower body negative pressure on glucose and lipid metabolism. Clin Physiol (1998); 18: 562-569. – reference: Koestinger A, Gillet M, Chiolero R, Mosimann F, Tappy L. Effect of liver transplantation on hepatic glucose metabolism in a patient with type 1 glycogen storage disease. Transplantation (2000); 69: 2205-2207. – reference: Newsholme EA, Leech AR. Biochemistry for the Medical Sciences (1983). John Wiley & Sons, Chichester. – reference: Proietto J, Rohner-Jeanrenaud F, Ionescu E, Terrettaz J, Sauter JF, Jeanrenaud B. Non-steady-state measurement of glucose turnover in rats by using a one-compartment model. Am J Physiol (1987); 252: E77-E84. – reference: Tappy L, Dussoix P, Iynedjian P et al. Abnormal regulation of hepatic glucose output in Maturity onset diabetes of the young caused by a specific mutation of the glucokinase gene. Diabetes (1997); 46: 204-208. – reference: Tappy L, Cayeux M-C, Schneiter P et al. Effects of lactate on glucose metabolism in healthy subjects and in severely injured hyperglycemic patients. Am J Physiol (1995); 268: E630-E635. – reference: DeMatteo RP, Fong Y, Blumgart LH. Surgical treatment of malignant liver tumours. Best Prac Res Clin Gastroenterol (1999); 13: 557-574. – reference: Houben KW, McCall JL. Liver transplantation for hepatocellular carcinoma in patients without underlying liver disease: a systematic review. Liver Transplant Surg (1999); 5: 91-95. – reference: Tourtellotte WW, Reinglass JL, Newkirk TA. Cerebral dehydration action of glycerol. I. Historical aspects with emphasis on the toxicity and intravenous administration. 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Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively... Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it... |
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| SubjectTerms | Adult Aged Biological and medical sciences Colectomy Fasting - metabolism Female gluconeogenesis Glucose - biosynthesis glucose production Glycerol - administration & dosage Glycerol - blood Glycerol - pharmacokinetics glycerol metabolism Hepatectomy Humans Infusions, Intravenous liver cancer Liver Function Tests Liver, biliary tract, pancreas, portal circulation, spleen Male Medical sciences Middle Aged Osmolar Concentration Postoperative Period Reference Values Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the digestive system |
| Title | Measurement of the whole body clearance of infused glycerol as a test of liver function after major hepatectomy |
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