- Email: [email protected]
Effect of a late evening snack on the blood glucose level and energy metabolism in patients with liver cirrhosis
Hepatology Research 27 (2003) 45 /50 www.elsevier.com/locate/ihepcom
Effect of a late evening snack on the blood glucose level and energy metabolism in patients with liver cirrhosis Mariko Okamoto, Isao Sakaida *, Masako Tsuchiya, Chieko Suzuki, Kiwamu Okita Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube 755-8505, Yamaguchi Pref., Japan Received 8 July 2002; received in revised form 19 February 2003; accepted 24 March 2003
Abstract Background/aim: Patients with liver cirrhosis suffer from energy malnutrition. Late evening snacks (LESs) have been recently reported to be effective for this. However, it is known that a significant proportion of patients with liver cirrhosis have glucose intolerance as a complication. For this reason, the influence of LES on the blood glucose level should be examined. Subjects/method: We administered an oral supplement with branched-chain amino acids (Aminoleban EN) to patients with liver cirrhosis at 10 P.M. to investigate the changes of the blood glucose level and energy metabolism with an indirect calorimeter. Ten patients (average age, 70; Child A/B/C, 5/4/1) participated in this study. The administration period was 7 days. Blood glucose levels were examined before and after breakfast, lunch, supper and at 10 P.M. Results: (1) The fat oxidation rate was significantly decreased and the carbohydrate oxidation rate significantly increased. As a result, RQ was significantly improved. (2) With many cases, an increase of glucose level after meals seemed to reduce with LES administration for 1 week. (3) BTR was significantly improved. Conclusions: LES could improve energy malnutrition, correct amino acid imbalance, and ultimately may improve glucose intolerance in patients with liver cirrhosis. # 2003 Elsevier Science B.V. All rights reserved. Keywords: Late evening snacks; Liver cirrhosis; Glucose intolerance
1. Introduction Patients with liver cirrhosis usually have the proteinenergy malnutrition (PEM) [1,2]. A clinical investigation on nutritional metabolism in patients with liver cirrhosis, using an indirect calorimeter showed decreased nocturnal glucose oxidation causing fat and myoprotein catabolism [3]. As an attempt to improve the state of energy malnutrition, late evening snacks (LESs) have been developed, and improved energy substrate metabolism has been reported [4 /8]. However, there are different opinions as to what substrate should be administered as the gold standard. In addition, it is known that a significant proportion of patients with liver cirrhosis have glucose intolerance as a complication. It has been reported that glucose intolerance is
* Corresponding author. Tel.: /81-836-22-2239; fax: /81-836-222240. E-mail address: [email protected] (I. Sakaida).
found in approximately 70% of patients with liver cirrhosis, and in about 40% of those with diabetes [9]. Thus, the influence of LES, especially on glucose metabolism, should be examined. In this study, we administered an oral supplement with branched-chain amino acids (Aminoleban EN) to patients with liver cirrhosis to examine the energy metabolism with an indirect calorimeter, and also investigated the change of the blood glucose level to elucidate the effects of LES on glucose metabolism.
2. Subject and methods This study was performed on 10 patients with liver cirrhosis hospitalized in our hospital (Table 1). The patients, aged from 47 to 80 years, consisted of eight males and two females. Liver cirrhosis was caused by HBV in two cases and HCV in eight cases. Seven patients had hepatocellular carcinoma (HCC) as a
1386-6346/03/$ - see front matter # 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S1386-6346(03)00190-6
43 41 36 82 81 40 51 97 46 44 80 74 55 85 68 77 87 65 72 76 3.1 2.5 2.3 2.7 3.3 3.2 3.7 2.6 2.6 3.9 0.3 1 1.2 2.3 2.4 0.4 1.2 1.1 1.3 1 A [5] A [6] C [10] B [9] B [7] A [5] A [5] B [8] B [7] A [5] 20.3 25.7 22.3 20.6 22.7 21.2 25 28.3 19.4 24.5 50.6 64.5 42.5 54 56.6 42.5 74.1 80 49 75 158 158.5 138 162 158 140.7 172.3 168 159 175 M M F M M F M M M M
complication. Among the cases with HCC complication, four had one or two lesions with a size of 2 cm or less, and three had one to three lesions with a size of 3 cm or less. Child-Pugh scores, used for severity of liver damage, were A in five cases, B in four cases and C in one case. The last patient also had diabetes and was receiving insulin treatment. Examination was performed when the patients were in stable condition without ascites or other complications at least 1 week after admission. Upon examination prior to LES supplementation, patients fasted for at least 12 h and rested in bed until indirect calorimetry was finished. The indirect calorimeter used was a CALORIE SCALE (Chest MI). With measured oxygen consumption per minute (VO2), carbon dioxide production per minute (VCO2) and total urine nitrogen (TUN) on the day prior to the examination, fat oxidation and the non-protein respiratory quotient (npRQ) were calculated. Administration of Aminoleban EN (210 kcal per pack) consisted of two packs per day: one pack was taken as portions at different times in the daytime (between after breakfast and before supper), and the other pack was taken at 10 P.M. Calculation of the diet for each patient was based on the following conditions: 30 /35 kcal/(kg per day) as total calories for ideal body weight (BMI, 22), 1/1.5 g protein/ (kg per day), fat content equivalent to 25% of the total calories (Table 2). During LES administration, reducedcalorie diets were used, i.e., the calories equivalent to two packs of Aminoleban EN (420 kcal, protein 27 g, fat 7 g) were subtracted. The administration period was 7 days and the consumption of all patients was 100%. On days 1 and 7, nutritional evaluation by the indirect calorimeter of the blood glucose level, and biochemical examinations were performed. Each patient had one pack of Aminoleban EN at 10 P.M. on day 1, and divided meals including LES consisting of the above-described reduced-calorie diets with two packs of Aminoleban EN for the remaining study period. The change in the blood glucose level was measured at seven time points: 30 min before and 2 h after each meal and at 10 P.M. The levels before meals and those after meals on days 1 and 7 were compared. The branched-chain amino acid/tyrosine ratio (BTR) was also examined on days 1 and 7. BTR [10] is the molar ratio of (valine/leucine/isoleucine)/tyrosine, determined by measuring only tyrosine as an aromatic amino acid (AAA), different from the Fischer ratio. The nutrition supplement (Aminoleban EN) used in this study was comprised mainly of carbohydrate (59%), protein (26%) and fat (15%), which allowed high protein intake.
75 75 77 68 70 80 66 73 73 47
2.1. Statistical analysis
1 2 3 4 5 6 7 8 9 10
PT (%) Ammonia (mmol/dl) Albumin (g/dl) Bilirubin (mg/dl) Child-Pugh classification [score] Body mass index (kg/m2) Weight (kg) Case Age Gender Height (cm)
Table 1 Clinical profiles of patients
5.8 4.6 7.1 4.5 4.1 5.2 4.6 5 5.2 3.6
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50 HbA1c (%)
46
Data were expressed as the mean9/SE. Differences were tested by the Wilcoxon’s signed rank test and were
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50
47
Table 2 Dietary composition before LES Case
Total calories of the diet (kcal)
Protein (g)
Fat (g) (25% of total calories)
Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Case 10 EN x 2
1900 1700 1260 1740 1900 1500 2200 2000 1900 2200 420
75 (1.5 g/kg) 70 (1.3 g/kg) 40 (1.0 g/kg) 60 (1.0 g/kg) 70 (1.3 g/kg) 65 (1.5 g/kg) 95 (1.5 g/kg) 80 (1.3 g/kg) 75 (1.3 g/kg) 100 (1.5 g/kg) 26
55 50 35 50 55 45 60 55 55 60 7
(35 kcal/kg) (31 kcal/kg) (30 kcal/kg) (30 kcal/kg) (35 kcal/kg) (35 kcal/kg) (34 kcal/kg) (32 kcal/kg) (35 kcal/kg) (33 kcal/kg)
considered significant when the P-values were less than 0.05.
3. Results 3.1. Indirect calorimetry The value of npRQ increased significantly after 1 week LES administration (0.829/0.02 vs. 0.799/0.01,
P B/0.05). The fat oxidation rate as an energy substrate decreased significantly (51.79/5.8 vs. 63.79/4.6, P B/ 0.05) with the increase of the glucose oxidation rate (36.69/5.4 vs. 25.89/4.4, P B/0.05). The ratio of resting energy expenditure to the basal metabolic rate was 1.119/0.03 before LES, indicating elevated metabolism. After LES, it changed to 1.059/ 0.03. Although there was no significant difference, an improving tendency was seen. Data of all patients are as shown in Fig. 1.
Fig. 1. Changes in energy metabolism 1 week after LES administration in patients with liver cirrhosis. Before: before LES administration. After: after LES administration. Data expressed as mean9/SE are described in the text.
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50
48
Fig. 2. Changes in blood glucose levels of all patients. Blood glucose level was measured at the time point described in the text.
3.2. BTR measurement
3.3. The change of the blood glucose level
A significant increase in BTR was also observed after LES (5.569/0.73 vs. 3.529/0.56, P B/0.05). However, no significant difference was observed in the blood ammonia level (data not shown).
The changes of glucose levels of 10 patients at each point are shown in Fig. 2. With many cases, an increase of glucose level after meals seemed to reduce with LES administration for 1 week. Unexpectedly, there was no
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50
49
Table 3 Carbohydrate oxidation rate (%) LES
Before
Child A
Case 1 Case 2 Case 6 Case 7 Case 10 Mean9/SE
Child B
Case Case Case Case
4 5 8 9
Mean9/SE Child C
Case 3
31 16 38 40 20 299/4.8 16 11 12 53 239/10.6 21
RQ After 39 30 33 80 28 429/9.7 35 34 22 45 349/4.7 20
significant elevation of FBS after 1 week LES administration. 3.4. Changes of parameters according to Child-Pugh classification Changes of carbohydrate oxidation, RQ and FBS were examined according to Child-Pugh score (see Table 3). There was not clear difference between groups A and B with the changes of carbohydrate oxidation, RQ and FBS.
4. Discussion It has been recently shown that malnutrition greatly affects the prognosis of patients with liver cirrhosis [11 / 14]. Nutritional control, including alimentary therapy, is therefore important for the improvement of the patient’s prognosis and quality of life (QOL). Patients with liver cirrhosis suffer from a state of energy malnutrition in the early morning before breakfast, when the energy substrate balance inclines toward fat because of a decreased liver glycogen reserve with accompanying disordered glucose oxidation [3]. Decreased npRQ characterizes malnutrition in liver cirrhosis. Recently, LES have been used as a means for improving the state of energy malnutrition [4 /8]. A desirable LES substrate presumably contains not only a carbohydrate for energy supplementation, because BCAA-rich amino acid supplementation has the possibility to allow nocturnal protein synthesis. In addition, it should be digestible and easy to take, because patients can take it at bedtime without cooking by themselves. In this study, we used a commercially available nutrition supplement that is not only rich in carbohydrates and BCAA as amino acids but also supplements of vitamins and trace elements usually lacking in patients with liver cirrhosis. However,
FBS (mg/dl)
Before
After
Before
After
0.81 0.76 0.83 0.82 0.77 0.799/0.01
0.84 0.8 0.82 0.96 0.8 0.849/0.03
103 89 89 80 87 89.69/3.7
104 92 93 90 87 93.29/2.9
0.76 0.75 0.75 0.87
0.82 0.81 0.78 0.84
78 93 103 114
84 92 88 110
0.789/0.29
0.819/0.01
0.77
0.77
97.09/7.6 127
93.59/5.7 102
further study is necessary in future whether Aminoleban EN is better than light snack with glucose-rich as LES. On the other hand, it is well known that glucose intolerance is a complication found very frequently in liver cirrhosis [9,15]. Since liver cirrhosis accompanied by diabetes presents a high risk of hepatic insufficiency [16], it is also a critical prognostic factor to maintain good glucose metabolism. To further develop LES as an alimentary therapy for liver cirrhosis, their effects on the blood glucose level must be investigated and, if possible, designing for improving glucose intolerance will be required. This study revealed that the combination of LES and divided meals could improve the elevated blood glucose levels after meals in patients with liver cirrhosis. Although the patients of cases 3, 5 and 8 had glucose intolerance, the glucose level after meals seems to reduce 1 week after LES administration, at least in this study. Yamashita et al. [17] reported that glucose oxidation is retarded and increased in peripheral tissues in cirrhotic patients, which support this study. The reduced fat oxidation, improved npRQ and increased BTR observed in this study also suggested that LES with nutritional supplement for liver cirrhosis could improve energy malnutrition and correct the amino acid imbalance, leading to the possibility of improvement of glucose intolerance. Patients showed excellent compliance to LES used tentatively in this study. Since they could all take every meal, including Aminoleban EN, none dropped out. For patients feeling the difficulty for taking one pack at 10 P.M., we modified the regimen by, for example, decreasing the amount of water used to dissolve Aminoleban EN. No complaints such as abdominal fullness the next morning were reported. Moreover, the positive effects of LES for patients shown by actual data seemed to result in good post-hospitalization compliance to LES. Since alimentary therapy may have an effect on prognosis,
50
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50
etc., effects of longer administration of LES on prognosis and QOL must be investigated in the future, including detailed examinations for glucose tolerance.
Acknowledgements This study was approved by the Institutional Review Board Yamaguchi University Hospital.
References [1] Muller MJ. Malnutrition in cirrhosis. J Hepatol 1995;23(Suppl. 1):31 /5. [2] Lautz HU, Selberg O, Korber J, Burger M, Muller MJ. Proteincalorie malnutrition in liver cirrhosis. Clin Invest 1992;70:478 /86. [3] Owen OE, Trapp VE, Reichard GA, Jr., et al. Nature and quantity of fuels consumed in patients with alcoholic cirrhosis. J Clin Invest 1983;72:1821 /32. [4] Swart GR, Zillikens MC, van Vuure JK, van den Berg JW. Effect of a late evening meal on nitrogen balance in patients with cirrhosis of the liver. Br Med J 1989;299:1202 /3. [5] Chang WK, Chao YC, Tang HS, Lang HF, Hsu CT. Effects of extra-carbohydrate supplementation in the late evening on energy expenditure and substrate oxidation in patients with liver cirrhosis. J Parenter Enteral Nutr 1997;21:96 /9. [6] Zillikens MC, van den Berg JW, Wattimena JL, Rietveld T, Swart GR. Nocturnal oral glucose supplementation: the effects on protein metabolism in cirrhotic patients and in healthy controls. J Hepatol 1993;17:377 /83.
[7] Miwa Y, Shiraki M, Kato M, et al. Improvement of fuel metabolism by nocturnal energy supplementation in patients with liver cirrhosis. Hepatol Res 2000;18:184 /9. [8] Yamauchi M, Takeda K, Sakamoto K, Ohata M, Toda G. Effect of oral branched-chain amino acid supplementation in the late evening on the nutritional state of patients with liver cirrhosis. Hepatol Res 2001;21:199 /204. [9] Muller MJ, Pirlich M, Balks HJ, et al. Impaired glucose tolerance in liver cirrhosis: the role of hepatic and non-hepatic factors. Eur J Clin Biochem 1994;32:749 /58. [10] Kawamura-Yasui N, Kaito M, Nakagawa N, et al. Evaluating response to nutritional therapy using the branched-chain amino acid/tyrosine ratio in patients with chronic liver disease. J Clin Lab Anal 1999;13:31 /4. [11] Kondrup J, Muller MJ. Energy and protein requirements of patients with chronic liver disease. J Hepatol 1997;27:239 /47. [12] Alberino F, Gatta A, Amodio P, et al. Nutrition and survival in patients with liver cirrhosis. Nutrition 2001;17:445 /50. [13] Tajika M, Kato M, Mohri H, et al. Prognostic value of energy metabolism in patients with viral liver cirrhosis. Nutrition 2002;18:229 /34. [14] Hirsch S, de la Maza MP, Gattas V, et al. Nutritional support in alcoholic cirrhotic patients improves host defenses. J Am Coll Nutr 1999;18:434 /41. [15] Custro N, Carroccio A, Ganci A, et al. Glycemic homeostasis in chronic viral hepatitis and liver cirrhosis. Diabetes Metab 2001;27:476 /81. [16] Bianchi G, Marchesini G, Zoli M, Bugianesi E, Fabbri A, Pisi E. Prognostic significance of diabetes in patients with cirrhosis. Hepatology 1994;20:119 /25. [17] Yamashita S, Suzuki C, Tanigawa K, Sakaida I, Okita K. Glucose utilization after administration of glucose in patients with cirrhosis. Acta Hepatol Japon 1999;40:636 /44.
Effect of a late evening snack on the blood glucose level and energy metabolism in patients with liver cirrhosis Mariko Okamoto, Isao Sakaida *, Masako Tsuchiya, Chieko Suzuki, Kiwamu Okita Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube 755-8505, Yamaguchi Pref., Japan Received 8 July 2002; received in revised form 19 February 2003; accepted 24 March 2003
Abstract Background/aim: Patients with liver cirrhosis suffer from energy malnutrition. Late evening snacks (LESs) have been recently reported to be effective for this. However, it is known that a significant proportion of patients with liver cirrhosis have glucose intolerance as a complication. For this reason, the influence of LES on the blood glucose level should be examined. Subjects/method: We administered an oral supplement with branched-chain amino acids (Aminoleban EN) to patients with liver cirrhosis at 10 P.M. to investigate the changes of the blood glucose level and energy metabolism with an indirect calorimeter. Ten patients (average age, 70; Child A/B/C, 5/4/1) participated in this study. The administration period was 7 days. Blood glucose levels were examined before and after breakfast, lunch, supper and at 10 P.M. Results: (1) The fat oxidation rate was significantly decreased and the carbohydrate oxidation rate significantly increased. As a result, RQ was significantly improved. (2) With many cases, an increase of glucose level after meals seemed to reduce with LES administration for 1 week. (3) BTR was significantly improved. Conclusions: LES could improve energy malnutrition, correct amino acid imbalance, and ultimately may improve glucose intolerance in patients with liver cirrhosis. # 2003 Elsevier Science B.V. All rights reserved. Keywords: Late evening snacks; Liver cirrhosis; Glucose intolerance
1. Introduction Patients with liver cirrhosis usually have the proteinenergy malnutrition (PEM) [1,2]. A clinical investigation on nutritional metabolism in patients with liver cirrhosis, using an indirect calorimeter showed decreased nocturnal glucose oxidation causing fat and myoprotein catabolism [3]. As an attempt to improve the state of energy malnutrition, late evening snacks (LESs) have been developed, and improved energy substrate metabolism has been reported [4 /8]. However, there are different opinions as to what substrate should be administered as the gold standard. In addition, it is known that a significant proportion of patients with liver cirrhosis have glucose intolerance as a complication. It has been reported that glucose intolerance is
* Corresponding author. Tel.: /81-836-22-2239; fax: /81-836-222240. E-mail address: [email protected] (I. Sakaida).
found in approximately 70% of patients with liver cirrhosis, and in about 40% of those with diabetes [9]. Thus, the influence of LES, especially on glucose metabolism, should be examined. In this study, we administered an oral supplement with branched-chain amino acids (Aminoleban EN) to patients with liver cirrhosis to examine the energy metabolism with an indirect calorimeter, and also investigated the change of the blood glucose level to elucidate the effects of LES on glucose metabolism.
2. Subject and methods This study was performed on 10 patients with liver cirrhosis hospitalized in our hospital (Table 1). The patients, aged from 47 to 80 years, consisted of eight males and two females. Liver cirrhosis was caused by HBV in two cases and HCV in eight cases. Seven patients had hepatocellular carcinoma (HCC) as a
1386-6346/03/$ - see front matter # 2003 Elsevier Science B.V. All rights reserved. doi:10.1016/S1386-6346(03)00190-6
43 41 36 82 81 40 51 97 46 44 80 74 55 85 68 77 87 65 72 76 3.1 2.5 2.3 2.7 3.3 3.2 3.7 2.6 2.6 3.9 0.3 1 1.2 2.3 2.4 0.4 1.2 1.1 1.3 1 A [5] A [6] C [10] B [9] B [7] A [5] A [5] B [8] B [7] A [5] 20.3 25.7 22.3 20.6 22.7 21.2 25 28.3 19.4 24.5 50.6 64.5 42.5 54 56.6 42.5 74.1 80 49 75 158 158.5 138 162 158 140.7 172.3 168 159 175 M M F M M F M M M M
complication. Among the cases with HCC complication, four had one or two lesions with a size of 2 cm or less, and three had one to three lesions with a size of 3 cm or less. Child-Pugh scores, used for severity of liver damage, were A in five cases, B in four cases and C in one case. The last patient also had diabetes and was receiving insulin treatment. Examination was performed when the patients were in stable condition without ascites or other complications at least 1 week after admission. Upon examination prior to LES supplementation, patients fasted for at least 12 h and rested in bed until indirect calorimetry was finished. The indirect calorimeter used was a CALORIE SCALE (Chest MI). With measured oxygen consumption per minute (VO2), carbon dioxide production per minute (VCO2) and total urine nitrogen (TUN) on the day prior to the examination, fat oxidation and the non-protein respiratory quotient (npRQ) were calculated. Administration of Aminoleban EN (210 kcal per pack) consisted of two packs per day: one pack was taken as portions at different times in the daytime (between after breakfast and before supper), and the other pack was taken at 10 P.M. Calculation of the diet for each patient was based on the following conditions: 30 /35 kcal/(kg per day) as total calories for ideal body weight (BMI, 22), 1/1.5 g protein/ (kg per day), fat content equivalent to 25% of the total calories (Table 2). During LES administration, reducedcalorie diets were used, i.e., the calories equivalent to two packs of Aminoleban EN (420 kcal, protein 27 g, fat 7 g) were subtracted. The administration period was 7 days and the consumption of all patients was 100%. On days 1 and 7, nutritional evaluation by the indirect calorimeter of the blood glucose level, and biochemical examinations were performed. Each patient had one pack of Aminoleban EN at 10 P.M. on day 1, and divided meals including LES consisting of the above-described reduced-calorie diets with two packs of Aminoleban EN for the remaining study period. The change in the blood glucose level was measured at seven time points: 30 min before and 2 h after each meal and at 10 P.M. The levels before meals and those after meals on days 1 and 7 were compared. The branched-chain amino acid/tyrosine ratio (BTR) was also examined on days 1 and 7. BTR [10] is the molar ratio of (valine/leucine/isoleucine)/tyrosine, determined by measuring only tyrosine as an aromatic amino acid (AAA), different from the Fischer ratio. The nutrition supplement (Aminoleban EN) used in this study was comprised mainly of carbohydrate (59%), protein (26%) and fat (15%), which allowed high protein intake.
75 75 77 68 70 80 66 73 73 47
2.1. Statistical analysis
1 2 3 4 5 6 7 8 9 10
PT (%) Ammonia (mmol/dl) Albumin (g/dl) Bilirubin (mg/dl) Child-Pugh classification [score] Body mass index (kg/m2) Weight (kg) Case Age Gender Height (cm)
Table 1 Clinical profiles of patients
5.8 4.6 7.1 4.5 4.1 5.2 4.6 5 5.2 3.6
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50 HbA1c (%)
46
Data were expressed as the mean9/SE. Differences were tested by the Wilcoxon’s signed rank test and were
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50
47
Table 2 Dietary composition before LES Case
Total calories of the diet (kcal)
Protein (g)
Fat (g) (25% of total calories)
Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Case 10 EN x 2
1900 1700 1260 1740 1900 1500 2200 2000 1900 2200 420
75 (1.5 g/kg) 70 (1.3 g/kg) 40 (1.0 g/kg) 60 (1.0 g/kg) 70 (1.3 g/kg) 65 (1.5 g/kg) 95 (1.5 g/kg) 80 (1.3 g/kg) 75 (1.3 g/kg) 100 (1.5 g/kg) 26
55 50 35 50 55 45 60 55 55 60 7
(35 kcal/kg) (31 kcal/kg) (30 kcal/kg) (30 kcal/kg) (35 kcal/kg) (35 kcal/kg) (34 kcal/kg) (32 kcal/kg) (35 kcal/kg) (33 kcal/kg)
considered significant when the P-values were less than 0.05.
3. Results 3.1. Indirect calorimetry The value of npRQ increased significantly after 1 week LES administration (0.829/0.02 vs. 0.799/0.01,
P B/0.05). The fat oxidation rate as an energy substrate decreased significantly (51.79/5.8 vs. 63.79/4.6, P B/ 0.05) with the increase of the glucose oxidation rate (36.69/5.4 vs. 25.89/4.4, P B/0.05). The ratio of resting energy expenditure to the basal metabolic rate was 1.119/0.03 before LES, indicating elevated metabolism. After LES, it changed to 1.059/ 0.03. Although there was no significant difference, an improving tendency was seen. Data of all patients are as shown in Fig. 1.
Fig. 1. Changes in energy metabolism 1 week after LES administration in patients with liver cirrhosis. Before: before LES administration. After: after LES administration. Data expressed as mean9/SE are described in the text.
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50
48
Fig. 2. Changes in blood glucose levels of all patients. Blood glucose level was measured at the time point described in the text.
3.2. BTR measurement
3.3. The change of the blood glucose level
A significant increase in BTR was also observed after LES (5.569/0.73 vs. 3.529/0.56, P B/0.05). However, no significant difference was observed in the blood ammonia level (data not shown).
The changes of glucose levels of 10 patients at each point are shown in Fig. 2. With many cases, an increase of glucose level after meals seemed to reduce with LES administration for 1 week. Unexpectedly, there was no
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50
49
Table 3 Carbohydrate oxidation rate (%) LES
Before
Child A
Case 1 Case 2 Case 6 Case 7 Case 10 Mean9/SE
Child B
Case Case Case Case
4 5 8 9
Mean9/SE Child C
Case 3
31 16 38 40 20 299/4.8 16 11 12 53 239/10.6 21
RQ After 39 30 33 80 28 429/9.7 35 34 22 45 349/4.7 20
significant elevation of FBS after 1 week LES administration. 3.4. Changes of parameters according to Child-Pugh classification Changes of carbohydrate oxidation, RQ and FBS were examined according to Child-Pugh score (see Table 3). There was not clear difference between groups A and B with the changes of carbohydrate oxidation, RQ and FBS.
4. Discussion It has been recently shown that malnutrition greatly affects the prognosis of patients with liver cirrhosis [11 / 14]. Nutritional control, including alimentary therapy, is therefore important for the improvement of the patient’s prognosis and quality of life (QOL). Patients with liver cirrhosis suffer from a state of energy malnutrition in the early morning before breakfast, when the energy substrate balance inclines toward fat because of a decreased liver glycogen reserve with accompanying disordered glucose oxidation [3]. Decreased npRQ characterizes malnutrition in liver cirrhosis. Recently, LES have been used as a means for improving the state of energy malnutrition [4 /8]. A desirable LES substrate presumably contains not only a carbohydrate for energy supplementation, because BCAA-rich amino acid supplementation has the possibility to allow nocturnal protein synthesis. In addition, it should be digestible and easy to take, because patients can take it at bedtime without cooking by themselves. In this study, we used a commercially available nutrition supplement that is not only rich in carbohydrates and BCAA as amino acids but also supplements of vitamins and trace elements usually lacking in patients with liver cirrhosis. However,
FBS (mg/dl)
Before
After
Before
After
0.81 0.76 0.83 0.82 0.77 0.799/0.01
0.84 0.8 0.82 0.96 0.8 0.849/0.03
103 89 89 80 87 89.69/3.7
104 92 93 90 87 93.29/2.9
0.76 0.75 0.75 0.87
0.82 0.81 0.78 0.84
78 93 103 114
84 92 88 110
0.789/0.29
0.819/0.01
0.77
0.77
97.09/7.6 127
93.59/5.7 102
further study is necessary in future whether Aminoleban EN is better than light snack with glucose-rich as LES. On the other hand, it is well known that glucose intolerance is a complication found very frequently in liver cirrhosis [9,15]. Since liver cirrhosis accompanied by diabetes presents a high risk of hepatic insufficiency [16], it is also a critical prognostic factor to maintain good glucose metabolism. To further develop LES as an alimentary therapy for liver cirrhosis, their effects on the blood glucose level must be investigated and, if possible, designing for improving glucose intolerance will be required. This study revealed that the combination of LES and divided meals could improve the elevated blood glucose levels after meals in patients with liver cirrhosis. Although the patients of cases 3, 5 and 8 had glucose intolerance, the glucose level after meals seems to reduce 1 week after LES administration, at least in this study. Yamashita et al. [17] reported that glucose oxidation is retarded and increased in peripheral tissues in cirrhotic patients, which support this study. The reduced fat oxidation, improved npRQ and increased BTR observed in this study also suggested that LES with nutritional supplement for liver cirrhosis could improve energy malnutrition and correct the amino acid imbalance, leading to the possibility of improvement of glucose intolerance. Patients showed excellent compliance to LES used tentatively in this study. Since they could all take every meal, including Aminoleban EN, none dropped out. For patients feeling the difficulty for taking one pack at 10 P.M., we modified the regimen by, for example, decreasing the amount of water used to dissolve Aminoleban EN. No complaints such as abdominal fullness the next morning were reported. Moreover, the positive effects of LES for patients shown by actual data seemed to result in good post-hospitalization compliance to LES. Since alimentary therapy may have an effect on prognosis,
50
M. Okamoto et al. / Hepatology Research 27 (2003) 45 /50
etc., effects of longer administration of LES on prognosis and QOL must be investigated in the future, including detailed examinations for glucose tolerance.
Acknowledgements This study was approved by the Institutional Review Board Yamaguchi University Hospital.
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