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O.10 Nutritional value of hexose esters
Session 2 - N U T R I T I O N A L A S S E S S M E N T A N D
0.8 Diet induced thermogenesis and substrate oxidation in Crohn's disease X. Hebuterne, R. AI Jaouni and P. Rampal
Service de Gastroent6rologie et Nutrition, HSpital de I'Archet, 06202 Nice Cedex 3, France. Weight loss and malnutrition are common features in patients with Crohn's disease. Malnutrition can not be explained by the small increases in resting energy expenditure (REE) previously observed, and affect mainly the fat mass. The aim of this study was to evaluate diet induced thermogenesis (DIT) and substrate oxidation in Crohn's disease patients, compared to a group of patients without any active disease. Methods: 23 patients (15F/8M; 34 ___2 years) with biopsy proven ileal or ileo-colonic Crohrfs disease, and ten controls (4F/6M; 42 ___7 years) were studied. REE and fasting substrate oxidation were measured by indirect calorimetry in the morning after an overnight fast. After a standard homogenized test meal (10 kcal/kg of body weight), indirect calorimetry was performed every 30 min for three hours which allows the measurement of DIT, lipid oxidation (Lox) and Glucid oxidation (Gox). In patients and controls fat free mass (FFM) was measured by bioelectric impedance analysis. Results: 1) In the fasting state, REE was not different between Crohn's patients and controls (33.0 _+1.0 vs 31.5 _+1.5 kcal/kgFFM/day). Lox was higher in Crohn's patients than in controls (1.08 _+ 0.09 vs 0.65 _+ 0.32 g/kg/min: P < 0.01 ), and Gox was higher in controls than in Crohn's patients. 2) Postprandially, DIT was higher in controls than in Crohn's patients (7.8 _+0.5 vs 4.5 _+0.5% of energy intake: P < 0.01). Lox was higher in Crohn's patients than in controls (0.71 + 0.06 vs 0.30 _+ 0.18g/kg/min: P < 0.01), and Gox was higher in controls than in Crohn's patients. 3) In Crehn's patients, Lox significantly correlates with the disease activity evaluated by the CDAI (R = 0.48, P = 0.02), and the plasma c~l-acid giycoprotein levels (R = 0.61, P< 0.01). Lox did not correlate with the usage of corl:icosteroid or the nutritional state. 4) In active Crohn's patients (CDAI _>150), fasting Lox (1.19 _+0.11 vs 0.88 + 0.16; P < 0.05) and post-prandiall Lox (0.81 _+0.08 vs 0.57 +_0.05 mg/kg/min; P < 0.05) were significantly higher than in non-active Crohn's patients. Conclusions: Patients with Crohn's disease have an increased fat oxidation which correlates with disease activity. These findings may explain the reduced fat stores in Crohn's patients and suggest that a lipid-rich diet could be useful in the nutritional management of these patients.
0.9 Factors influencing control measurements using the hyperinsulinemic euglycemic clamp technique M. Seep, J. Nygren, A. Thorell and O. Ljungqvist
Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
Aims: The purpose of the present study was to determine the reproducibility of the hyperinsulinemic eugiycemic clamp technique at different intervals, and the effects of prolonged insulin infusions on glucose infusion rates (GIR). Methods: Seven healthy subjects, age 50 (26-58) (median (25th-75th percentile)), BMI 23 (21-25) were studied on 3 occasions. The first 2 studies were performed 48 hours apart and involved a 2 hour clamp (standard clamp). The 3rd study was performed 11-15 days later and involved a standard clamp that was extended to 8 hours (prolonged clamp). At all studies insulin was infused at 0.8 mU/kg/min and glucose maintained at 4.5mmol/L. Substrate oxidation rates were estimated using indirect calorimetry. Complete suppression of endogenous glucose production during clamps was assumed. Nonparametric statistics were used. Results: GIR during the standard clamp was very similar between the 3 occasions: 7.5 (4.9-9.9), 7.3 (5.4-9.5), and 6.6 (4.6-10.1) mg/kg/min (CV 10.5%), difference ns. During the prolonged clamp, GIR increased in all subjects, but to quite different degrees. GIR peaked during the 6th hour at a 25% (7-94%) increase from the standard clamp. The increase in GIR was significant from the standard clamp during the 3rd to the 7th hour (P < 0.05). The increase in GIR was inversely correlated to GIR during the standard clamp (r = -0.79, P < 0.05) and positively correlated to age (r = 0.86, P< 0.05), while BMI only tended to correlate positively (r = 0.57). Substrate oxidation rates were stable during the 3 standard clamps. Glucose oxidation was unchanged during the prolonged clamp while fat oxidation tended to decrease. Similarly to GIR, estimated non-oxidative glucose disposal increased (P < 0.05) during the prolonged clamp.
TECHNIQUES
Conclusions: The reproducibility of the hyperinsulinemic euglycemic clamp method is acceptable, even when 2 measurements are performed within 48 hours. Prolonged insulin infusions result in increased GIR, highly variable in magnitude. The increase in GIR seems to be mainly due to increased non-oxidative glucose disposal. The findings emphasize the importance of matching controls carefully regarding insulin sensitivity. Age and BMI were identified as important matching factors.
O.10
Nutritional value of hexose esters
L. Ladri~re, O. Kirk and W. J. Malaisse
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium and Novo Nordisk, Bagsvaerd, Denmark. An impairment of the carrier-mediated process of D-glucose transport across the plasma membrane represents a far from exceptional cause of altered hexose metabolism in several cell types. Such is the case, for instance, in diabetes mellitus. In order to bypass such a defect, advantage could conceivably be taken from the use of hexose esters, that might be able to enter into the cell without requiring the intervention of a specific carrier. The intracellular hydrolysis of the esters would then render the sugar readily available for phosphorylation and further metabolism. The present study aims at exploring such a novel approach of hexose supply. For this purpose, rat erythrocytes were incubated for 60rain in the absence or presence of D-glucose, (~-D-galactose pentaacetate (c~GaIPA), 6-O-acetyI-D-glucose (GluMA), c(-D-galactose paentaacetate (c(GaIPA) or J~-D-galactose pentaacetate (J3GaIPA), all tested at a 1.7 mM concentration. The production of lactic acid was then measured by an enzymatic procedure. The basal value for lactate production averaged 0.98 _+0.16 nmol per ~1 of erythrocytes (n -- 23). The increment in lactate formation above paired basal value averaged 1.83 -+ 0.08 nmol/l~l in the case of D-glucose (n = 18), 1.33 _+0.10 nmol/~l with o~GluPA(n = 18), 0.58 _+0.03 nmol/pl (n = 10) with GluMA, 0.13 + 0.03 nmol/pl with c~GaIPA(n = 4) and 0.11 -+ 0.03 nmol/~LI with ~GalPA (n = 15). The esters of D-glucose thus markedly augmented lactate production, albeit to a lesser extent than the unesterified hexose, whilst the esters of D-galactose only caused a minor increase in the formation of the acidic metabolite. A higher concentration (10.0 mM) of GluMA was able, however, to provoke an increment in lactate output (1.86 _+0.06 nmoI/,LLI;n = 5) comparable to that recorded in the presence of 1.7 mM D-glucose. These findings reveal that suitable hexose esters are indeed able to fuel the glycolytic pathway. They could be used, therefore, to prevent cellular glucopenia in situations characterized by a defect of carrier-mediated hexose transport.
0.11 Contributing factors to weight loss in chronic bronchitis and emphysema E. M. Baarends, E. C. Creutzberg, E. F M. Wouters and A. M. W. J. Schols Dept of Pulmonology, University Hospital Maastricht, Maastricht, The Netherlands. Weight loss is a common feature in patients with chronic obstructive pulmonary disease (COPD) and is related to a disturbed energy balance. Recently we demonstrated an increased total daily energy expenditure (TDE) (AJRRCM 1997), independently of resting energy expenditure (REE), in a subgroup of patients with COPD who were predominantly emphysematous. The aim of this study was to investigate whether patients with emphysema (n = 43:32M) or chronic bronchitis (n = 43:37M) differ in the factors contributing to weight loss. Recent weight loss and food intake were assessed by the diet history method and resting energy expenditure (REE) by indirect calorimetry. In addition, static lung volumes and inspiratory muscle strength were measured. The proportion of patients expressing weight loss was significantly higher in emphysema (n = 21) compared to chronic bronchitis (n = 11, P< 0.05), despite a similar intake (1967 _+558 vs 2116 _+530 kcal/24 h). REE was higher in chronic bronchitis compared to emphysema (1641 _+291 vs 1472 _+ 192 kcal/24 h, P < 0.01), however this difference was eliminated after correction for body composition. In addition, weight-losing patients did not demonstrate a different intake and REE from weight-stable patients. Weight-losing patients with emphysema demonstrated a higher ratio residual volume/total lung capacity (0.63 _+0.11 vs 0.56 _+0.08, P < 0.05) and a lower maximal inspiratory pressure than weight-stable patients with emphysema (-65 -+23 vs -79 _+18cm H20, P< 0.05).
0.8 Diet induced thermogenesis and substrate oxidation in Crohn's disease X. Hebuterne, R. AI Jaouni and P. Rampal
Service de Gastroent6rologie et Nutrition, HSpital de I'Archet, 06202 Nice Cedex 3, France. Weight loss and malnutrition are common features in patients with Crohn's disease. Malnutrition can not be explained by the small increases in resting energy expenditure (REE) previously observed, and affect mainly the fat mass. The aim of this study was to evaluate diet induced thermogenesis (DIT) and substrate oxidation in Crohn's disease patients, compared to a group of patients without any active disease. Methods: 23 patients (15F/8M; 34 ___2 years) with biopsy proven ileal or ileo-colonic Crohrfs disease, and ten controls (4F/6M; 42 ___7 years) were studied. REE and fasting substrate oxidation were measured by indirect calorimetry in the morning after an overnight fast. After a standard homogenized test meal (10 kcal/kg of body weight), indirect calorimetry was performed every 30 min for three hours which allows the measurement of DIT, lipid oxidation (Lox) and Glucid oxidation (Gox). In patients and controls fat free mass (FFM) was measured by bioelectric impedance analysis. Results: 1) In the fasting state, REE was not different between Crohn's patients and controls (33.0 _+1.0 vs 31.5 _+1.5 kcal/kgFFM/day). Lox was higher in Crohn's patients than in controls (1.08 _+ 0.09 vs 0.65 _+ 0.32 g/kg/min: P < 0.01 ), and Gox was higher in controls than in Crohn's patients. 2) Postprandially, DIT was higher in controls than in Crohn's patients (7.8 _+0.5 vs 4.5 _+0.5% of energy intake: P < 0.01). Lox was higher in Crohn's patients than in controls (0.71 + 0.06 vs 0.30 _+ 0.18g/kg/min: P < 0.01), and Gox was higher in controls than in Crohn's patients. 3) In Crehn's patients, Lox significantly correlates with the disease activity evaluated by the CDAI (R = 0.48, P = 0.02), and the plasma c~l-acid giycoprotein levels (R = 0.61, P< 0.01). Lox did not correlate with the usage of corl:icosteroid or the nutritional state. 4) In active Crohn's patients (CDAI _>150), fasting Lox (1.19 _+0.11 vs 0.88 + 0.16; P < 0.05) and post-prandiall Lox (0.81 _+0.08 vs 0.57 +_0.05 mg/kg/min; P < 0.05) were significantly higher than in non-active Crohn's patients. Conclusions: Patients with Crohn's disease have an increased fat oxidation which correlates with disease activity. These findings may explain the reduced fat stores in Crohn's patients and suggest that a lipid-rich diet could be useful in the nutritional management of these patients.
0.9 Factors influencing control measurements using the hyperinsulinemic euglycemic clamp technique M. Seep, J. Nygren, A. Thorell and O. Ljungqvist
Dept of Surgery, Karolinska Hospital, Stockholm, Sweden.
Aims: The purpose of the present study was to determine the reproducibility of the hyperinsulinemic eugiycemic clamp technique at different intervals, and the effects of prolonged insulin infusions on glucose infusion rates (GIR). Methods: Seven healthy subjects, age 50 (26-58) (median (25th-75th percentile)), BMI 23 (21-25) were studied on 3 occasions. The first 2 studies were performed 48 hours apart and involved a 2 hour clamp (standard clamp). The 3rd study was performed 11-15 days later and involved a standard clamp that was extended to 8 hours (prolonged clamp). At all studies insulin was infused at 0.8 mU/kg/min and glucose maintained at 4.5mmol/L. Substrate oxidation rates were estimated using indirect calorimetry. Complete suppression of endogenous glucose production during clamps was assumed. Nonparametric statistics were used. Results: GIR during the standard clamp was very similar between the 3 occasions: 7.5 (4.9-9.9), 7.3 (5.4-9.5), and 6.6 (4.6-10.1) mg/kg/min (CV 10.5%), difference ns. During the prolonged clamp, GIR increased in all subjects, but to quite different degrees. GIR peaked during the 6th hour at a 25% (7-94%) increase from the standard clamp. The increase in GIR was significant from the standard clamp during the 3rd to the 7th hour (P < 0.05). The increase in GIR was inversely correlated to GIR during the standard clamp (r = -0.79, P < 0.05) and positively correlated to age (r = 0.86, P< 0.05), while BMI only tended to correlate positively (r = 0.57). Substrate oxidation rates were stable during the 3 standard clamps. Glucose oxidation was unchanged during the prolonged clamp while fat oxidation tended to decrease. Similarly to GIR, estimated non-oxidative glucose disposal increased (P < 0.05) during the prolonged clamp.
TECHNIQUES
Conclusions: The reproducibility of the hyperinsulinemic euglycemic clamp method is acceptable, even when 2 measurements are performed within 48 hours. Prolonged insulin infusions result in increased GIR, highly variable in magnitude. The increase in GIR seems to be mainly due to increased non-oxidative glucose disposal. The findings emphasize the importance of matching controls carefully regarding insulin sensitivity. Age and BMI were identified as important matching factors.
O.10
Nutritional value of hexose esters
L. Ladri~re, O. Kirk and W. J. Malaisse
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium and Novo Nordisk, Bagsvaerd, Denmark. An impairment of the carrier-mediated process of D-glucose transport across the plasma membrane represents a far from exceptional cause of altered hexose metabolism in several cell types. Such is the case, for instance, in diabetes mellitus. In order to bypass such a defect, advantage could conceivably be taken from the use of hexose esters, that might be able to enter into the cell without requiring the intervention of a specific carrier. The intracellular hydrolysis of the esters would then render the sugar readily available for phosphorylation and further metabolism. The present study aims at exploring such a novel approach of hexose supply. For this purpose, rat erythrocytes were incubated for 60rain in the absence or presence of D-glucose, (~-D-galactose pentaacetate (c~GaIPA), 6-O-acetyI-D-glucose (GluMA), c(-D-galactose paentaacetate (c(GaIPA) or J~-D-galactose pentaacetate (J3GaIPA), all tested at a 1.7 mM concentration. The production of lactic acid was then measured by an enzymatic procedure. The basal value for lactate production averaged 0.98 _+0.16 nmol per ~1 of erythrocytes (n -- 23). The increment in lactate formation above paired basal value averaged 1.83 -+ 0.08 nmol/l~l in the case of D-glucose (n = 18), 1.33 _+0.10 nmol/~l with o~GluPA(n = 18), 0.58 _+0.03 nmol/pl (n = 10) with GluMA, 0.13 + 0.03 nmol/pl with c~GaIPA(n = 4) and 0.11 -+ 0.03 nmol/~LI with ~GalPA (n = 15). The esters of D-glucose thus markedly augmented lactate production, albeit to a lesser extent than the unesterified hexose, whilst the esters of D-galactose only caused a minor increase in the formation of the acidic metabolite. A higher concentration (10.0 mM) of GluMA was able, however, to provoke an increment in lactate output (1.86 _+0.06 nmoI/,LLI;n = 5) comparable to that recorded in the presence of 1.7 mM D-glucose. These findings reveal that suitable hexose esters are indeed able to fuel the glycolytic pathway. They could be used, therefore, to prevent cellular glucopenia in situations characterized by a defect of carrier-mediated hexose transport.
0.11 Contributing factors to weight loss in chronic bronchitis and emphysema E. M. Baarends, E. C. Creutzberg, E. F M. Wouters and A. M. W. J. Schols Dept of Pulmonology, University Hospital Maastricht, Maastricht, The Netherlands. Weight loss is a common feature in patients with chronic obstructive pulmonary disease (COPD) and is related to a disturbed energy balance. Recently we demonstrated an increased total daily energy expenditure (TDE) (AJRRCM 1997), independently of resting energy expenditure (REE), in a subgroup of patients with COPD who were predominantly emphysematous. The aim of this study was to investigate whether patients with emphysema (n = 43:32M) or chronic bronchitis (n = 43:37M) differ in the factors contributing to weight loss. Recent weight loss and food intake were assessed by the diet history method and resting energy expenditure (REE) by indirect calorimetry. In addition, static lung volumes and inspiratory muscle strength were measured. The proportion of patients expressing weight loss was significantly higher in emphysema (n = 21) compared to chronic bronchitis (n = 11, P< 0.05), despite a similar intake (1967 _+558 vs 2116 _+530 kcal/24 h). REE was higher in chronic bronchitis compared to emphysema (1641 _+291 vs 1472 _+ 192 kcal/24 h, P < 0.01), however this difference was eliminated after correction for body composition. In addition, weight-losing patients did not demonstrate a different intake and REE from weight-stable patients. Weight-losing patients with emphysema demonstrated a higher ratio residual volume/total lung capacity (0.63 _+0.11 vs 0.56 _+0.08, P < 0.05) and a lower maximal inspiratory pressure than weight-stable patients with emphysema (-65 -+23 vs -79 _+18cm H20, P< 0.05).