Circulating cytokines and anorexia in pancreatic cancer patients
1
April 1995 Growth, Development, and Nutrition A715 Growth. Develooment. and Nutrition COMPARISONS OF METABOLIC RESPONSES TO DIGESTIBLE AND PARTLY UNDIGESTIBLE STARCHES IN HEALTHY HUMANS L. AchouL B. Flourie, F. Briet, C. Franchisseur, F. Bomet, J.C. Rambaud, B. Messing INSERM U290, h6pital saint-Lazare, 75010 et l~ridania Bdghin-Say, 75008, Paris Starch is the main energetic fuel in the human diet. Most starches are extensively digested in the human small intestine. It is now technologically possible to modify starch in order to slow down its digestion in the small intestine. The digestion of technologically modified starches will start in the small intestine and continue in the colon, where its fermentation releases short chain fatty acids (mainly acetate) and gases 0-I2, COO. The metabolic consequences of this shift in starch digestion could have potential health benefits. In this study, we measured certain metabolic indexes in healthy humans consuming a highly digestible corn starch and the same corn starch after ratrogradation, which is 50% digested in the human small intestine and completely fermented in the colon (Eur J Clin Nutr 1992, 46; S 131- S132) Methods: 8 healthy volunteers were studied during 2 periods separated by one week. In each period, fasting volunteers consumed at 8 am the test meal containing either the digestible or retrograded corn starch; blood and breath were sampled in the absorptive period hourly for 8 hours. The same meal was given again the same day at 10 pm; at 8 am on the next morning, i.e. 10 hours after the ingestion of the test meal, blood and breath were sampled in the fasting subjects hourly for 3 hours i.e~ in the post-absorptive period. Results In the absorptive period, after the ingestion of digestible starch the glycemic index and area under the insulin curve were higher, and blood glycerol concentrations were lower (p<0,05) than after the ingestion of retrograded starch. In the post-absorptive period, after the ingestion of digestible starch the respiratory quotient, 13CO2 and H2 excretion in breath, blood acetate concentrations and satiety index were significantlylower, whereas blood glycerol concentrations were higher (13<0,05) than after the ingestion of retrograded starch. Conclusions In healthy humans, the digestion of retrograded corn starch is slow in the small intestine and its colonic fermentation continues 10 to 13 hours after its ingestion. Compared to the highly digestible com starch, the shift in starch digestion induced by retrogradation leads to changes in metabolic responses: retrograded corn starch reduces the giycemic and insulinic responses in the absorptive period, and lipolysis in the post-absorptive period. This last effect could be related to mainhibitory action on the lipolysis of short chain fatty acids produced during the colonic fermentation of unabsorbed starch. • FECAL ENERGETIC LOSSES: IMPORTANCE OF THE BACTERIAL MASS L. Achour, B. Flourit, F. Briat, C. Franchisseur, M Maurel, F. Thnillier, J.C. Rambaud, B. Messing INSERM U290, hfpital Saint-Lazare, 75010 Paris, France. In humans, nutrients which escape intestinal absorption and colonic fermentation will be lost in stools. These losses will be increased in patients with malabsorptiun syndrome. In addition, stools contain endogenous substrates among them bacteria are a major component, whose the growth may be stimulated when more dietary nutrients are available for bacterial fermentation. In assessing/he extent of nutrient and calorie absorption along the gastrointestinal tract, the magnitude of error introduces by the bacterial fraction of stools is unknown. Methods: We studied 6 healthy volunteers and 6 patients with short bowel and colon in continuity (SBC) under free oral intake. The bacterial mass of stools collected for 24 hours was isolated (fractionation procedure). Total fecal and bacterial calorie contents were determined by bomb calorimetry. Total fecal and bacterial fat was measured by the method of Van de Kamer and total and bacterial nitrogen by pyrochemihiminescance. Results (means-+-SEM) Stool Dry Total Bacterial Bacterial weight weight energy weight energy (g/d) (g/d) (kcal/d) (g/d) (kcal/d) Volunteers 150a:16 424-4 208±20 19~-2 104±13 Patients 1228±276 1494-33 9524-235 53-4-15 312:t:85 In healthy volunteers and patients with short bowel and colon in continuity, fecal bacterial mass accounted for 44 and 35 % of fecal dry weight, and contained 50 and 31% of total fecal energy. Bacterial calorie contents were close to 6 kcal/g of bacteria. In healthy volunteers, 59 and 24 % of total fecal lipid and nitrogen belonged to bacteria; these percentages were respectively 38 and 19 % in short bowel patients. Conclusions: Nutrient and energetic balance studies by calculating the difference between ingested nutriants/calories and fecally excreted nutrients/calories assume that fecal losses are from dietary origin and do not take into account endogenous energetic losses, as fecal bacteria. This assumption leads to an underestimation of the amounts of nutriants and calories which are absorbed in the gastrointestinal tract. From a nutritional point of view, this error is significant in patients with malabsorption syndrome and colon in continuity. • QUANTIFICATION OF ARTIFICIAL FAT MALABSORPTION BY THE 13C-HIOLEIN BREATH TEST IN HEALTHY VOLUNTEERS. H.Ashraf. P.Hildebrand, R.Meier*, B.Meyer-Wyss, C.Beglinger A.Chdst, K.Gyr. Division of Gastroenterology and Department of Internal Medicine University Hospital, CH-4031 Base and *D vision of Gastroenterology, Kantonsspital, CH-4410 Liestal, Switzerland Tetrahydrolipstatin (THL) is a potent irreversible inhibitor of gastrointestinal lipases which induces fat malabsorption in humans and was developed with the intention to support weight loss in obesity. THL is therefore an excellent tool to investigate artificially induced fat malabsorption by a non-invasive breath test. Various 13C-labeled triglycerides have been previously used in breath tests assessing fat maldigestion or malabsorption. The aim of the present study was to use the 13C-hiolein breath test to assess THL-induced fat malabsorption in healthy volunteers. 13C-hiolein is a long-chain triglycedde with all C atoms of the molecule 13C-labeled. We assume that this test yields faster and higher 13002 recovery than carboxyMabeled 13C-triglycerides. Methods: 8 healthy volunteers of normal weight underwent 2 study periods of 4 days of diet (100 g fat/day) with or without THL 120 mg t.i.d. On the last day o[ each phase, a 13C-hiolein breath test (2 mg/kg with the test meal) was performed. 13002 recovery in breath samples was measured over 24 hours by isotope ratio mass spectrometry. Results: The peak 13002 excretion occurred only after 5 hours in both treatments with little difference during the first 4 hours. THL potently reduced fat digestion and absorption with the most pronounced effect observed after 8 hours: 1.1 _+ 0.2 vs. 2.3 + 0.3% dose/h in control experiments (p<0.05). The 24 hours cumulative 13002 excretion was also significantly reduced by THL: 14.9 + 2.2 vs. 28.4 _+ 4.1% dose in control experiments (p<0.05). Summary: 13002 recovery after 13C-hiolein administration was slow and in the same range as in other trigtyceride breath tests indicating that the high number of labeled C atoms per molecule does not substantially alter the metabolism. THL 120 mg t.i.d, induced a fat malabsorption that could be detected 'by the 13C-hiolein breath test most efficiently between 5 and 12 hours after administration of the tracer. We conclude that 13C-hiolein is not superior to other labeled triglycerides to detect fat malabsorption in humans. • CIRCULATING CYTOKINES AND ANOREXIA IN PANCREATIC CANCER PATIENTS. lAB Ballin2er, 1M Armed, 2N Rudd, IM McHugh, 3jA Woolley, 1EM Alstend, 1ML Clark. Depts. of ~Gastroenterology & ~Chemical Pathology, St Bartholomew's Hospital and 2palliative Care Medicine, Whipps Cross Hospital, London UK. Anorexia is a common symptom in patients with malignant bile duct obstruction and is significantly improved following stent insertion and relief of the obstruction ~. Animals with a ligated bile duet also have a reduced food intake and this is associated with increased circulating concentrations of IL-6 and TNF-a. These cytoldnes, together with IL-la, are implicated in the pathogenesis of anorexia and cachexia seen in patients with inflammatory and malignant conditions. The aim of this study was to explore the hypothesis that circulating cytoldnes contribute to the anorexia seen in jaundiced pancreatic cancer patients. 16 pancreatic cancer patients completed a graded symptom questionnaire (0=no loss of appetite, 3=severe anorexia) pre stent and 1 and 4 weeks after stenting. 13 patients with other cancers (cancer controls) and 10 healthy controls completed the questionnaire on a single occasion. Blood was taken when each questionnaire was completed. TNF-~ and IL-I~ were measured by ELISA (Amersham UK) and IL-6 by IRMA. All patients with pancreatic cancer were jaundiced before stent insertion (mean serum bilirubin 143 pmol/l) with complete relief by 4 weeks. There was marked anorexia before stenting (median score 2.5 [interquartile range 1-3]) with significant improvement by 4 weeks after stent insertion (0 [0-1 ]). 5 of the cancer control patients were anorexic (1[0-1]). Plasma concentrations of TNF-a and IL-lcc in pancreatic cancer and cancer control patients were no different from healthy controls. 1L-6 concentrations were less than 5 pg/ml in all healthy controls. IL-6 was raised in 9 of the pancreatic cancer patients (19.9 [12.1-26] pg/ml) before stent insertion and fell to below 5 pg/ml after relief of biliary obstruction. IL-6 was raised in only 3 of the cancer control patients, all with anorexia. There was a significant correlation (0.46) between the anorexia score and IL-6 concentrations and IL-6 may play a role in causation of anorexia in these patients. 1) Ballingcr et al. Gut 1994:35,467-470.
Transcript of Circulating cytokines and anorexia in pancreatic cancer patients
April 1995 Growth, Development, and Nutrition A715
Growth . Deve looment . and Nutr i t ion
COMPARISONS OF METABOLIC RESPONSES TO DIGESTIBLE AND PARTLY UNDIGESTIBLE STARCHES IN HEALTHY HUMANS L. AchouL B. Flourie, F. Briet, C. Franchisseur, F. Bomet, J.C. Rambaud, B. Messing INSERM U290, h6pital saint-Lazare, 75010 et l~ridania Bdghin-Say, 75008, Paris
Starch is the main energetic fuel in the human diet. Most starches are extensively digested in the human small intestine. It is now technologically possible to modify starch in order to slow down its digestion in the small intestine. The digestion of technologically modified starches will start in the small intestine and continue in the colon, where its fermentation releases short chain fatty acids (mainly acetate) and gases 0-I2, COO. The metabolic consequences of this shift in starch digestion could have potential health benefits. In this study, we measured certain metabolic indexes in healthy humans consuming a highly digestible corn starch and the same corn starch after ratrogradation, which is 50% digested in the human small intestine and completely fermented in the colon (Eur J Clin Nutr 1992, 46; S 131- S132)
Methods: 8 healthy volunteers were studied during 2 periods separated by one week. In each period, fasting volunteers consumed at 8 am the test meal containing either the digestible or retrograded corn starch; blood and breath were sampled in the absorptive period hourly for 8 hours. The same meal was given again the same day at 10 pm; at 8 am on the next morning, i.e. 10 hours after the ingestion of the test meal, blood and breath were sampled in the fasting subjects hourly for 3 hours i.e~ in the post-absorptive period.
Results In the absorptive period, after the ingestion of digestible starch the glycemic index and area under the insulin curve were higher, and blood glycerol concentrations were lower (p<0,05) than after the ingestion of retrograded starch. In the post-absorptive period, after the ingestion of digestible starch the respiratory quotient, 13CO2 and H2 excretion in breath, blood acetate concentrations and satiety index were significantly lower, whereas blood glycerol concentrations were higher (13<0,05) than after the ingestion of retrograded starch.
Conclusions In healthy humans, the digestion of retrograded corn starch is slow in the small intestine and its colonic fermentation continues 10 to 13 hours after its ingestion. Compared to the highly digestible com starch, the shift in starch digestion induced by retrogradation leads to changes in metabolic responses: retrograded corn starch reduces the giycemic and insulinic responses in the absorptive period, and lipolysis in the post-absorptive period. This last effect could be related to ma inhibitory action on the lipolysis of short chain fatty acids produced during the colonic fermentation of unabsorbed starch.
• FECAL ENERGETIC LOSSES: IMPORTANCE OF THE BACTERIAL MASS L. Achour, B. Flourit, F. Briat, C. Franchisseur, M Maurel, F. Thnillier, J.C. Rambaud, B. Messing INSERM U290, hfpital Saint-Lazare, 75010 Paris, France.
In humans, nutrients which escape intestinal absorption and colonic fermentation will be lost in stools. These losses will be increased in patients with malabsorptiun syndrome. In addition, stools contain endogenous substrates among them bacteria are a major component, whose the growth may be stimulated when more dietary nutrients are available for bacterial fermentation. In assessing/he extent of nutrient and calorie absorption along the gastrointestinal tract, the magnitude of error introduces by the bacterial fraction of stools is unknown.
Methods: We studied 6 healthy volunteers and 6 patients with short bowel and colon in continuity (SBC) under free oral intake. The bacterial mass of stools collected for 24 hours was isolated (fractionation procedure). Total fecal and bacterial calorie contents were determined by bomb calorimetry. Total fecal and bacterial fat was measured by the method of Van de Kamer and total and bacterial nitrogen by pyrochemihiminescance.
Results (means-+-SEM)
Stool Dry Total Bacterial Bacterial weight weight energy weight energy (g/d) (g/d) (kcal/d) (g/d) (kcal/d)
Volunteers 150a:16 424-4 208±20 19~-2 104±13 Patients 1228±276 1494-33 9524-235 53-4-15 312:t:85
In healthy volunteers and patients with short bowel and colon in continuity, fecal bacterial mass accounted for 44 and 35 % of fecal dry weight, and contained 50 and 3 1 % of total fecal energy. Bacterial calorie contents were close to 6 kcal/g of bacteria. In healthy volunteers, 59 and 24 % of total fecal lipid and nitrogen belonged to bacteria; these percentages were respectively 38 and 19 % in short bowel patients.
Conclusions: Nutrient and energetic balance studies by calculating the difference between ingested nutriants/calories and fecally excreted nutrients/calories assume that fecal losses are from dietary origin and do not take into account endogenous energetic losses, as fecal bacteria. This assumption leads to an underestimation of the amounts of nutriants and calories which are absorbed in the gastrointestinal tract. From a nutritional point of view, this error is significant in patients with malabsorption syndrome and colon in continuity.
• QUANTIFICATION OF ARTIFICIAL FAT MALABSORPTION BY THE 13C-HIOLEIN BREATH TEST IN HEALTHY VOLUNTEERS. H.Ashraf. P.Hildebrand, R.Meier*, B.Meyer-Wyss, C.Beglinger A.Chdst, K.Gyr. Division of Gastroenterology and Department of Internal Medicine University Hospital, CH-4031 Base and *D vision of Gastroenterology, Kantonsspital, CH-4410 Liestal, Switzerland
Tetrahydrolipstatin (THL) is a potent irreversible inhibitor of gastrointestinal lipases which induces fat malabsorption in humans and was developed with the intention to support weight loss in obesity. THL is therefore an excellent tool to investigate artificially induced fat malabsorption by a non-invasive breath test. Various 13C-labeled triglycerides have been previously used in breath tests assessing fat maldigestion or malabsorption. The aim of the present study was to use the 13C-hiolein breath test to assess THL-induced fat malabsorption in healthy volunteers. 13C-hiolein is a long-chain triglycedde with all C atoms of the molecule 13C-labeled. We assume that this test yields faster and higher 13002 recovery than carboxyMabeled 13C-triglycerides. Methods: 8 healthy volunteers of normal weight underwent 2 study periods of 4 days of diet (100 g fat/day) with or without THL 120 mg t.i.d. On the last day o[ each phase, a 13C-hiolein breath test (2 mg/kg with the test meal) was performed. 13002 recovery in breath samples was measured over 24 hours by isotope ratio mass spectrometry. Results: The peak 13002 excretion occurred only after 5 hours in both treatments with little difference during the first 4 hours. THL potently reduced fat digestion and absorption with the most pronounced effect observed after 8 hours: 1.1 _+ 0.2 vs. 2.3 + 0.3% dose/h in control experiments (p<0.05). The 24 hours cumulative 13002 excretion was also significantly reduced by THL: 14.9 + 2.2 vs. 28.4 _+ 4.1% dose in control experiments (p<0.05). Summary: 13002 recovery after 13C-hiolein administration was slow and in the same range as in other trigtyceride breath tests indicating that the high number of labeled C atoms per molecule does not substantially alter the metabolism. THL 120 mg t.i.d, induced a fat malabsorption that could be detected 'by the 13C-hiolein breath test most efficiently between 5 and 12 hours after administration of the tracer. We conclude that 13C-hiolein is not superior to other labeled triglycerides to detect fat malabsorption in humans.
• CIRCULATING CYTOKINES AND ANOREXIA IN PANCREATIC CANCER PATIENTS. lAB Ballin2er, 1M Armed, 2N Rudd, IM McHugh, 3jA Woolley, 1EM Alstend, 1ML Clark. Depts. of ~Gastroenterology & ~Chemical Pathology, St Bartholomew's Hospital and 2palliative Care Medicine, Whipps Cross Hospital, London UK.
Anorexia is a common symptom in patients with malignant bile duct obstruction and is significantly improved following stent insertion and relief of the obstruction ~. Animals with a ligated bile duet also have a reduced food intake and this is associated with increased circulating concentrations of IL-6 and TNF-a. These cytoldnes, together with IL- la , are implicated in the pathogenesis of anorexia and cachexia seen in patients with inflammatory and malignant conditions. The aim of this study was to explore the hypothesis that circulating cytoldnes contribute to the anorexia seen in jaundiced pancreatic cancer patients. 16 pancreatic cancer patients completed a graded symptom questionnaire (0=no loss of appetite, 3=severe anorexia) pre stent and 1 and 4 weeks after stenting. 13 patients with other cancers (cancer controls) and 10 healthy controls completed the questionnaire on a single occasion. Blood was taken when each questionnaire was completed. TNF-~ and IL-I~ were measured by ELISA (Amersham UK) and IL-6 by IRMA. All patients with pancreatic cancer were jaundiced before stent insertion (mean serum bilirubin 143 pmol/l) with complete relief by 4 weeks. There was marked anorexia before stenting (median score 2.5 [interquartile range 1-3]) with significant improvement by 4 weeks after stent insertion (0 [0-1 ]). 5 of the cancer control patients were anorexic (1[0-1]). Plasma concentrations of TNF-a and IL-lcc in pancreatic cancer and cancer control patients were no different from healthy controls. 1L-6 concentrations were less than 5 pg/ml in all healthy controls. IL-6 was raised in 9 of the pancreatic cancer patients (19.9 [12.1-26] pg/ml) before stent insertion and fell to below 5 pg/ml after relief of biliary obstruction. IL-6 was raised in only 3 of the cancer control patients, all with anorexia. There was a significant correlation (0.46) between the anorexia score and IL-6 concentrations and IL-6 may play a role in causation of anorexia in these patients.
1) Ballingcr et al. Gut 1994:35,467-470.
