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Luc Tappy

Publications and source records attributed to Luc Tappy.

At least 19 recordsLinked to original sources
PubMed2006

Effects of fish oil on the neuro-endocrine responses to an endotoxin challenge in healthy volunteers.

BACKGROUND & AIMS: Fish oil (FO) has been shown to modulate the acute and chronic inflammatory responses. Endotoxin (LPS) has been shown to mimic several aspects of sepsis. The study aimed at testing the effects of oral FO supplements in healthy subjects submitted to intravenous LPS on systemic and endocrine response. SUBJECTS AND METHODS: Fifteen healthy men (aged 26.0+/-3.1 years, BMI 23.8+/-1.9 kg/m2), were enrolled. Subjects were randomised to 3-4 weeks of oral FO supplementation (7.2 g/day, providing 1.1 g/day of 20:5 (n-3) and 0.7 g/day of 22:6 (n-3) fatty acids) or no supplementation and then submitted to endotoxin challenge: 2 ng/kg of LPS. All subjects were studied twice (placebo and LPS). MEASUREMENTS: vital signs, energy expenditure (EE), glucose and lipid metabolism ((2)H2-glucose), plasma cytokines and stress hormones for 6 h after LPS or placebo. RESULTS: LPS caused cytokine release, fever, increases in heart rate, resting EE and substrate oxidation, plasma glucagon and glucose concentrations; the neuro-endocrine response was characterised by increased plasma stress hormones. FO significantly blunted fever, ACTH and cortisol plasma levels (no effect on cytokine release). FO blunted the peak norepinephrine after LPS. CONCLUSION: FO supplements blunted the endocrine stress response and the increase in body temperature, but had no impact on cytokine production after LPS. These findings conflict with the postulated anti-inflammatory effects of FO on arachidonic acid metabolism and cytokine release. These results suggest that FO may exert beneficial effects in sepsis though non-inflammatory which require further investigations.

Adrenocorticotropic Hormone↗
PubMed2006

Metabolic effects of parenteral nutrition enriched with n-3 polyunsaturated fatty acids in critically ill patients.

BACKGROUND & AIMS: n-3 fatty acids are expected to downregulate the inflammatory responses, and hence may decrease insulin resistance. On the other hand, n-3 fatty acid supplementation has been reported to increase glycemia in type 2 diabetes. We therefore assessed the effect of n-3 fatty acids delivered with parenteral nutrition on glucose metabolism in surgical intensive care patients. METHODS: Twenty-four surgical intensive care patients were randomized to receive parenteral nutrition providing 1.25 times their fasting energy expenditure, with 0.25 g of either an n-3 fatty acid enriched-or a soy bean-lipid emulsion. Energy metabolism, glucose production, gluconeogenesis and hepatic de novo lipogenesis were evaluated after 4 days. RESULTS: Total energy expenditure was significantly lower in patients receiving n-3 fatty acids (0.015+/-0.001 vs. 0.019+/-0.001 kcal/kg/min with soy bean lipids (P<0.05)). Glucose oxidation, lipid oxidation, glucose production, gluconeogenesis, hepatic de novo lipogenesis, plasma glucose, insulin and glucagon concentrations did not differ (all P>0.05) in the 2 groups. CONCLUSIONS: n-3 fatty acids were well tolerated in this group of severely ill patients. They decreased total energy expenditure without adverse metabolic effects.

Adult↗
PubMed2006

Effects of hyperglycemia on glucose metabolism before and after oral glucose ingestion in normal men.

The plasma glucose excursion may influence the metabolic responses after oral glucose ingestion. Although previous studies addressed the effects of hyperglycemia in conditions of hyperinsulinemia, it has not been evaluated whether the route of glucose administration (oral vs. intravenous) plays a role. Our aim was to determine the effects of moderately controlled hyperglycemia on glucose metabolism before and after oral glucose ingestion. Eight normal men underwent two oral glucose clamps at 6 and 10 mmol/l plasma glucose. Glucose turnover and cycling rates were measured by infusion of [2H7]glucose. The oral glucose load was labeled by D-[6,6-2H2]glucose to monitor exogenous glucose appearance, and respiratory exchanges were measured by indirect calorimetry. Sixty percent of the oral glucose load appeared in the systemic circulation during both the 6 and 10 mmol/l plasma glucose tests, although less endogenous glucose appeared during the 10 mmol/l tests before glucose ingestion (P < 0.05). This inhibitory effect of hyperglycemia was not detectable after oral glucose ingestion, although glucose utilization was increased (+28%, P < 0.05) due to increased nonoxidative glucose disposal [10 vs. 6 mmol/l: +20%, not significant (NS) before oral glucose ingestion; +40%, P < 0.05 after oral glucose ingestion]. Glucose cycling rates were increased by hyperglycemia (+13% before oral glucose ingestion, P < 0.001; +31% after oral glucose ingestion, P < 0.05) and oral glucose ingestion during both the 6 (+10%, P < 0.05) and 10 mmol/l (+26%, P < 0.005) tests. A moderate hyperglycemia inhibits endogenous glucose production and contributes to glucose tolerance by enhancing nonoxidative glucose disposal. Hyperglycemia and oral glucose ingestion both stimulate glucose cycling.

Administration, Oral↗
PubMed2006

A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans.

BACKGROUND: High fructose consumption is suspected to be causally linked to the epidemics of obesity and metabolic disorders. In rodents, fructose leads to insulin resistance and ectopic lipid deposition. In humans, the effects of fructose on insulin sensitivity remain debated, whereas its effect on ectopic lipids has never been investigated. OBJECTIVE: We assessed the effect of moderate fructose supplementation on insulin sensitivity (IS) and ectopic lipids in healthy male volunteers (n = 7). DESIGN: IS, intrahepatocellular lipids (IHCL), and intramyocellular lipids (IMCL) were measured before and after 1 and 4 wk of a high-fructose diet containing 1.5 g fructose . kg body wt(-1) . d(-1). Adipose tissue IS was evaluated from nonesterified fatty acid suppression, hepatic IS from suppression of hepatic glucose output (6,6-2H2-glucose), and muscle IS from the whole-body glucose disposal rate during a 2-step hyperinsulinemic euglycemic clamp. IHCL and IMCL were measured by 1H magnetic resonance spectroscopy. RESULTS: Fructose caused significant (P < 0.05) increases in fasting plasma concentrations of triacylglycerol (36%), VLDL-triacylglycerol (72%), lactate (49%), glucose (5.5%), and leptin (48%) without any significant changes in body weight, IHCL, IMCL, or IS. IHCL were negatively correlated with triacylglycerol after 4 wk of the high-fructose diet (r = -0.78, P < 0.05). CONCLUSION: Moderate fructose supplementation over 4 wk increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans.

Adult↗
PubMed2006

Metabolic effects of fructose.

PURPOSE OF REVIEW: Fructose is consumed in significant amounts in Western diets. An increase in fructose consumption over the past 10-20 years has been linked with a rise in obesity and metabolic disorders. Fructose/sucrose produces deleterious metabolic effects in animal models. This raises concern regarding the short-term and long-term effects of fructose and its risk in humans. RECENT FINDINGS: In rodents, fructose stimulates lipogenesis and leads to hepatic and extrahepatic insulin resistance, dyslipidaemia and high blood pressure. Insulin resistance appears to be related to ectopic lipid deposition. In humans, short-term fructose feeding increases de-novo lipogenesis and blood triglycerides and causes hepatic insulin resistance. There is presently no evidence for fructose-induced muscle insulin resistance in humans. The cellular mechanisms underlying the metabolic effects of fructose involve production of reactive oxygen species, activation of cellular stress pathways and possibly an increase in uric acid synthesis. SUMMARY: Consuming large amounts of fructose can lead to the development of a complete metabolic syndrome in rodents. In humans, fructose consumed in moderate to high quantities in the diet increases plasma triglycerides and alters hepatic glucose homeostasis, but does not appear to cause muscle insulin resistance or high blood pressure in the short term. Further human studies are required to delineate the effects of fructose in humans.

Blood Glucose↗
PubMed2005

Effect of somatostatin on duodenal glucose absorption in man.

OBJECTIVE: The hyperglycemic hyperinsulinemic clamp technique using intraduodenally infused glucose is an attractive tool for studying postprandial glucose metabolism under strictly controlled conditions. Because it requires the use of somatostatin (SST), we examined, in this study, the effect of SST on intestinal glucose absorption. CONTEXT: Twenty-six normal volunteers were given a constant 3-h intraduodenal infusion of glucose (6 mg.kg(-1).min(-1)) labeled with [2-(3)H]glucose for glucose absorption measurement. During glucose infusion, 19 subjects received iv SST at doses of 10-100 ng.kg(-1).min(-1) plus insulin and glucagon, and seven subjects were studied under control conditions. In the controls, glucose was absorbed at a rate that, after a 20-min lag period, equaled the infusion rate. RESULTS: With all the doses of SST tested, absorption was considerably delayed but equaled the rate of infusion after 3 h. At that time, only 5 +/- 2% of the total amount of infused glucose was unabsorbed in the control subjects vs. 36 +/- 2% (P < 0.001) in the SST-infused subjects. In the latter, the intraluminal residue was almost totally absorbed within 40 min of the cessation of SST infusion. At the lowest dose of SST tested (10 ng.kg(-1).min(-1)), suppression of insulin secretion was incomplete. CONCLUSION: These properties of SST hamper the use of intraduodenal hyperglycemic hyperinsulinemic clamps as a tool for exploring postprandial glucose metabolism.

Adult↗
PubMed2005

Changes in insulin secretion and glucose metabolism induced by dexamethasone in lean and obese females.

OBJECTIVE: In healthy lean individuals, changes in insulin sensitivity occurring as a consequence of a 2-day dexamethasone administration are compensated for by changes in insulin secretion, allowing glucose homeostasis to be maintained. This study evaluated the changes in glucose metabolism and insulin secretion induced by short-term dexamethasone administration in obese women. RESEARCH METHODS AND PROCEDURES: Eleven obese women with normal glucose tolerance were studied on two occasions, without and after 2 days of low-dose dexamethasone administration. A two-step hyperglycemic clamp (7.5 and 10 mM glucose) with 6,6 (2)H(2) glucose was used to assess insulin secretion and whole body glucose metabolism. Results were compared with those obtained in a group of eight lean women. RESULTS: Without dexamethasone, obese women had higher plasma insulin concentrations in the fasting state, during the first phase of insulin secretion, and at the two hyperglycemic plateaus. However, they had normal whole body glucose metabolism compared with lean women, indicating adequate compensation. After dexamethasone, obese women had a 66% to 92% increase in plasma insulin concentrations but a 15.4% decrease in whole body glucose disposal. This contrasted with lean women, who had a 91% to 113% increase in plasma insulin concentrations, with no change in whole body glucose disposal. DISCUSSION: Dexamethasone administration led to a significant reduction in whole body glucose disposal at fixed glycemia in obese but not lean women. This indicates that obese women are unable to increase their insulin secretion appropriately.

Adult↗
PubMed2005

Lactate and glucose metabolism in severe sepsis and cardiogenic shock.

OBJECTIVE: To evaluate the relative importance of increased lactate production as opposed to decreased utilization in hyperlactatemic patients, as well as their relation to glucose metabolism. DESIGN: Prospective observational study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Seven patients with severe sepsis or septic shock, seven patients with cardiogenic shock, and seven healthy volunteers. INTERVENTIONS: C-labeled sodium lactate was infused at 10 micromol/kg/min and then at 20 micromol/kg/min over 120 mins each. H-labeled glucose was infused throughout. MEASUREMENTS AND MAIN RESULTS: Baseline arterial lactate was higher in septic (3.2 +/- 2.6) and cardiogenic shock patients (2.8 +/- 0.4) than in healthy volunteers (0.9 +/- 0.20 mmol/L, p < .05). Lactate clearance, computed using pharmacokinetic calculations, was similar in septic, cardiogenic shock, and controls, respectively: 10.8 +/- 5.4, 9.6 +/- 2.1, and 12.0 +/- 2.6 mL/kg/min. Endogenous lactate production was determined as the initial lactate concentration multiplied by lactate clearance. It was markedly enhanced in the patients (septic 26.2 +/- 10.5; cardiogenic shock 26.6 +/- 5.1) compared with controls (11.2 +/- 2.7 micromol/kg/min, p < .01). C-lactate oxidation (septic 54 +/- 25; cardiogenic shock 43 +/- 16; controls 65 +/- 15% of a lactate load of 10 micromol/kg/min) and transformation of C-lactate into C-glucose were not different (respectively, 15 +/- 15, 9 +/- 18, and 10 +/- 7%). Endogenous glucose production was markedly increased in the patients (septic 14.8 +/- 1.8; cardiogenic shock 15.0 +/- 1.5) compared with controls (7.2 +/- 1.1 micromol/kg/min, p < .01) and was not influenced by lactate infusion. CONCLUSIONS: In patients suffering from septic or cardiogenic shock, hyperlactatemia was mainly related to increased production, whereas lactate clearance was similar to healthy subjects. Increased lactate production was concomitant to hyperglycemia and increased glucose turnover, suggesting that the latter substantially influences lactate metabolism during critical illness.

Adult↗
PubMed2005

Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men.

High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes hypertriglyceridemia and insulin resistance in rodents. Fructose-induced insulin resistance may be secondary to alterations of lipid metabolism. In contrast, fish oil supplementation decreases triglycerides and may improve insulin resistance. Therefore, we studied the effect of high-fructose diet and fish oil on DNL and VLDL triglycerides and their impact on insulin resistance. Seven normal men were studied on four occasions: after fish oil (7.2 g/day) for 28 days; a 6-day high-fructose diet (corresponding to an extra 25% of total calories); fish oil plus high-fructose diet; and control conditions. Following each condition, fasting fractional DNL and endogenous glucose production (EGP) were evaluated using [1-13C]sodium acetate and 6,6-2H2 glucose and a two-step hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity. High-fructose diet significantly increased fasting glycemia (7 +/- 2%), triglycerides (79 +/- 22%), fractional DNL (sixfold), and EGP (14 +/- 3%, all P < 0.05). It also impaired insulin-induced suppression of adipose tissue lipolysis and EGP (P < 0.05) but had no effect on whole- body insulin-mediated glucose disposal. Fish oil significantly decreased triglycerides (37%, P < 0.05) after high-fructose diet compared with high-fructose diet without fish oil and tended to reduce DNL but had no other significant effect. In conclusion, high-fructose diet induced dyslipidemia and hepatic and adipose tissue insulin resistance. Fish oil reversed dyslipidemia but not insulin resistance.

Adult↗
PubMed2005

Interaction between dietary lipids and physical inactivity on insulin sensitivity and on intramyocellular lipids in healthy men.

OBJECTIVE: To assess the effect of a possible interaction between dietary fat and physical inactivity on whole-body insulin sensitivity and intramyocellular lipids (IMCLs). RESEARCH DESIGN AND METHODS: Eight healthy male volunteers were studied on two occasions. After 2 days of an equilibrated diet and moderate physical activity, participants remained inactive (bed rest) for 60 h and consumed either a high-saturated fat (45% fat, of which approximately 60% was saturated fat [BR-HF]) or a high-carbohydrate (70% carbohydrate [BR-HCHO]) diet. To evaluate the effect of a high-fat diet alone, six of the eight volunteers were restudied after a 2-day equilibrated diet followed by 60 h on a high-saturated fat diet and controlled physical activity (PA-HF). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and IMCL concentrations by (1)H-magnetic resonance spectroscopy. RESULTS: Insulin-mediated glucose disposal was decreased by BR-HF condition (-24 +/- 6%, P < 0.05) but did not change with BR-HCHO (+19 +/- 10%, NS). BR-HF and BR-HCHO increased IMCL levels (+32 +/- 7%, P < 0.05 and +17 +/- 8%, P < 0.0011, respectively). Although the increase in IMCL levels with PA-HF (+31 +/- 19%, P = 0.12) was similar to that during BR-HF, insulin-mediated glucose disposal (-7 +/- 9%, NS) was not decreased. CONCLUSIONS: These data indicate that physical inactivity and a high-saturated fat diet may interact to reduce whole-body insulin sensitivity. IMCL content was influenced by dietary lipid and physical inactivity but was not directly associated with insulin resistance.

Adult↗
PubMed2004

Assessment of hepatic glucose metabolism by indirect calorimetry in combination with a non-invasive technique using naturally enriched 13C glucose in healthy children and adolescents.

The metabolic fate of hepatic glucose can be best studied using invasive techniques such as tracer infusions and frequent blood sampling which have been revealed to be impractical in the pediatric age group. The aim of this study was to develop a non-invasive method based on indirect calorimetry and expired 13CO2 monitoring in order to gain insight into the mechanisms leading to impaired glucose tolerance in children and teenagers. As a first step, net glucose oxidation (NGO) and energy expenditure (EE) were measured in 47 subjects (range 7.5-17.3 years) of whom 18 were prepubertal (P1), 11 in early puberty (P2-P3) and 18 in late puberty (P4-P5) after 3-hourly loads of 180 mg/kg of oral maize glucose containing naturally enriched 13C. Isotope analysis allowed to calculate exogenous and endogenous glucose oxidation (EXGO, ENGO) and, hence, to derive TGS and NGS, that is glycogen turnover. NGO and EE decreased significantly with pubertal progression, reflecting higher metabolism at younger ages, whereas EXGO remained constant. TGS did not change significantly whereas NGS showed a significant negative correlation with pubertal progression: this can be explained by the fact that glycogenolysis exceeded glycogen synthesis in this experimental setting. This non-invasive method appears to be a promising tool to study the fate of hepatic glucose and therefore glycogen turnover in children at risk of developing glucose intolerance and/or type 2 diabetes.

Adolescent↗
PubMed2004

Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.

OBJECTIVE: To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. DESIGN AND SETTINGS: Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. PATIENTS: Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. INTERVENTION: Each patient received the two buffers in a randomized sequence over two consecutive days. MEASUREMENTS AND RESULTS: The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. CONCLUSION: Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.

Acid-Base Equilibrium↗
PubMed2004

Short-term administration of isotretinoin elevates plasma triglyceride concentrations without affecting insulin sensitivity in healthy humans.

The mechanism underlying hypertriglyceridemia-associated insulin resistance in humans remains poorly understood. It has been proposed that hypertriglyceridemia only produces insulin resistance when associated with an increased lipid delivery to muscle. Accordingly, hypertriglyceridemia secondary to a decreased clearance of triglyceride-rich particles should not cause insulin resistance. To verify this hypothesis, we assessed whole body and adipose tissue insulin sensitivity in 15 healthy male volunteers before and after a 5-day administration of isotretinoin (1 mg/kg/d), a vitamin A derivative that decreases the clearance of triglyceride-rich particles. Whole body insulin-mediated glucose disposal (6,6 (2)H(2)glucose), glucose oxidation (indirect calorimetry), lipolysis ((2)H(5) glycerol), and subcutaneous adipose lipolysis (microdialysis) were evaluated during a 3-step hyperinsulinemic euglycemic clamp. Isotretinoin increased plasma triglyceride from 0.97 +/- 0.15 to 1.30 +/- 0.22 mmol/L (P <.02), but did not change whole body insulin-mediated glucose disposal and lipolysis. These observations are consistent with an isotretinoin-induced inhibition of very-low-density lipoprotein (VLDL)-triglyceride clearance. The suppression of endogenous glucose production and the reduction in subcutaneous adipose glycerol concentrations by insulin remained equally unaffected after isotretinoin administration. We conclude that the impaired clearance of triglyceride-rich particles secondary to a 5-day isotretinoin administration does not impair insulin-mediated antilipolysis or glucose disposal. The data support the concept that hypertriglyceridemia-associated insulin resistance develops primarily when triglyceride production is increased.

Adipose Tissue↗
PubMed2004

Metabolism of oral glucose in children born small for gestational age: evidence for an impaired whole body glucose oxidation.

Epidemiological studies indicate that intrauterine growth restriction confers an increased risk of developing type 2 diabetes mellitus in subsequent life. Several studies have further documented the presence of insulin resistance in young adults or adolescent children born small for gestational age. Since most studies addressed postpubertal individuals, and since puberty markedly affects energy metabolism, we evaluated the disposal of oral glucose in a group including mainly prepubertal and early pubertal children with intrauterine growth restriction and in healthy age- and weight-matched control children. All children had an evaluation of their body composition by skinfold thickness measurements. They were then studied in standardized conditions and received 4 consecutive hourly loads of 180 mg glucose/kg body weight to reach a near steady state. Energy expenditure and substrate oxidation were evaluated during the fourth hour by indirect calorimetry. Compared to both age- and weight-matched children, children born small for gestational age had lower stature. Their energy expenditure was not significantly decreased, but they had lower glucose oxidation rates. These results indicate that metabolic alterations are present early in children born small for gestational age, and are possibly related to alterations of body composition.

Adipose Tissue↗