Effects of duodenal infusion of lauric acid and L-tryptophan, alone and combined, on fasting glucose, insulin and glucagon in healthy men

Published: 7 November 2019The fatty acid, lauric acid ('C12'), and the amino acid, tryptophan ('Trp'), when given intraduodenally at loads that individually do not affect energy intake, have recently been shown to stimulate plasma cholecystokinin, suppress ghrelin and reduce energy intake much more markedly when combined. Both fatty acids and amino acids stimulate insulin secretion by distinct mechanisms; fatty acids enhance glucose-stimulated insulin secretion, while amino acids may have a direct effect on pancreatic β cells. Therefore, it is possible that, by combining these nutrients, their effects to lower blood glucose may be enhanced. We have investigated the potential for the combination of C12 and Trp to have additive effects to reduce blood glucose. To address this question, plasma concentrations of glucose, insulin and glucagon were measured in 16 healthy, lean males during duodenal infusions of saline (control), C12 (0.3 kcal/min), Trp (0.1 kcal/min), or C12+Trp (0.4 kcal/min), for 90 min. Both C12 and C12+Trp moderately reduced plasma glucose compared with control (p < 0.05). C12+Trp, but not C12 or Trp, stimulated insulin and increased the insulin-to-glucose ratio (p < 0.05). There was no effect on plasma glucagon. In conclusion, combined intraduodenal administration of C12 and Trp reduced fasting glucose in healthy men, and this decrease was driven primarily by C12. The effects of these nutrients on postprandial blood glucose and elevated fasting blood glucose in type 2 diabetes warrant evaluation.Christina McVeay, Penelope C. E. Fitzgerald, Michael Horowitz and Christine Feinle-Bisse

SARS-CoV-2 infection and venous thromboembolism after surgery: an international prospective cohort study

This article is accompanied by an editorial by Marshall and Duggan. Anaesthesia 2022; 77: 3–6.SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1–6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARSCoV- 2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARSCoV- 2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1–2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2–3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9–3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality (5.4 (95%CI 4.3–6.7)). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.COVIDSurg Collaborative and GlobalSurg Collaborative (Australia: Daniel Cox ... Hidde M Kroon ... Christina McVeay ... Matheesha Herath ... Luke Traeger ... Robert Fitridge ... Tarik Sammour ... et al.

Effects of intraduodenal infusion of lauric acid and L-tryptophan, alone and combined, on glucoregulatory hormones, gastric emptying and glycaemia in healthy men

Background and aim: In healthy men, intraduodenal administration of the fatty acid, lauric acid (‘C12’) and the amino acid, L-tryptophan (‘TRP’), at loads that individually do not affect energy intake, reduce energy intake sub- stantially when combined. C12 and TRP may also stimulate cholecystokinin and glucagon-like peptide-1 (GLP-1), which both slow gastric emptying, a key determinant of postprandial blood glucose. Accordingly, combination of C12 and TRP has the potential to reduce post-meal glycaemia more than either nutrient alone. Methods: Twelve healthy, lean men (age (mean ± SD): 28 ± 7 years) received, on 4 separate occasions, 45-min intraduodenal infusions of C12 (0.3 kcal/min), TRP (0.1 kcal/min), C12 + TRP (0.4 kcal/min), or 0.9% saline (control), in a randomised, double-blind fashion. 30 min after commencement of the infusion a mixed- nutrient drink was consumed and gastric emptying measured (13C breath-test) for 3 h. Blood samples were obtained at baseline, in response to treatments alone, and for 2 h post-drink for measurements of plasma glucose, cholecystokinin, GLP-1, C-peptide, insulin and glucagon. ‘Early’ (first 30 min) and ‘overall’ glycaemic and hormone responses were evaluated. Results: C12 + TRP and C12 delayed the rise in, but did not affect the overall glycaemic response to the drink, compared with control and TRP (all P < 0.05). C12 + TRP slowed gastric emptying compared with control and TRP (both P < 0.005), and C12 non-significantly slowed gastric emptying compared with control (P = 0.090). C12 + TRP and C12 delayed the rise in C-peptide and insulin, and also stimulated CCK and glucagon, compared with control and TRP (all P < 0.05). Only C12 + TRP stimulated early and overall GLP-1 compared with control (P < 0.05). Conclusions: In healthy men, C12 + TRP and C12, in the loads administered, had comparable effects to delay the rise in glucose following a nutrient drink, probably primarily by slowing of gastric emptying, as a result of CCK and GLP-1 stimulation, while TRP had no effect.M. Hajishafiee, C. McVeay. K. Lange, J.F. Rehfeld, M. Horowitz, C. Feinle-Bisse

Effects of intraduodenal administration of lauric acid and L-tryptophan, alone and combined, on gut hormones, pyloric pressures, and energy intake in healthy men

BACKGROUND:The fatty acid, lauric acid ('C12'), and the amino acid, L-tryptophan ('Trp'), modulate gastrointestinal functions including gut hormones and pyloric pressures, which are important for the regulation of energy intake, and both potently suppress energy intake. OBJECTIVE:We hypothesized that the intraduodenal administration of C12 and Trp, at loads that do not affect energy intake individually, when combined will reduce energy intake, which is associated with greater modulation of gut hormones and pyloric pressures. DESIGN:Sixteen healthy, lean males (age: 24 ± 1.5 y) received 90-min intraduodenal infusions of saline (control), C12 (0.3 kcal/min), Trp (0.1 kcal/min), or C12 + Trp (0.4 kcal/min), in a randomized, double-blind, cross-over study. Antropyloroduodenal pressures were measured continuously, and plasma cholecystokinin (CCK), ghrelin, and glucagon-like peptide-1 (GLP-1) concentrations, appetite perceptions, and gastrointestinal symptoms at 15-min intervals. Immediately after the infusions, energy intake from a standardized buffet meal was quantified. RESULTS:C12 + Trp markedly reduced energy intake (kcal; control: 1,232 ± 72, C12: 1,180 ± 82, Trp: 1,269 ± 73, C12 + Trp: 1,056 ± 106), stimulated plasma CCK (AUC(area under the curve)0-90 min, pmol/L*min; control: 21 ± 8; C12: 129 ± 15; Trp: 97 ± 16; C12 + Trp: 229 ± 22) and GLP-1 (AUC0-90 min, pmol/L*min; control: 102 ± 41; C12: 522 ± 102; Trp: 198 ± 63; C12 + Trp: 545 ± 138), and suppressed ghrelin (AUC0-90 min, pg/mL*min; control: -3,433 ± 2,647; C12: -11,825 ± 3,521; Trp: -8,417 ± 3,734; C12 + Trp: -18,188 ± 4,165) concentrations, but did not stimulate tonic, or phasic, pyloric pressures, compared with the control (all P < 0.05), or have adverse effects. C12 and Trp each stimulated CCK (P < 0.05), but to a lesser degree than C12 + Trp, and did not suppress energy intake or ghrelin. C12, but not Trp, stimulated GLP-1 (P < 0.05) and phasic pyloric pressures (P < 0.05), compared with the control. CONCLUSION:The combined intraduodenal administration of C12 and Trp, at loads that individually do not affect energy intake, substantially reduces energy intake, which is associated with a marked stimulation of CCK and suppression of ghrelin. The study was registered as a clinical trial at the Australian and New Zealand Clinical Trial Registry (www.anzctr.org.au,) as 12613000899741.Christina McVeay, Penelope C E Fitzgerald, Sina S Ullrich, Robert E Steinert, Michael Horowitz, Christine Feinle-Bisse

Effects of intraduodenal co-administration of lauric acid and leucine on gut motility, plasma cholecystokinin and energy intake in healthy men

The fatty acid, lauric acid ("C12"), and the amino acid, leucine ("Leu"), stimulate gut hormones, including CCK, associated with suppression of energy intake. In our recent study, intraduodenal infusion of a combination of C12 and L-tryptophan, at loads that individually did not affect energy intake, reduced energy intake substantially, associated with much greater stimulation of CCK. We have now investigated whether combined administration of C12 and Leu would enhance the intake-suppressant effects of each nutrient, when given at loads that each suppress energy intake individually. 16 healthy, lean males (age: 23±2 years) received, in randomized, double-blind fashion, 90-min intraduodenal infusions of control (saline), C12 (0.4 kcal/min), Leu (0.45 kcal/min) or C12+Leu (0.85 kcal/min). Antropyloroduodenal pressures were measured continuously and plasma CCK at 15-min intervals, and energy intake from a standardized buffet-meal, consumed immediately post-infusion, was quantified. All nutrient infusions stimulated plasma CCK compared with control (P<0.05). Moreover, C12 and C12+Leu stimulated CCK compared with Leu (P<0.05) (mean concentration, pmol/L; control: 2.3±0.3, C12: 3.8±0.3; Leu: 2.7±0.3; C12+Leu: 4.0±0.4). C12+Leu, but not C12 or Leu, stimulated pyloric pressures (P<0.05). C12+Leu and C12 reduced (P<0.05), and there was a trend for Leu to reduce (P=0.06), energy intake compared with control, with no differences between the three nutrient treatments (kcal; control: 1398±84, C12: 1226±80; Leu: 1260±92; C12+Leu: 1208±83). In conclusion, combination of C12 and Leu, at the loads given, did not reduce energy intake beyond their individual effects, possibly because maximal effects had been evoked.Christina McVeay, Robert E. Steinert, Penelope C. E. Fitzgerald, Sina S. Ullric