None listed
Conditions
Brief summary
There is increasing evidence that nutrient stimuli in the gut, especially in the small intestine, induce changes in gut motor and hormonal functions that play a central role in the control of energy intake and blood glucose. Previous research by our group has shown individual amino acids (L-tryptophan) and free fatty acids (lauric acid) to markedly reduce energy intake at a subsequent meal when administered intraduodenally or orally, respectively. This study aims to investigate the effects of the amino acids L-leucine, alone or in combination with L-tryptophan or lauric acid, on gut motility, gut hormone release, blood glucose control and energy intake in healthy lean individuals and obese patients with T2DM. We hypothesise that L-leucine, administered in combination with L-tryptophan or lauric acid, will take advantage of the several pathways activated by these two classes of nutrients enhancing their potency and thus, resulting in a marked improvement in the beneficial effects on gut functions and energy intake regulation previously associated with these nutrients alone.
Interventions
The study is comprised of nine sub-studies, with separate recruitment conducted for each sub-study.
Gut motility (measured by a manometric tube, study A, F-H), gastric emptying (measured by 2D ultrasound and breath testing, studies B-E, I), blood glucose, gut hormones release, insulin concentrations, appetite perceptions (measured by Visual Analogue Scales, VAS) and energy intake during a buffet meal, will be measured.
Study A, F-H: Subjects enrolled in each sub-study will receive, in randomi
The study is comprised of nine sub-studies, with separate recruitment conducted for each sub-study. Gut motility (measured by a manometric tube, study A, F-H), gastric emptying (measured by 2D ultrasound and breath testing, studies B-E, I), blood glucose, gut hormones release, insulin concentrations, appetite perceptions (measured by Visual Analogue Scales, VAS) and energy intake during a buffet meal, will be measured. Study A, F-H: Subjects enrolled in each sub-study will receive, in randomized, double-blind fashion, each of the intraduodenal infusions described for that study. All intraduodenal infusions are administered over a 90-min period. All visits within a sub-study are separated by 3-7 days. Study A (i) 0.15 kcal/min L-leucine, (ii) 0.45 kcal/min L-leucine, or (iii) saline (control). Study F (i) 0.45 kcal/min L-leucine, (ii) 0.15 kcal/min L-tryptophan, (iii) combination of (i) and (ii), (iv) saline (control). Study G (i) 0.45 kcal/min L-leucine, (ii) 0.4 kcal/min Lauric Acid, (iii) combination of (i) and (ii), (iv) saline (control). Study H (i) 0.1 kcal/min L-tryptophan, (ii) 0.3 kcal/min lauric acid, (iii) combination of (i) and (ii), (iv) saline (control). Blood samples will be collected and VAS completed every 15 min from t = -15 to 90 min. At t = 90 min, the manometric assembly will be removed and subjects will be presented with a cold, buffet-style meal. Studies B-E, I: Subjects enrolled in each sub-study will receive, in randomized, double-blind fashion, each of the intragastric bolus infusions described for that study. Infusions will be administered over 3 minutes using a feeding tube. Study visits will be separated by 3-7 days. Study B (i) 5g L-leucine, (ii) 10g L-leucine, or (iii) saline (control) Study C (i) 3g L-tryptophan, (ii) 1.5g L-tryptophan, or (iii) saline (control) Study D (i) 10g L-leucine, (ii) 3g L-tryptophan, (iii) combination of (i) and (ii), (iv) saline (control) Study E (i) 10g L-leucine, (ii) 6g lauric acid, (iii) combination of (i) and (ii), (iv) saline (control). Study I (i) 3g L-tryptophan, (ii) 6g lauric acid, (iii) combination of (i) and (ii), (iv) saline (control) For each study visit, a mixed nutrient drink (Ensure, 400 kcal, 300ml) will be administered 15 min after the infusion (t=0). Blood samples will be collected and VAS completed every 15 min from t = -15 to 60 min. Gastric emptying measurements will be taken at t= -15 and every 5 min from t = 0 to 60 min. At t = 60 min, subjects will be presented with a cold, buffet-style meal. For all studies, subjects will be allowed 30 min to freely consume the buffet meal until comfortably full. At t = 120 min (study A, F-H) or t = 90 min (studies B-E, I), a final blood sample will be taken, and VAS administered
Sponsors
Christine Feinle-Bisset
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
A total of 16 healthy, lean (BMI 19-25 kg/m2) and 16 obese T2DM (BMI 30-35 kg/m2) male and female Caucasian subjects, aged between 18 - 55 years, will be included in each Study A-I. T2DM diagnosis will be based on WHO criteria. HbA1c will be >=6.5 - <=7.9% at screening. Patients will be diet-controlled, with or without metformin (<2 g/d). All subjects will be required to be weight stable (ie <5% fluctuation) at study entry, which will be ascertained by a stable body weight in the preceeding 4 weeks. Subjects will be required to maintain their normal physical activity over the course of the study, which will be assessed using diaries
Exclusion criteria
Healthy Subjects: Significant gastrointestinal symptoms, disease or surgery; use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, gastrointestinal function, body weight or appetite (eg domperidone and cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.); lactose intolerance/other food allergy(ies); current gallbladder or pancreatic disease; cardiovascular or respiratory diseases; individuals with low ferritin levels (females less than 15 ng/mL, males less than 30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study; any other illnesses as assessed by the investigator (including chronic illnesses not explicitly listed above); high performance athletes; current intake of greater than 2 standard drinks on greater than 5 days per week; current smokers of cigarettes/cigars/marijuana; current intake of any illicit substance; vegetarians; inability to comprehend study protocol; in female subjects, pregnancy or lactation; restrained eaters (score >12 on the three factor eating questionnaire); fasting glucose >6.9 mmol/l or HbA1c >=6.5%. Obese T2DM subjects: As for healthy subjects, except, HbA1c <6.5% - >7.9%; metformin medication >2g/d; estimated glomerular filtration rate <45ml/min. The degree of eating restraint will be assessed, but not used as an exclusion criteria, as obese often have some degree of eating restraint.
Outcome results
None listed