Long Term Effects of Weight Loss on Post-prandial Gut Hormone Responses and Meal Induced Thermogenesis

Postprandial Gut Hormone Responses and Meal-induced Thermogenesis After Non-surgical Long-term Weight Loss; Comparison With Surgically Treated Obese Individuals

A study to examine post-prandial gut-hormone secretion, meal-induced thermogenesis, fasting plasma metabolomic/lipidomic and cardiovascular indices among surgically managed obese individuals in the long term compared to conservatively managed obese patients.

Study Overview

• Status: Recruiting
• Conditions: Morbid Obesity

Detailed Description

This is a protocol for the study of post-prandial gut peptide response and meal-induced thermogenesis in a group of 15 conservatively managed (through diet and exercise) morbidly obese individuals. During two separate visits in the study site, anthropometric and bioelectric impendence data will be collected, resting metabolic rate will be measured, and the patients will undergo a panel of cardiovascular examinations (heart rate variability, baroreflex sensitivity, heart ultrasound). On a separate occasion, they will consume a standardized test mixed meal and complete visual analog scales for the subjective assessment of hunger and fullness every 30 minutes for 3 hours. At the same time points, blood samples will be collected for the consequent measurement of glucose, insulin, lipids, and gastrointestinal hormones. Additionally, immediately before and at 60', 120', 180' after the start of the consumption of the test meal, the resting metabolic rate of each participant will be assessed through indirect calorimetry, to quantify meal-induced thermogenesis. The observed induction of satiety and suppression of hunger, post prandial gut-peptide mobilization and change in metabolic rate will be compared to those of participants of trial no NCT03851874 (Morbidly obese patients that have undergone either Roux en Y gastric bypass or sleeve gastrectomy and participated in trial NCT03851874). Participants in the aforementioned cohort have been already followed-up during the first postoperative year and will attend the study site for another follow-up visit approximately 10 years postoperatively, whereby the same diagnostic evaluation described above will take place. Data analysis will take place within the bariatric cohort (longitudinal analysis of the effects of surgery and surgery types on anthropometric parameters, fasting and postprandial glycemia and lipemia, fasting NMR-Metabolomic/Lipidomic profiles, Indices of insulin resistance, echocardiography, energy expenditure) as well as between the two groups in a cross-sectional manner.

• Study Type: Observational
• Enrollment (Anticipated): 45

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11527
    • Recruiting
    • Diabetes Clinical Research Laboratory, 1st Department of Propaedeutic Internal Medicine
    • Contact: Alexander Kokkinos, MD, PhD; Phone Number: +302132061248; Email: akokkinos@med.uoa.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Intervention group: participants of NCT03851874 trial Control group: conservatively (non-surgically, non-pharmaceutically) managed obese individuals among ambulatory patients of the obesity outpatient clinic of the 1st Department of Propaedeutic Internal Medicine ("Laiko" General Hospital)

Description

Inclusion Criteria:

• For the conservatively managed cohort:

  1. Morbid obesity based on BMI > 40kg/m2, managed exclusively with conservative measures (hypocaloric diet and/or increased physical activity and/or behavioral therapy)
  2. Age between 18 and 65 years
• For the bariatric cohort: Participation in NCT03851874 trial

Exclusion Criteria:

1. Serious and life threatening comorbidities (renal, cardiac, liver failure, or malignancy)
2. Alcohol or other substance abuse
3. Use of licenced or off-label weight loss medications during the past 6 months
4. Concurrent psychiatric illness
5. Known history of diabetes mellitus (remitted cases excluded)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Conservatively managed group; Individuals with conservatively managed obesity
Surgically managed group; Individuals with a past history of bariatric surgery (Roux-en-Y gastric bypass/Sleeve gastrectomy) for the management of obesity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in postprandial Gut peptide (ghrelin, Gastric Inhibitory Peptide, Secretin, Peptide Tyrosine-Tyrosine - , Glucagon-like peptide - 1, Oxyntomodulin, Glicentin) responses	Change in the cumulative postprandial response for the aforementioned gut hormones	8-10 years following primary weight-loss intervention
Change in weight, fat mass and lean body mass	Change in weight (percentage of weight following each intervention)	8-10 years following primary weight-loss intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in postprandial glycemia	Change in postprandial glycemia	8-10 years following primary weight-loss intervention
Change in postprandial insulinemia	Change in the cumulative postprandial response for insulin	8-10 years following primary weight-loss intervention
Change in postprandial triglyceridemia	Change in the cumulative postprandial response for triglycerides	8-10 years following primary weight-loss intervention
Change in Insulin resistance	Change in Insulin resistance indices (HOMA-R, MMTT-derived Matsuda index)	8-10 years following primary weight-loss intervention
Change in serum metabolomic and lipidomic parameters	Change in levels of lipoprotein clusters, branched-chain amino-acids, LDL/HDL-Subtypes, Trimethylamine N-oxide assessed by NMR spectroscopy	8-10 years following primary weight-loss intervention
Change in resting metabolic rate following meal ingestion	Change in the cumulative postprandial thermogenesis	8-10 years following primary weight-loss intervention
Change in fasting serum adipokines	Change of fasting leptin, adiponektin concentrations	8-10 years following primary weight-loss intervention
Change in fasting plasma Activins and follistatins	Change in fasting plasma Activin A, B, AB, follistatin and follistatin-like 3	8-10 years following primary weight-loss intervention
Change in postprandial Visual Analog Scale scores for hunger and satiety	Change in postprandial areas under the curve of subjective hunger and satiety expressed in Visual Analog Scales	8-10 years following primary weight-loss intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in baroreflex sensitivity	Changes in baroreflex sensitivity	8-10 years following primary weight-loss intervention
Change in heart rate variability	Changes in heart rate variability	8-10 years following primary weight-loss intervention
Change in aortic distensibility	Aortic distensibility will be evaluated by calculating the systolic and diastolic aortic diameter through M-mode echocardiography, 3 cm above the aortic valve, using the formula described in reference no 4 (PMID: 2282929)	8-10 years following primary weight-loss intervention
Change in echocardiographic cardiac phenotype	Change in echocardiographic cardiac structural indices and measures of systolic and diastolic function	8-10 years following primary weight-loss intervention

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Alexandros Kokkinos, MD, PhD, First Department of Propaedeutic Medicine, NKUA

Publications and helpful links

General Publications

• Yousseif A, Emmanuel J, Karra E, Millet Q, Elkalaawy M, Jenkinson AD, Hashemi M, Adamo M, Finer N, Fiennes AG, Withers DJ, Batterham RL. Differential effects of laparoscopic sleeve gastrectomy and laparoscopic gastric bypass on appetite, circulating acyl-ghrelin, peptide YY3-36 and active GLP-1 levels in non-diabetic humans. Obes Surg. 2014 Feb;24(2):241-52. doi: 10.1007/s11695-013-1066-0.
• Perakakis N, Kokkinos A, Peradze N, Tentolouris N, Ghaly W, Pilitsi E, Upadhyay J, Alexandrou A, Mantzoros CS. Circulating levels of gastrointestinal hormones in response to the most common types of bariatric surgery and predictive value for weight loss over one year: Evidence from two independent trials. Metabolism. 2019 Dec;101:153997. doi: 10.1016/j.metabol.2019.153997. Epub 2019 Oct 28.
• Liaskos C, Koliaki C, Alexiadou K, Argyrakopoulou G, Tentolouris N, Diamantis T, Alexandrou A, Katsilambros N, Kokkinos A. Roux-en-Y Gastric Bypass Is More Effective than Sleeve Gastrectomy in Improving Postprandial Glycaemia and Lipaemia in Non-diabetic Morbidly Obese Patients: a Short-term Follow-up Analysis. Obes Surg. 2018 Dec;28(12):3997-4005. doi: 10.1007/s11695-018-3454-y.
• Stefanadis C, Stratos C, Boudoulas H, Kourouklis C, Toutouzas P. Distensibility of the ascending aorta: comparison of invasive and non-invasive techniques in healthy men and in men with coronary artery disease. Eur Heart J. 1990 Nov;11(11):990-6. doi: 10.1093/oxfordjournals.eurheartj.a059639.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2019
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): August 18, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Weight loss; Gut peptides; Glycemia; Meal-induced thermogenesis
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Body Weight Changes; Obesity; Weight Loss; Obesity, Morbid
• Other Study ID Numbers: Weight loss gut peptide study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No