Splanchnic Blood Redistribution After Incretin Hormone Infusion and Obesity Surgery
NCT ID: NCT01880827
Last Updated: 2021-10-20
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
36 participants
INTERVENTIONAL
2013-01-31
2016-01-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Bariatric surgeries are a growing field as a treatment choice for morbid obesity (BMI \> 35 kg/m2). Clinical and research evidence shows that shortly after RYGB, T2DM resolves with improving glucose tolerance. Foregut hypothesis behind bariatric surgeries postulate, that bypassed portions of intestine contain a substance, that acts as an anti-incretin, ie. to counteract metabolically favourable incretins. In view of the recent studies, it may be that GIP is really the anti-incretin behind this hypothesis.
The current study is conducted to investigate the vasoactive roles of the GIP. The investigators aim to show that GIP is the major contributor to the blood flow and tissue blood volume observed in postprandial state.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Intestine is able to produce endocrinologically active substances, which affect to body's intermediary metabolism. One of these substances in glucose-dependent insulinotrophic polypeptide (GIP, part of the incretin family), which potentiates the release of insulin postprandially. However, recent evidence suggests, that GIP may have more harmful than beneficial role in the pathogenesis: it has been shown that GIP participates in the development of insulin resistance, the key defect in the process of metabolic dysfunction. GIP may also regulate postprandial redistribution of splanchnic blood flow which might act in the body's nutrition handling \[8\].
Bariatric surgeries are a growing field as a treatment choice for morbid obesity (BMI \> 35 kg/m2). Most established of these procedures is a Roux-en-Y gastric bypass (RYGB), where duodenum and proximal jejunum is bypassed. Clinical and research evidence shows that shortly (before any significant weight loss) after RYGB, T2DM resolves with improving glucose tolerance. Foregut hypothesis behind bariatric surgeries postulate, that bypassed portions of intestine contain a substance, that acts as an anti-incretin¬, ie. to counteract metabolically favourable incretins. In view of the recent studies, it may be that GIP is really the anti-incretin behind this hypothesis.
Positron emission tomography (PET) is a modern imaging technique, which can be used to study perfusion and metabolism of different organs non-invasively. When radiowater measurement is combined with \[15O\]CO, both tissues specific perfusion and blood volume can be measured, respectively. When coupled with magnetic imaging (ie. PET-MRI), the volumes-of-interests can be accurately drawn to the desired organs.
The current study is conducted to investigate the vasoactive roles of the GIP. We aim to show that GIP is the major contributor to the blood flow and tissue blood volume observed in postprandial state. Moreover, we hypothesize that the elimination of GIP-effect has a central role in the improved intermediary metabolism observed after bariatric surgery procedures, and that part this change is mediated by changes in splanchnic circulation. Furthermore, we investigate the effect of GLP-1 (glucagon-like peptide 1, another member of incretin family) on splanchnic circulation.
In the present study intestinal, hepatic and pancreatic blood flow and volume are measured using \[15O\]H2O- and \[15O\]CO radiotracers and PET-MRI imaging in healthy normal weight volunteers (n = 20, BMI ≤ 27 kg/m2) and in morbidly obese T2DM patients (n = 30, BMI ≤ 35 kg/m2) before and after the bariatric surgery operation. The PET imaging will be performed at fasting state but also separately either during 1) mixed meal solution (MMS), 2) GIP-, or 3) GLP-1-infusion. Also abdominal subcutaneous and visceral adipose tissue, intestinal and hepatic tissue samples will be collected.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
BASIC_SCIENCE
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Royx-en-Y surgery
Mixed meal test (MMS) with flow studies before and 2 months after the operation
Roux-en-Y
Subjects in the intervention group will be divided into two consecutive surgical groups, RYGB or SG. After the surgery, subjects are controlled in hospital ward for approximately three days.
GIP-infusion
Blood flow and volume during infusion
MMS
Blood flow and volume after meal solution
Control
Healthy volunteer group, GIP, GLP-1 and MMS studies
GIP-infusion
Blood flow and volume during infusion
GLP-1
Blood flow and volume during infusion
MMS
Blood flow and volume after meal solution
Sleeve gastrectomy
Mixed meal test (MMS) with flow studies before and 2 months after the operation
GIP-infusion
Blood flow and volume during infusion
MMS
Blood flow and volume after meal solution
Sleeve gastrectomy
as in RYGS group
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Roux-en-Y
Subjects in the intervention group will be divided into two consecutive surgical groups, RYGB or SG. After the surgery, subjects are controlled in hospital ward for approximately three days.
GIP-infusion
Blood flow and volume during infusion
GLP-1
Blood flow and volume during infusion
MMS
Blood flow and volume after meal solution
Sleeve gastrectomy
as in RYGS group
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Type 2 diabetes mellitus (fasting glucose more than 7 mmol/l)
3. Age: 18-60 years
4. Previous, carefully planned, conservative treatments for obesity have failed
1. BMI 18-27 kg/m2
2. Age 18-60 years
3. Fasting plasma glucose less than 6.1 mmol/l
4. Normal glucose tolerance test (OGTT)
Exclusion Criteria
2. Weight more than 170 kg
3. Waist circumference \> 150 cm
4. Insulin treatment requiring type 2 diabetes mellitus
5. Mental disorder or poor compliance
6. Eating disorder or excessive use of alcohol
7. Active ulcus-disease
8. Pregnancy
9. Past dose of radiation
10. Presence of any ferromagnetic objects that would make MR imaging contraindicated
11. Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results
1. Blood pressure \> 140/90 mmHg
2. Any chronic disease
3. Mental disorder or poor compliance
4. Any chronic medical defect or injury which hinder/interfere everyday life
5. Eating disorder or excessive use of alcohol
6. Pregnancy
7. Past dose of radiation
8. Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results
9. Presence of any ferromagnetic objects that would make MR imaging contraindicated
10. Smoking
18 Years
60 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Lund University
OTHER
Turku University Hospital
OTHER_GOV
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Pirjo Nuutila
Professor
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Pirjo Nuutila, Prof
Role: PRINCIPAL_INVESTIGATOR
PET centre, Turku
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Turku univercity hospital, PET center
Turku, , Finland
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Saari T, Koffert J, Honka H, Kauhanen S, U-Din M, Wierup N, Lindqvist A, Groop L, Virtanen KA, Nuutila P. Obesity-associated Blunted Subcutaneous Adipose Tissue Blood Flow After Meal Improves After Bariatric Surgery. J Clin Endocrinol Metab. 2022 Jun 16;107(7):1930-1938. doi: 10.1210/clinem/dgac191.
Honka H, Koffert J, Kauhanen S, Teuho J, Hurme S, Mari A, Lindqvist A, Wierup N, Groop L, Nuutila P. Bariatric Surgery Enhances Splanchnic Vascular Responses in Patients With Type 2 Diabetes. Diabetes. 2017 Apr;66(4):880-885. doi: 10.2337/db16-0762. Epub 2017 Jan 17.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2012-002689-10
Identifier Type: -
Identifier Source: org_study_id