Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT01880827 |
Other study ID # |
2012-002689-10 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
January 2013 |
Est. completion date |
January 2016 |
Study information
Verified date |
October 2021 |
Source |
Turku University Hospital |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Obesity is a worldwide problem and leads to multiple metabolic and endocrinological problems.
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.
Description:
Obesity is a worldwide problem and leads to multiple metabolic and endocrinological problems,
including type 2 diabetes mellitus (T2DM). In T2DM, body is unable to response to circulating
insulin levels, which ultimately destroys pancreatic β-cells, leading to chronic
hyperglycaemia with ensuing consequences
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.