We aim to study the role of PVAT in regulation of vascular function, tissue perfusion and glucose uptake in muscle. We hypothesize that PVAT determines insulin-induced vasoreactivity when studied ex vivo and correlates with insulin-induced…
ID
Source
Brief title
Condition
- Heart failures
- Diabetic complications
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
From the pre- and post operative time points we will study functional and
inflammatory properties of PVAT and correlate them with whole-body and
microvascular insulin sensitivity. We will correct for anthropometry and
systemic inflammation and circulating adipocytokines (IL-6, IL-8, leptin,
TNF-*, MCP-1, adiponectin, resistin and PAI-1, fibrinogen) .
Secondary outcome
-
Background summary
Despite the central role of obesity in the pathogenesis of diabetes mellitus
type 2 (DM2) and cardiovascular diseases (CVD), a large subgroup of obese
individuals is metabolically healthy. Perivascular adipose tissue (PVAT)
probably plays a role in the regulation of local muscle perfusion and glucose
uptake. To what extent PVAT determines the metabolic phenotype of obese
individuals is still largely unknown. To further elucidate the role of PVAT in
human (patho)physiology, we want to study the phenotypical changes that PVAT
undergoes after weight loss and how these changes influences vascular and whole
body insulin sensitivity. For these endpoints, patients undergoing gastric
bypass bariatric surgery are to be included in this study.
Study objective
We aim to study the role of PVAT in regulation of vascular function, tissue
perfusion and glucose uptake in muscle. We hypothesize that PVAT determines
insulin-induced vasoreactivity when studied ex vivo and correlates with
insulin-induced microvascular recruitment in skeletal muscle and metabolic
insulin sensitivity independent of anthropometry and systemic inflammation.We
aim to further study the effects of weight loss on the properties of PVAT. As a
secondary objective we want to test if insulin-induced microvascular
recruitment in the myocardium correlates with PVAT properties, anthropometry
and systemic inflammation. We also want to measure intimal-media thickness of
the radial artery and the amount of PVAT of the radial artery and whether they
change before and after the surgery.
Study design
This is an observational study in relatively healthy (no DM2, no hypertension,
no hyperlipidemia, or other CVDs) and type 2 diabetic obese females (BMI >35),
who will undergo bariatric surgery through standard care. At two time points
corresponding to before and after (12 weeks) the surgery, we will study the
following variables: metabolic insulin sensitivity and vascular insulin
sensitivity in vivo. We will also measure systemic levels of inflammation and
other anthropometric parameters to include in our analyses. Corresponding to
the same two pre- and post operative time points, we will obtain skeletal
muscle and subcutaneous adipose tissue biopsies to study the characteristics of
PVAT using different in-vitro and ex-vivo assays. participants will wear the
accelerometer device for one week time before the operation and another one
week 12 weeks after their operation to measure the amount of movement the
participants make.
Study burden and risks
Participants will visit the clinical research unit twice times. On the first
visit (6 hours duration), subjects will undergo a Hyperinsulinemic-euglycemic
clamp (HEC), with microvascular measurements (CEU for the skeletal muscle and
the heart). Thereafter, participants will undergo another skeletal muscle
biopsy under local anesthesia.The participants will wear an accelerometer
during 7 consecutive days after the testing day.
During their scheduled bariatric surgery, the surgeon will obtain the visceral
adipose tissue biopsies.
On the second visit (12 weeks after their operation), subjects will undergo a
similar test day to their first visit (HEC and CEUS, intima-media thickness
measurement and another skeletal muscle biopsy from the other leg). The
participants will wear an accelerometer during 7 consecutive.
Risks associated with these measurements consist of (not necessarily) myalgia
and bleeding after biopsy, risks of hypoglycaemia or hyperglycaemia during HEC,
headache, nausea, transient pulmonary hypertension and allergic reactions
during CEU (rare). Bruising and local pain in the antecubital fold may be
experienced during and after placement of venous catheters and/or during blood
sampling.
As a compensation for their time and effort, as well as the burden of the
invasive procedures, subjects will receive ¤340 after completion of the
investigation. Burden and risk of participation are limited.
Control subjects will visit the CRU twice: pre-operative and 12 weeks
post-operative CEUS and HEC measurements. They will not receive skeletal
muscle biopsies. Control subjects will receive 200 euros as a compensation for
their time and effort.
Van der Boechorststraat 7
Amsterdam 1081BT
NL
Van der Boechorststraat 7
Amsterdam 1081BT
NL
Listed location countries
Age
Inclusion criteria
Female -Caucasian -age 18-55 years -BMI is *35 kg/m2
Bariatric surgery participants getting an operation at the OLVG, location West. Control participants getting a cholecystectomy at the OLVG west.
Exclusion criteria
Documented CVD -Stage 2 hypertension (resting blood pressure >160/100 mmHg) -Obstructive sleeping apnea syndrome (OSAS). -History of severe inflammatory conditions in the past 15 years -Recent infections -recent history (<12 months) of high alcohol use > 4 U/day, more than 3 days in a row -Use of medication potentially affection insulin sensitivity, microvascular function or inflammation -Use of anticoagulants (types Warfarin and Coumadin derivatives) that can increase the risk of bleeding during the muscle biopsy (exception is made for aspirin). -Malignancies (except those of the skin), renal and hepatic diseases. -Smoking -Recent (<6 months) marked (>10%) changes in body weight.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL57982.029.16 |