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
Functional and inflammatory properties of PVAT will be quantified and
correlations with whole-body and microvascular insulin sensitivity will be
analysed. Vasoreactivity of skeletal muscle arterioles with and without
perivascular adipose tissue will be studied. We will measure markers of
low-grade systemic inflammation and adipocytokines (IL-6, IL-8, leptin, TNF-*,
MCP-1, adiponectin, resistin and PAI-1, fibrinogen) .
Pearson's and Spearman correlation analyses will be conducted as appropriate to
select the variable that is best correlating with insulin sensitivity.
step-wise multivariate linear regressions will be performed to examine the
relations between two variables, controlling for anthropometry and systemic
inflammation, and standardized betas (B) are reported.
Secondary outcome
Pearson's and Spearman correlation analyses will be conducted as appropriate.
Correlations of microvascular recruitment in the heart will be correlated in a
regression analysis using PVAT properties, anthropometric properties and
inflammatory properties.
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.
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. As
a secondary objective we want to test if insulin-induced microvascular
recruitment in the myocardium correlates with PVAT properties, anthropometry
and systemic inflammation .
Study design
This is an observational study in healthy male subjects exhibiting a wide range
of BMI's. We will study metabolic insulin sensitivity combined with the
assessment of vascular insulin sensitivity in vivo, We will also measure
systemic levels of inflammation and other anthropometric parameters to include
in our analyses. At the final visit to the clinic, we will obtain a skeletal
muscle biopsy to study ex vivo the effects of insulin on microvessels isolated
from the biopsies in a pressure myograph with and without their surrounding
PVAT, and study the characteristics of PVAT using different in-vitro and
ex-vivo assays.
Study burden and risks
Subjects will visit the clinical research unit three times. On the first visit,
they will undergo basic physical examination and blood samples will be
collected. On the second visit, subjects will undergo a
Hyperinsulinemic-euglycemic clamp (HEC), with microvascular measurements (CEU
for the skeletal muscle and the heart). The third visit is to do the muscle
biopsies. 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 ¤200 after completion
of the investigation. Burden and risk of participation are limited.
Van der Boechorststraat 7
Amsterdam 1081BT
NL
Van der Boechorststraat 7
Amsterdam 1081BT
NL
Listed location countries
Age
Inclusion criteria
- Male
- Caucasian
- age 18-60 years
- BMI is *23 and <40 kg/m2
To obtain enough variation between individuals 30 individuals with a wide range of BMI will be recruited:
o 10 individuals with a BMI 23-28
o 10 individuals with a BMI 28-34
o 10 individuals with a BMI 34-40
Exclusion criteria
- Documented CVD
- Diabetes mellitus
- Stage 2 hypertension (resting blood pressure >160/100 mmHg)
- 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 | NL54182.029.15 |