Endothelial function after adjustable gastric banding, vasomotion and glucose tolerance

The global epidemic of obesity is bringing in its wake a catastrophic increase
in the prevalence of metabolic diseases. As a result, obesity-related diseases,
such as diabetes, hypertension, dyslipidaemia have surpassed tobacco use as a
cause of death1, 2. Obesity is a major cause of insulin resistance, which has
been implicated in the rising prevalence of the metabolic syndrome, a cluster
of risk factors which confers an increased risk for type 2 diabetes and
cardiovascular disease (CVD)3. The mechanisms underlying this clustering are
incompletely understood. Obesity-associated microvascular dysfunction
(especially the impaired vasodilator response) explains part of this clustering
and predisposes obese subjects to CVD4, 5. Microvascular dysfunction, by
affecting both flow resistance and perfusion, is important not only in the
development of obesity-related target-organ damage in the heart and kidney, but
also in the development of cardiovascular risk factors such as hypertension and
insulin resistance 6-9.

Prevention of cardiovascular risk can be achieved by addressing all
risk-factors independently, as is most often done, however targeting obesity
will possibly yield better effects 10.
The most effective treatment for obesity is bariatric surgery 11. Bariatric
surgery comprises all gastrointestinal surgery aimed at a reduction of (excess)
weight. There are several types of bariatric surgery, such as Laparoscopic
Adjustable Gastric Banding (LAGB), a gastric sleeve operation, Roux-en-Y
Gastric Bypass (RYGB) along with other techniques.

After bariatric surgery, insulin sensitivity is known to ameliorate, as well as
blood pressure, cardiac function, endothelial function and overall
cardiovascular risk 10, 12, 13. Endothelial function in the brachial artery -
studied by flow mediated dilation- has been found to improve three months after
bariatric surgery 14. Endothelial function has also been found to improve four
months after bariatric surgery in the dorsal hand vein15, as well as in the
whole forearm (using strain-gauge plethysmography) 16. These studies assessed
large vessels or indirect measures of the microcirculation. However, the
microcirculation seems to be the most interesting site to study, since all
aforementioned risk factors are believed to be linked through microvascular
dysfunction 4.
The microcirculation is the main site for pressure dissipation, and thus an
important contributor to the peripheral resistance 17. Also, because the
microcirculation constitutes a ubiquitous vascular network in the body, it has
a large total area available for the distribution of nutrients, waste products,
and hormones such as insulin 18. Insulin promotes its own delivery through an
increased microvascular recruitment with higher insulin levels 19. This effect
is blunted in obese subjects 19.

One non-invase method of determining microvascular function is to use
LaserDoppler flowmetry (LDF). LDF utilises a laser beam which penetrates the
skin. A fraction of the light is backscattered by moving blood cells and
undergoes a frequency shift according to the Doppler principle, generating a
received signal proportional to local tissue perfusion 6, 20-23. In this LDF
signal, repeating oscillations, so called vasomotion, can be distinguished.
This rhythmic dilatation and contraction of arterioles is thought to be an
important regulator of microvascular blood flow and thus even tissue
perfusion.
Within the LDF signal, six frequency domains can be distinguished, a cardiac,
respiratory, myogenic, neurogenic, endothelial-NO dependent and an
endothelial-NO independent domain. The latter 4 domains are thought to
contribute to arteriolar vasoreactivity. With insulin resistance, the
insulin-mediated increase in the myogenic domain is impaired in rats 24.
Vasomotion analysis in obese humans has shown an impaired neurogenic and
endothelial domain compared to normal weight subjects(22).

A second use of LDF to investigate microvascular function is in combination
with iontophoresis. Iontophoresis is a non-invasive method of drug application
which allows the local transfer of charged substances across the skin using a
small electric current. Acetylcholine - endothelium dependent vasodilation -
(1%, Miochol) will be delivered using an anodal current 7 x (0.1 mA for 20
sec.), with 60 sec. interval between each dose. Sodium nitroprusside -
ednothelium independent vasodilation - (0.01%, Nipride) will be delivered using
a cathodal current; 9 x (0.2 mA for 20 sec.), with 90 sec. intervals.

We will study microvascular function using these non-invasive non-burdening
methods in patients before, and after bariatric surgery at 2-4-8 weeks, to see
whether endothelial function improves with weight loss, and at which
time-point.

We will investigate endothelial function before and after bariatric surgery.

An observational study with invasive measurements in subjects scheduled for
bariatric surgery

participants will visit our facility 5 times, for a screening/first visit
before BS procedure, and a second visit before the surgery, and for three
visits after bariatric surgery procedure. A visit involves a 5 point OGTT,
laserDoppler analysis (no risks involved), and iontophoresis of acetylcholine
(ACh) and sodiumnitroprusside (SNP) (no risk involved). Participants will have
no direct health benefit from participation. They will receive a fee of ¤80 for
participating, as well as remuneration of their travelling expenses.