*Diabetes and vascular complications: normoxia versus hypoxia*

Type 2 diabetes mellitus (T2DM) represents a major health problem in the
Western society. Aging, increasing prevalence of obesity and decreasing
physical activity levels will even further increase the prevalence of T2DM. In
addition to the presence of insulin resistance, the primary pathologic
consequence of T2DM involves vascular impairment. Consequently, T2DM is an
independent cardiovascular risk factor and relates to micro- and macrovascular
complications. Endothelial dysfunction is believed to importantly contribute to
the vascular complications in diabetes.
Several previous studies, including from our laboratory, have demonstrated that
aerobic exercise training is an effective therapeutic strategy to improve
insulin resistance, but also reverses endothelial dysfunction. Recent studies
have adopted novel exercise training strategies to further improve the
beneficial effects of exercise training. For example, aerobic exercise training
combined with mild hypoxia (~2,000 m altitude) is suggested to enhance weight
loss, decrease leptin levels (with suppression of appetite), increases activity
of glycolytic enzymes, elevate the number of mitochondria and glucose
transporter GLUT-4 and produce peripheral vasodilation and arteriogenesis.
Consequently, one may hypothesise that exercise training under hypoxia may have
a superior effect to improve insulin resistance and improve endothelial
function compared to traditional exercise training in DMT2.

Our aim is to compare the effect of 8-week exercise training and exercise
training under hypoxia on vascular adaptations in function and structure, but
also metabolic control (insulin resistance)

Intervention study

Patients with type 2 diabetes will undergo blood withdrawal (for measures of
metabolic control) and non-invasive measurements of vascular function and
structure before and after the 8-week intervention. The Department of
Physiology has a long track-record using the proposed techniques to examine the
vasculature and metabolic control in healthy subjects as well as in patient
groups (e.g. spinal cord injury, older subjects, type 1 and 2 diabetes
mellitus). These tests involve the repetitive inflation of blood pressure cuffs
and application of the non-invasive echo-Doppler technique. We have never had
problems regarding these non-invasive tests nor complaints from our test
subjects.
The Department of Physiology has a long and strong history of performing
exercise training studies in healthy volunteers (children, adolescents,
middle-aged and older subjects) as well as various patient groups (including
diabetes mellitus type 1 and 2). Hypoxic exercise training will be performed in
a specifically designed room with air mixture of 16.5% O2 (b-Cat mobile high
altitude chamber, b-Cat B.V., Tiel, the Netherlands). This type of exercise
training is safe as it is comparable to performing exercise at ~2,000 m
altitude. Therefore, this type of exercise is comparable to the type of
exercise that a large part of the world*s population is being exposed to (those
who live at >2,000 m altitude). This type of training is not associated with
any health risk. Normoxic and hypoxic exercise training will take place under
supervision of an experienced researcher. Taken together, our study involves
non-invasive measures and makes use of novel and safe exercise training
strategies that are believed to have a strong and potent health benefit for
DMT2.