Measurement of cytokines, bloodflow and erythema after shear- force application of the skin in patients with Diabetes Mellitus

1. Pressure ulcers, also known as bedsores occurs as a result of mechanical
loading (combination of pressure and shear- force) of the skin. We proved that
IL-1alpha (measurement of skin damage) and reactive hyperaemia (RH) are
increased after a combined loading of pressure and shear- force with our own
developed shear- force model. This RH is propably a protective mechanism of the
loaded skin and is clinically seen as blanchable erythema. Blanchable erythema
is seen as an important risk indicator for the development of pressure ulcers.
Patients with Diabetes Mellitus type 2, however, will develop less blanchable
erythema (RH), because of a decreased micro vascular function. Therefore, they
will get less preventive measures against pressure ulcers. We do expect,
however, that more skin damage occurs when RH is decreased, so we want to
investigate if patients with type 2 diabetes (with or without neuropathy) will
develop less RH and more skin damage (IL-1alpha) after shear force application
at the skin compared with healthy volunteers.

2. Charcot- neuro- ostheoarthropathy is a rare, but serious complication of
polyneuropathy. Most of the times it occurs at the feet in patients with
diabetes with neuropathy. It is associated with inflammation, hyperaemia, bone
deformation and luxation of the joints. The pathogenesis is not well
understood: the hypermic response of the skin to external stimuli is increased,
but we do not know if this hyperaemia is a result of primary hypervascularity
or a increase in primary cytokines. Our research model gives us the opportunity
to investigate if: the local cytokine production is increased in patients with
diabetes type with neuropathy and a history of charcot ostheoarthropathy after
shear- force application at the skin compared with patients with type 2
diabetes with neuropathy.

1. The objective of this study is to aquire knowledge about the development of
reactive hyperaemia and inflammatory responses of the skin after shear- force
and pressure loading. We want to investigate if patients with diabetes type 2
will develop more skin damage, because of a decreased microvascular function.

2. The second objective of this study is: to investigate if the cytokine
production of the skin is increased in patients with type 2 diabetes with a
history of Charcot ostheoarthropathy in comparison with patients with
neuropathy without a history of Charcot ostheoarthropathy.

3. The third objective is to investigate the differences in cutaneous
microbiome between the different groups. We also want to investigate if the
cutaneous microbiome changes after the application of pressure and shear

First we draw at which arm we are going to apply pressure and shear- force and
at which arm we are going to apply pressure only.
The participant is asked to put arms on a support cushion. Then we mark an
area of 2.5 cm x 3 cm with a permanent marker at the plantar aspect of both
fore-arms and the adhesive side of a Sebutape is placed within this area for
collection of IL-1*/ total protein concentrations in a non- loaded situation
(event 1) for two minutes. Second, we measure the microbiome by taking a skin
swab. Third we measure the cutaneous blood cell flux within the borders of the
marked area with a Laser doppler. Finally, we measure the erythema index in
this area with a colorimeter. Then we place the shear- pad over the marked area
we apply 9,8 Newton (N) pressure with 19 N shear- force for half an hour. After
this period a new swab is taken from the skin and a Sebutape is placed for two
minutes, followed by cutaneous blood cell flux and the erythema index
measurement within the borders of the marked area. We repeat these measures
(excpet for the skin swab) after 5, 10, 15, 20, 60 minutes
At the same time we performed the same experiment at thethe other arm, but
instead of loading this arm with shear- force and pressure, we apply only 9,8 N
pressure at this arm. The same measures with the skin swab, sebutape, laser
dopler and colorimeter are done before and after loading of the skin. The
measures are repeated at 5, 10, 15, 20, 60 minutes.

Very low risk, this shear- force model was shown to be safe in healhty
volunteers. The shear- force range in normal life is between 0 -100Newton. We
will only administer 19 Newton shear-force which is much lower. The
invasiveness of this study is the 3 hours duration of the experiment.