The Effect of Shear- Force at the Skin in Patients With Diabetes Mellitus
The Effect of Shear- Force at the Skin in Patients With Diabetes Mellitus
1. The objective of this study is to acquire 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
 osteoarthropathy in comparison with patients with neuropathy without a history of
 Charcot osteoarthropathy.

 The participant is asked to put his left arm 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 the left fore-arm and the
 adhesive side of a Sebutape is placed within this area for collection of IL-1α/ total protein
 concentrations in a non- loaded situation (event 1) for two minutes. Second, 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 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 after 15 minutes, 30 minutes, 45 minutes and 60 minutes, At
 the same time we performed the same experiment at the right 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 sebutape, laser doppler and colorimeter are done before and after loading
 of the skin. The measures are repeated at 15 minutes, 30 minutes, 45 minutes and 60 minutes.
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 probably 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- osteoarthropathy 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 hyperemic 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 osteoarthropathy after
 shear- force application at the skin compared with patients with type 2 diabetes with
 neuropathy.

 Study population:

 Group A:

 -  Healthy volunteers

 -  > 40 years

 Group B;

 -  patients with Diabetes Mellitus type 2 (DM) without neuropathy

 -  age > 40 years

 -  Valk score < 4

 Group C:

 -  Patients with DM type 2 with neuropathy

 -  age > 40 years

 -  Valk score > 4

 Group D

 -  Patients with (pre)- existing Charcot Osteoarhtropathy

 -  age > 40 years

 -  Valk score > 4 Primary study parameters/outcome of the study

 1. IL-1 α/ total protein ratio

 2. Bloodflow of the skin (in flux )

 3. Erythema index of the skin

 The participant is asked to put his left arm 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 the left fore-arm and the
 adhesive side of a Sebutape is placed within this area for collection of IL-1α/ total protein
 concentrations in a non- loaded situation (event 1) for two minutes. Second, 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 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 after 15 minutes, 30 minutes, 45 minutes and 60 minutes, At
 the same time we performed the same experiment at the right 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 sebutape, laser doppler and colorimeter are done before and after loading
 of the skin. The measures are repeated at 15 minutes, 30 minutes, 45 minutes and 60 minutes.

 Outcomes; IL-1alpha/ total protein- ratio Cutaneous blood cell flux Erythema index
Inclusion Criteria:

 -  Group A:

 -  Healthy volunteers

 -  > 40 years

 Group B;

 -  patients with Diabetes Mellitus type 2 (DM) without neuropathy

 -  age > 40 years

 -  Valk score < 4

 Group C:

 -  Patients with DM type 2 with neuropathy

 -  age > 40 years

 -  Valk score > 4

 Group D

 -  Patients with (pre)- existing Charcot Osteoarhtropathy

 -  age > 40 years

 -  Valk score > 4

 Exclusion Criteria:

 -  Trauma fore arms

 -  Skin diseases (psoriasis, eczema)

 -  NSAID use in last seven days

 -  Bèta blocker use

 -  Corticosteroids

 -  Auto- immune diseases

 -  Muscular dystrophy

 -  Malignancy

 -  Participant is unable to give informed consent

 -  Peripheral artery disease (doppler eai <0.9)

 -  Hab1c percentage last 3 months > 11%