Evidence for Associated Cutaneous Microangiopathy in Diabetic Patients With Neuropathic Foot Ulceration

Diabetes complicated by diabetic neuropathy is a risk factor initiating chronic foot ulceration, which may lead to amputation (1).

We postulated that a form of functional cutaneous microangiopathy is associated with diabetic neuropathy, and we assessed the cutaneous vasoreactivity reserve (CVR) using laser-Doppler flowmetry.

We investigated 42 patients with type 2 diabetes but without cutaneous foot ischemia. They were divided into two groups, respectively comprising 30 patients with no current or previous foot ulceration and 12 with diabetic neuropathy and foot ulceration. A total of 17 healthy subjects served as the control group.

A laser-Doppler probe was placed on the dorsum of the foot. Blood flux was recorded as previously published (2), under three conditions: supine, sitting (to record the venous arteriolar reflex [VAR]), and after postocclusive hyperemia (H). CVR is the sum of these vasoconstriction (VAR) and vasodilation (H) capacities and is expressed in percent of the supine blood flux. In addition, we measured the transcutaneous oxygen pressure (TcPo₂) of the foot dorsum.

In diabetic patients with foot ulceration, CVR was 219 ± 86%, which was significantly lower than in either the group without foot ulceration (566 ± 76%, P < 0.01) or the healthy control subjects (472 ± 217%, P < 0.017).

In diabetic patients with foot ulceration, TcPo₂ was 44.5 ± 5 mmHg, which was also lower than in either the group without foot ulceration (50 ± 1 mmHg, P = NS) or the healthy control subjects (68 ± 8 mmHg, P = 0.0005).

In diabetic patients with neuropathy complicated by foot ulceration, this study demonstrated a significant reduction in CVR, indicating the presence of cutaneous microangiopahy.

Our study is the first to have explored both VAR and H simultaneously, thus enabling them to be summed in a single parameter (CVR) that expresses the cutaneous vasoreactivity reserve.

The relationship between neuropathy and cutaneous microangiopathy might involve two mechanisms: 1) the impairment of microvascular reactivity and limitation of hyperemia by the neuropathy 2) disturbance of the vasa nervorum and interference in the pathogenesis of the neuropathy.

Note that the functional microcirculatory abnormalities shown by our results had nutritional consequences for the blood oxygen supply to the skin, as TcPo₂ was lower in patients with diabetes than in the control subjects, the lowest values being in the group with foot ulceration.

The cutaneous microvascular vasodilation capacity (i.e., hyperemia in response to injury) is of particular importance for ulcer healing, and the capillary hyperperfusion on dependency due to an abnormal postural venoarteriolar reflex accounts for edema and stimulates capillary basement membrane thickening. Therefore, the traditional causative chain of neuropathy + minor trauma → ulceration + faulty healing → gangrene → amputation does not take into account the associated cutaneous microangiopathy that may be expected to increase the proneness to trauma and foot ulceration and, hence, the possible failure of healing.