Comparative Roles of Microvascular and Nerve Function in Foot Ulceration in Type 2 Diabetes

Abstract

OBJECTIVE -To determine the relative roles of different modalities of sensory nerve function (large and small fiber) and the role of microvascular dysfunction in foot ulceration in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS-A total of 20 control subjects and 18 type 2 diabetic subjects with foot ulceration and 20 without were studied. None of the subjects had clinical features of peripheral vascular disease. The Computer-Aided Sensory Evaluator IV (CASE IV) was used to determine vibration detection threshold (VDT), cold detection threshold (CDT), warm detection threshold (WDT), and heat pain onset threshold (HPO). Vibration perception threshold (VPT) was also assessed by a neurothesiometer. Microvascular function (maximum hyperemia to skin heating to 44°C) was assessed using laser Doppler flowmetry (mean maximum hyperemia using laser Doppler flowmeter [LDF max ]), laser Doppler imaging (mean maximum hyperemia using laser Doppler imager [LDI max ]), and skin oxygenation with transcutaneous oxygen tension (TcpO 2 ).RESULTS -VPT, VDT, CDT, and HPO were all significantly higher in individuals with ulceration than in those without (VPT and VDT: P Ͻ 0.0001) (CDT and HPO: P ϭ 0.01). LDF max , LDI max , and TcpO 2 were significantly lower in the two diabetic groups than in the control subjects, but there was no difference between individuals with and without ulceration. CONCLUSIONS -This study found that there was no additional value in measuring smallfiber function with the CASE IV over measuring vibration by either CASE IV or the inexpensive neurothesiometer in discriminating between individuals with and without ulceration. Furthermore, none of the tests of microvascular function including the TcpO 2 were able to discriminate between individuals with and without ulceration, suggesting that such tests may not be of benefit in identifying subjects at greater risk of foot ulceration. Diabetes Care 27:1343-1348, 2004T he incidence of diabetes-related lower-extremity amputations continues to increase in the developed and developing world; in the U.S., it has been estimated to cost nearly $2 billion and account for 2,600 patient-years of hospital stays per year (1). Up to 80% of these amputations are preceded by foot ulceration (2). Furthermore, between 1995 and 1996, the Medicare costs for patients with foot ulcers were on an average three times higher than those of Medicare patients in general (3). Thus, there is a pressing need for a better understanding of the etiopathogenic factors involved in foot ulceration so that robust screening and preventative measures can be developed.In the absence of macrovascular disease, impaired nerve function and deranged microvascular function have been implicated as important etiological factors (4 -10). With regard to neuropathy, clinical assessment using simple clinical tools such as the neuropathy disability score, neuropathy symptom score, pressure perception using Semmes-Weinstein monofilaments, and vibration sensation with the neurothesiometer (Horwell Scientific Labora...

The LDIflare

“…The reduction in LDImax in type 2 diabetic subjects confirms our previous observations and those of others (46,47,55). The pathogenesis of this abnormality is not fully understood, but we have previously demonstrated in type 1 diabetic subjects an inverse relationship with capillary basement membrane thickness and have suggested that this may limit microvascular distensibility (56).…”

Role of the Microcirculation in Diabetic Foot Ulceration

“…Krishnan et al did not show any difference in microcirculatory function between diabetic patients with and without a history of foot ulcer. 33 Furthermore, there was no relationship between wound healing and microvascular dysfunction in diabetic patients and control individuals.…”

Combined Use of Acid Fibroblast Growth Factor, Granulocyte Colony-stimulating Factor and Zinc Sulphate Accelerates Diabetic Ulcer Healing

“…blood capillary buds appeared and fibroblasts began to proliferate, and the blood capillary which was regarded as nutrition supplier provided material needed for wound healing 48) and fibroblast proliferation was required to repair the skin structural defect; in the final stage, tissue extracellular matrix formation and reconstruction was initiated. 49) Previous study showed that aFGF mainly enhanced fibroblast mitosis to accelerate diabetic wound healing.…”