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

OBJECTIVE — To determine the relative roles of different modalities of sensory nerve func-tion (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 [LDFmax]), laser Doppler imaging (mean maximum hyperemia using laser Doppler imager [LDImax]), and skin oxygenation with transcutaneous oxygen tension (TcpO2). RESULTS — VPT, VDT, CDT, and HPO were all significantly higher in individuals with ulceration than in those without (VPT and VDT: P 0.0001) (CDT and HPO: P 0.01). LDFmax, LDImax, and TcpO2 were significantly lower in the two diabetic groups than in the control subjects, but there was no difference between individuals with and without ulceration. Univariate logistic regression analysis revealed similar odds ratios for foot ulceration for VDT, CDT, HPO, and VPT (OR 1.97 [95 % CI 1.30–2.98], 1.58 [1.20–2.08], 2.30 [1.21–4.37], and 1.24 [1.08–1.42], respectively). None of the microvascular parameters yielded significant odds ratios for ulceration. CONCLUSIONS — This study found that there was no additional value in measuring small-fiber function with the CASE IV over measuring vibration by either CASE IV or the inexpensive neurothesiometer in discriminating between individuals with and without ulceration. Further-more, none of the tests of microvascular function including the TcpO2 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