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

From the Ipswich Diabetic Foot Unit and Diabetes Centre, Ipswich Hospital National Health Service Trust, Ipswich, U.K.

Address correspondence and reprint requests to Dr. G. Rayman, MD, FRCP, Ipswich Diabetes Centre, Ipswich Hospital NHS Trust, Heath Road, Ipswich, U.K. E-mail: gerry.rayman{at}ipswichhospital.nhs.uk

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 (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). LDF_max, LDI_max, 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. Furthermore, 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.

Abbreviations: C, healthy control subjects • CASE IV, Computer-Aided Sensory Evaluator IV • CDT, cold detection threshold • D, type 2 diabetic subjects without foot ulceration • DU, subjects with type 2 diabetes with a current or previous history of foot ulceration • HPO, heat pain onset threshold • JND, just noticeable difference • LDF, laser Doppler flowmeter • LDF_max, mean maximum hyperemia using laser Doppler flowmeter • LDI, laser Doppler imager • LDI_max, mean maximum hyperemia using laser Doppler imager • TcpO₂, transcutaneous oxygen tension • VDT, vibration detection threshold • VPT, vibration perception threshold • WDT, warmth detection threshold

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