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Human diabetic peripheral neuropathy is believed to have, at least in part, a microvascular basis. This study was designed to examine the effects of restoration of arterial blood supply on peripheral nerve function in six non-insulin-dependent diabetic patients with peripheral occlusive vascular disease. In the revascularised legs, transcutaneous oxygen increased from a median 37.5 (28.5-45.7 interquartile range) mmHg to 55.5 (53.5-62.5) mmHg, p = 0.036, mean increase 20.2 (14.8-25.6, 95% confidence intervals(CI) mmHg. This was accompanied by a significant improvement in peroneal motor nerve conduction velocity from 31.7 (26.5-36.3) m/s to 33.5 (32.9-39.4) m/s, p = 0.04, mean increase 4.7 (1.7-7.7, 95% CI) m/s. There was no significant change in transcutaneous oxygen or peroneal nerve motor conduction velocity in the contralateral control limbs. This improvement in conduction velocity with improved tissue oxygenation suggests that studies of agents which might indirectly bring about improvements in microvascular blood flow should be urgently considered.

Foot ulceration results in substantial morbidity amongst diabetic patients. We have studied prospectively the relationship between high foot pressures and foot ulceration using an optical pedobarograph. A series of 86 diabetic patients, mean age 53.3 (range 17-77) years, mean duration of diabetes 17.1 (range 1-36) years, were followed-up for a mean period of 30 (range 15-34) months. Clinical neuropathy was present in 58 (67%) patients at baseline examination. Mean peak foot pressure was higher at the follow-up compared to baseline (13.5 kg.cm-2 +/- 7.1 SD vs 11.2 +/- 5.4, p less than 0.001) with abnormally high foot pressures (greater than 12.3) being present in 55 patients at follow-up and 43 at the baseline visit (p = NS). Plantar foot ulcers developed in 21 feet of 15 patients (17%), all of whom had abnormally high pressures at baseline; neuropathy was present in 14 patients at baseline. Non-plantar ulcers occurred in 8 (9%) patients. Thus, plantar ulceration occurred in 35% of diabetic patients with high foot pressures but in none of those with normal pressures. We have shown for the first time in a prospective study that high plantar foot pressures in diabetic patients are strongly predictive of subsequent plantar ulceration, especially in the presence of neuropathy.

Hypoxia is considered to be one of the main aetiopathogenic factors of diabetic neuropathy. We have examined the effects of the reversal of hypoxia, achieved by revascularization, on peripheral nerve function in diabetic patients with or without clinical neuropathy. Fifty-six patients [mean age 62 (range 30-74) years, 44 (79%) males, 15 (27%) with insulin-dependent diabetes of 20 years (range 1-57) duration, and creatinine level 92.8 +/- 30.9 mumol/l (mean +/- SD)] were tested pre-operatively while 30 (54%) were reexamined at least 6 weeks post-operatively. At baseline the leg scheduled for operation showed worse measurements compared to the control leg when tested for Semmes-Weinstein monofilaments, peroneal motor conduction velocity (PMCV) (33.7 +/- 7.18 vs 35.7 +/- 6.09 m.s-1, p0.05) and transcutaneous oxygen tension (37.4 +/- 24.6 vs 52.0 +/- 21.5 mm Hg, p0.0001) while no differences were found in the vibration perception threshold and leg temperature. When baseline and post-operative measurements were later compared in the operated leg, no differences were noticed in the vibration perception threshold, PMCV and Semmes-Weinstein monofilaments but the transcutaneous oxygen tension increased significantly (32.7 +/- 27.1 vs 64.6 +/- 14.5 mm Hg, p0.001). No differences were noticed in any of the above parameters in the contralateral leg. No correlations were found between changes in transcutaneous oxygen tension and PMCV values measured at baseline and at the follow-up visit in either leg. Similar results were found when patients were stratified according to severity of neuropathy, ischaemia and the level of the bypass. We conclude that although there is greater impairment of nerve function in the more ischaemic leg, reversal of hypoxia does not result in any significant improvement of the nerve function measurements.

Twenty diabetic patients with neuropathy underwent clinical and neurophysiological evaluation together with a detailed morphometric assessment of capillary pathology in endoneurial and epineurial microvascular beds of the sural nerve. Morphological data were compared with ten non-diabetic control subjects. There were no significant differences in control subjects between basement membrane area, endothelial cell area, endothelial cell profile number or luminal area of endoneurial when compared with epineurial capillaries. In contrast, when compared with epineurial capillaries, endoneurial capillaries from diabetic patients demonstrated a significant increase in basement membrane (p

Transcutaneous oxygen, laser Doppler flowmetry, peroneal nerve motor conduction velocity and skin temperature were assessed in both legs of 34 diabetic patients, who had a mean age of 41 (range 29–77) years, and diabetes duration of 21 (3–34) years. Transcutaneous oxygen significantly correlated with peroneal nerve motor conduction velocity (r=0.59 p

The Neurometer is a variable constant current sine wave stimulator, and has recently been proposed as a simple non-invasive and quantitative measure of peripheral nerve function. The device is portable and battery operated; assessment of upper and lower extremities takes only a few min, in contrast to conventional assessment techniques. In order to assess its potential in the quantification of diabetic neuropathy, detection thresholds for constant current electric sine wave stimulation were measured at three different frequencies in different sites in 31 healthy control subjects and 90 diabetic patients with and without neuropathy. The device provides good discrimination between neuropathic and non-neuropathic groups (p less than 0.001) and is quick and easy to use. Comparisons with results of conventional tests of nerve function show that high frequency detection thresholds correlate best with tests of large fibre function (r = 0.42-0.69, p less than 0.001), and low frequency detection thresholds correlate with tests of small fibre function (r = 0.34-0.46, p less than 0.005). It is concluded that the device may be a simple and comprehensive way of assessing peripheral nerve function.