An iontophoretic study of the endothelial response in the diabetic foot with symmetrical sensory neuropathy

The present study investigated the involvement of peripheral sensory neuropathy in endothelial dependent and endothelial independent vasodilation in three groups of age and sex matched subjects. Six non-insulin dependent diabetes mellitus subjects with diabetic neuropathy, six dependent diabetes mellitus subjects without neuropathy and six non diabetic controls were studied. Dorsal foot skin blood flow was measured by Laser Doppler flowmetry in response to iontophoresis of acetylcholine and sodium nitroprusside. Previous studies have employed low currents and long durations of iontophoresis. In this study a constant high current (40 milliamps) and short (9 × 60 seconds) iontophoresis duration protocol was used, providing a cumulative effect over time. The transcutaneous oxygen tension (TCPO₂) was also determined between groups. Analysis of the acetylcholine dependent response did not reach significance between groups (P > 0.05 2-way ANOVA). Mean baseline arbitrary unit values (AU's) were 3.7 +/- 1.6 in the diabetic neuropathy group, 4.3 +/- 2.6 in diabetic controls and 4.2 +/- 2.5 in controls respectively. After iontophoretic administration, peak values recorded were; in the diabetic neuropathy group 26.5 +/- 10.7, in the diabetic controls 16.1 +/- 8.4 and in controls 27.0 +/- 8.6. A significant difference within each group with respect to effects over time was reached (P < 0.001 2-way ANOVA). Nitroprusside mean baseline values were; 6.0 +/- 2.4 in the diabetic group, 7.7 +/- 4.1 in the diabetic controls and in the healthy controls, 9.1 +/- 7.0 units respectively. Peak recorded values in the diabetic experiment were 38.2 +/- 18.4, in the diabetic neuropathy controls 44.3 +/- 24.1 and in the healthy controls 49.8 +/- 18.7AU's. No significant difference between groups was determined (P > 0.05 2-way ANOVA), however, significance was reached for a time effect (P < 0.001). Analysis of PO₂values reached significance in correlation with acetylcholine (r =.60, P < 0.01) but not with nitroprusside (r =.32, P > 0.05). The results from this study support a hypotheses of current induced hyperaemia or denervation hypersensitivity. Further investigations with high currents in neuropathic subjects, other than people with diabetes, are required and will be useful in evaluating the exact contribution of any current effects used in iontophoretic techniques.