Neural and endothelial control of the microcirculation in diabetic peripheral neuropathy

Objective: To examine the role played by endothelium-dependent and endothelium-independent vasodilation of the cutaneous microcirculation and their relationship to neural microcirculatory control in type 1 and type 2 diabetic patients. Methods: Acetylcholine and sodium nitroprusside were iontophoresed using a dose-response technique. Endothelium-dependent, endothelium-independent, and C-fiber-mediated vasodilation were measured with a laser Doppler device. Results: Endothelium-dependent vasodilation of the forearm cutaneous microcirculation was attenuated in diabetic subjects. The response was less in type 2 diabetic subjects than in controls (p < 0.005). In contrast, there was no significant difference between type 1 diabetic subjects and controls. There was no significant abnormality in endothelium-independent vasodilation in either diabetic group. The C-fiber-mediated axon reflex in the forearm was impaired in both type 1 and type 2 diabetics, which is consistent with a small-fiber neuropathy (p < 0.005). The duration of diabetes in type 2 diabetics was a significant predictor of the maximum endothelium-mediated vasodilation. Conclusion: Changes in cutaneous blood flow are seen relatively early in the course of diabetic peripheral neuropathy and are characterized by endothelial and neural but not smooth muscle dysfunction. The presence of significant C-fiber impairment in both diabetic groups, together with significantly greater dysfunction in endothelium-dependent vasodilation in type 2 diabetics, suggests that the endothelial function and nitric oxide may play a greater role in the pathogenesis of diabetic peripheral neuropathy in type 2 diabetic patients.