Microvascular Reactivity and Inflammatory Cytokines in Painful and Painless Peripheral Diabetic Neuropathy Short Title: Inflammation and Diabetic Neuropathy

ABSTRACT Objective : We investigated the association between inflammation, microvascular reactivity and the development of peripheral diabetic neuropathy. Research Design and Methods. We studied three groups: 55 healthy control subjects, 80 non-neuropathic and 77 neuropathic DM patients. We also subdivided the neuropathic patients to a subgroup of 31 subjects with painless neuropathy and 46 with painful neuropathy. We measured the foot skin endothelium dependent and independent vasodilation, the nerve axon reflex-related vasodilation (NARV) and inflammatory cytokines and biochemical markers of endothelial function. Results. The endothelium dependent and independent vasodilation and NARV were lower in the neuropathic group (p<0.05). NARV was further reduced in the subgroup of painless neuropathy when compared to painful neuropathy (p<0.05). Comparing to the other two groups, the neuropathic group had also higher serum levels of PDGF AA/BB (p<0.05), RANTES (p<0.01), leptin (p<0.0001), osteoprotegerin (p<0.01), G-CSF (p<0.05), sE-Selectin (p<0.01), sICAM (p<0.0001), sVCAM (p<0.001), CRP (p<0.0001), TNFα (p<0.05), and fibrinogen (p<0.05). Patients with painful neuropathy had higher cICAM-1 (p <0.05) and CRP levels (p <0.01) when compared to painless neuropathy. No major changes in the above results were observed in 78 diabetic patients who were seen for a second visit 21 months after the first visit.