Diabetic Neuropathy: A cross-sectional study of the relationships among tests of neurophysiology

OBJECTIVE — To determine the relationships among large, small, and autonomic fiber neurophysiological measures in a cross-sectional study of patients with diabetes. RESEARCH DESIGN AND METHODS — We assessed 130 individuals: 25 healthy subjects and 105 subjects with diabetes. Subjects were classified by the presence or absence of neuropathy by physical examination. All subjects underwent autonomic testing, nerve conduc-tion studies, quantitative sensory testing, and nerve-axon reflex vasodilation in addition to quantifiable neurological examination and symptom scores. Correlation and cluster analysis were used to determine relationships between and among different neurophysiological testing parameters. RESULTS — Results of neurophysiological tests were abnormal in patients with clinical evi-dence of diabetic neuropathy compared with results in healthy control subjects and in those without neuropathy (P 0.01, all tests). The correlations among individual tests varied widely, both within (r range0.5–0.9, NS to0.001) and between test groups (r range0.2–0.5, NS to0.01). A two-step hierarchical cluster analysis revealed that neurophysiological tests do not aggregate by typical “small, ” “large, ” or “autonomic ” nerve fiber subtypes

Cold Exposure Exacerbates the Development of Diabetic Polyneuropathy in the Rat

Diabetic polyneuropathy (DPN) and cold-induced nerve injury share several pathogenic mechanisms. This study explores whether cold exposure contributes to the development of DPN. Streptozotocin-induced diabetic rats and controls were exposed to a room temperature (23°C) or cold environment (10°C). H-reflex, tail and sciatic motor, and sensory nerve conduction studies were performed. Analyses of sural nerve, intraepidermal nerve fibers, and skin and nerve nitrotyrosine ELISAs were performed. Diabetic animals exposed to a cold environment had an increased H-reflex four weeks earlier than diabetic room temperature animals (P = .03). Cold-exposed diabetic animals also had greater reduction in motor conduction velocities at 20 weeks (P = .017), decreased skin nerve fiber density (P = .037), and increased skin nitrotyrosine levels (P = .047). Cold exposure appears to hasten the development of DPN in the rat STZ model of diabetes. These findings support that further study into the relationship between ambient temperature and DPN is warranted

A randomised trial to compare the performance of Oxyzyme® and Iodozyme® with standard care in the treatment of patients with venous and mixed venous/arterial ulceration

This study was to evaluate the potential benefits of two products (Oxyzyme® and Iodozyme®) into a leg ulcer service in South Staffordshire, UK. A randomised controlled trial (RCT) was used to evaluate time to ulcer healing, quality of life, pain and cost effectiveness. 100 patients were randomised to receive either Oxyzyme/Iodozyme (active group) or standard care (control group) with venous or mixed arterio-venous ulcers. Patients were evaluated weekly up to 12 weeks, with further follow up at 24 weeks. Whilst there was a small benefit in terms of healing over follow up using the Cox Proportional Hazards Model, this did not achieve a standard level of statistical significance (hazard ratio = 1.13, 95%CI 0.64 to 2.02, p = 0.67) after adjustment for confounding factors. Patients with high protease activity showed an improved and faster healing in the active group, (HR = 1.35, 95%CI 0.63, 2.87) p = 0.44. The active group required significantly fewer dressing changes (14.8 versus 10.0, p = 0.033). Despite the dressing costs being higher, there was a significantly lower cost of nursing time, leading to a greater cost effectiveness in terms of cost per healed ulcer (£977 versus £1071. A Markov model used to assess cost effectiveness in the main trial found that the control group had slightly better outcomes (12 more ulcer free weeks), but at a substantially greater cost (£5031). When those with high protease activity the cost in the active group dominated, with lower cost (−£2450) and an improved outcome (29 more ulcer free weeks). Health related quality of life (HRQoL) and pain significantly improved over the assessment period, though there was no difference between the treatment groups. The use of Oxyzyme® and Iodozyme® could provide better value for money in the management of venous and mixed arterio-venous ulcers than standard care in a community leg ulcer service

Mechanisms involved in the development and healing of diabetic foot ulceration

We examined the role of vascular function and inflammation in the development and failure to heal diabetic foot ulcers (DFUs). We followed 104 diabetic patients for a period of 18.4 \ub1 10.8 months. At the beginning of the study, we evaluated vascular reactivity and serum inflammatory cytokines and growth factors. DFUs developed in 30 (29%) patients. DFU patients had more severe neuropathy, higher white blood cell count, and lower endothelium-dependent and -independent vasodilation in the macrocirculation. Complete ulcer healing was achieved in 16 (53%) patients, whereas 13 (47%) patients did not heal. There were no differences in the above parameters between the two groups, but patients whose ulcers failed to heal had higher tumor necrosis factor-\u3b1, monocyte chemoattractant protein-1, matrix metallopeptidase 9 (MMP-9), and fibroblast growth factor 2 serum levels when compared with those who healed. Skin biopsy analysis showed that compared with control subjects, diabetic patients had increased immune cell infiltration, expression of MMP-9, and protein tyrosine phosphatase-1B (PTP1B), which negatively regulates the signaling of insulin, leptin, and growth factors. We conclude that increased inflammation, expression of MMP-9, PTP1B, and aberrant growth factor levels are the main factors associated with failure to heal DFUs. Targeting these factors may prove helpful in the management of DFUs

Mechanisms Involved in the Development and Healing of Diabetic Foot Ulceration

We examined the role of vascular function and inflammation in the development and failure to heal diabetic foot ulcers (DFUs). We followed 104 diabetic patients for a period of 18.4 ± 10.8 months. At the beginning of the study, we evaluated vascular reactivity and serum inflammatory cytokines and growth factors. DFUs developed in 30 (29%) patients. DFU patients had more severe neuropathy, higher white blood cell count, and lower endothelium-dependent and -independent vasodilation in the macrocirculation. Complete ulcer healing was achieved in 16 (53%) patients, whereas 13 (47%) patients did not heal. There were no differences in the above parameters between the two groups, but patients whose ulcers failed to heal had higher tumor necrosis factor-α, monocyte chemoattractant protein-1, matrix metallopeptidase 9 (MMP-9), and fibroblast growth factor 2 serum levels when compared with those who healed. Skin biopsy analysis showed that compared with control subjects, diabetic patients had increased immune cell infiltration, expression of MMP-9, and protein tyrosine phosphatase-1B (PTP1B), which negatively regulates the signaling of insulin, leptin, and growth factors. We conclude that increased inflammation, expression of MMP-9, PTP1B, and aberrant growth factor levels are the main factors associated with failure to heal DFUs. Targeting these factors may prove helpful in the management of DFUs

Guidelines for the treatment of diabetic ulcers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72913/1/j.1524-475X.2006.00176.x.pd

Role of Endothelial Progenitor Cells and Inflammatory Cytokines in Healing of Diabetic Foot Ulcers

Background: To evaluate changes in endothelial progenitor cells (EPCs) and cytokines in patients with diabetic foot ulceration (DFU) in association with wound healing. Methods: We studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing. Results: All EPC phenotypes except the kinase insert domain receptor (KDR)+CD133+ were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor (SCF) were increased in DFU patients. DFU patients who healed their ulcers had lower CD34+KDR+ count at visits 3 and 4, serum c-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin-1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding. Conclusions: Uncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34+KDR+ reduction, suggesting possible increased homing. Low baseline CRP, IL-1α and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models