Influence of diabetes on ambulation and inflammation in men and women with symptomatic peripheral artery disease

OBJECTIVE: To determine whether diabetes and sex were factors associated with ambulatory function, endothelial cell inflammation, oxidative stress, and apoptosis, and with circulating biomarkers of inflammation and antioxidant capacity in patients with peripheral artery disease (PAD) and claudication. MATERIALS/METHODS: Ambulatory function of 180 symptomatic men and women with PAD was assessed during a graded maximal treadmill test, 6-minute walk test, and 4-meter walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells, and on circulating inflammatory and vascular biomarkers. RESULTS: Men and women with diabetes had greater prevalence (p = 0.007 and p = 0.015, respectively) of coronary artery disease (CAD) than patients without diabetes. To assure that this difference did not influence planned comparisons, the data set was stratified on CAD. Diabetic men with CAD had a lower peak walking time (PWT) during the treadmill test and a slower 4-meter gait speed compared to non-diabetic men with CAD (p < 0.05). Diabetic women with CAD had a lower PWT compared to their non-diabetic counterparts (p < 0.01). Additionally, diabetic men with CAD had higher pigment epithelium-derived factor (p < 0.05) than their non-diabetic counterparts, and diabetic women with CAD had higher leptin (p < 0.01) and interleukin-8 levels (p < 0.05). CONCLUSIONS: In patients with PAD, diabetic men and women with CAD had more severe claudication than their non-diabetic counterparts, as measured by shorter PWT, and the men had further ambulatory impairment manifested by slower 4-meter gait speed. Furthermore, the diabetic patients with CAD had elevations in interleukin-8, leptin, and PEDF.