OBJECTIVE -To assess the ability of the 4-week healing rate to predict complete healing over a 12-week period in a large prospective multicenter trial of diabetic patients with foot ulceration.RESEARCH DESIGN AND METHODS -We examined the change in ulcer area over a 4-week period as a predictor of wound healing within 12 weeks in patients who were seen weekly in a prospective, randomized controlled trial.RESULTS -Wound area measurements at baseline and after 4 weeks were performed in 203 patients. The midpoint between the percentage area reduction from baseline at 4 weeks in patients healed versus those not healed at 12 weeks was found to be 53%. Subjects with a reduction in ulcer area greater than the 4-week median had a 12-week healing rate of 58%, whereas those with reduction in ulcer area less than the 4-week median had a healing rate of only 9% (P Ͻ 0.01). The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers (1.5 vs. 0.8 cm 2 , P Ͻ 0.02). The percent change in wound area at 4 weeks in those who healed was 82% (95% CI 70 -94), whereas in those who failed to heal, the percent change in wound area was 25% (15-35; P Ͻ 0.001).CONCLUSIONS -The percent change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks. This simple tool may serve as a pivotal clinical decision point in the care of diabetic foot ulcers for early identification of patients who may not respond to standard care and may need additional treatment.

OBJECTIVE -Endothelial dysfunction has been reported in type 2 diabetic patients and in obese subjects with insulin resistance syndrome (IRS). This study evaluates the effects of weight reduction and exercise on vascular reactivity of the macro-and the microcirculation in obese subjects with IRS.RESEARCH DESIGN AND METHODS -We studied 24 obese subjects (9 men and 15 women, age 49.3 Ϯ 1.9 years, BMI 36.7 Ϯ 0.94 kg/m 2 , mean Ϯ SEM) with IRS at baseline and after 6 months of weight reduction and exercise. Brachial artery flow-mediated dilation (FMD) and response to sublingual glyceryltrinitrate (GTN) were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated by the laser-Doppler perfusion imaging after iontophoresis of acetylcholine and sodium nitroprusside. We also measured plasma levels of soluble intercellular adhesion molecule (sICAM), vascular adhesion molecule, von Willebrand factor, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator antigen.RESULTS -This intervention resulted in 6.6 Ϯ 1% reduction in body weight (P Ͻ 0.001) and significant improvement of insulin sensitivity index (2.9 Ϯ 0.36 vs. 1.9 Ϯ 0.33 [10 Ϫ4 ⅐ min Ϫ1 ⅐ (U ml Ϫ1 )], P Ͻ 0.001). FMD significantly improved (12.9 Ϯ 1.2% vs. 7.9 Ϯ 1.0%, P Ͻ 0.001), whereas response to GTN and microvascular reactivity did not change. Similar observations were seen when the subjects were subclassified according to their glucose tolerance to normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. sICAM and PAI-1 significantly decreased (251.3 Ϯ 7.7 vs. 265.6 Ϯ 9.3 ng/ml, P ϭ 0.018 and 36.2 Ϯ 3.6 vs. 48.6 Ϯ 3.9 ng/ml, P ϭ 0.001, respectively). The relationship between percentage weight reduction and improved FMD was linear (R 2 ϭ 0.47, P ϭ 0.001).CONCLUSIONS -We conclude that 6 months of weight reduction and exercise improve macrovascular endothelial function and reduces selective markers of endothelial activation and coagulation in obese subjects with IRS regardless of the degree of glucose tolerance. Diabetes Care 26:2119 -2125, 2003O besity and insulin resistance are often associated with hyperinsulinemia, glucose intolerance, hypertension, dyslipidemia, premature atherosclerosis, and increased risk for coronary artery disease (1). This cluster of abnormalities is known as the insulin resistance syndrome (IRS) or the metabolic syndrome (2). According to the recently suggested Adult Treatment Panel-III clinical guidelines of the National Cholesterol Education Program, it is estimated that the age-adjusted prevalence of the metabolic syndrome is ϳ23.7% of the adult population (3). This population has an overall excess coronary artery disease risk of ϳ70% (4).Endothelial dysfunction, an early step in the development of atherosclerosis (5), has been reported in patients with type 2 diabetes (6) and in obese nondiabetic individuals (7). It also exists in subjects at high risk for developing diabetes, including subjects with impaired glucose tolerance and normoglycemic first-degree relati...

OBJECTIVE -We have previously demonstrated that high plantar pressures can predict foot ulceration in diabetic patients. The aim of the present study was to evaluate both the relationship between forefoot and rearfoot plantar pressure in diabetic patients with different degrees of peripheral neuropathy and their role in ulcer development. RESEARCH DESIGN AND METHODS-Diabetic patients of a 30-month prospective study were classified according to the neuropathy disability score: scores of 0, 1-5, 6 -16, and 17-28 are defined as absent (n ϭ 20), mild (n ϭ 66), moderate (n ϭ 95), and severe (n ϭ 57) neuropathy, respectively. The F-Scan mat system was used to measure dynamic plantar pressures. The peak pressures under the forefoot and the rearfoot were selectively measured for each foot, and the forefoot-to-rearfoot ratio (F/R ratio) was calculated.RESULTS -Foot ulcers developed in 73 (19%) feet. The peak pressures were increased in the forefoot of the severe and moderate neuropathic groups compared with the mild neuropathic and nonneuropathic groups (6.2 Ϯ 4.5 and 3.8 Ϯ 2.7 vs. 3.0 Ϯ 2.1 and 3.3 Ϯ 2.1 kg/cm 2 [mean Ϯ SD], respectively; P Ͻ 0.0001). The rearfoot pressures were also higher in the severe and moderate neuropathic groups compared with the mild neuropathic and nonneuropathic groups (3.2 Ϯ 2.0 and 3.2 Ϯ 1.9 vs. 2.5 Ϯ 1.3 and 2.3 Ϯ 1.0, respectively; P Ͻ 0.0001). The F/R ratio was increased only in the severe group compared with the moderate and mild neuropathic and nonneuropathic groups (2.3 Ϯ 2.4 vs. 1.5 Ϯ 1.2, 1.3 Ϯ 0.9, and 1.6 Ϯ 1.0, respectively; P Ͻ 0.0001). In a logistic regression analysis, both forefoot pressure (odds ratio 1.19 [95% CI 1.11-1.28], P Ͻ 0.0001) and the F/R ratio (1.37 [1.16 -1.61], P Ͻ 0.0001) were related to risk of foot ulceration, whereas rearfoot pressure was not.CONCLUSIONS -Both the rearfoot and forefoot pressures are increased in the diabetic neuropathic foot, whereas the F/R ratio is increased only in severe diabetic neuropathy, indicating an imbalance in pressure distribution with increasing degrees of neuropathy. This may lend further evidence toward the concept that equinus develops in the latest stages of peripheral neuropathy and may play an important role in the etiology of diabetic foot ulceration.

OBJECTIVE -Diabetic neuropathic patients show a peculiar loading pattern of the foot, which led us to hypothesize that a substantial modification exists in their deambulatory strategy. The aim of the present study was to support this hypothesis by quantifying the changes of the loading patterns and by monitoring the excursion of center of pressure (COP) during gait. RESEARCH DESIGN AND METHODS-A total of 21 healthy volunteers (C) and 61 diabetic patients were evaluated: 27 diabetic subjects without neuropathy (D), 19 with neuropathy (DN), and 15 with previous neuropathic ulcer (DPU). A piezo-dynamometric platform was used to record the foot-to-floor interaction by measuring loading time and the instantaneous COP position during the stance phase of gait.RESULTS -Loading time was significantly longer in neuropathic patients than in control subjects (DPU: 816.8 Ϯ 150 ms; DN: 828.6 Ϯ 152 ms; D: 766.5 Ϯ 89.9 ms; C: 723.7 Ϯ 65.7 ms; P Ͻ 0.05). COP excursion along the medio-lateral axis of the foot clearly decreased from C to DPU groups (C: 6.41 Ϯ 0.1 cm; D: 4.88 Ϯ 0.2 cm; DN: 4.57 Ϯ 0.1 cm; DPU: 3.36 Ϯ 0.1 cm; P Ͻ 0.05) as well as COP excursion along the longitudinal axis for the DPU group only (C: 26.6 Ϯ 1 cm; D: 26.9 Ϯ 1 cm; DN: 27.2 Ϯ 1 cm; DPU: 24.2 Ϯ 1 cm; P Ͻ 0.05). COP integrals were significantly reduced for all pathological classes (DPU: 14.2 Ϯ 8 cm 2 ; DN: 25.8 Ϯ 6 cm 2 ; D: 27.7 Ϯ 3 cm 2 ; C: 38.6 Ϯ 6 cm 2 ; P Ͻ 0.05).CONCLUSIONS -The accurate quantification of loading patterns and of COP excursions and integrals highlights changes of foot-to-floor interaction in diabetic neuropathic patients. The decreased medio-lateral and longitudinal COP excursions and corresponding changes of loading times and patterns support our hypothesis that a change in the walking strategy of diabetic patients with peripheral neuropathy does occur. Diabetes Care 25:1451-1457, 2002A bnormal plantar pressures are considered the main cause of neuropathic foot ulceration (1-5). However, high pressures are only the last ring of a chain to which several factors contribute, including peripheral neuropathy and limited joint mobility. It is worth emphasizing that those factors may influence not only the foot loading, but, more widely, the whole performance of the lower limb during gait.A few authors have suggested that patients with peripheral neuropathy develop a change in their walking strategy, shifting from an ankle to a hip strategy (6,7). In a recent article, our group also hypothesized this kind of change by analyzing the foot loading pattern (8). The aim of the present work was to further support this hypothesis by using a different parameter, namely the evolution of the center of pressure (COP) that is the point of application of the ground reaction force (GRF). COP records the succession of instantaneous positions during the entire period of contact between foot and floor and is plotted as a sequence of points on the ground plane. It takes into account the displacement of load throughout the foot during the stance phase of a wal...