Aristidis Veves

The risk of foot ulceration in diabetic patients with high foot pressure: a prospective study

SummaryFoot ulceration results in substantial morbidity amongst diabetic patients. We have studied prospectively the relationship between high foot pressures and foot ulceration using an optical pedobarograph. A series of 86 diabetic patients, mean age 53.3 (range 17–77) years, mean duration of diabetes 17.1 (range 1–36) years, were followed-up for a mean period of 30 (range 15–34) months. Clinical neuropathy was present in 58 (67%) patients at baseline examination. Mean peak foot pressure was higher at the follow-up compared to baseline (13.5 kg·cm−2±7.1 SD vs 11.2±5.4, p<0.001) with abnormally high foot pressures (>12.3) being present in 55 patients at follow-up and 43 at the baseline visit (p=NS). Plantar foot ulcers developed in 21 feet of 15 patients (17%), all of whom had abnormally high pressures at baseline; neuropathy was present in 14 patients at baseline. Non-plantar ulcers occurred in 8 (9%) patients. Thus, plantar ulceration occurred in 35% of diabetic patients with high foot pressures but in none of those with normal pressures. We have shown for the first time in a prospective study that high plantar foot pressures in diabetic patients are strongly predictive of subsequent plantar ulceration, especially in the presence of neuropathy.

The Prediction of Diabetic Neuropathic Foot Ulceration Using Vibration Perception Thresholds: A prospective study

OBJECTIVE To assess the ability of vibration perception threshold (VPT) to predict the development of diabetic foot ulceration. RESEARCH DESIGN AND METHODS A prospective follow-up study of consecutive patients with vibration perception measured by biothesiometry from April 1988 to March 1989. Patients were stratified in various risk groups. RESULTS Patients with a VPT <15 V had a cumulative incidence of foot ulceration of 2.9% compared with 19.8% in patients with a VPT >25 V, odds ratio (OR) 7.99 (3.65–17.5, 95% confidence intervals), P < 0.01. The incidence of ulceration increased with duration of diabetes, but even with this effect removed, the excess of ulceration persisted, OR 6.82 (2.75–16.92), P < 0.01. CONCLUSIONS VPT is an effective predictor of the risk of foot ulceration in diabetes and therefore could be used to target foot-care education to those patients most likely to benefit and, thereby, possibly improve its effectiveness.

Diabetes Enhances Vulnerability to Particulate Air Pollution–Associated Impairment in Vascular Reactivity and Endothelial Function

Background—Epidemiological studies suggest that people with diabetes are vulnerable to cardiovascular health effects associated with exposure to particle air pollution. Endothelial and vascular function is impaired in diabetes and may be related to increased cardiovascular risk. We examined whether endothelium-dependent and -independent vascular reactivity was associated with particle exposure in individuals with and without diabetes. Methods and Results—Study subjects were 270 greater-Boston residents. We measured 24-hour average ambient levels of air pollution (fine particles [PM2.5], particle number, black carbon, and sulfates [SO42−]) ≈500 m from the patient examination site. Pollutant concentrations were evaluated for associations with vascular reactivity. Linear regressions were fit to the percent change in brachial artery diameter (flow mediated and nitroglycerin mediated), with the particulate pollutant index, apparent temperature, season, age, race, sex, smoking history, and body mass index as predictors. Models were fit to all subjects and then stratified by diagnosed diabetes versus at risk for diabetes. Six-day moving averages of all 4 particle metrics were associated with decreased vascular reactivity among patients with diabetes but not those at risk. Interquartile range increases in SO42− were associated with decreased flow-mediated (−10.7%; 95% CI, −17.3 to −3.5) and nitroglycerin-mediated (−5.4%; 95% CI, −10.5 to −0.1) vascular reactivity among those with diabetes. Black carbon increases were associated with decreased flow-mediated vascular reactivity (−12.6%; 95% CI, −21.7 to −2.4), and PM2.5 was associated with nitroglycerin-mediated reactivity (−7.6%; 95% CI, −12.8 to −2.1). Effects were stronger in type II than type I diabetes. Conclusions—Diabetes confers vulnerability to particles associated with coal-burning power plants and traffic.

Role of Neuropathy and High Foot Pressures in Diabetic Foot Ulceration

OBJECTIVE High plantar foot pressures in association with peripheral neuropathy have been ascertained to be important risk factors for ulceration in the diabetic foot. Most studies investigating these parameters have been limited by their size and the homogeneity of study subjects. The objective of this study was therefore to ascertain the risk of ulceration associated with high foot pressures and peripheral neuropathy in a large and diverse diabetic population. RESEARCH DESIGN AND METHODS We studied a cross-sectional group of 251 diabetic patients of Caucasian (group C) (n = 121), black (group B) (n = 36), and Hispanic (group H) (n = 94) racial origins with an overall age of 58.5 ± 12.5 years (range 20–83). There was an equal distribution of men and women across the entire study population. All patients underwent a complete medical history and lower extremity evaluation for neuropathy and foot pressures. Neuropathic parameters were dichotomized (0/1) into two high-risk variables: patients with a vibration perception threshold (VPT) ≥25 V were categorized as HiVPT (n = 132) and those with Semmes-Weinstein monofilament tests ≥5.07 were classified as HiSWF (n = 190). The mean dynamic foot pressures of three footsteps were measured using the F-scan mat system with patients walking without shoes. Maximum plantar pressures were dichotomized into a high-pressure variable (Pmax6) indicating those subjects with pressures ≥6 kg/cm2 (n = 96). A total of 99 patients had a current or prior history of ulceration at baseline. RESULTS Joint mobility was significantly greater in the Hispanic cohort compared with the other groups at the first metatarsal-phalangeal joint (C 67 ± 23°, B 69 ± 23°, H 82 ± 23°, P = 0.000), while the subtalar joint mobility was reduced in the Caucasian group (C 21 ± 8°, B 26 ± 7°, H 27 ± 11°, P = 0.000). Maximum plantar foot pressures were significantly higher in the Caucasian group (C 6.7 ± 2.9 kg/cm2, B 5.7 ± 2.8 kg/cm2, H 4.4 ±1.9 kg/cm2 P = 0.000). Univariate logistic regression for Pmax6 on the history of ulceration yielded an odds ratio (OR) of 3.9 (P = 0.000). For HiVPT, the OR was 11.7 (P = 0.000), and for HiSWF, the OR was 9.6 (P = 0.000). Controlling for age, diabetes duration, sex, and race (all P < 0.05), multivariate logistic regression yielded the following significant associations with ulceration: Pmax6 (OR = 2.1, P = 0.002), HiVPT (OR = 4.4, P = 0.000), and HiSWF (OR = 4.1, P = 0.000). CONCLUSIONS We conclude that both high foot pressures (≥6 kg/cm2) and neuropathy are independently associated with ulceration in a diverse diabetic population, with the latter having the greater magnitude of effect. In black and Hispanic diabetic patients especially, joint mobility and plantar pressures are less predictive of ulceration than in Caucasians.

Relationship of Limited Joint Mobility to Abnormal Foot Pressures and Diabetic Foot Ulceration

Objective To investigate the role of limited joint mobility (LJM) in causing abnormal foot pressures and foot ulceration. Research Design and Methods The subjects were recruited from a general diabetes clinic where patients were screened for neuropathy, retinopathy, and elevated plantar foot pressure. Sixty-four patients in five groups were matched by age and sex in the following groups: group 1, patients with LJM and neuropathy; group 2, nonneuropathic diabetic patients with LJM; group 3, patients with neuropathy and no LJM; group 4, diabetic control subjects; and group 5, nondiabetic control subjects. Joint mobility was assessed in the foot at subtalar and metatarsophalangeal joints; plantar foot pressures were assessed by optical pedobarography and neuropathic status by a Biothesiometer and electrophysiology. Results Joint mobility was reduced at both sites in groups 1 and 2 compared with groups 3, 4, and 5 (P < 0.001). Plantar foot pressures were significantly higher in groups 1 and 2 compared with groups 3, 4, and 5 (P < 0.001). No differences in plantar foot pressures were observed between groups 1 and 2. There were strong correlations between plantar foot pressures and joint mobility in the foot (r = −0.7, P < 0.001). Previous foot ulceration was present in 65% of patients in group 1, none in group 2, and 5% in group 3. Conclusions 1) LJM may be a major factor in causing abnormally high plantar foot pressures, 2) abnormal plantar foot pressures alone do not lead to foot ulceration, and 3) LJM contributes to foot ulceration in the susceptible neuropathic foot.

Semmes-Weinstein monofilaments: a simple, effective and inexpensive screening device for identifying diabetic patients at risk of foot ulceration.

Both vibration perception threshold (VPT) by biothesiometry and pressure perception using Semmes-Weinstein monofilaments (filaments) have been proposed to identify diabetic patients at risk of foot ulceration. The two methods were compared in 182 subjects attending a national patients conference. Both measures were made over the great toe. Filaments of three calibres were used: 4.17, 5.07 and 6.10 bending with 1, 10 and 75 g force, respectively. Pressure perception was normal (4.17) in 122 patients (group 1) whereas in 45 patients it was grade 5.07 (group 2) and 6.10 or greater in 15 (group 3). The corresponding mean VPT (+/- SD) for the three groups were 10.6 (+/- 6.7), 22.8 (+/- 12.7) and 32 (+/- 14.3), respectively. The mean VPT for the 3 groups were significantly different (P less than 0.001). The filaments were more sensitive (100%) but less specific (77.7%) in identifying patients who had foot ulcers compared to biothesiometry which was less sensitive (78.6%) but more specific (93.4%). The filaments are therefore reliable and may be superior to biothesiometry in screening for patients at risk of foot ulceration since sensitivity is the more important parameter. In addition, they are inexpensive (12 pounds) compared to the biothesiometer (400 pounds) and are simple and easy to use.

Noise-enhanced balance control in patients with diabetes and patients with stroke

Somatosensory function declines with diabetic neuropathy and often with stroke, resulting in diminished motor performance. Recently, it has been shown that input noise can enhance human sensorimotor function. The goal of this study was to investigate whether subsensory mechanical noise applied to the soles of the feet via vibrating insoles can be used to improve quiet‐standing balance control in 15 patients with diabetic neuropathy and 15 patients with stroke. Sway data of 12 healthy elderly subjects from a previous study on vibrating insoles were added for comparison.

Guidelines for the treatment of diabetic ulcers

1. Chaired this panel2. University of Pittsburgh/UPMC, Pittsburgh, PA3. Georgetown University Hospital, Washington, DC4. Colaizzi Pedorthic Center, Pittsburgh, PA5. HCA Richmond Retreat Hospital, Richmond, VA6. University of Michigan Hospital, Ann Arbor, MI7. University of Texas Health Science Center, San Antonio, TX8. Covance, Princeton, NJ9. St Joseph’s Hospital, Belleville, IL10. University of South Florida, Tampa, FL11. Penn North Centers for Advanced Wound Care, Warren, PA12. Cabrini Medical Center, NY, NY13. Beth Israel Deaconess Medical Center, Boston, MA, and14. Barnes-Jewish Hospital at Washington University Medical Center, St Louis, MO

Elevated Plasma Levels of the Atherogenic Mediator Soluble CD40 Ligand in Diabetic Patients A Novel Target of Thiazolidinediones

Background—Considerable evidence implicates the proinflammatory cytokine CD40 ligand (CD40L) in atherosclerosis and accumulating data link type 1 and 2 diabetes, conditions associated with accelerated atherosclerosis, to inflammation. This study therefore evaluated the hypothesis that diabetic patients have elevated plasma levels of soluble CD40L (sCD40L) and that treatment with the insulin-sensitizing thiazolidinediones lowers this index of inflammation. Methods and Results—Subjects with type 1 (n=49) or type 2 diabetes (n=48) had higher (P <0.001) sCD40L plasma levels (6.56±3.27 and 6.67±2.90 ng/mL, respectively) compared with age-matched control groups (1.40±2.21 and 1.32±2.68 ng/mL, respectively). Multiple regression analysis demonstrated a significant (P <0.001) association between plasma sCD40L and type 1 as well as type 2 diabetes, independent of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, blood pressure, body mass index, gender, C-reactive protein, and soluble intracellular adhesion molecule-1. Furthermore, in a pilot study, administration of troglitazone (12 weeks, 600 mg/day), but not placebo, to type 2 diabetics (n=68) significantly (P <0.001) diminished sCD40L plasma levels by 29%. The thiazolidinedione lowered plasma sCD40L in type 2 diabetic patients with long-standing disease (>3 years) with or without macrovascular complications (−34% and −29%, respectively) as well as in type 2 diabetic patients with more recent (<3 years) onset of the disease (−27%; all P <0.05). Conclusions—This study provides new evidence that individuals with type 1 or 2 diabetes have a proinflammatory state as indicated by elevated levels of plasma sCD40L. Troglitazone treatment of type 2 diabetic patients diminishes sCD40L levels, suggesting a novel antiinflammatory mechanism for limiting diabetes-associated arterial disease.

Air pollution and inflammation in type 2 diabetes: A mechanism for susceptibility

Background: Particulate air pollution has been associated with several adverse cardiovascular health outcomes, and people with diabetes may be especially vulnerable. One potential pathway is inflammation and endothelial dysfunction—processes in which cell adhesion molecules and inflammatory markers play important roles. Aim: To examine whether plasma levels of soluble intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and von Willebrand factor (vWF) were associated with particle exposure in 92 Boston area residents with type 2 diabetes. Methods: Daily average ambient levels of air pollution (fine particles (PM2.5), black carbon (BC) and sulphates) were measured approximately 500 m from the patient examination site and evaluated for associations with ICAM-1, VCAM-1 and vWF. Linear regressions were fit to plasma levels of ICAM-1, VCAM-1 and vWF, with the particulate pollutant index, apparent temperature, season, age, race, sex, glycosylated haemoglobin, cholesterol, smoking history and body mass index as predictors. Results: Air pollutant exposure measures showed consistently positive point estimates of association with the inflammatory markers. Among participants not taking statins and those with a history of smoking, associations between PM2.5, BC and VCAM-1 were particularly strong. Conclusions: These results corroborate evidence suggesting that inflammatory mechanisms may explain the increased risk of air pollution-associated cardiovascular events among those with diabetes.