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Biomedical subjects

A Veves

Publications and source records attributed to A Veves.

At least 19 recordsLinked to original sources
PubMed2001

Sural nerve fibre pathology in diabetic patients with mild neuropathy: relationship to pain, quantitative sensory testing and peripheral nerve electrophysiology.

Nerve fibre pathology is poorly described in diabetic patients with mild neuropathy and has not been adequately related to clinical evaluation, quantitative sensory examination and neurophysiology. Sural nerve myelinated and unmyelinated fibre pathology was morphometrically quantified and related to the presence of pain and conventional measures of neuropathic severity in 15 diabetic patients with mild neuropathy and 14 control subjects. Diabetic patients demonstrated a significant (P < 0.01) reduction in myelinated fibre density, but no change in fibre/axonal area, or g-ratio, compared to control subjects. Unmyelinated fibre degeneration was evidenced by an increase in the percentage of unassociated Schwann cell profiles (P < 0.0001) and a reduction in axon density (P < 0.0008) in diabetic patients. This was associated with a significant reduction in unmyelinated axon diameter (P < 0.001) with a shift of the size frequency distribution to the left (P < 0.02). Neurophysiology, quantitative sensory testing and nerve fibre pathology failed to differentiate diabetic patients with painful and painless neuropathy and failed to correlate with any measure of unmyelinated fibre pathology.

Action Potentials↗
PubMed2001

Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial.

OBJECTIVE: We assessed in a randomized prospective trial the effectiveness of Graftskin, a living skin equivalent, in treating noninfected nonischemic chronic plantar diabetic foot ulcers. RESEARCH DESIGN AND METHODS: In 24 centers in the U.S., 208 patients were randomly assigned to ulcer treatment either with Graftskin (112 patients) or saline-moistened gauze (96 patients, control group). Standard state-of-the-art adjunctive therapy, which included extensive surgical debridement and adequate foot off-loading, was provided in both groups. Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks (maximum of five applications) or earlier if complete healing occurred. The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit. RESULTS: At the 12-week follow-up visit, 63 (56%) Graftskin-treated patients achieved complete wound healing compared with 36 (38%) in the control group (P = 0.0042). The Kaplan-Meier median time to complete closure was 65 days for Graftskin, significantly lower than the 90 days observed in the control group (P = 0.0026). The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 (95% CI 1.23-3.74). The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations, both of which were less frequent in the Graftskin group. CONCLUSIONS: Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects. Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available standard of care.

Adolescent↗
PubMed2001

Contribution of nerve-axon reflex-related vasodilation to the total skin vasodilation in diabetic patients with and without neuropathy.

OBJECTIVE: To examine the contribution of nerve-axon reflex-related vasodilation to total acetylcholine-induced vasodilation in the skin of normal and diabetic subjects. RESEARCH DESIGN AND METHODS: The skin microcirculation was evaluated at the forearm level in 69 healthy subjects and 42 nonneuropathic diabetic patients and at the foot level in 27 healthy subjects and 101 diabetic patients (33 with neuropathy, 23 with Charcot arthropathy, 32 with peripheral vascular disease and neuropathy, and 13 without complications). Two single-point laser probes were used to measure total and neurovascular vasodilation response to the iontophoresis of 1% acetylcholine, 1% sodium nitroprusside, and deionized water. RESULTS: The neurovascular response to acetylcholine was significantly higher than the response to sodium nitroprusside and deionized water (P < 0.01). At the forearm level, the contribution of neurovascular response to the total response to acetylcholine was 35% in diabetic patients and 31% in control subjects. At the foot level, the contribution was 29% in diabetic patients without neuropathy and 36% in control subjects, while it was significantly diminished in the three neuropathic groups. A significantly lower nonspecific nerve-axon-related vasodilation was observed during the iontophoresis of sodium nitroprusside, which does not specifically stimulate the C nociceptive fibers. CONCLUSIONS: Neurovascular vasodilation accounts for approximately one-third of the total acetylcholine-induced vasodilation at both the forearm and foot levels. The presence of diabetic neuropathy results in reduction of both the total vasodilatory response to acetylcholine and the percentage contribution of neurovascular vasodilation to the total response. Acetylcholine and sodium nitroprusside cause vasodilation in the skin microcirculation through different pathways.

Acetylcholine↗
PubMed2000

Screening techniques to identify people at high risk for diabetic foot ulceration: a prospective multicenter trial.

OBJECTIVE: Diabetic foot ulceration is a preventable long-term complication of diabetes. A multicenter prospective follow-up study was conducted to determine which risk factors in foot screening have a high association with the development of foot ulceration. RESEARCH DESIGN AND METHODS: A total of 248 patients from 3 large diabetic foot centers were enrolled in a prospective study. Neuropathy symptom score, neuropathy disability score (NDS), vibration perception threshold (VPT), Semmes-Weinstein monofilaments (SWFs), joint mobility, peak plantar foot pressures, and vascular status were evaluated in all patients at the beginning of the study. Patients were followed-up every 6 months for a mean period of 30 months (range 6-40), and all new foot ulcers were recorded. The sensitivity, specificity, and positive predictive value of each risk factor were evaluated. RESULTS: Foot ulcers developed in 95 feet (19%) or 73 patients (29%) during the study. Patients who developed foot ulcers were more frequently men, had diabetes for a longer duration, had nonpalpable pedal pulses, had reduced joint mobility, had a high NDS, had a high VPT, and had an inability to feel a 5.07 SWE NDS alone had the best sensitivity, whereas the combination of the NDS and the inability to feel a 5.07 SWF reached a sensitivity of 99%. On the other hand, the best specificity for a single factor was offered by foot pressures, and the best combination was that of NDS and foot pressures. Univariate logistical regression analysis yielded a statistically significant odds ratio (OR) for sex, race, duration of diabetes, palpable pulses, history of foot ulceration, high NDSs, high VPTs, high SWFs, and high foot pressures. In addition, 94 (99%) of the 95 ulcerated feet had a high NDS and/or SWF which resulted in the highest OR of 26.2 (95% CI 3.6-190). Furthermore, in multivariate logistical regression analysis, the only significant factors were high NDSs, VPTs, SWFs, and foot pressures. CONCLUSIONS: Clinical examination and a 5.07 SWF test are the two most sensitive tests in identifying patients at risk for foot ulceration, especially when the tests are used in conjunction with each other. VPT measurements are also helpful and can be used as an alternative. Finally, foot pressure measurements offer a substantially higher specificity and can be used as a postscreening test in conjunction with providing appropriate footwear.

Adult↗
PubMed1999

The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes.

Estrogens protect healthy women from cardiovascular disease. However, epidemiological data suggest that women with diabetes are denied the cardioprotection associated with estrogens. Whether or not hormonal replacement therapy (HRT) confers cardiovascular benefits in postmenopausal women with diabetes is not known. The aim of this study was to examine the effects of HRT on the microvascular reactivity and endothelial function of individuals with and without diabetes. We studied the following groups of individuals: premenopausal healthy women [n = 28, age 41 +/- 8 yr (mean +/- SD)], premenopausal women with type 2 diabetes (n = 16, age 43 +/- 6 yr); postmenopausal healthy women (n = 12, age 57 +/- 4 yr), postmenopausal women with diabetes (n = 17, age 62 +/- 5 yr); postmenopausal healthy women on HRT (n = 13, age 51 +/- 5 yr), postmenopausal women with diabetes on HRT (n = 11, age 57 +/- 7 yr). We used laser Doppler flowmetry to measure forearm cutaneous vasodilatation in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium independent). The endothelium-dependent vasodilation was significantly higher in premenopausal healthy women (180 +/- 67%; increase over baseline) compared to premenopausal diabetic women (87 +/- 41%; P < 0.001). endothelium-dependent vasodilation was also higher in postmenopausal healthy women on HRT (143 +/- 52) compared with postmenopausal diabetic women on HRT (86 +/- 61), postmenopausal healthy women without HRT (104 +/- 43), and postmenopausal diabetic women without HRT (74 +/- 28; P < 0.001). A similar pattern of responses was observed in the endothelium-independent vasodilation (premenopausal healthy women, 126 +/- 56; premenopausal diabetic women, 88 +/- 26; postmenopausal healthy women on HRT, 121 +/- 37; postmenopausal diabetic women on HRT, 88 +/- 41; postmenopausal healthy women without HRT, 84 +/- 36; and postmenopausal diabetic women without HRT, 73 +/- 36; P < 0.001). Soluble intercellular adhesion molecule (sICAM) was also measured among all the women with diabetes. Premenopausal women with diabetes (248.9 +/- 56 ng/ml) and postmenopausal women with diabetes on HRT (257.7 +/- 49 ng/ml) had lower sICAM levels compared with the postmenopausal diabetic women without HRT (346.4 +/- 149 ng/ml; P < 0.05). We conclude that menopausal status and type 2 diabetes are associated with impaired microvascular reactivity. HRT substantially improves microvascular reactivity in postmenopausal healthy women. In contrast, the effect of HRT on the microvascular reactivity of postmenopausal diabetic women is less apparent. However, the use of HRT among women with diabetes is associated with lower sICAM levels, suggesting an attenuation in endothelial activation.

Acetylcholine↗
PubMed1999

Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.

Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation, the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure, fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent vasodilation. In the macrocirculation, systolic blood pressure, HbA1c, HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glucose, and BMI were the most important contributing factors to the variation of vascular reactivity. Addition of all clinical and biochemical measures explained only 32-37% of the variation in vascular reactivity. These results suggest that abnormalities in vascular reactivity and biochemical markers of endothelial cell activation are present early in individuals at risk of developing type 2 diabetes, even at a stage when normal glucose tolerance exists, and that factors in addition to insulin resistance may be operative.

Acetylcholine↗
PubMed1999

Soluble intercellular adhesion molecule, vascular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 diabetic individuals without microalbuminuria.

OBJECTIVE: Using von Willebrand Factor (vWF) as a marker of endothelial function, previous studies have shown that the development of microalbuminuria is associated with the onset of endothelial dysfunction in individuals with type 2 diabetes. We tested the hypothesis that endothelial dysfunction is already evident in normoalbuminuric individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: We used laser Doppler imaging scanning to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent). Multiple indicators of endothelial function--soluble intercellular adhesion molecule (sICAM), soluble vascular cell adhesion molecule (sVCAM), vWF, and microvascular reactivity--were measured in 20 healthy control subjects, 45 normoalbuminuric (urinary albumin/creatinine ratio < 30 micrograms/mg) individuals with type 2 diabetes, and 14 microalbuminuric (urinary albumin/creatinine ratio between 30 and 300 micrograms/mg) individuals with type 2 diabetes. RESULTS: Serum sICAM and sVCAM levels were elevated in the normoalbuminuric (305 +/- 120, 851 +/- 284 ng/ml) and microalbuminuric (300 +/- 89, 845 +/- 252 ng/ml) individuals with diabetes when compared with the healthy control subjects (213 +/- 58, 661 +/- 176 ng/ml) (P < 0.01). Furthermore, the microvascular endothelium-dependent and -independent vasodilation was reduced in the normoalbuminuric (76 +/- 44, 70 +/- 33) (percent increase in perfusion over baseline) and microalbuminuric (74 +/- 41, 73 +/- 28) individuals with diabetes compared with healthy control subjects (126 +/- 67, 120 +/- 47) (P < 0.05). In contrast, plasma vWF was elevated only in the microalbuminuric individuals with diabetes (129 +/- 35%) compared with the normoalbuminuric individuals with diabetes (110 +/- 34) and healthy control subjects (111.3 +/- 39) (P < 0.05). On stepwise multivariate analysis, fasting blood glucose was the most important contributing factor to the variation in microvascular reactivity and sVCAM, whereas insulin resistance (by homeostasis model assessment) was the most important contributing factor to the variation in sICAM. Addition of all clinical and biochemical measures explained only 15-22% of the variation in sICAM, sVCAM, and microvascular reactivity. CONCLUSIONS: Multiple markers of endothelial dysfunction were evident in normoalbuminuric individuals with type 2 diabetes. The pathogenic process of vasculopathy in type 2 diabetes occurs early and may be operative before the development of microalbuminuria.

Adult↗
PubMed1998

Estrogen improves endothelial function.

PURPOSE: To determine the effect of estrogen on endothelium-dependent relaxation in the cutaneous microcirculation of women. METHODS: Three groups of women participated in the study. Group 1 (n = 20) was premenopausal and had a mean age of 39 years (range 24-50 years). Group 2 (n = 9) was postmenopausal and had a mean age of 58 years (range 53-65 years). Group 3 (n = 11) was postmenopausal and taking estrogen replacement therapy; the mean age was 53 years (range 43-58 years). Eleven women in group 1 underwent testing twice, once during menstruation (mean serum estradiol level 73 +/- 30 pg/ml) and once during midcycle (mean serum estradiol level 268 +/- 193 pg/ml; p = 0.003). Single-point laser Doppler ultrasound and laser Doppler imaging with a scanner were used to measure vasodilatation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium-independent smooth muscle relaxant). RESULTS: All three groups were matched for body mass index and fasting glucose, total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglyceride levels. All women had normal blood pressure, and none smoked. Mean serum estradiol levels were 196 +/- 170 pg/ml (group 1), 35 +/- 12 pg/ml (group 2), and 107 +/- 78 pg/ml (group 3) (p = 0.004). Maximum microvascular vasodilatation (percentage increase over baseline) in response to acetylcholine was reduced in group 2 (93% +/- 43%) compared with group 1 (187% +/- 63%) and group 3 (142% +/- 56%) (p = 0.001). The response to sodium nitroprusside also was diminished in group 2 (73% +/- 27%) compared with group 1 (126% +/- 45%) and group 3 (100% +/- 32%) (p = 0.02). Within group 1 the acetylcholine response was higher during the midcycle phase (186% +/- 31%) compared with the menstrual phase (147% +/- 57%) (p < 0.05). The sodium nitroprusside response also was higher during the midcycle phase (144% +/- 31%) compared with the menstrual phase (94% +/- 41%) (p < 0.05) CONCLUSION: The results indicate that estrogens might enhance endothelium-dependent and endothelium-independent vasodilatation in the microcirculation of women.

Acetylcholine↗
PubMed1998

Endothelium-dependent vasodilatation is impaired in both microcirculation and macrocirculation during acute hyperglycemia.

PURPOSE: Endothelial dysfunction is associated with atheromatosis and is a common finding with diabetes. We have studied the effects of acute hyperglycemia on the endothelium-dependent vasodilatation of both the microcirculation and the macrocirculation of healthy subjects. Because of the presence of endothelial dysfunction with diabetes, we hypothesize that acute hyperglycemia causes impaired endothelial-dependent responses. METHODS: Twenty healthy subjects (15 men, 5 women) with a mean age of 32.3 years (range, 23 to 49 years) were examined during fasting conditions and at 1 hour after the ingestion of 75 g of glucose. The endothelium-dependent vasodilatation of the brachial artery, a conduit vessel, was evaluated with high-resolution ultrasound scan to measure the changes in the vessel diameter induced with reactive hyperemia. In the microcirculation, the endothelial function was assessed by measuring the changes in the erythrocyte flux after the acetylcholine iontophoresis. RESULTS: The brachial artery endothelium-dependent dilatation was greater during fasting as compared with the response after the glucose load was administered (11.7% [8.3 to 14.3] vs 4.2% [1.5 to 9.6]; P < .001; median, first, and third quartile). Both peak and average blood flow velocities during the hyperemic response were higher after the administration of the glucose load as compared with the fasting period (P < .05), but no changes were found in the blood flow volume. During fasting, microcirculatory endothelial-dependent vasodilatation was also significantly greater than the response after the administration of the glucose load (1293% [591 to 1856] vs 863% [385 to 1180]; P < .01). CONCLUSIONS: In healthy subjects, the ingestion of a glucose load impairs the endothelial-dependent vasodilation in both the microcirculation and the macrocirculation. Because impairment of endothelial responses is associated with the early changes of atherosclerosis, it is possible that prolonged hyperglycemia and endothelial dysfunction may lead to the early and accelerated atherosclerosis of diabetes. Further studies are necessary to examine the long-term effects of hyperglycemia.

Acute Disease↗
PubMed1998

Reactive hyperemic response of the brachial artery: comparison of proximal and distal occlusion.

RATIONALE AND OBJECTIVES: The authors compared the postocclusion hyperemic responses of the brachial artery after occluding blood flow proximal to and distal to the studied area. MATERIALS AND METHODS: Response of the brachial artery to hypoxia was evaluated with duplex Doppler ultrasound in 13 healthy subjects. A pneumatic tourniquet was first positioned 2-5 cm superior to the left elbow, proximal to the area of artery studied. Two hours later the response was remeasured with the tourniquet positioned 2-5 cm inferior to the elbow, distal to the artery studied. Arterial diameter, mean and peak flow velocities, and heart rate were assessed. RESULTS: No significant differences were observed between measurements of baseline and postischemic arterial diameter, percentage diameter change, baseline mean arterial blood flow velocity, baseline peak arterial blood flow velocity, or postischemic heart rate obtained with proximal occlusion of the artery and those obtained with distal occlusion. In contrast, mean and peak postischemic arterial blood flow velocity and preocclusion heart rate were higher in measurements made during proximal artery occlusion. Significant correlation was found between measurements of percentage change in artery diameter obtained with proximal artery occlusion and those obtained with distal occlusion (r = 0.611, P < .05). CONCLUSION: There are no major differences in postischemic changes in brachial artery diameter related to reactive hyperemia between blood flow occlusion applied proximal and distal to the studied area. However, there are significant differences in the mean and peak systolic velocities. Either occlusion site can be used for clinical studies if arterial diameter change is monitored, but if velocity measurements are being compared, a single occlusion site should be chosen.

Adult↗
PubMed1998

Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration.

We studied endothelial-mediated microvascular blood flow in neuropathic diabetic patients to determine the association between endothelial regulation of the microcirculation and the expression of endothelial constitutive nitric oxide synthetase (ecNOS) in the skin. Vasodilation on the dorsal foot in response to heating and iontophoresis of acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) were measured using single-point laser Doppler and laser Doppler imaging in diabetic patients with neuropathy (DN), with neuropathy and vascular disease (DI), with Charcot arthropathy (DA), and without complications (D), and in healthy control subjects (C). The response to heat was reduced in the DN (321 [21-629] percentage of increase over the baseline, median [interquartile range]) and DI (225 [122-470]) groups but was preserved in the DA (895 [359-1,229]), D (699 [466-1,029]), and C (810 [440-1,064], P < 0.0001) groups. The endothelial-mediated response to acetylcholine was reduced in the DN (17 [11-25]), DA (22 [2-34]), and DI (13 [2-30]) groups compared with the D (47 [24-58]) and C (44 [31-70], P < 0.001) groups. The non-endothelial-mediated response to sodium nitroprusside was also reduced in the DI (4 [0-18]), DN (17 [9-26]), and DA (21 [11-31]) groups compared with the D (37 [19-41]) and C (44 [26-67], P < 0.0001) groups. There was a significant reduction in vasodilation in the DI group compared with all other groups (P < 0.0001). Full thickness skin biopsies from the dorsum of the foot of 15 DN, 10 DI, and 11 C study subjects were immunostained with antiserum to human ecNOS, the functional endothelial marker GLUT1, and the anatomical endothelial marker von Willebrand factor. The staining intensity of ecNOS was reduced in both diabetic groups. No differences were found among the three groups in the staining intensity of von Willebrand factor and GLUT1. We conclude that the endothelium-dependent and endothelium-independent vasodilations are impaired in diabetic patients predisposed to foot ulceration and that neuropathy is the main factor associated with this abnormality. Reduced expression of ecNOS may be a major contributing factor for endothelial dysfunction. These data provide support for a close association of neuropathy and microcirculation in the pathogenesis of foot ulceration.

Acetylcholine↗
PubMed1998

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) > or =25 V were categorized as HiVPT (n=132) and those with Semmes-Weinstein monofilament tests > or =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 > or =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 degrees, B 69+/-23 degrees, H 82+/-23 degrees, P=0.000), while the subtalar joint mobility was reduced in the Caucasian group (C 21+/-8 degrees, B 26+/-7 degrees, H 27+/-11 degrees, 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 (> or =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.

Adult↗
PubMed1998

Differences in foot and forearm skin microcirculation in diabetic patients with and without neuropathy.

OBJECTIVE: We have compared the hyperemic response to heat and the endothelium-dependent and endothelium-independent vasodilatation between the dorsum of the foot and the forearm in diabetic neuropathic and non-neuropathic patients and healthy control subjects. RESEARCH DESIGN AND METHODS: We studied the cutaneous microcirculation in the forearm and foot in 15 diabetic patients with neuropathy, in 14 diabetic patients without neuropathy, and in 15 control subjects matched for age, sex, BMI, and in the case of diabetic patients, for the duration of diabetes. Patients with peripheral vascular disease and/or renal impairment were excluded. The cutaneous microcirculation of the dorsum of the foot and the flexor aspect of the forearm was tested in all subjects. Single-point laser Doppler was employed to measure the maximal hyperemic response to heating of the skin to 44 degrees C and laser Doppler imaging scanner was used to evaluate the response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent response) and 1% sodium nitroprusside (NaNP) (endothelium-independent response). RESULTS: The transcutaneous oxygen tension was lower in the neuropathic group at both foot and forearm level, while the maximal hyperemic response to heat was similar at the foot and forearm level in all three groups. The endothelium-dependent vasodilation (percent increase over baseline) was lower in the foot compared to the forearm in the neuropathic group (23 +/- 4 vs. 55 +/- 10 [mean +/- SEM]; P < 0.01)], the non-neuropathic group (33 +/- 6 vs. 88 +/- 14; P < 0.01), and the control subjects (43 +/- 6 vs. 93 +/- 13; P < 0.001). Similar results were observed during the iontophoresis of NaNP (P < 0.05). No differences were found among the three groups when the ratio of the forearm:foot response was calculated for both the endothelium-dependent (neuropathic group, 2.25 +/- 0.24; non-neuropathic group, 2.55 +/- 0.35; and control subjects, 2.11 +/- 0.26; P = NS) and endothelium-independent vasodilation (neuropathic group, 1.54 +/- 0.27; non-neuropathic group, 2.08 +/- 0.33; and control subjects, 2.77 +/- 1.03; P = NS). The vasodilatory response, which is related to the C nociceptive fiber action, was reduced at the foot level during iontophoresis of Ach in the neuropathic group. In contrast, no difference was found during the iontophoresis of NaNP at the foot and forearm level and of Ach at the forearm level among all three groups. CONCLUSIONS: In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm.

Adult↗
PubMed1998

The role of endothelial function on the foot. Microcirculation and wound healing in patients with diabetes.

Wound healing is defective in patients with diabetes, which may be attributed to many factors. Our data indicate that impairment of the microcirculation is a major factor. Although the exact causes of microvascular impairment are not known, dysfunction of the endothelium has emerged over the last decade as the prominent abnormality related to vascular disease in diabetes. Further studies are required to clarify the causes of endothelial dysfunction and identify potential therapeutic interventions in the future.

Diabetic Foot↗
PubMed1997

The effect of arterial reconstruction on the natural history of diabetic neuropathy.

OBJECTIVE: To determine whether reversal of hypoxia slows the progression of neuropathy. DESIGN: Cohort study with a mean follow-up of 19.2 months. SETTING: Institutional and private hospital. PATIENTS: A volunteer sample of 55 patients with diabetes (mean age, 62 years; range, 30-74 years; mean duration of diabetes, 21 years; range, 1-57 years) requiring lower-extremity arterial bypass. Twenty-one successfully treated patients were reexamined at the conclusion of the study. Neuropathy and hypoxia were assessed the day before the operation and during the follow-up visit. INTERVENTION: Lower-extremity arterial reconstruction. MAIN OUTCOME MEASURES: Peroneal nerve conduction velocity and transcutaneous oxygen tension. RESULTS: In the leg operated on, the peroneal nerve conduction velocity remained unchanged during the follow-up period (preoperative, mean [+/- SD] 35.79 +/- 6.02 vs postoperative 35.33 +/- 7.51 m/s; P > .05), but deteriorated in the leg not operated on (36.68 +/- 6.22 vs 33.64 +/- 7.30 m/s; P < .05, Wilcoxon signed rank test). Transcutaneous oxygen tension increased in the revascularized extremity (mean [+/- SD] 40.62 +/- 24.76 vs 66.73 +/- 14.89 mm Hg) but remained unchanged in the leg not operated on (56.76 +/- 17.07 vs 62.00 +/- 15.66 mm Hg; P > .05). Of the entire cohort, 5 patients died during the study period. Graft occlusion occurred in 10 (17%) of 59 extremities. Subset analysis disclosed that the preoperative transcutaneous oxygen tension was significantly higher in the successfully revascularized extremities (41.98 +/- 23.58 vs 24.10 +/- 21.50 mm Hg; P < .001). CONCLUSIONS: Reversal of hypoxia halts the progression of diabetic neuropathy, lending further support to the role of hypoxia in the pathogenesis of nerve destruction in diabetes mellitus. Preoperative transcutaneous oxygen tension is lower in patients with bypass failure, but the severity of neuropathy does not affect the outcome of the operation.

Adult↗
PubMed1997

Difference in treatment of foot ulcerations in Boston, USA and Pisa, Italy.

Primary care of the diabetic patient with foot ulcer can be provided by medically or surgically trained practitioners. We have prospectively followed 90 sequential patients with newly developed foot ulcers from two major centers. One in the USA where the primary doctor was a podiatrist and one in Europe with a diabetologist. Thirty-four patients from Boston and 56 from Pisa (mean age, 55.6; range, 26-75 years; vs. 66.5; range, 35-94; P < 0.001), matched for sex, weight, type, duration of diabetes, renal impairment and retinopathy took part. Boston patients had more severe neuropathy, assessed with clinical examination utilizing a neuropathy disability score (NDS) (16 +/- 6 vs. 6 +/- 3 (mean +/- S.D.) P < 0.001) and vibration perception threshold (46 +/- 8 vs. 35 +/- 12 V: P < 0.001) while no difference existed in the number of patients with clinical infection, a history of lower extremity by-pass operation (6 (18%) vs. 3 (5%); P = NS) and in the size and the severity of the ulcer, according to the Wagner classification. Initial treatment was similar in both centers with emphasis on outpatient ulcer debridement, pressure relieving foot-wear and topical wound care. Hospitalization was needed in five (15%) Boston and 12 (21%) Pisa patients (P = NS) while surgery was performed on five (15%) Boston and 16 (29%) Pisa patients (P = NS). The in-hospital stay was similar in both centers (1.4 +/- 4.4 vs. 2.1 +/- 5.9 days; P = NS). The most common operations in both centers were incision, drainage and bone debridement. Ulcers healed in all patients but the amount of healing time was shorter in Boston patients (6.7 +/- 4.2 vs. 10.5 +/- 6.5 weeks; P < 0.02). We conclude that despite the differences in the two systems similar success rates were achieved in the two centers while a more surgically oriented strategy may have resulted in a slightly shorter healing time.

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PubMed1997

Aerobic exercise capacity remains normal despite impaired endothelial function in the micro- and macrocirculation of physically active IDDM patients.

The aim of the present study was to examine if diabetes in the absence of neuropathy affects the exercising capacity of IDDM patients, and whether regular, intense training has a beneficial effect on endothelial function. Five groups of subjects were studied: 23 healthy control subjects who exercised regularly (age 33 +/- 6 years), 23 nonneuropathic type 1 diabetic patients who exercised regularly (age 33 +/- 6 years, IDDM duration 11 +/- 8 years), 7 neuropathic type 1 diabetic patients who exercised regularly (age 36 +/- 7 years, IDDM duration 22 +/- 8 years), 18 healthy subjects who did not exercise regularly (age 34 +/- 7 years), and 5 nonneuropathic type 1 diabetic patients who did not exercise regularly (age 31 +/- 4 years, IDDM duration 20 +/- 3 years). All groups were matched for age, sex, and body weight. No differences existed in the energy expenditure per week in physical activity among the three exercising groups or between the two nonexercising groups. The maximal oxygen uptake was similar between control and diabetic nonneuropathic exercisers, and among diabetic neuropathic exercisers, control nonexercisers, and diabetic nonexercisers; however, a significant difference existed between the first two and the last three groups (P < 0.0001). A stepwise increase was found in the resting heart rate among the groups, ranging from the lowest in control exercisers to the highest in diabetic nonexercisers, but the maximal heart rate was lower only in diabetic neuropathic exercisers compared with all other groups (P < 0.05). Assessments of endothelial function in both macro- and microcirculation were performed in 12 control exercisers, 10 diabetic nonneuropathic exercisers, 5 diabetic neuropathic exercisers, 17 control nonexercisers, and 4 diabetic nonexercisers. When all diabetic patients were considered as one group and all control subjects as another, the microcirculation endothelial function in the diabetic group was reduced compared with the control subjects (91 +/- 49 vs. 122 +/- 41% flux increase over baseline; P < 0.05). In contrast, no differences existed among the three diabetic groups or between the two control groups. Similarly, in macrocirculation, a reduced response during reactive hyperemia was observed in the diabetic patients compared with control subjects (7.0 +/- 4.5 vs. 11.2 +/- 6.6% diameter increase; P < 0.05), whereas again no difference existed among the three diabetic groups or between the two control groups. These data suggest that diabetes per se does not affect aerobic exercise capacity (VO2max) in physically active individuals, but is reduced in the presence of neuropathy. In addition, regular exercise training involving the lower extremities does not improve the endothelial function in the micro- and macrocirculation of the nonexercised upper extremity in type 1 diabetic patients.

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