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Biomedical subjects

Aristidis Veves

Publications and source records attributed to Aristidis Veves.

At least 19 recordsLinked to original sources
PubMed2007

Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study.

BACKGROUND: Talactoferrin alfa, a recombinant form of human lactoferrin, is a novel immunomodulatory protein with demonstrated ulcer healing properties in animal models. METHODS: A phase 1/2 clinical study was conducted at 7 clinical sites to determine if talactoferrin can improve wound healing in diabetic patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a sequential design, to their ulcer for 30 days. No drug-related adverse events were found at any dose level. Phase 2 was a randomized, placebo-controlled, single-blind study of 2.5% and 8.5% gels, with patients equally divided between the 3 groups. In combination with good wound care, treatment was administered topically twice daily to the ulcers for 12 weeks. The primary endpoint was the incidence of > or = 75% healing (relative to baseline size). RESULTS: The study, which in phase 2 was powered to detect a difference between the placebo and combined talactoferrin arms with P < .1, met the primary objective. The groups receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of > or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%, 53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2 active groups when compared with the placebo group showed a strong trend toward statistical significance (P = .09). There were no talactoferrin-related adverse events or laboratory abnormalities. CONCLUSIONS: Topical talactoferrin appears to be safe and well tolerated and improves healing of diabetic neuropathic ulcers.

Administration, Topical↗
PubMed2006

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

OBJECTIVE: 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. METHODS: Five traditional sway parameters and three sway parameters from random-walk analysis were computed for each trial (no noise or noise). RESULTS: Application of noise resulted in a statistically significant reduction in each of the eight sway parameters in the subjects with diabetic neuropathy, the subjects with stroke, and the elderly subjects. We also found that higher levels of baseline postural sway in sensory-impaired individuals was correlated with greater improvements in balance control with input noise. INTERPRETATION: This work indicates that noise-based devices could ameliorate diabetic and stroke impairments in balance control.

Adult↗
PubMed2006

Valsartan improves resting skin blood flow in type 2 diabetic patients and reduces poly(adenosine diphosphate-ribose) polymerase activation.

OBJECTIVE: To examine the effect of a 12-week daily treatment with 160 mg of valsartan, an angiotensin II receptor blocker, on the microcirculation and macrocirculation of type 2 diabetic patients (T2DM) and healthy subjects. METHODS: This was a prospective, randomized, double-blind, placebo-controlled crossover study. Thirteen T2DM with no severe complications and 13 healthy subjects completed the trial. RESULTS: Treatment with valsartan in T2DM improved the resting forearm skin blood flow and increased the resting brachial artery diameter but had no effects on arterial blood pressure, large vessel vascular reactivity, or carotid intima-media thickness. Resting skin blood flow increased by 60% (2%-90%; median and 25th-75th percentiles) during valsartan treatment and by only 2% (-22% to 27%) during placebo treatment (P < .05). No changes were observed in the nondiabetic subjects. Immunostaining studies of forearm skin biopsy samples from T2DM and healthy subjects showed that valsartan reduced poly(adenosine diphosphate-ribose) polymerase (PARP) activity in 50% (6/12) of the subjects. PARP activity remained unchanged in placebo-treated subjects (P < .02). In addition, valsartan treatment increased CD31 staining in 33% (4/12) of the subjects, whereas no change was noted in sequential skin biopsy samples of placebo-treated subjects (P = .057). Valsartan had no effect on the biochemical markers of endothelial cell activation and other cytokines, including CAMs, interleukin 6, tumor necrosis factor alpha, C-reactive protein, adiponectin, and plasma activator inhibitor 1. CONCLUSIONS: Valsartan increases the resting skin blood flow in T2DM, likely through reduction of PARP activity.

Administration, Oral↗
PubMed2006

The efficacy of Apligraf in the treatment of diabetic foot ulcers.

Diabetic foot ulcerations can be a devastating complication of diabetes, causing prolonged hospitalization and significant morbidity. Previously identified risk factors include peripheral neuropathy, foot deformities, and poor wound healing due to an altered wound environment. Despite appropriate treatment, many diabetic ulcers fail to heal. Bioengineered tissue, such as Apligraf (Graftskin; Organogenesis Inc., Canton, Mass.), has been effectively and safely used to increase the incidence of complete wound closure and decrease the healing time. Studies have demonstrated that Apligraf works through the delivery of growth factors and cytokines to the chronic wound environment.

Biocompatible Materials↗
PubMed2006

Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial.

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 < 0.01). The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers (1.5 versus 0.8 cm2, P < 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 < 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.

Journal Article↗
PubMed2006

Microvascular changes in the diabetic foot.

Impairment of the microcirculation of diabetic patients may contribute to secondary complications in the lower extremity, such as foot infections and ulcerations. These microcirculatory changes, which are mainly functional rather than structural, are responsible for the impaired ability of the microvasculature to vasodilate in response to injury. Dysfunction of vascular endothelial cells and vascular smooth muscle cells both contribute to the reduction in vasodilation that is observed in diabetic patients. Nerve-axon reflex related microvascular vasodilation is also impaired in the diabetic population, and there is a growing belief that both the failure of the vessels to dilate and the impairment of the nerve axon reflex are major causes for impaired wound healing in diabetic patients. Further studies are necessary to clarify the precise etiology of endothelial and smooth muscle dysfunction in diabetic patients so that potential therapeutic interventions may be identified.

Blood Gas Monitoring, Transcutaneous↗
PubMed2005

Early changes in the skin microcirculation and muscle metabolism of the diabetic foot.

BACKGROUND: Changes in the large vessels and microcirculation of the diabetic foot are important in the development of foot ulceration and subsequent failure to heal existing ulcers. We investigated whether oxygen delivery and muscle metabolism of the lower extremity were factors in diabetic foot disease. METHODS: We studied 108 patients (21 control individuals who did not have diabetes, 36 patients with diabetes who did not have neuropathy, and 51 patients with both diabetes and neuropathy). We used medical hyperspectral imaging (MHSI) to investigate the haemoglobin saturation (S(HSI)O2; % of oxyhaemoglobin in total haemoglobin [the sum of oxyhaemoglobin and deoxyhaemoglobin]) in the forearm and foot; we also used 31P-MRI scans to study the cellular metabolism of the foot muscles by measuring the concentrations of inorganic phosphate and phosphocreatine and calculating the ratio of inorganic phosphate to phosphocreatine (Pi/PCr). FINDINGS: The forearm S(HSI)O2 during resting was different in all three groups, with the highest value in controls (mean 42 [SD 17]), followed by the non-neuropathic (32 [8]) and neuropathic (28 [8]) groups (p<0.0001). In the foot at resting, S(HSI)O2 was higher in the control (38 [22]) and non-neuropathic groups (37 [12]) than in the neuropathic group (30 [12]; p=0.027). The Pi/PCr ratio was higher in the non-neuropathic (0.41 [0.10]) and neuropathic groups (0.58 [0.26]) than in controls (0.20 [0.06]; p<0.0001). INTERPRETATION: Our results indicate that tissue S(HSI)O2 is reduced in the skin of patients with diabetes, and that this impairment is accentuated in the presence of neuropathy in the diabetic foot. Additionally, energy reserves of the foot muscles are reduced in the presence of diabetes, suggesting that microcirculation could be a major reason for this difference.

Case-Control Studies↗
PubMed2005

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 [SO4(2-)]) approximately 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 SO4(2-) 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.

Adult↗
PubMed2005

Troglitazone-induced changes in adiponectin do not affect endothelial function in diabetes.

OBJECTIVE: Adiponectin has been proposed to be related to endothelial function. We have examined the relationship between the increase in adiponectin levels that is associated with troglitazone treatment and endothelium-dependent vasodilation in type 2 diabetic patients. RESEARCH METHODS AND PROCEDURES: Seventy-two patients participated in this randomized, placebo-controlled, double-blinded study. High-resolution ultrasound images were used to measure the flow-mediated dilation (endothelium-dependent) and nitroglycerin-induced dilation (endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was employed to measure the vascular reactivity in the forearm skin. RESULTS: Troglitazone treatment resulted in an average 75% increase in the adiponectin levels, but no changes were observed in the endothelium-dependent vasodilation, any other measurement of vascular reactivity, or any other markers of endothelial activation. Also, no changes were observed in the expression of the receptor for advanced glycation end-products in skin biopsies taken from the forearm. Significant correlations were observed during troglitazone treatment between the changes in the adiponectin levels and the changes in fasting plasma glucose (r = -0.29, p < 0.05), hemoglobin A(1c) (r = -0.30, p < 0.05), total cholesterol (r = 0.25, p < 0.05), and low-density lipoprotein-cholesterol (r = 0.34, p < 0.01). DISCUSSION: The increase in adiponectin levels after troglitazone treatment is not associated with an improvement in the endothelium-dependent vasodilation, indicating that adiponectin is not a major determinant of endothelial function. In addition, receptor for advanced glycation end-products expression in the skin microcirculation is not affected by troglitazone treatment.

Adiponectin↗
PubMed2005

A review of the mechanisms implicated in the pathogenesis of the diabetic foot.

The developmental pathway toward diabetic foot ulceration is best described as multifactorial. A critical triad of neuropathy, minor foot trauma, and foot deformity has been identified in greater than 63% of foot ulcers. In addition to these risk factors, increased peak plantar pressures, autonomic and motor neuropathy, limited joint mobility, and impaired wound healing contribute to the formation of diabetic foot ulcers. It is essential to understand the pathogenesis of foot ulcers so that appropriate treatments may be developed.

Diabetic Foot↗
PubMed2005

The effect of vitamin E on endothelial function of micro- and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients.

We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients. Subjects (n = 89) were randomized to vitamin E (1,800 IU daily) or placebo and were followed for 12 months. High-resolution ultrasound images were used to measure the flow-mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (NID; endothelium independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin. Left ventricular function was evaluated using transthoracic echocardiogram. At the end of the 6-month period, a worsening in endothelium-dependent skin vasodilation (P = 0.02) and rise in endothelin levels (P = 0.01) were found in the vitamin E compared with the placebo group. At the end of the 12-month period, a worsening was observed in NID (P = 0.02) and a marginal worsening was seen in systolic blood pressure (P = 0.04) and FMD (P = 0.04) in the vitamin E compared with the placebo group. In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group (P = 0.05). No changes were observed in left ventricular function. We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients. Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects, the use of high dosages of vitamin E cannot be recommended.

Adult↗
PubMed2005

Foot small muscle atrophy is present before the detection of clinical neuropathy.

OBJECTIVE: To characterize structural changes and the metabolic profile of foot muscles and correlate them with diabetic neuropathy measurements using phosphorus-31 ((31)P) rapid acquisition with relaxation enhancement (RARE) magnetic resonance imaging (MRI). RESEARCH DESIGN AND METHODS: We studied 12 control subjects, 9 non-neuropathic diabetic patients, and 12 neuropathic diabetic patients using (31)P RARE and proton ((1)H) MRI at 3 Tesla. The ratio of the total cross-sectional area of the foot to that of the muscle tissue was calculated from transaxial (1)H and (31)P images. The average (31)P concentration across the metatarsal head region was measured from the (31)P images. RESULTS: The muscle area-to-total area ratio differed among all three groups (means +/- SD): 0.55 +/- 0.04 vs. 0.44 +/- 0.05 vs. 0.06 +/- 0.06 for control, non-neuropathic, and neuropathic subjects, respectively (P < 0.0001). The average (31)P concentration also differed among all groups: 27.7 +/- 3.8 vs. 21.7 +/- 4.8 vs. 7.9 +/- 8.8 mmol/l for control, non-neuropathic, and neuropathic subjects (P < 0.0001). The muscle area-to-total area ratio strongly correlated with clinical measurements: Neuropathy Disability Score, r = -0.83, P < 0.0001; vibration perception threshold, r = -0.79, P < 0.0001; and Semmes-Weinstein monofilaments, r = -0.87, P < 0.0001. CONCLUSIONS: Small muscle atrophy is present in diabetes before clinical peripheral neuropathy can be detected using standard clinical techniques. The (31)P RARE MRI method evaluates the severity of muscle atrophy, even in the early stages when neuropathy is absent. This technique may prove to be a useful diagnostic tool in identifying early-stage diabetic foot problems.

Atrophy↗
PubMed2004

Kidney oxygenation during water diuresis and endothelial function in patients with type 2 diabetes and subjects at risk to develop diabetes.

The aim of the present study was to examine the relationship among water diuresis-induced changes in renal oxygenation, endothelial function, and various metabolic parameters in type 2 diabetic patients and healthy subjects at risk of type 2 diabetes. Thirty-eight subjects with type 2 diabetes (D: age, 54 +/- 10 years, mean +/- SD, 24 men) and 7 healthy subjects with parental history of type 2 diabetes or with impaired glucose tolerance (IGT) (relatives [R]: age 46 +/- 11 years, 4 men) were included. Laser Doppler imaging scanning was used to measure vasodilatation in the forearm skin in response to iontophoresis of 1% acetylcholine (Ach) and 1% sodium nitroprusside (SNP), and ultrasound was used to measure the flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) in the brachial artery. Renal oxygenation was assessed by magnetic resonance imaging (MRI) before and during water diuresis. A decrease in the magnetic parameter R2* implies an increase in oxygenation. Renal medullary oxygenation did not improve with diuresis in either group (D: -0.5 +/- 1.9, R: -0.4 +/- 2.1, P = not significant [NS]). The renal cortical oxygenation showed a small, but statistically significant, improvement after diuresis in the 2 groups (D: -0.6 +/- 1.1, R: -0.5 +/- 0.5, P <.05). There were no correlations between the change in cortical R2* (R2* post-minus R2* prewater diuresis) and the micro- and macrovascular reactivity. The postdiuresis renal cortical R2* was negatively correlated with both the Ach- and SNP-induced skin vasodilation (% change over baseline)(r = -.40, P <.01 and r = -.39, P <.05, respectively), while no correlation existed with the FMD and NID. The baseline renal cortical oxygenation was also negatively correlated with the SNP-induced skin vasodilation (r = -.36, P <.05) and positively correlated with the fasting plasma glucose, total cholesterol, and vascular cell adhesion molecule (VCAM) concentrations (r =.34, P <.05, r =.31, P <.05 and r =.37, P <.05, respectively). These preliminary findings suggest an association between the kidney cortical oxygenation and the skin microvascular reactivity, glycemia, and lipidemia. Water diuresis failed to produce an improvement in renal medullary oxygenation in both patients with diabetes and subjects at risk for diabetes.

Aged↗
PubMed2004

The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes.

We have investigated the effect of atorvastatin on the endothelial function of patients with diabetes and subjects at risk for type 2 diabetes in a 12-wk, prospective, randomized, placebo-controlled, double-blind clinical trial. The flow- mediated dilation (FMD; endothelium dependent) and nitroglycerin-induced dilation (endothelium independent) in the brachial artery and the vascular reactivity at the forearm skin were measured. FMD improved in the atorvastatin-treated, at-risk subjects [median (25-75 percentile), 7.2% (2.9-9.6%) at exit visit vs. 6.6% (2.9-9.5%) at baseline; P < 0.05]. A similar improvement of FMD was found in atorvastatin-treated diabetic patients [median (25-75 percentile), 5.6 (3.9-7.9) at exit visit vs. 4.2 (3.2-7.2) at baseline; P = 0.07]. No changes were observed in nitroglycerin-induced dilation and the microcirculation reactivity measurements in either group. In the at-risk group, there was a decrease in the C-reactive protein [median (25-75 percentile), 0.12 mg/dl (0.07-0.27 mg/dl) at exit visit vs. 0.24 mg/dl (0.07-0.35 mg/dl) at baseline; P < 0.05] and TNF alpha [median (25-75 percentile), 2.6 pg/ml (1.8-4.1 pg/ml) at exit visit vs. 4.4 pg/ml (3.6-6.0 pg/ml) at baseline; P < 0.05] in the atorvastatin-treated patients, whereas in the diabetes group, a decrease in endothelin-1 (mean +/- SD, 0.97 +/- 0.29 pg/ml at exit visit vs. 1.19 +/- 0.42 pg/ml at baseline; P < 0.05) and plasminogen activator inhibitor-1 [median (25-75 percentile), 18 ng/ml (9-24 ng/ml) at exit visit vs. 27 ng/ml (7-41 ng/ml) at baseline; P < 0.05] were observed. We conclude that atorvastatin improves endothelial function and decreases levels of markers of endothelial activation and inflammation.

Adult↗
PubMed2004

Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes.

OBJECTIVE: Adiponectin and resistin, two recently discovered adipocyte-secreted hormones, may link obesity with insulin resistance and/or metabolic and cardiovascular risk factors. We performed a cross-sectional study to investigate the association of adiponectin and resistin with inflammatory markers, hyperlipidemia, and vascular reactivity and an interventional study to investigate whether atorvastatin mediates its beneficial effects by altering adiponectin or resistin levels. RESEARCH DESIGN AND METHODS: Associations among vascular reactivity, inflammatory markers, resistin, and adiponectin were assessed cross-sectionally using fasting blood samples obtained from 77 subjects who had diabetes or were at high risk to develop diabetes. The effect of atorvastatin on adiponectin and resistin levels was investigated in a 12-week-long randomized, double-blind, placebo-controlled study. RESULTS: In the cross-sectional study, we confirm prior positive correlations of adiponectin with HDL and negative correlations with BMI, triglycerides, C-reactive protein (CRP), and plasma activator inhibitor (PAI)-1 and report a negative correlation with tissue plasminogen activator. The positive association with HDL and the negative association with PAI-1 remained significant after adjusting for sex and BMI. We also confirm prior findings of a negative correlation of resistin with HDL and report for the first time a positive correlation with CRP. All of these associations remained significant after adjusting for sex and BMI. No associations of adiponectin or resistin with any aspects of vascular reactivity were detected. In the interventional study, atorvastatin decreased lipid and CRP levels, but adiponectin and resistin were not specifically altered. CONCLUSIONS: We conclude that adiponectin is significantly associated with inflammatory markers, in part, through an underlying association with obesity, whereas resistin's associations with inflammatory markers appear to be independent of BMI. Lipid profile and inflammatory marker changes produced by atorvastatin cannot be attributed to changes of either adiponectin or resistin.

Adiponectin↗
PubMed2003

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.

Acute Disease↗
PubMed2003

Diabetic neuropathy and microcirculation.

The microcirculation in diabetic and neuropathic feet is subject to the same changes found in other end organs of diabetic patients, such as the retina or the kidney. Complications such as foot ulceration lead to further morbidity and hospitalizations. Research into the causes of microcirculatory dysfunction has revealed an interplay of numerous factors. The most prominent findings are impaired endothelium-dependent and -independent vasodilation and reduced or absent nerve-axon reflex-related vasodilation. This renders the diabetic foot unable to mount a vasodilatory response under conditions of stress, such as injury, and makes it functionally ischemic even in the presence of satisfactory blood flow under normal conditions.

Axons↗