Z. Matas

Effect of high doses of vitamin D on arterial properties, adiponectin, leptin and glucose homeostasis in type 2 diabetic patients.

BACKGROUND & AIMS Vitamin D supplementation has the potential to alleviate the cardiovascular damage in diabetic patients. The present study was designed to evaluate long term impact of high doses of vitamin D on arterial properties, glucose homeostasis, adiponectin and leptin in patients with type 2 diabetes mellitus. METHODS AND RESULTS In randomized, placebo-controlled study 47 diabetic patients were assigned into two groups: Group 1 received oral daily supplementation with vitamin D at a dose of 1000 U/day for 12 months. Group 2 received matching placebo capsules. Blood sampling for metabolic parameters, including fasting glucose, lipid profile, HbA1C, insulin, hs-CRP, 25 OH Vit D, adiponectin and leptin was performed at baseline and at the end of the study. Insulin resistance was assessed by homeostasis model assessment (HOMA-IR). Central aortic augmentation index (AI) was evaluated using SphygmoCor. RESULTS The two groups were similar at baseline in terms of hemodynamic parameters. After 12 months, AI decreased significantly during the treatment period in patients received vitamin D (p < 0.0001) and did not change in placebo group. Glucose homeostasis parameters, leptin as well as leptin adiponectin ratio did not change in both groups. 25 OH Vit D level significantly increased (p = 0.022) and circulating adiponectin marginally increased (p = 0.065) during 12 month treatment period in active treatment and did not change in placebo group. CONCLUSIONS High doses of vitamin D supplementation in diabetic patients was associated with significant decrease in AI during one year treatment. This beneficial vascular effect was not associated with improvement in glucose homeostasis parameters.

5-ASA and lycopene decrease the oxidative stress and inflammation induced by iron in rats with colitis.

BackgroundSupplementation of 5-aminosalicylic acid (5-ASA) and of iron are among the principal therapies in patients with inflammatory bowel disease. Therapeutic iron, as well as heme iron from chronic mucosal bleeding, can increase iron-mediated oxidative stress in colitis. This study was designed to examine the influence of iron supplementation on histological expression and oxidative status relative to 5-ASA treatment and antioxidant treatment.MethodsColitis was induced using the iodoacetamide rat model, and rats were divided into different dietary groups of 6 rats each: 1, normal chow diet (control); 2, diet supplemented with iron; 3, iron supplementation and lycopene; 4, iron and Β-carotene; 5, 5-ASA; 6, 5-ASA and lycopene; 7, 5-ASA and iron; 8, 5-ASA, iron, and lycopene. The animals were killed after 3 days and the weight of the ulcerated area recorded. Mucosal specimens were histologically evaluated. Myeloperoxidase (MPO) was measured to evaluate inflammatory status (U/g). Malondialdehyde (MDA) was measured in colonic tissue (µmol/g) and superoxide dismutase (SOD) in erythrocytes to assess the degree of tissue oxidative stress.ResultsSignificantly more severe colitis, including necrosis, ulceration, and hemorrhage, was seen in colonic biopsies of rats with colitis when iron was supplemented. This pathology was attenuated when iron was given in combination with 5-ASA and/or lycopene. There was no significant benefit from adding Β-carotene.ConclusionsIron supplementation can amplify the inflammatory response and subsequent mucosal damage in a rat model of colitis. We suggest that the resultant oxidative stress generated by iron supplementation leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through the generation of secondary toxic oxidants. Simultaneous treatment with 5-ASA and/or lycopene minimizes the potential hazard of iron. Therefore, we suggest giving iron supplementation with 5-ASA or lycopene or both.

Iron supplementation may aggravate inflammatory status of colitis in a rat model.

Iron supplementation is one of the principal therapies in inflammatory bowel disease. Iron is a major prooxidative agent; therefore therapeutic iron as well as heme iron from chronic mucosal bleeding can increase the iron-mediated oxidative stress in colitis by facilitating the Fenton reaction, namely production of hydroxyl radicals. In the present study colitis was induced in the iodoacetamide rat model. Forty male Whistar rats were divided into four groups, each group receiving a different diet regimen in parallel with colitis induction: Malondialdehyde was measured to assess the degree of tissue oxidative stress. There were microscopic changes, and significantly more severe colitis was seen in colonic biopsies when iron was supplemented. It was concluded that iron supplementation can amplify the inflammatory response and enhance the subsequent mucosal damage in a rat model of colitis. We suggest that the resultant oxidative stress generated by iron supplementation leads to the extension and propagation of crypt abscesses.

Adiponectin and vascular properties in obese patients: is it a novel biomarker of early atherosclerosis?

Objectives:Adiponectin is an adipocyte-derived collagen-like protein, highly specific to adipose tissue and may represent an important link between obesity and atherosclerosis. The present study was designed to investigate a possible association between serum adiponectin levels and early vascular changes in obese patients as determined by intima media thickness (IMT) and arterial pulse-wave contour analysis.Design:Obese subjects (n=47) were evaluated for arterial structure and function, metabolic parameters and serum adiponectin levels.Measurements:IMT was measured by ultrasound. Arterial elasticity was evaluated using pulse-wave contour analysis. Insulin resistance was assessed by homeostasis model assessment (HOMA-IR).Results:Adiponectin was significantly, inversely associated with mean IMT (r=−0.369, P=0.011) and significantly positively associated with large artery elasticity index (LAEI) (r=0.467, P=0.001) as well as small artery elasticity index (SAEI) (r=0.462, P=0.001). In separate multivariate models, adiponectin remained significantly associated with mean IMT, LAEI and SAEI even after adjustment for cardiovascular confounders. Among metabolic parameters, adiponectin was significantly positively associated with HDL cholesterol and inversely associated with triglycerides. Adiponectin was significantly inversely associated with fasting insulin and HOMA-IR. In addition, a marginally inverse association between adiponectin and ALT was observed.Conclusions:In this study, serum adiponectin levels were significantly associated with indices of subclinical atherosclerosis, such as IMT and arterial compliance in obese patients. This association was independent of traditional cardiovascular risk factors.

Serum leptin level in women with idiopathic intracranial hypertension

Leptin is a protein secreted by adipose cells which influences regulation of energy balance and body weight. Idiopathic intracranial hypertension (IIH) is recognised as a neurological disorder mainly affecting obese females. The aim of this study was to evaluate the association between IIH and serum leptin level in 15 obese patients and compare the results with those for 16 obese and 15 non-obese women. A significantly higher serum leptin level was found in patients with IIH than in controls (p<0.0001), and this did not correlate with body mass index (BMI). Serum leptin levels were significantly associated with BMI in both control groups (p<0.0006). Additional factors must therefore be involved in the phenomenon of serum leptin increase beyond weight gain. The cause can only be hypothesised, but it seems that the origin is central, probably hypothalamic.

Weight loss induced by nutritional and exercise intervention decreases arterial stiffness in obese subjects.

BACKGROUND & AIMS Obesity is associated with increased arterial stiffness, an early marker of vascular wall damage. However, data on the long-term vascular impact of intentional weight loss are limited. The aim of the present study was to evaluate the effect of weight loss induced by nutritional and exercise intervention on arterial compliance, metabolic and inflammatory parameters in obese patients who participated in a weight reduction program. METHODS In an open label, prospective study, 37 obese subjects attended a 24 weeks nutritional and exercise interventional program. Arterial elasticity was evaluated using pulse-wave contour analysis (HDI CR-2000, Eagan, Minnesota) at baseline and at the end of the study. Fasting glucose, HbA1C, insulin, lipid profile, hs-CRP, fibrinogen were measured at baseline and after 6 months. Insulin resistance was assessed by homeostasis model assessment-insulin resistance (HOMA-IR). RESULTS BMI decreased from 36.1 +/- 7.4 kg/m(2) at baseline to 32.8 +/- 7.4 kg/m(2) after 6 months (p<0.0001). Large artery elasticity index (LAEI) increased from 12.1 +/- 4.1 to 15.8 +/- 4.7 ml/mmHg x 10 during the study (p<0.0001). Small artery elasticity index (SAEI) increased from 4.4+/-2.4 to 5.5 +/- 2.7 ml/mmHg x 100 (p<0.0001). There was a significant improvement in fasting hyperglycemia, HbA1C and significant decrease in LDL-cholesterol, fibrinogen and C-reactive protein. Modest reduction in HOMA-IR was observed. The change in weight was positively associated with LAEI, SAEI, total cholesterol, insulin and HOMA-IR. CONCLUSIONS Moderate weight loss induced by nutritional and exercise intervention improved small and large artery elasticity. The increase in arterial elasticity was associated with improvement in glucose and lipids homeostasis as well as markers of inflammation.

Osteoprotegerin as an independent marker of subclinical atherosclerosis in osteoporotic postmenopausal women

Osteoprotegerin (OPG) appears to represent the molecular link between bone resorption and vascular calcification, and may help to explain the high prevalence of atherosclerosis and osteoporosis in postmenopausal women. We investigated a possible association between serum OPG levels and arterial stiffness in postmenopausal women with osteoporosis. 70 postmenopausal women with osteoporosis and cardiovascular risk factors but without coronary artery disease were evaluated for metabolic, inflammatory parameters and serum OPG levels. Pulse wave velocity (PWV) and augmentation index (AIx) were performed as a simple noninvasive recording of the two artery sites pressure waveform using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). Serum OPG levels were significantly, positively associated with AIx (r=0.39, p=0.003) and with PWV (r=0.81, p<0.0001). No association between OPG levels and hemodynamic variables or measures of glucose metabolism was observed. Among inflammatory markers, OPG was significantly, positively associated with fibrinogen (r=0.323, p=0.015). In a multiple linear regression analysis, OPG was independent predictor of PWV (standardized beta=0.75, p<0.0001) and AIx (standardized beta=0.41, p=0.01). Serum OPG is potentially an independent predictor of early vascular adverse changes in osteoporotic postmenopausal women.

Different degrees of fetal oxidative stress in elective and emergent cesarean section.

Background: Several studies have addressed the influence of labor and mode of delivery on oxidative stress. Still it is unclear whether oxidative stress is related to delivery itself or whether it reflects a pre-existing fetal oxidative status. Objective: To investigate whether the degree of fetal oxidative stress is different between distressed fetuses that were delivered by emergent cesarean section and non-distressed fetuses that were delivered by elective cesarean section. Methods: The protocol of this prospective study was approved by the Institutional Review Board Committee. Amniotic fluid and umbilical artery blood were prospectively collected from 21 parturients who were delivered by an emergent cesarean section for non-reassuring fetal heart rate pattern and from 21 parturients who were delivered by an elective cesarean section in a tertiary care center. Oxidative stress was evaluated in amniotic fluid, umbilical cord plasma and erythrocytes by determining malondialdehyde concentration and glutathione peroxidase (GPX) activity. Results: Malondialdehyde concentration was higher in amniotic fluid (mean ± SEM) (2.2 ± 0.7 nmol/l vs. 0.6 ± 0.02 nmol/l, p < 0.05), in umbilical cord plasma (1.2 ± 0.2 nmol/l vs. 0.7 ± 0.3 nmol/l, p < 0.05) and in umbilical cord erythrocytes (159.6 ± 48.6 nmol/g Hb vs. 85.8 ± 5.2 nmol/g Hb, p < 0.05) in women delivering by emergent cesarean compared to those delivering by elective cesarean. GPX activity was enhanced in amniotic fluid (12.4 ± 2.2 U/l vs. 5.1 ± 0.6 U/l, p < 0.05) and GPX activity/hemoglobin ratio was higher in cord blood (22.0 ± 0.8 U/g Hb vs. 18.7 ± 0.9 U/g Hb, p < 0.05) in women delivering by emergent cesarean compared to those delivering by elective cesarean. Conclusion: Distressed fetuses delivered by emergency cesarean exhibited increased malondialdehyde concentrations, an indicative parameter for oxidative damage, and enhanced GPX activity an antioxidant enzyme, in amniotic fluid and umbilical cord blood compared to non-distressed fetuses delivered by elective cesarean section. This is probably an indication of higher fetal oxidative stress.

Peripheral vascular disease and serum phosphorus in hemodialysis: a nested case-control study.

BACKGROUND Serum phosphorus (P) and the product of serum calcium x serum P (Ca x P), are frequently elevated in end-stage renal disease patients on maintenance hemodialysis (HD). Elevated P and Ca x P have been associated with vascular calcification in dialysis patients. OBJECTIVE [corrected] To examine the role of P and Ca x P as risk factors for incident peripheral vascular disease (PVD) in HD patients with pre-existing CVD. METHODS This nested case-control study is drawn from the 11 incident PVD events reported in the cohort of the Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease (SPACE): a randomized placebo-controlled trial. PVD was defined clinically and confirmed ultrasonographically. Each individual with a PVD event was matched for SPACE treatment group (vitamin E or placebo), age (in 4-year categories) and gender with two individuals who had no CVD end point during the follow-up period. RESULTS Serum P and Ca x P levels were significantly higher in PVD patients than in controls. In univariate logistic regression analysis, only serum P predicted PVD in this population (OR 2.02, 95% CI 1.07 - 3.81, p = 0.03). In multivariate analysis, adjustment was made for variables dissimilar by PVD status including underlying renal disease, diabetes, smoking, history of angina pectoris, prescription for vitamin D3, erythropoietin, calcium channel blockers and aspirin. In this model, serum P remained the only significant predictor of incident PVD (OR 2.4, 95% CI 1.01 - 5.74, p = 0.04). CONCLUSIONS Findings of the present study are consistent with a role for serum P and Ca x P in the pathogenesis of PVD in HD patients.

Increasing derangement of glucose homeostasis is associated with increased arterial stiffness in patients with diabetes, impaired fasting glucose and normal controls

Glucose intolerance produces structural and functional changes in the arterial wall. The present study investigated association between glucose tolerance status and arterial stiffness in subjects with normal and impaired glucose regulation (IGR).