Inpatient hyperglycaemia improvement quality program.

BACKGROUND: Poorly controlled hyperglycaemia is associated with increased morbidity and mortality in hospitalised patients. Based on the view that hospitalisation provides a window of opportunity to improve patient quality of care and health status, a comprehensive program for treating hospitalised diabetic patients was initiated. This study assessed the effectiveness of the Inpatient Hyperglycaemia Improvement Quality Program (IHIQP) over a 4-year period. METHODS: Pre-test post-test design. In the pre-intervention period (August-December 2007), an institution-wide blood glucose monitoring system was introduced in August 2007. The remaining program components were introduced in January 2008, including implementing a hospital care protocol based on the 2007 American Diabetes Association Standards, a multidisciplinary team that participates in patient care and arranges continuing care after discharge and comprehensive patient education prior to discharge. Program results from January 2008 through October 2011 were evaluated. RESULTS: During follow-up, more than 600,000 blood glucose tests were performed. Blood glucose values declined from 196.4 ± 98.4 mg/dl pre-IHIQP (August-December 2007) to 174.5 ± 82.0 mg/dl post-IHIQP (January-October 2011) (p < 0.0001). Prevalence of glucose values lower than 60 mg/dl declined from 2% to 1.3% (p < 0.004). Prevalence of glucose values ≥ 300 mg/dl declined from 13.6% to 8.4% (p < 0.0001). Concomitantly, the proportion of in-target values of 80-180 mg/dl increased from 47.7% to 58.1% (p < 0.0001). CONCLUSION: This in-patient hyperglycaemia quality improvement program led to improvements in-patient glycaemic control, which continued over time. The effect of this improvement on in-patient mortality and morbidity needs additional follow-up.

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.

Does adiponectin level explain the atherogenic properties of Hp 2-2 phenotype in type 2 diabetic patients?

OBJECTIVES: Haptoglobin (Hb) and adiponectin are antioxidant proteins and independent predictors of atherosclerotic vascular disease in diabetic patients. The link between Hp phenotype and circulating adiponectin levels were examined. METHODS: Diabetic patients were divided into two groups by Hp phenotype: Hp 2-2 group and non-Hp 2-2 group (Hp 2-1 and Hp 1-1). Blood glucose, HbA1C, insulin, lipids, CRP, HOMA-IR, 25OH vitamin D, leptin and adiponectin levels were measured. Pulse wave velocity (PWV) was performed using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). RESULTS: PWV was significantly higher in patients homozygous for the 2 allele (Hp 2-2) compared to non-Hp 2-2 patients (Hp 1-1 and Hp 1-2), p < 0.0001. Adiponectin was significantly lower in Hp 2-2 patients than in non-Hp 2-2 group (p < 0.016). Neither leptin nor the leptin adiponectin ratio (LAR) differed significantly between groups. CONCLUSIONS: PWV was significantly higher and plasma adiponectin levels were significantly lower in diabetic patients homozygous for the 2 allele (Hp 2-2). These differences were detected despite the lack of by-phenotype differences in glycemic control, blood pressure level or presence of cardiovascular risk factor and suggest an active role of adiponectin in the pathophysiology of vascular disease in this population.

Relation of adiponectin to glucose tolerance status, adiposity, and cardiovascular risk factor load.

OBJECTIVE: Adiponectin has anti-atherogenic and anti-inflammatory properties. We investigated the influence of adiponectin on glucose tolerance status, adiposity and cardiovascular risk factors (CVRFs). DESIGN AND PATIENTS: Study consisted of 107 subjects: 55 with normal glucose tolerance (NGT) and 52 with impaired glucose regulation (IGR) who were divided into two groups: 24 subjects with impaired fasting glucose (IFG Group) and 28 patients with type 2 diabetes mellitus (DM Group). In additional analysis, study participants were divided into two groups, according to CVRFs: low and high risk. MEASUREMENTS: Patients were evaluated for glucose, HbA1C, insulin, lipids, CRP, HOMA-IR and adiponectin. RESULTS: Adiponectin was significantly higher in NGT group than in IFG (P = 0.003) and DM (P = 0.01) groups. Adiponectin was significantly, positively associated with HDL and inversely associated with glucose, HbA1c, ALT, AST, TG, HOMA-IR. Patients with higher CVRFs load have lesser adiponectin compared to patients with low cardiovascular risk P < 0.0001). Adiponectin was inversely associated with the number of risk factors (r = -0.430, P = 0.0001). CONCLUSIONS: Circulating adiponectin was significantly lower in subjects with different degree of IGR compared to subjects with normal glucose homeostasis. Adiponectin was significantly lower in high risk group than low risk group and decreased concurrently with increased number of CVRFs.

Jewish New Year associated with decreased point of care glucose in hospitalised patient population.

BACKGROUND: In individuals with diabetes, glycaemic control has been shown to be disrupted during the winter holiday period. OBJECTIVES: The aim of this study was to examine whether blood glucose levels are influenced by the Jewish New Year period in hospitalised individuals with diabetes. METHODS: At E. Wolfson Medical Center, Holon, Israel, blood glucose values from individuals hospitalised in internal medicine units were collected and analysed during the period surrounding Rosh Hashanah, the Jewish New Year, 2010. Values obtained from 4 to 7 September 2010 were categorised as preholiday values; values from 8 to 11 September 2010 were classed as holiday values; and values from 12 to 15 September 2010 were labelled postholiday values. All values were collected at point of care (POC) using an automated, institutional glucometer located in each department, the data from which is downloaded to a central database. RESULTS: A total of 3403 POC glucose values were recorded during the observation period. POC glucose values were significantly lower during the Rosh Hashanah holiday than the pre holiday or postholiday periods: 176.8 ± 81.3 mg/dl vs. 181.4 ± 78.8 mg/dl or 184.9 ± 83.02 mg/dl, p = 0.03. During the Rosh Hashanah holiday, mean patient age was significantly older than the preholiday or postholiday period: 77.4 ± 10.9 years vs. 74.9 ± 12.0 years or 75.3 ± 11.8 years, p < 0.0001; however, age predicted less than 1% of the variability in POC glucose: r = 0.02, p = 0.23. Significantly more women were hospitalised during the preholiday than during the holiday or postholiday periods. In a linear regression model, holiday period remained a significant independent predictor of POC glucose even after controlling for age and gender. CONCLUSIONS: Point of care glucose was significantly lower during the Rosh Hashanah period relative to preholiday and postholiday values. This may reflect a shift in the composition of the hospitalised patient population during the holidays towards older individuals with more restricted dietary intake.

Effect of weight loss maintenance on arterial compliance and metabolic and inflammatory parameters: a three-year follow-up study.

BACKGROUND/AIMS: To evaluate the effect of long-term weight loss maintenance on arterial compliance, and metabolic and inflammatory parameters in obese patients who participated in a 6-month weight loss program featuring nutritional and exercise intervention. METHODS: Sixty-seven obese subjects who participated in a 6-month weight loss program were followed for an additional 30 months. The 47 patients who fully completed the 3-year follow-up were divided into two groups according to change in BMI from the end of the weight loss program to the long-term follow-up visit. Group 1 included 22 patients whose BMI decreased or remained stable; group 2 included 25 patients whose BMI increased after program discontinuation. Arterial compliance and metabolic measures were evaluated at baseline, and at 3, 6 and 36 months of follow-up. RESULTS: BMI changed from 35.4 ± 6.9 to 32.6 ± 6.6 after 6 months and to 33.4 ± 7.0 after 36 months. While 53% of participants regained weight after program discontinuation, the mean weight at 3 years remained lower than at entry into the study. Large artery elasticity index (LAEI) as well as small artery elasticity index (SAEI) increased during initial weight loss program in both groups. After program discontinuation, significant improvement in SAEI was observed in patients who decreased or did not change BMI, whereas SAEI decreased in subjects who gained weight. LAEI increased marginally in group 1, while it significantly decreased in group 2. CONCLUSIONS: Obese subjects who successfully completed a 6-month behavioral weight loss program and decreased or maintained weight during 30 additional months exhibited improved arterial stiffness compared to subjects who regained weight.

Relation of arterial properties to left ventricular hypertrophy in hypertensive adults: focus on gender-related differences.

BACKGROUND: Although gender-related differences in ventricular remodeling and arterial stiffness have been described, the impact of gender on the association between vascular compliance and left ventricular hypertrophy (LVH) has not been investigated. The current study was designed to determine the gender-related differences in the association between echographically determined LVH measures and arterial stiffness in hypertensive men and women. METHODS: In the current study, 104 hypertensive participants (61 men and 43 women) were enrolled. Large artery elasticity index (LAEI) and small artery elasticity index (SAEI) were determined using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota). Left ventricular hypertrophy parameters including intraventricular septum thickness (IVST), posterior wall thickness (PWT), and left ventricular mass index (LVMI) were assessed echographically. RESULTS: Hypertensive male versus female were similar in terms of age, body mass index (BMI), blood pressure, concomitant medications, and cardiovascular risk factors. Left ventricular mass index was significantly, inversely associated with IVST (r = -.32, P = .01), PWT (r = -.32, P = .01), and LVMI (r = -.28, P = .03) in men and significantly, inversely associated with IVST (r = -39, P = .01), PWT (r = -.42, P = .005), LVMI (r = -.54, P < .0001) in women. Small artery elasticity index was significantly, inversely associated with LVMI (r = -0.36, P = .02) in women only. In regression analysis, LAEI explained more variability than SAEI and was an independent predictor of LVH parameters in hypertensive men and women. CONCLUSIONS: Compliance of large arteries is potentially an independent predictor of LVH in hypertensive men and women. Therefore, arterial compliance is being considered an important tool in predicting LVH in hypertensive participants.

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

AIM: 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). METHODS: The study group consisted of 284 subjects, including 111 subjects with normal fasting glucose (NFG), 61 subjects classed as impaired fasting glucose (IFG) according of the new fasting blood glucose (FBG) cut-off point of 100 mg/dL and 112 patients with diabetes mellitus (DM). All patients were evaluated for glucose, HbA1C, insulin, lipids, C-reactive protein (CRP) and homeostasis model assessment-insulin resistance. Pulse wave velocity (PWV) and augmentation index (AI) were performed as a noninvasive recording of the two artery sites pressure waveform using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). RESULTS: Pulse wave velocity, augmentation index and central arterial pressure increased consistently with deterioration of glucose tolerance. PWV was significantly higher in subjects with diabetes than in the normal and IFG groups (p < 0.0001 and p = 0.007, respectively). IFG subjects had marginally higher PWV than normal subjects (p = 0.050). Compared to normal subjects, IFG and diabetes groups were associated with increased AI (p = 0.003 and p < 0.0001, respectively). Arterial stiffness parameters remained significantly higher in both IFG and diabetes groups compared to normal after adjustment for cardiovascular risk factors and concomitant medications. Positive correlations between FBG, HbA1C and arterial stiffness parameters were detected. CONCLUSIONS: Arterial stiffness parameters varied significantly across subgroups of patients with different degrees of impaired glucose regulation, such that increasingly deranged glucose homeostasis was associated with increased arterial stiffness. Early adverse vascular changes were detected in subjects with IFG.

Increased insulin resistance and risk of incident cerebrovascular events in patients with pre-existing atherothrombotic disease.

BACKGROUND AND PURPOSE: Diabetes and the metabolic syndrome are known risk factors for ischaemic stroke. Our aim was to examine whether amongst patients with pre-existing atherothrombotic disease, increased insulin resistance is associated with incident cerebrovascular events. METHODS: Patients with stable coronary heart disease included in a secondary prevention trial were followed up for a mean of 6.2 years. Coronary heart disease was documented by a history of myocardial infarction > or =6 months and <5 years before enrollment and/or stable angina pectoris with evidence of ischaemia confirmed by ancillary diagnostic testing. Main exclusion criteria were insulin treated diabetes, hepatic or renal failure, and disabling stroke. Baseline insulin levels were measured in 2938 patients from stored frozen plasma samples and increased insulin resistance assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), categorized into tertiles or quartiles. RESULTS: Crude rates of incident cerebrovascular events rose from 5.0% for HOMA-IR at the bottom tertile to 5.7% at the middle tertile, and 7.0% at the top tertile (P = 0.07). HOMA-IR at the top versus bottom tertile was associated with an unadjusted hazard ratio (HR) of 1.37 (95%CI, 0.94-1.98) and a 1-unit increase in the ln HOMA-IR was associated with a HR of 1.14 (95%CI, 0.97-1.35). In further analyses adjusting for potential confounders, or categorizing baseline HOMA-IR into quartiles, or excluding diabetic patients, we did not identify an increased risk for incident cerebrovascular events conferred by the top category. CONCLUSIONS: Increased insulin resistance did not predict incident cerebrovascular events amongst patients with pre-existing atherothrombotic disease.

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: diponectin 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.

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.

Serum homocysteine, folate, vitamin B12 levels and arterial stiffness in diabetic patients: which of them is really important in atherogenesis?

AIM: Hyperhomocystinaemia is associated with macro- and microangiopathic diabetic complications. However, the role of homocysteine (Hcy), serum folate, and vitamin B12 level in the development of premature vascular damage in type 2 diabetic patients is not clear. The present study was designed to assess the relationship between total Hcy, folate, and vitamin B12 levels and arterial stiffness, an early marker of generalized atherosclerosis. METHODS: As many as 86 subjects with type 2 diabetes mellitus were studied. All participants were evaluated for glucose, HbA(1C), lipid profile, hs-CRP, endothelin, Hcy, vitamin B12, and folate. Pulse wave velocity (PWV) and augmentation index (AI) were performed as a non-invasive recording and computer analysis of the two artery sites pressure waveform using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). RESULTS: Hcy was significantly positively associated with age, serum creatinine, and vitamin B12 levels. No association between Hcy and folate was observed. The Hcy concentration was significantly positively associated with PWV (r = 0.540, p < 0.0001) and AI (r = 0.390, p < 0.0001). In a general linear model of PWV, Hcy emerged as an independent predictor of PWV even after controlling for age, creatinine, vitamin B12, and folate levels. In a multiple linear regression analysis, the association between Hcy and arterial stiffness was independent of traditional cardiovascular risk factors. Vitamin B12 levels were significantly inversely associated with tHcy (r = - 0.263, p = 0.015) and marginally associated with PWV(r = - 0.212, p = 0.052). Significant associations between folate levels and PWV were not detected. CONCLUSIONS: The results lend support to the hypothesis that elevated Hcy may have a key role in the development of atherogenesis in diabetic patients. Additionally, vitamin B12 is significantly associated with tHcy concentrations and is identified as a marginally independent correlate of PWV in diabetic patients in the absence of folate deficiency.

Effect of long-term treatment with risedronate on arterial compliance in osteoporotic patients with cardiovascular risk factors.

Accumulating evidence suggests that osteoporosis and coronary artery disease have epidemiologic similarities. Moreover, the anti-atherogenic effects of bisphosphonates have been observed in vitro and in animal models. The present study investigated the effect of risedronate on indices of arterial compliance, serum osteoprotegerin (OPG) level, inflammatory and metabolic parameters in osteoporotic women with cardiovascular risk factors. In an open label, prospective study 68 postmenopausal osteoporotic women were evaluated for the study. Patients received risedronate orally in a dose of 35 mg per week, daily supplements of calcium and cholecalciferol during 6month treatment period. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, fibrinogen, hs-CRP and plasma osreoprotegerin. Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota). Large artery elasticity index (LAEI) increased from 9.86+/-3.66 to 11.54+/-">+/-3.16 ml/mm HgX10 (p<0.0001) during treatment period. Small artery elasticity index (SAEI) increased from 2.64+/-1.10 to 3.28+/-1.16 ml/mm HgX100 (p<0.0001). Systemic vascular resistance (SVR) decreased from 1876.12+/-457.72 to 1646.12+/-260.17 dyn/s/cm(- 5) (p<0.013). Metabolic parameters did not change during the treatment period. Plasma osteoprotegerin was significantly, positively correlated to SVR at baseline (r=0.36, p=0.045). At the final visit, OPG was marginally inversely associated with LAE (r=- 0.312, p=0.09), and significantly, positively associated with total vascular impedance (r=0.43, p=0.015). In conclusion, prolonged treatment with risedronate improved arterial elasticity of small and large arteries, and decreased SVR. These beneficial vascular effects were not related to changes in cardiovascular risk factors and may be attributed to direct effects of risedronate on the vascular wall.

The association between the renin-angiotensin-aldosterone system and arterial stiffness in young healthy subjects.

Aldosterone might affect arterial stiffening, in both the short- and long-term. We investigated a possible association between excess aldosterone, reflected by an increased aldosterone : renin ratio (ARR) and pulse wave velocity (PWV) in young healthy adults. In a single-centre study, 60 subjects were evaluated for lipid profile, glucose, hs-CRP, renin and aldosterone. PWV was performed as a simple non-invasive recording and computer analysis of the two artery sites pressure waveform using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). The ARR was significantly, positively associated with PWV: r = 0.298, P = 0.02. ARR was not associated with anthropometric variables, blood pressure (BP), metabolic and inflammatory parameters. In conclusion, the ARR was significantly associated with PWV and may exhibit direct effects of aldosterone on the vascular wall, which are not related to changes in conventional cardiovascular risk factors.

Effect of homocysteine-lowering therapy on arterial elasticity and metabolic parameters in metformin-treated diabetic patients.

Metformin may affect the risk of atherothrombotic disease. However, metformin increases levels of homocysteine (Hcy), considered an independent risk factor for atherosclerosis. We evaluate whether homocysteine-lowering has a beneficial effect on arterial elasticity and metabolic parameters in metformin-treated diabetic patients. In double-blind, placebo-controlled study, 60 diabetic patients treated with high dose of metformin were randomly assigned to receive daily oral supplementation with folate (1000 mcg), vitamins B12 (400 mcg) and B6 (10mg) (group 1) or placebo (group 2). Lipid profile, HbA1C, insulin, C-peptide, hs-CRP, vitamin B12, folic acid, homocysteine, endothelin, homeostasis model assessment-insulin resistance (HOMA-IR) were measured. Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, MN). The two groups were similar at baseline in terms of hemodynamic and arterial elasticity parameters. After a 4-month small artery elasticity index (SAEI) was significantly greater in patients who received Hcy-lowering agents than in the placebo group: 4.3+/-2.04 ml/mm Hg x 100 versus 3.2+/-1.1 ml/mm Hg x 100, p=0.01. Post-treatment vitamin B12 and folic acid levels were greater in group 1 versus group 2: 738.1+/-279.9 pg/ml versus 566.1+/-167.4 pg/ml, p=0.007 and 14.9+/-4.8 ng/ml versus 8.3+/-2.9 ng/ml, p<0.0001, respectively. Hcy level decreased significantly in the treatment group from 10.0+/-4.4 to 7.6+/-2.5 micromol/l, p=0.002 and did not change in placebo group (p=0.9). Hcy-lowering therapy improved small arterial elasticity in diabetic patients treated with high dose of metformin. The improvement was associated with a decrease in Hcy as well as an increase in folic acid and vitamin B12. These findings suggest that Hcy-lowering may have beneficial vascular effect in metformin-treated diabetic patients.

C-reactive protein distribution and correlates among men and women with chronic coronary heart disease.

BACKGROUND: C-reactive protein (CRP) elevated in inflammation is associated with atherosclerotic disease. We describe the distribution of CRP and its association with coronary heart disease (CHD) risk factors in a large CHD patient group. METHODS: This analysis comprises 2,723 male and 256 female CHD patients, included in the Bezafibrate Infarction Prevention (BIP) study. High sensitive CRP levels were determined in frozen plasma samples. RESULTS: CRP distribution, was normalized upon log transformation. Levels among women were higher than in men in the entire group (4.4 vs. 3.5 mg/l) and in each age group. Co-morbidities, smoking, lower education level, and use of cardiovascular drugs, were associated with elevated CRP levels in both sexes. The correlation between CRP and body mass index (BMI), insulin and glucose was stronger among women. The explained variability in CRP level was larger in women (20%) compared to men (13%). Among women, BMI explained 10% of CRP variability, whereas the contribution of each variable among men was significantly smaller. CONCLUSIONS: Among men and women with CHD, CRP level was correlated with traditional risk factors and to a lesser degree to manifestation of CHD. BMI is the main contributor to CRP variability, explained by these factors among women.

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.

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.

Prevention of hepatic cirrhosis in rats by hydroxyl radical scavengers.

BACKGROUND/AIMS: Reactive oxygen species and oxidative stress were implicated in hepatic stellate cell activation and liver fibrosis. The aim of the present study was to examine whether the administration of free radical scavengers in vivo would prevent experimentally-induced hepatic cirrhosis in rats. METHODS: Cirrhosis was induced by administration of thioacetamide (TAA; 200 mg/kg, i.p.) twice/week, for 12 weeks. Rats were treated concurrently with either dimethylsulfoxide (DMSO; 4 g/kg, s.c. or p.o.) or dimethylthiourea (DMTU; 200 mg/kg i.p.) three times a week. RESULTS: Liver fibrosis (histopathological score, spleen weight, and hepatic hydroxyproline) was abolished in rats treated with TAA and either DMSO or DMTU (P < 0.001). Accordingly, the hepatic expression of alpha smooth muscle actin, tissue inhibitor of metalloproteinase 2 and collagen alpha1 (I) gene were inhibited. The hepatic level of methane-sulfinic acid (produced by the interaction of DMSO with hydroxyl radicals) was increased in rats treated with TAA + DMSO (P = 0.0005) and decreased after pretreatment of these rats with DMTU (P = 0.008). However, the hepatic levels of malondialdehyde, lipid peroxides and protein carbonyls were not lower in the DMSO- and DMTU-treated groups. CONCLUSIONS: The administration of free radical scavengers prevented the development of TAA-induced liver cirrhosis probably associated with decreased oxidative stress.