Gene expression profile of CD14+ blood monocytes following lifestyle-induced weight loss in individuals with metabolic syndrome.

Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. The objective of this study was to investigate whether lifestyle-induced weight loss modulates gene expression in circulating monocytes. We analyzed and compared gene expression in monocytes (CD14+ cells) and subcutaneous adipose tissue biopsies by unbiased mRNA profiling. Samples were obtained before and after diet-induced weight loss in well-defined male individuals in a prospective controlled clinical trial (ICTRP Trial Number: U1111-1158-3672). The BMI declined significantly (- 12.6%) in the treatment arm (N = 39) during the 6-month weight loss intervention. This was associated with a significant reduction in hsCRP (- 45.84%) and circulating CD14+ cells (- 21.0%). Four genes were differentially expressed (DEG's) in CD14+ cells following weight loss (ZRANB1, RNF25, RB1CC1 and KMT2C). Comparative analyses of paired CD14+ monocytes and subcutaneous adipose tissue samples before and after weight loss did not identify common genes differentially regulated in both sample types. Lifestyle-induced weight loss is associated with specific changes in gene expression in circulating CD14+ monocytes, which may affect ubiquitination, histone methylation and autophagy.

Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial.

Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45-55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control arm. Before and after a 6 months intervention period clinical and laboratory parameters, body composition, serum BA profile, FGF-19, and GLP-1 concentrations were determined in fasting blood samples. 30 participants in the control and 33 participants in the treatment arm completed the study and were included in the data analysis. In participants of the treatment arm lifestyle-induced weight loss resulted in markedly improved insulin sensitivity. Serum levels of BA species and total GLP-1 decreased, while FGF-19 remained stable. Serum BA composition changed towards an increased 12α-hydroxylated/non-12α-hydroxylated ratio. None of these parameters changed in participants of the control arm. Our results demonstrate that improved metabolic control by lifestyle modifications lowers serum levels of BAs and GLP-1 and changes serum BA composition towards an increased 12α/non-12α ratio (ICTRP Trial Number: U1111-1158-3672).

Long-Term Follow-Up of the Telemonitoring Weight-Reduction Program "Active Body Control".

The Active Body Control (ABC) weight-reduction program is based on telemonitoring of physical activity and nutrition together with telecoaching by weekly counseling letters sent by post or by e-mail. The study presented here reports the results of a 1-year follow-up of 49 patients with the metabolic syndrome who had lost weight with the aid of the ABC program in the preceding year. The weight regain after the second year in patients not receiving any further care ("ABC discontinued" group; n = 24) and the potential benefit of continuing with the ABC program with monthly counseling letters ("ABC continued" group; n = 25) were investigated. The relative weight changes after the first year had been, respectively, -13.4% and -11.4% in the "ABC discontinued" and "ABC continued" groups, and after the second year they decreased by, respectively, 4.4 and 2.8%. However, this difference in weight regains between the two groups was not statistically significant. It is concluded that three-quarters of the weight loss after 1 year is maintained after the second year. The decision whether to continue with the ABC program after 1 year should be made individually.

Weight loss by telemonitoring of nutrition and physical activity in patients with metabolic syndrome for 1 year.

OBJECTIVE: Mobile technology can improve lifestyle programs, but the monitoring techniques and carer feedback need to be optimized. To this end, we investigated the efficacy of telemonitoring physical activity and nutrition over 12 months in patients with metabolic syndrome in a randomized, parallel-group, open trial. METHODS: Screening all over Germany yielded 184 patients with metabolic syndrome. All patients attended a single 2-hour instruction meeting in their region concerning a combination diet and the importance of physical activity. Thereafter they were randomized into a control group (controls, n = 62) or one of 2 different intervention groups. Both intervention groups were issued accelerometers, which measured physical activity, recorded daily weight and calorie intake, and transmitted these data to a central server for use by patient carers. In the Active Body Control Program of University of Magdeburg (ABC) intervention group (n = 60), information and motivation was ensured by weekly letters. In the 4sigma telephone coaching (4S) intervention group (n = 58), this was accomplished by monthly telephone calls from the carers. Clinical and biochemical data for all patients were collected at 0, 4, 8, and 12 months without any regular face-to-face meetings between patients and carers. The primary endpoint was weight loss and the secondary endpoint was the presence of metabolic syndrome. RESULTS: After 12 months the dropout rates in the control, 4S, and ABC groups were respectively 35%, 17%, and 18%. The adjusted relative weight losses after 12 months were respectively 3.7%, 8.6%, and 11.4% (all p < 0.000 versus baseline). ABC was more effective than 4S (p = 0.041); 43% of the patients completing the study in the ABC group lost more than 15% of their baseline weight. The diagnosis of metabolic syndrome was no longer applicable in 58% of the cases in the ABC group, in 41% of the 4S group, and in 33% of the controls. CONCLUSIONS: Telemonitoring of physical activity and nutrition markedly improves weight loss and markers of metabolic syndrome.

Weight loss and changes in salivary ghrelin and adiponectin: comparison between sleeve gastrectomy and Roux-en-Y gastric bypass and gastric banding.

BACKGROUND: Weight loss is associated with increased levels of adiponectin with a greater increase observed following Roux-en-Y gastric bypass (RYGB) compared to restrictive procedures. However, currently there are no data on changes in adiponectin following laparoscopic sleeve gastrectomy (LSG). Ghrelin was reported to be also produced by the salivary glands. There are also no data available regarding its changes following bariatric surgery. METHODS: The present study examined weight loss, and salivary ghrelin and HMW adiponectin levels in 43 morbidly obese subjects undergoing three different types of bariatric surgery. RESULTS: We found that weight loss following LSG is superior to laparoscopic adjustable gastric banding (LAGB) and comparable to RYGB at 12 months after surgery. Although blood glucose decreased similarly following all three procedures, fasting insulin continuously declined only in LSG and RYGB patients. Changes in both fasting and postprandial salivary ghrelin greatly varied between all three procedures with no similarities to changes in serum ghrelin reported in the literature. HMW adiponectin significantly increased following LSG, and this increase was more marked than in LAGB patients and almost identical compared to RYGB. CONCLUSIONS: Weight loss following LSG is comparable to RYGB in the short term. Changes in HMW adiponectin are comparable following LSG and RYGB which may further contribute to the successful results after LSG. Furthermore, the results of the present study support the hypothesis that there is an autonomous production of ghrelin in salivary glands irrespective of nutritional status and weight loss.

Serum lipoproteins improve after successful pharmacologic antidepressant treatment: a randomized open-label prospective trial.

OBJECTIVE: Despite reports of lower plasma cholesterol in depressed patients, major depressive disorder has been shown to increase cardiovascular risk. Our objective was to study the composition of lipoproteins in depressed patients and controls and to examine the effects of pharmacologic treatment and treatment response on lipoprotein composition. METHOD: Lipoprotein composition was analyzed in 65 adult inpatients at a university psychiatric hospital in Germany with DSM-IV major depressive disorder and 33 healthy controls (recruited via newspaper and radio ads) matched for age and sex. After the cross-sectional study phase, the patients were randomized in an open-label prospective trial to treatment with either mirtazapine or venlafaxine. Lipoproteins were reanalyzed after 4 weeks of treatment. Main outcome measures were total cholesterol, the low-density lipoprotein (LDL) to high-density lipoprotein (HDL) cholesterol ratio, and the LDL triglycerides to apolipoprotein B ratio. Secondary outcome measures were total triglycerides, HDL and LDL cholesterol levels, and apolipoproteins A1 and B levels. Comparisons were made between the 2 drug groups and between remitters and nonremitters as measured by the 21-item Hamilton Depression Rating Scale. The study was conducted from April 2003 through December 2007. RESULTS: Total cholesterol at baseline was lower in patients than in controls (mean ± SD = 4.99 ± 0.98 mmol/L vs 5.63 ± 1.01 mmol/L; P = .003), with significantly lower HDL cholesterol (P < .001) and LDL cholesterol (P = .03) in patients. However, the ratio of LDL triglycerides to apolipoprotein B, an index of size and atherogenic potential of LDL particles, was higher in depressed subjects (mean ± SD = 0.46 ± 0.14 mmol/g vs 0.38 ± 0.09 mmol/g; P = .002). Irrespective of treatment allocation, we found significant improvement of cardiovascular risk parameters in remitters but found deterioration in nonresponders. The LDL cholesterol mean change from baseline (remitters vs partial responders vs nonresponders) was -0.06 mmol/L versus +0.39 mmol/L versus +0.56 mmol/L (P = .014); the mean change in LDL/HDL cholesterol ratio was -0.50 versus +0.14 versus +0.80 (P = .002); and the mean change in the LDL triglycerides per apolipoprotein B ratio was -0.01 versus -0.01 versus +0.08 (P = .045). No drug-specific changes in lipid concentrations during treatment were observed except for total cholesterol (venlafaxine group mean = -0.02 mmol/L and mirtazapine group mean = +0.37 mmol/L; P = .033). CONCLUSIONS: In depressed patients, lipoprotein structure is changed toward LDL particles with a higher atherogenic potential. Remission from depression is associated with an improvement of the LDL/HDL cholesterol ratio, shifting lipoproteins toward a less atherogenic composition. Our findings should be confirmed in a larger study, as they have relevance for both researchers and clinicians. TRIAL REGISTRATION: German Clinical Trial Registry Identifier: DRKS00000008.

Comparison of serum and salivary ghrelin in healthy adults, morbidly obese, and patients with metastatic carcinoma.

BACKGROUND: Ghrelin, a known orexigenic hormone, has been demonstrated to be produced and released by salivary glands. Obtaining saliva for metabolism studies would be preferable for patients since the procedure is non-invasive. METHODS: The present study examined serum and salivary ghrelin levels in 41 morbidly obese subjects, 45 healthy controls, and 17 patients with metastatic carcinoma by using a commercial radioimmunoassay. RESULTS: When comparing serum and salivary levels under fasting conditions, ghrelin levels were significantly higher in saliva for morbidly obese and healthy subjects. A significant correlation between salivary and serum ghrelin could only be demonstrated for healthy subjects. Fasting serum ghrelin concentrations in morbidly obese patients were significantly lower compared with healthy controls and cancer patients, however the levels in whole saliva did not differ significantly between all groups. There was only a highly significant inverse correlation between BMI and serum ghrelin. Serum ghrelin correlated positively with age in morbidly obese. There was no significant difference in serum and saliva ghrelin concentrations between men and women. Following the standardized meal, no significant suppression of serum ghrelin levels in morbidly obese was observed, however salivary ghrelin concentrations were significantly decreased. CONCLUSIONS: The results of the present study support the hypothesis that there is an autonomous production of ghrelin in the salivary glands. Further research should focus on factors involved in the regulation of salivary ghrelin. Until the mechanism of regulation is fully understood, the testing of ghrelin levels in saliva is too limited to recommend a switch from serum testing.

Pharmacokinetics and dose recommendations of Niaspan® in chronic kidney disease and dialysis patients.

BACKGROUND: Niaspan® is an extended-release formulation of nicotinic acid with improved tolerability compared with the immediate-release and sustained-release formulations. It is used to treat hypertriglyceridaemia with low high-density lipoprotein levels. This type of dyslipidaemia frequently appears in patients with chronic kidney disease (CKD). Dose recommendations for these patients are not available because pharmacokinetic data are missing. The present study was performed to analyse the pharmacokinetics of prolonged-release nicotinic acid in CKD and in dialysis patients to derive dose recommendations. METHODS: Ten dialysis patients and eight patients with CKD were enrolled in a prospective, three-period, open-label pharmacokinetic study. They received in the first week 500 mg Niaspan® per day, in the second week 1000 mg/day and in the third week 1500 mg/day. On the fourth day of every treatment unit, 11 plasma samples were collected for 24 h post-dose and analysed for nicotinic acid (NA) and its metabolites nicotinamide and nicotinuric acid (NUA). RESULTS: Median plasma NA concentrations in subjects with CKD were obviously higher than in dialysis patients, but not higher than reported in patients without renal impairment. t(max) of NA were on average 0.75 h in dialysis patients and 3.0 h in CKD patients and, therefore, especially for dialysis patients, clearly shorter than expected for extended-release formulations. It is particularly noticeable that the AUC, C(max) and t(1/2) of the metabolite NUA are significantly higher in dialysis patients in comparison to CKD patients. This may indicate that the dialysis was not effective in removing this metabolite. However, there was no correlation between the incidence of flush and the concentration of NUA. Another possibility could be a drug-drug interaction with omeprazole via CYP450 enzymes. CONCLUSIONS: These data suggest that no dose adjustment of Niaspan® is necessary in patients with renal impairment. Despite an extended-release formulation of NA, we could not detect a delay in t(max) especially in dialysis patients. We found no correlation between the incidence of flush and the NUA concentration. Furthermore, there were hints of an interaction with omeprazole.

Weight loss in obese patients with type 2 diabetes: effects of telemonitoring plus a diet combination - the Active Body Control (ABC) Program.

AIMS: We evaluate the efficacy of the "Active Body Control (ABC) Program" for weight reduction in patients with type 2 diabetes. METHODS: The ABC program combines telemonitoring of the physical activity with a low-calorie diet also preferring carbohydrates with low glycemic indexes. In this 6-month, randomized, clinical trial 35 patients (aged 57 ± 9 years; BMI=35.3 ± 5.7 kg/m(2)) were treated according to the ABC program and 35 control patients (aged 58 ± 7 years; BMI=34.8 ± 5.9 kg/m(2)) received standard therapy. RESULTS: After 6 months the mean weight loss in the intervention group was 11.8 kg ± 8.0 kg. Glucose and HbA1c were lowered by respectively 1.0 mmol/l and 0.8 percentage points (p=0.000, respectively). The proportion of patients with HbA1c>7% fell from 57% to 26%. Antidiabetic drugs were discontinued in 13 patients (39%) and reduced in 14 (42%). The reduction of costs on medication per patient was € 83 in 6 months. In the control group, there were no relevant changes in body weight, laboratory values or drug treatment. CONCLUSIONS: The ABC program effectively lowers body weight, Hb1Ac and antidiabetic drug use in patients with type 2 diabetes.

Flavanol-rich cocoa ameliorates lipemia-induced endothelial dysfunction.

Consumption of flavanols improves chronic endothelial dysfunction. We investigated whether it can also improve acute lipemia-induced endothelial dysfunction. In this randomized, placebo-controlled, double-blind, crossover trial, 18 healthy subjects received a fatty meal with cocoa either rich in flavanols (918 mg) or flavanol-poor. Flow-mediated dilation (FMD), triglycerides, and free fatty acids were then determined over 6 h. After the flavanol-poor fat loading, the FMD deteriorated over 4 h. The consumption of flavanol-rich cocoa, in contrast, improved this deterioration in hours 2, 3, and 4 without abolishing it completely. Flavanols did not have any influence on triglycerides or on free fatty acids. Flavanol-rich cocoa can alleviate the lipemia-induced endothelial dysfunction, probably through an improvement in endothelial NO synthase.

B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease: results of a randomized controlled trial.

BACKGROUND: In observational studies, hyperhomocysteinemia has been found to be a risk factor for total mortality and cardiovascular events in patients with end-stage renal disease. These patients have grossly elevated homocysteine levels that can be lowered by supplementation with folic acid and vitamin B(12). We conducted a randomized clinical trial with B vitamins to reduce homocysteine levels and therefore cardiovascular events and total mortality. METHODS AND RESULTS: This randomized, double-blind multicenter study was conducted in 33 dialysis centers in north and east Germany between July 2002 and July 2008. We randomly assigned 650 patients with end-stage renal disease who were undergoing hemodialysis to 2 postdialysis treatments: 5 mg folic acid, 50 microg vitamin B(12), and 20 mg vitamin B(6) (active treatment) or 0.2 mg folic acid, 4 microg vitamin B(12), and 1.0 mg vitamin B(6) (placebo) given 3 times per week for an average of 2 years. The primary outcome was total mortality; the secondary outcome was fatal and nonfatal cardiovascular events. The primary outcome occurred in 102 patients (31%) receiving the active treatment and in 92 (28%) receiving placebo (hazard ratio, 1.13; 95% confidence interval, 0.85 to 1.50; P=0.51). The secondary outcome occurred in 83 patients (25%) receiving the active treatment and in 98 (30%) receiving placebo (hazard ratio, 0.80; 95% confidence interval, 0.60 to 1.07; P=0.13). CONCLUSIONS: Increased intake of folic acid, vitamin B(12), and vitamin B(6) did not reduce total mortality and had no significant effect on the risk of cardiovascular events in patients with end-stage renal disease. Clinical Trial Registration- URL: www.anzctr.org.au. Unique identifier: ACTRN12609000911291. URL: www.cochrane-renal.org. Unique identifier: CRG010600027.

Haplotypes in the UGT1A1 gene and their role as genetic determinants of bilirubin concentration in healthy German volunteers.

BACKGROUND: Genetic variations of UDP-glucuronyltransferase 1A1 (UGT1A1) influence the concentration of serum bilirubin. We investigated the association of four common polymorphisms including UGT1A1-53(TA)(n), and common haplotypes of the UGT1A1 gene with bilirubin levels in 218 Caucasian volunteers. METHODS: Total bilirubin was measured in serum of 218 healthy Caucasian volunteers. Genotyping of four genetic variants was performed: UGT1A1-53(TA)(6/7), UGT1A1c.-3279T>G, UGT1A1c.-3156G>A, and UGT1A1c.211G>A. The association between polymorphisms/haplotypes and bilirubin levels were determined. RESULTS: Minor allele frequencies were 0.36 for UGT1A1-53(TA)(7), 0.47 for c.-3279G, 0.33 for c.-3156A and 0.006 for c.211A. The three promoter polymorphisms were in close linkage disequilibrium. Common haplotypes were: -53(TA)(6)/c.-3279T/c.211G (frequency 0.530), -53(TA)(7)/c.-3279G/c.211G (frequency 0.365), and -53(TA)(6)/c.-3279G/c.211G (frequency 0.099). Male sex, UGT1A1-53(TA)(6/7) and the c.-3279GG variant were significantly associated with higher bilirubin concentrations. CONCLUSIONS: Two UGT1A1 promoter polymorphisms (-53(TA)(6/7) and c.-3279T>G) and a common haplotype of the UGT1A1 gene are associated with serum bilirubin concentrations in Caucasians.

Homocysteine as a risk factor for cardiovascular disease in patients treated by dialysis: a meta-analysis.

BACKGROUND: In the general population, increased homocysteine concentrations are a risk factor for cardiovascular disease and mortality. However, it is not known whether this also applies to patients with end-stage renal disease. STUDY DESIGN: Meta-analysis of retrospective (11 studies including 1,506 individuals), prospective observational studies (12 studies including 1,975 individuals), and intervention trials (5 studies including 1,642 dialysis patients). Analyses were carried out separately, according to the study design. SETTING & POPULATION: Studies of patients with end-stage renal disease treated by means of hemodialysis or peritoneal dialysis. SELECTION CRITERIA FOR STUDIES: Studies investigating the association between total homocysteine level and cardiovascular disease or total mortality or the influence of vitamin supplementation on cardiovascular or mortality risk. INTERVENTION: In intervention studies, vitamin preparations with folic acid alone or in combination with other vitamins, such as vitamin B(12) and B(6), were used. OUTCOMES: In retrospective studies, cases are patients with cardiovascular diseases. Outcomes for prospective observational and intervention studies are cardiovascular events and total mortality. RESULTS: In retrospective studies, there was no significant overall difference in homocysteine concentrations between cases and controls (weighted mean difference in homocysteine, 2.82 micromol/L; 95% confidence interval [CI], -2.22 to 7.86; P = 0.3). The pooled overall risk estimate for prospective observational studies suggests no association between homocysteine level (5-micromol/L increase) and total mortality (hazard ratio [HR], 1.02; 95% CI, 0.93 to 1.12; P = 0.7), but there was an association with cardiovascular events (HR, 1.09; 95% CI, 1.03 to 1.14; P = 0.001). In subgroup analysis of patients not receiving vitamins, an increase in homocysteine level was associated with increased mortality (HR, 1.07; 95% CI, 1.02 to 1.13; P = 0.01). For intervention trials with B vitamins, there was a significant risk reduction for cardiovascular disease (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = 0.02), but no risk reduction for total mortality or the composite end point including total mortality (relative risk, 1.01; 95% CI, 0.88 to 1.15; P = 0.9). LIMITATIONS: Many studies are small, which may lead to the observed heterogeneity. Some intervention trials are neither placebo controlled nor randomized. Separate analyses for specific end points and patients treated by means of hemodialysis or peritoneal dialysis were not possible. CONCLUSION: Total homocysteine level may be a risk factor for cardiovascular events and total mortality in patients with end-stage renal disease not receiving vitamin supplementation or folic acid food fortification. There may be a potential for reducing cardiovascular disease in this population by folic acid supplementation.

Different galenic formulations of fluvastatin have equal lipid-lowering potential but differ in reducing lipemia-induced endothelial dysfunction.

BACKGROUND: Postprandial lipemia is known to exert a reversible detrimental effect on endothelium-dependent flow-mediated vasodilation (FMD). Fasting FMD has shown to be improved by fluvastatin. In this study, we investigated whether lipemia-induced endothelial dysfunction can be mitigated by fluvastatin in two (immediate-release and extended-release) formulations. METHODS: In 27 patients with the metabolic syndrome, randomized in a three-period crossover design for 5 weeks each to 80 mg extended-release fluvastatin daily, 40 mg immediate-release fluvastatin twice daily (b.i.d.) or placebo, the fasting and postprandial lipids and FMD of the brachial artery were measured at baseline and after 5 weeks of each treatment period. Postprandial lipemia was induced by administration of whipping cream containing 33% fat (1 g fat/kg body weight). FMD was determined by two-dimensional ultrasonography of the brachial artery in the fasting state and 4 h after the fatty meal. Lipids were determined using routine methods. RESULTS: Fasting triglycerides were reduced after immediate-release and extended-release fluvastatin by 16 and 23%, respectively, and postprandial triglycerides by 20 and 29%, respectively. The fasting FMD was also improved by each treatment. The postprandial FMD impairment, however, was mitigated only after 40 mg b.i.d. After 80 mg fluvastatin, the last dose of which had been administered the previous evening, the lipemic FMD impairment was the same as after the placebo. CONCLUSION: Fluvastatin improves fasting FMD regardless of whether it is administered as 40 mg b.i.d. or 80 mg daily given in the evening. The lipemic FMD impairment, in contrast, is improved only by 40 mg b.i.d. when the tablet is taken in the morning of the test day. As the half-life of fluvastatin is about 2 h, we surmise that an improvement occurs only when sufficient amounts of fluvastatin are present in the bloodstream.

Addition of 2.5 g L-arginine in a fatty meal prevents the lipemia-induced endothelial dysfunction in healthy volunteers.

BACKGROUND: Endothelial function as determined by flow-mediated dilation (FMD) deteriorates during postprandial lipemia. The impairment can be neutralized by adding 50 g casein to the fatty meal. The objective of this study was to see which of the casein constituents is responsible for this neutralization effect. DESIGN: A crossover design was used in 15 healthy volunteers, who were given 3 ml cream/kg body weight with and without 2.5 g L-arginine. Lipids and FMD were then determined hourly over a period of 6h. In substudies this design was repeated with 2.5 g phenylalanine and 5 g leucine in 11 subjects. The effect of 2.5 g L-arginine on FMD in the absence of cream was tested in seven subjects. RESULTS: Without L-arginine the FMD deteriorated during 4h after the fat loading. Addition of L-arginine prevented this deterioration at 3 and 4h. Phenylalanine and leucine, in contrast, did not prevent the lipemic endothelial dysfunction. L-Arginine alone similarly had no acute effect on the FMD. CONCLUSION: 2.5 g L-arginine, but not phenyalanine or leucine, is able to prevent the lipemic dysfunction of the endothelium.

Washout of water-soluble vitamins and of homocysteine during haemodialysis: effect of high-flux and low-flux dialyser membranes.

AIM: Vitamin deficiencies are common in patients with end-stage renal disease (ESRD) owing to dietary restrictions, drug-nutrient interactions, changes in metabolism, and vitamin losses during dialysis. The present study investigated the levels of serum and red blood cell (RBC) folate, plasma pyridoxal-5'-phosphate (PLP), serum cobalamin, blood thiamine, blood riboflavin, and plasma homocysteine (tHcy) before and after haemodialysis treatment. METHODS: Vitamin and tHcy blood concentrations were measured in 30 patients with ESRD before and after dialysis session either with low-flux (n = 15) or high-flux (n = 15) dialysers. RESULTS: After the dialysis procedure, significantly lower concentrations of serum folate (37%), plasma PLP (35%), blood thiamine (6%) and blood riboflavin (7%) were observed. No significant changes were found for serum cobalamin or for RBC folate. There were no differences in the washout of water-soluble vitamins between treatments with low-flux and high-flux membranes. Furthermore, a 41% lower concentration in tHcy was observed. The percentage decrease in tHcy was significantly greater in the patients treated with high-flux dialysers (48% vs 37%; P < 0.01). The percentage change during dialysis was significantly inversely related to the molecular weight of the vitamins measured (r =-0.867, P < 0.01). CONCLUSION: This study showed significantly lower blood or serum levels of various water-soluble vitamins after dialysis, independently of the dialyser membrane. The monitoring of the vitamin status is essential in patients treated with high-flux dialysers as well as in patients treated with low-flux dialysers.

Fluvastatin treatment and withdrawal: effects on endothelial function.

Fluvastatin lowers lipids and protects endothelial function. This study investigated how 2 preparations of fluvastatin would affect endothelial function after treatment and early after its discontinuation. Twenty-seven patients received 80 mg extended-release fluvastatin every day, 40 mg immediate-release fluvastatin twice a day, or placebo for 5 weeks. Fasting lipids and flow-mediated dilation were measured at baseline and after each treatment period. In 21 patients, flow-mediated vasodilation was also measured 24 hours after discontinuation of therapy. Both forms of fluvastatin improved flow-mediated vasodilation (extended release: P < .037 and immediate release: P < .001). However, this improvement occurred preferentially in patients with low baseline flow-mediated vasodilation (<5%). Twenty-four hours after treatment discontinuation, the flow-mediated vasodilation deteriorated again to baseline (extended release and immediate release: P < .001). Fluvastatin improved flow-mediated vasodilation only in patients with low baseline values. Twenty-four hours after discontinuation, the flow-mediated vasodilation deteriorated again, surprisingly irrespective of prior improvement.

Preferential increase in high-molecular weight adiponectin after niacin.

OBJECTIVE: Recently we have demonstrated that treatment with niacin raises adiponectin between 52% and 95% in patients with the metabolic syndrome. In this study we investigated whether all three adiponectin fractions are increased equally, and, secondly, whether the increase in the biologically most active high-molecular weight (HMW) fraction can prevent the deterioration of insulin sensitivity that was also observed after niacin. METHODS AND RESULTS: We used sera frozen at -80 degrees C from a randomized double-blind placebo-controlled treatment study in which 20 men with the metabolic syndrome received 1500 mg niacin for 6 weeks. Low- and medium-molecular weight adiponectin increased by 35% and 33%, respectively, but HMW adiponectin by 88% (all p<0.05). The increase in HMW adiponectin was almost two times as large in patients with lower BMI and better insulin sensitivity. However, treatment with niacin induced a deterioration of insulin sensitivity, as assessed by the HOMA-IR, independently of the increase in HMW adiponectin. CONCLUSION: HMW adiponectin is the fraction most affected by treatment with niacin. The niacin-associated deterioration of insulin sensitivity, however, occurs even in subgroups with the greatest increase of HMW adiponectin.

B vitamin plasma levels and the risk of ischemic stroke and transient ischemic attack in a German cohort.

BACKGROUND AND PURPOSE: Data from prospective studies on the associations between B vitamin plasma levels and the risk of stroke are limited. We investigated the individual and combined effects of plasma folate, vitamin B12, and pyridoxal 5-phosphate (PLP) levels on the risk of ischemic stroke and transient ischemic attack (TIA) in a large, prospective German cohort. METHODS: Incident cases of ischemic stroke or TIA were identified among 25 770 participants (age 35 to 65 years) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study during 6.0+/-1.5 years of follow-up. The present analysis is based on a case-cohort study comprising 779 subjects free from cardiovascular disease and 188 incident cases of cerebral ischemia (ischemic stroke or TIA). Multivariable Cox proportional-hazard models were applied to evaluate the association between B vitamin levels and risk of cerebral ischemia. RESULTS: Participants in the lowest tertile of vitamin B12 values were at increased risk of cerebral ischemia compared with subjects in the highest tertile; this was not observed, however, for either folate or PLP. In subgroup analyses, the relative risks were similar in magnitude for stroke and TIA. When various combinations of B vitamin tertile levels were analyzed, only combined low folate and vitamin B12 levels (relative risk, 2.24; 95% CI, 1.10 to 4.54) were significantly related to an increased risk of cerebrovascular ischemia. CONCLUSIONS: Our data suggest that low vitamin B12 plasma levels, particularly in combination with low folate levels, increase the risk of cerebral ischemia. This effect may be mediated at least partly through elevations of homocysteine levels.