Norbert J. Tripolt

The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: an open label, randomized pilot study

Background/objectives:Obesity and metabolic disorders are linked to inflammation via gut microbiota and/or gut permeability. Gut-derived endotoxin triggers inflammation leading to metabolic syndrome (MetS) and contributing to oxidative stress. We intended to investigate the effect of Lactobacillus casei Shirota on gut permeability, presence of endotoxin and neutrophil function in MetS.Subjects/methods:Patients with MetS were randomized to receive 3 × 6.5 × 109 CFU L. casei Shirota (probiotic group) or not for 3 months. Gut permeability was assessed by a differential sugar absorption method and by determination of diaminooxidase serum levels, endotoxin by an adapted limulus amoebocyte lysate assay, neutrophil function and toll-like receptor (TLR) expression by flow cytometry and ELISA was used to detect lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14) levels.Results:Twenty-eight patients and 10 healthy controls were included. Gut permeability was significantly increased in MetS compared with controls but did not differ between patient groups. None of the patients were positive for endotoxin. LBP and sCD14 levels were not significantly different from healthy controls. High-sensitive C-reactive protein and LBP levels slightly but significantly increased after 3 months within the probiotics group. Neutrophil function and TLR expression did not differ from healthy controls or within the patient groups.Conclusions:Gut permeability of MetS patients was increased significantly compared with healthy controls. L. casei Shirota administration in the MetS patients did not have any influence on any parameter tested possibly due to too-short study duration or underdosing of L. casei Shirota.

Short communication: Effect of supplementation with Lactobacillus casei Shirota on insulin sensitivity, β-cell function, and markers of endothelial function and inflammation in subjects with metabolic syndrome—A pilot study

Based on animal studies, intake of probiotic bacteria was suggested to improve insulin sensitivity by reducing endotoxinemia and inflammation. The objective of this study was to determine the effects of supplementation with the probiotic strain Lactobacillus casei Shirota (LcS) over 12 wk on insulin sensitivity, β-cell function, inflammation, and endothelial dysfunction parameters in subjects with metabolic syndrome. In a randomized-controlled study, 30 subjects with metabolic syndrome either received Lactobacillus casei Shirota 3 times daily for 12 wk or served as controls with standard medical therapy. Fasting blood samples were taken and a 75-g oral glucose tolerance test was performed to derive indices for insulin sensitivity and β-cell function. In addition, parameters to assess endothelial function and inflammation markers were determined. Even though the insulin sensitivity index significantly improved after 3 mo of probiotic supplementation (0.058±0.021 vs. 0.038±0.025), the change was not significantly different compared with the control group. No improvements were seen in additional indices of insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity by oral glucose tolerance test, and homeostasis model assessment for insulin resistance) and β-cell function (first and second phase insulin secretion, and homeostasis model assessment for β-cell function). Probiotic supplementation resulted in a significant reduction in soluble vascular cell adhesion molecule-1 (sVCAM-1) level (1,614±343 vs. 1,418±265 ng/mL). No significant changes in parameters used to assess low-grade inflammation or endothelial dysfunction were observed. Intake of LcS for 12 wk in subjects with metabolic syndrome did not improve insulin sensitivity, β-cell function, endothelial function, or inflammation markers in this trial.

Multifactorial risk factor intervention in patients with Type 2 diabetes improves arginine bioavailability ratios.

Diabet. Med. 29, e365–e368 (2012)

Multiple risk factor intervention reduces carotid atherosclerosis in patients with type 2 diabetes.

BackgroundPatients with rapid progression of carotid intima media thickness (CIMT) were shown to have a higher future risk for cardiovascular events.The aim of this study was to investigate the impact of multiple risk factor intervention on CIMT progression and to establish whether new cardiovascular surrogate measurements would allow prediction of CIMT changes.Materials and methodsIn this prospective, open, 2-years study, we included 97 patients with type 2 diabetes and at least two insufficiently treated cardiovascular risk factors, i.e. HbA1c > 7.5% (58 mmol/mol); LDL-cholesterol >3.1 mmol/l or blood pressure >140/90 mmHg. Treatment was intensified according to current guidelines over 3 months with the aim to maintain intensification over 2 years.The primary outcome was the change in CIMT after 2 years. We also assessed markers of mechanical and biochemical endothelial function and endothelial progenitor cells before and after 3 months of treatment intensification. For testing differences between before and after multifactorial treatment measurements we used either the paired student’s t-test or the Wilcoxon signed-rank test, depending on the distribution of the data. Additional, explorative statistical data analysis was done on CIMT progression building a linear multivariate regression model.ResultsBlood glucose, lipids and blood pressure significantly improved during the first 3 months of intensified treatment, which was sustained over the 2-year study duration. Mean CIMT significantly decreased from baseline to 2 year (0.883 ± 0.120 mm vs. 0.860 ± 0.130 mm; p = 0.021). None of the investigated surrogate measures, however, was able to predict changes in IMT early after treatment intensification.ConclusionsIntensification of risk factor intervention in type 2 diabetes results in CIMT regression over a period of 2 years. None of the biomarkers used including endothelial function parameters or endothelial progenitor cells turned out to be useful to predict CIMT changes.Trial registrationClinical Trial Registration – Unique identifier:NCT00660790

A retrospective analysis of securing autologous split-thickness skin grafts with negative pressure wound therapy in paediatric burn patients

BACKGROUND AND AIM Deep dermal and full-thickness burn wounds are excised and grafted with split-thickness skin grafts. Especially in less compliant patients such as young children, conventional fixing methods can often be ineffective due to high mobility rates in this age group. The aim of this retrospective single-centre study was to give an overview of our experience in the fixation of autologous split-thickness skin grafts (ASTSGs) on burn wounds by negative pressure wound therapy (NPWT) in paediatric patients. METHODS A retrospective analysis describing 53 paediatric patients with burns or burn-related injuries who were treated as 60 individual cases were conducted. All patients received ASTSGs secured by NPWT. RESULTS Of the individual cases, 60 cases with a mean age of 8±6 years (the youngest was 3 months, the eldest was 24 years old) were treated in a single procedure with ASTSG and NPWT. Total burn surface area (TBSA) was, median (med) 4.5% (3.0-12.0%). The TBSA of deep dermal thickness to full-thickness (IIb-III°) burns was med 4.0% (2.0-6.0%). The TBSA treated with ASTSG and NPWT was med 3.5% (2.0-6.0%). Take rate was, med 96% (90-99%) with a total range of 70-100%. The only significant correlation that could be found was between the grafted TBSA and the take rate. The smaller the grafted TBSA the better the take rate resulted, as expected. In three cases, major complications were noted. CONCLUSION To sum up our experience, the NPWT system has developed itself to be a constant, well-implemented and useful tool in securing ASTSGs to the wound bed. The main advantage of the technique is a much higher mobility of the patient compared to conventional fixation methods. The high compliance rate of an often challenging group of patients such as children recompenses possible higher costs compared to conventional fixation methods.

Lactobacillus casei Shirota Supplementation Does Not Restore Gut Microbiota Composition and Gut Barrier in Metabolic Syndrome: A Randomized Pilot Study

Metabolic syndrome is associated with disturbances in gut microbiota composition. We aimed to investigate the effect of Lactobacillus casei Shirota (LcS) on gut microbiota composition, gut barrier integrity, intestinal inflammation and serum bile acid profile in metabolic syndrome. In a single-centre, prospective, randomised controlled pilot study, 28 subjects with metabolic syndrome received either LcS for 12 weeks (n = 13) or no LcS (n = 15). Data were compared to healthy controls (n = 16). Gut microbiota composition was characterised from stool using 454 pyrosequencing of 16S rRNA genes. Serum bile acids were quantified by tandem mass spectrometry. Zonulin and calprotectin were measured in serum and stool by ELISA. Bacteroidetes/Firmicutes ratio was significantly higher in healthy controls compared to metabolic syndrome but was not influenced by LcS. LcS supplementation led to enrichment of Parabacteroides. Zonulin and calprotectin were increased in metabolic syndrome stool samples but not influenced by LcS supplementation. Serum bile acids were similar to controls and not influenced by LcS supplementation. Metabolic syndrome is associated with a higher Bacteroidetes/Firmicutes ratio and gut barrier dysfunction but LcS was not able to change this. LcS administration was associated with subtle microbiota changes at genus level. Trial Registration ClinicalTrials.gov NCT01182844

Effect of Lactobacillus casei Shirota supplementation on trimethylamine-N-oxide levels in patients with metabolic syndrome: An open-label, randomized study

BACKGROUND Recent studies in animal models have shown a link between ingestion of dietary phosphatidylcholine (PC), choline, l-carnitine and cardiovascular risk. Intestinal microbiota-dependent metabolism of PC and l-carnitine is involved in formation of trimethylamine (TMA), which is further metabolized to the proatherogenic compound trimethylamine-N-oxide (TMAO). It has been suggested that changes in gut microbiota by supplementation of probiotic drinks might alter TMAO levels. Hence, the aim of this analysis was to investigate the impact of Lactobacillus casei Shirota (LcS) on formation of TMAO in subjects with metabolic syndrome. METHODS In a single-center, prospective, randomized-controlled study 30 subjects with metabolic syndrome were randomized to receive either 3 times daily 6.5 × 10(9) CFU (colony-forming units) LcS (probiotic group) or not (standard therapy group) for 12 weeks. TMAO plasma levels were quantified by means of liquid chromatography and tandem mass spectrometry. RESULTS Thirteen patients in the probiotic group and 15 in the standard therapy group finished the study. Mean age was 52 ± 11 and 55 ± 9 years, respectively. TMAO levels decreased during the intervention period in both groups (from 4.66 ± 2.66 μM to 4.31 ± 2.04 μM in the probiotic group and from 4.64 ± 2.75 μM to 4.40 ± 2.14 μM in the control group). Changes in TMAO between subjects receiving LcS (-0.25 ± 2.39 μM) and controls (-0.34 ± 2.23 μM) were not significantly different (p = 0.510). CONCLUSION In conclusion, intake of LcS for 12 weeks did not affect levels of TMAO in patients with metabolic syndrome.

New American College of Cardiology and American Heart Association cholesterol treatment guidelines: subjects with Type 2 diabetes are under treated with high‐intensity statins

Recently, the American College of Cardiology and American Heart Association (ACC/AHA) task force has published their new guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults [1]. The paradigm shift in this new guideline is the change from an LDL cholesterol-target centred treatment recommendation to an approach of identifying statin benefit groups and to estimate the cardiovascular risk of individuals and, subsequently, to recommend moderate or high-intensity statin treatment only, without any LDL cholesterol targets. The authors of the guideline speculate that the ‘LDL-target approach may result in under-treatment with evidence-based statin therapy or over-treatment with non-statin drugs that have not been shown to reduce atherosclerotic cardiovascular disease events in RCTs’. We aimed to test this hypothesis in a recently performed study to investigate the impact of multifactorial risk factor intervention in subjects with Type 2 diabetes without manifest cardiovascular disease on the progression of carotid atherosclerosis [2]. For the current analysis, we included 94 subjects with a mean age of 60 years and mean diabetes duration of 7.7 years. All subjects underwent treatment intensification according to current diabetes guidelines over a 3-month period, after which a mean LDL cholesterol of 1.9 1.0 mmol/l was achieved. Seventy-two subjects (79.1%) met the National Cholesterol Education Program/ Adult Treatment Panel III (NCEP/ATP III) [3] treatment target of an LDL cholesterol < 2.6 mmol/mol. Out of ninety-four subjects, 88 (93.6%) had an atherosclerotic cardiovascular disease (ASCVD) risk score of > 7.5% and, according to the new ACC/AHA cholesterol treatment guideline, they would have required high-intensity statin treatment. However, only two subjects (2.0%) out of these were on high-intensity statin therapy, while 58 subjects were on moderate-intensity statin therapy only and 34 subjects had no lipid-lowering medication, because they either did not tolerate a statin, refused treatment or met the treatment target without lipid-lowering medication (21 subjects) (Table 1). The percentage of subjects meeting the LDL cholesterol treatment target in our study was comparable with other multifactorial intervention trials, such as the STENO-2 or the MIND.IT study [4,5]. These data clearly show that, although four out of five participants in our study reached the LDL cholesterol treatment targets of < 2.6 mmol/l, only two out of 88 (2.3%) subjects in the high-risk group were adequately treated according to the new ACC/AHA guidelines. This analysis clearly confirms the expectation of the guideline committee that the LDL cholesterol target approach leads to an under treatment with high-intensity statin therapy, at least in this cohort of subjects with Type 2 diabetes.

Feasibility and safety of using an automated decision support system for insulin therapy in the treatment of steroid-induced hyperglycemia in patients with acute graft-versus-host disease: A randomized trial

Steroid‐induced hyperglycemia (SIHG) has shown to independently increase the risk for mortality in patients with acute graft‐versus‐host disease, and it is still unclear whether SIHG might be a modifiable risk factor. Therefore, a feasibility trial was carried out aiming to evaluate the performance of a standardized decision support system (GlucoTab [GT]) for insulin therapy in patients with SIHG. A total of 10 hyperglycemic acute graft‐versus‐host disease patients were included and treated either with GT or standard of care during hospitalization. Follow‐up duration was 6 months. Comparing the GT versus standard of care group, 364 versus 1,020 glucose readings were available during a median of 41 days (interquartile range [IQR] 22–89) and 101 days (IQR 55–147) of hospitalization. The median overall glucose levels were 151 mg/dL (123–192) versus 162 mg/dL (IQR 138–193) for GT and standard of care, respectively (P < 0.001); hypoglycemia rates were comparably low. Treatment of SIHG with an algorithm‐based system for subcutaneous insulin was feasible and safe.

l-Arginine and Cardiovascular Disease

Cardiovascular disease (CVD) encompasses a group of disorders of the heart and blood vessels, including coronary heart, cerebrovascular, peripheral artery disease, or deep vein thrombosis and pulmonary embolism (Definition of cardiovascular diseases. http://www.euro.who.int/en/health-topics/noncommunicable-diseases/cardiovascular-diseases/cardiovascular-diseases2/definition-of-cardiovascular-diseases. Accessed 30 Oct 2014). Although the mortality rates of CVD decreased substantially over the last decade, still almost a half of all deaths in Europe are attributable to CVD (Nichols et al. Eur Heart J 34:3017–3027, 2013).