Effect of Laparoscopic Sleeve Gastrectomy on Serum Adipokine Levels.

Bariatric procedures are considered to be the most effective treatment options for obesity. One of them is laparoscopic sleeve gastrectomy (LSG), which is nowadays very popular and widely used. LSG leads to weight loss and metabolic improvement and also changes adipokine levels, although it is just a restrictive operation. We describe changes in pro-inflammatory (leptin, resistin, visfatin and chemerin) and anti-inflammatory adipokines (adiponectin, omentin), with adiponectin and leptin being most studied. Their levels are markedly changed after LSG and this may partially explain the weight loss seen after LSG. Adipokines are closely connected to insulin resistance and chronic inflammation both being positively influenced after LSG. Leptin regulates amount of body fat, appetite, thermogenesis and metabolic rate and its levels are positively correlated with both weight and BMI changes after operation. Resistin influences insulin sensitivity, modulates body cholesterol trafficking and its changes after operation correlate with BMI, waist circumference, fat mass, LDL cholesterol and C-reactive protein. Chemerin, an important component of immune system, decreases after bariatric surgery and its levels correlate with BMI, triglyceride levels, and blood glucose. On the other hand, pro-inflammatory adipokine adiponectin, which influences fatty acid oxidation, browning of fat tissue and energy metabolism, is declining after LSG. This decline explains improvement of glucose status after bariatric surgery in patients with diabetes and is correlated with BMI loss, waist circumference and LDL cholesterol level. Effect of LSG goes beyond calory restriction and the changes of adipokines have a great impact on health status of the bariatric patients.

Erratum for: Pregnancy lipid profile and different lipid patterns of gestational diabetes treated by diet itself.

List of changes Authors and affiliation: Lubica CIBICKOVA1,3, Katerina LANGOVA2, Jan SCHOVANEK1,3, Dominika MACAKOVA1,3, Ondrej KRYSTYNIK1,3, David KARASEK1,3 1Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic, 2Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic, 3Department of Internal Medicine III - Nephrology, Rheumatology and Endocrinology, University Hospital Olomouc, Olomouc, Czech Republic Acknowledgement: Supported by the grants: MH CZ - DRO (FNOl, 00098892); AZV NV18-01-00139.

Pregnancy lipid profile and different lipid patterns of gestational diabetes treated by diet itself.

The development of gestational diabetes mellitus (GDM) affects lipid metabolism during pregnancy. However, the magnitude of changes in lipid parameters is unclear. In addition, the patterns of these changes may vary based on the criteria selected for making the diagnosis of GDM. Thus, our aim was to compare the anthropometric and laboratory profiles of GDM-associated vs. GDM-free gestation with those of healthy non-pregnant women. We designed a cross-sectional study involving a group of females affected by GDM, a group of healthy pregnant controls and a group of healthy non-pregnant counterparts. GDM patients were divided into 3 subgroups according to the fulfilled diagnostic criteria, that is, those presenting with high fasting plasma glucose in the first trimester (subgroup 1), high fasting plasma glucose in the second trimester (subgroup 2) and high plasma glucose following oral glucose load in the second trimester (subgroup 3). The anthropometric and metabolic profiles of GDM subjects resembled the facets of metabolic syndrome (highest body mass index, waist circumference, C-peptide level, triglycerides) significantly more than the respective profiles of healthy non-pregnant women (p<0.0001). While total cholesterol (TC) (together with LDL-C and non-HDL-C) in pregnant women with GDM and without GDM did not differ, both groups had significantly higher levels of triglycerides (TG) than non-pregnant women (p<0.0001). Subgroup 1 had the highest fasting glucose level in the second trimester whereas subgroup 3 had the lowest fasting glucose level (p=0.019). Concentration of TG increased, being the lowest in subgroup 1 and the highest in subgroup 3 (p=0.006). Women with GDM had more pronounced features of metabolic syndrome than pregnant women without GDM. Both groups reached higher levels of TC (LDL-C, non-HDL-C) than non-pregnant controls and did not differ from each other. We found differences in TG and fasting glucose levels among different types of GDM.

Associations Between Homeostasis Model Assessment (HOMA) and Routinely Examined Parameters in Individuals With Metabolic Syndrome.

The aim of the study was to investigate whether routine clinical parameters, including visceral adiposity index (VAI) and atherogenic index of plasma (AIP), could become widely applicable predictors of insulin resistance (IR), evaluated using homeostasis model assessment (HOMA-IR, HOMA-ß), with regard to presence of metabolic syndrome (MS). The study comprised 188 individuals identified to meet the MS criteria during regular health examinations and an equal number of age, sex-matched controls without MS. The strongest correlations were noted between HOMA-IR and waist circumference (WC) in the MS group (r=0.57) as well as between HOMA-IR and alanine aminotransferase (ALT, r=0.57) or aspartate aminotransferase (r=0.56) in the controls, with a statistical significance of p<0.001. In a multivariate linear regression model, the predictors of HOMA-IR were WC (linear coefficient ß=0.1, p<0.001), ALT (ß=2.28, p<0.001) and systolic blood pressure (ß=0.04, p<0.001). HOMA-ß was determined by WC (ß=1.97, p=0.032) and ALT (ß=99.49, p=0.004) and inversely associated with age (ß=-1.31, p=0.004). Neither VAI nor AIP were significant predictors. The presence of MS was significantly associated with both HOMA-IR and HOMA-ß. These results indicate that WC and ALT appear to be reliable predictors of IR. Comprehensive assessment of these parameters may serve for estimating the level of IR.

Superior Role of Waist Circumference to Body-Mass Index in the Prediction of Cardiometabolic Risk in Dyslipidemic Patients.

Coronary risk evaluation by conventional factors (age, gender, smoking, blood pressure and cholesterol) may further be specified by facets of the metabolic syndrome, namely insulin resistance, hypertriglyceridemia and obesity. Although obesity is usually defined as elevated body mass index (BMI), recent data indicate a superior role of waist circumference or hypertri-glyceridemic waist (HTGW) over BMI in the assessment of cardiometabolic risk. In dyslipidemic patients, the specific contributions of risky waist, HTGW or BMI have not been evaluated as yet. 686 dyslipidemic subjects (322 males and 364 females) were enrolled into a cross-sectional study. In each subject basic antropometry (i.e. waist circumference, HTGW, BMI) and laboratory parameters of lipid profile and insulin resistance were determined. Cardiometabolic risk was given by fulfilling the criteria (harmonized definition) of metabolic syndrome. The significance of risky waist, HTGW and BMI were assessed by comparing the respective predictive values for the presence of metabolic syndrome. Dyslipidemic patients with risky waist, HTGW or high BMI have a more atherogenic lipid profile and higher insulin resistance compared to those without risky waist, HTGW or high BMI. Risky waist is stronger predictor of metabolic syndrome (PPV 66 %, NPV 90 %) and thus posesa greater cardiometabolic risk than higher BMI per se does (PPV 42 %, NPV 97 %). The contribution of triglycerides (i.e. HTGW) to these predictive values is marginal (PPV 66 %, NPV 92 %). The present results highlight the superior role of waist circumference as a screening tool over BMI for the evaluation of cardiometabolic risk in dyslipidemic subjects. HTGW brings little additional benefit in risk stratification. Lower BMI proved to be optimal for identifying the subjects with inferior risk.

Association of pigment epithelium derived factor with von Willebrand factor and plasminogen activator inhibitor 1 in patients with type 2 diabetes.

To compare circulating pigment epithelium derived factor (PEDF) levels in type 2 diabetes patients (T2D) with and without metabolic syndrome (MetS+/-) to healthy controls and assess PEDF association with plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF) as markers of endothelial dysfunction. Fifty T2D individuals and forty healthy controls were included. PEDF, PAI-1, vWF, anthropological parameters, lipids, and markers of insulin resistance were investigated in all subjects. Compared to controls only MetS+ diabetics had higher PEDF levels [14.2 (10.2-16.0) mg/l vs. 11.1 (8.6-14.4) mg/l; p<0.05]. PEDF significantly correlated: positively with body mass index (rho=0.25), smoking (rho=0.21), C-reactive protein (rho=0.22), triglycerides (rho=0.38), non-HDL-cholesterol (rho=0.39), apolipoprotein B (rho=0.38), fasting glucose (rho=0.22), glycated hemoglobin (rho=0.24), C-peptide (rho=0.28), insulin (rho=0.26); and negatively with HDL-cholesterol (rho=-0.42) and apolipoprotein A1 (rho=-0.27). Independent association of PEDF with vWF in T2DMetS- subjects was found. Significantly elevated PEDF in T2DMet+ patients and its association with adverse metabolic profile confirmed PEDF as a marker of insulin resistance. Negative independent association of PEDF with vWF in T2DMetS- patients may reveal its angio-protective role.

Inverse association of lipoprotein (a) with markers of insulin resistance in dyslipidemic subjects.

Lipoprotein (a) [Lp(a)] is an LDL-like particle that contains an apolipoprotein B100 molecule covalently bound to a plasminogen-like glycoprotein, apolipoprotein (a) [apo(a)]. Epidemiological evidence supports a direct and causal association between Lp(a) levels and coronary risk. On the contrary, a few prospective findings demonstrate inverse association of Lp(a) levels with risk of type 2 diabetes (T2DM). The aim of our study was to evaluate the association of Lp(a) with indicators of insulin resistance (IR) and metabolic syndrome (MS), which precede development of T2DM. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women, mean age 45.6+/-14.0 years) into our cross-sectional study. Lp(a) concentrations correlated inversely with TG, AIP, insulin, HOMA, C-peptide, BMI, waist circumference, and number of MS components (p<0.01 for all). Subjects with MS had significantly lower Lp(a) concentrations in comparison with those without the presence of this phenotype (p<0.0001). Serum concentrations of Lp(a) in the lower (1(th)-3(rd)) quartiles of insulin and HOMA were significantly higher than in the 4(th) quartile of these insulin resistance markers (p<0.001). Odds ratios of having increased markers of IR (TG, HOMA) and MS in top quartile of Lp(a) also indicate inverse association of Lp(a) with IR. The results of our study support an inverse association of Lp(a) levels with IR and MS that precedes overt T2DM diagnosis.

Correlation of uric acid levels and parameters of metabolic syndrome.

Hyperuricemia has been described as associated with the risk of development metabolic syndrome; however the relationship between the uric acid level and particular parameters of metabolic syndrome remained unclear. We performed a cross-sectional study on a cohort of 833 dyslipidemic patients and correlated their levels of uric acid with parameters of insulin resistance, lipid metabolism, C-reactive protein, anthropometric parameters. We also defined patients with hypertriglyceridemic waist phenotype and compered their uric acid levels with those without this phenotype. We found that levels of uric acid are associated with parameters of metabolic syndrome. Specifically, dyslipidemia characteristic for metabolic syndrome (low HDL-cholesterol and high triglycerides) correlates better with uric acid levels than parameters of insulin resistance. Also waist circumference correlates better with uric acid levels than body mass index. Patients with hypertriglyceridemic waist phenotype had higher levels of uric acid when compared with patients without this phenotype. Serum uric acid levels are even in low levels linearly correlated with parameters of metabolic syndrome (better with typical lipid characteristics than with parameters of insulin resistance) and could be associated with higher cardiovascular risk.

Correlation of lipid parameters and markers of insulin resistance: does smoking make a difference?

Insulin resistance associated with dyslipidemia enhances cardiovascular risk. Several atherogenic indexes have been suggested to give more precise information about the risk. The aim of our study was to estimate, which atherogenic index correlates better with parameters of insulin resistance. Furthermore, we compared the parameters of lipid metabolism and insulin resistance between smokers and non-smokers. In our cross-sectional study we enrolled 729 patients with dyslipidemia which were divided into two groups - non-smokers (586) and smokers (143). We measured lipid profile, parameters of insulin resistance (fasting glycemia, insulin, HOMA-IR, C-peptide, proinsulin) and calculated atherogenic indexes - atherogenic index of plasma (log (TAG/HDL-C), AIP), ApoB/ApoA1 index and nonHDL-C. AIP was found out to show stronger correlations with parameters of insulin resistance (p<0.001, correlation coefficients ranging between 0.457 and 0.243) than other indexes (ApoB/ApoA1 or nonHDL cholesterol). AIP correlated with parameters of insulin resistance both in smokers and non-smokers, but after adjustment (for age, body mass index, waist circumference) persisting only in non-smokers. Smokers had a wider waist circumference and a proatherogenic lipid profile. Smoking increases the risk of developing metabolic syndrome. AIP can be used in daily praxis for predicting insulin resistance in patients with dyslipidemia, predominantly in non-smokers.

[Hypergastrinaemia without detection of gastrinoma]. / Hypergastrinemie bez detekce gastrinomu.

We present a case-report of a woman with persisting gastric ulcers, who had elevated gastrin blood levels. First of all, a rare cause of hypergastrinaemia was excluded - a gastrinoma. It was not found despite of extensive investigation. Ulcers were repetitively biopted and transition of high grade dysplasia to adenocarcinoma was detected. Gastrin levels normalised after surgical antrectomia. Afterwards pernicious anaemia was diagnosed as the underlining cause of hypergastrinaemia.

Statins and their influence on brain cholesterol.

BACKGROUND: Growing evidence suggests that different statins are able to lower brain cholesterol synthesis. It is not clear yet whether lipophilic statins influence brain cholesterol in different way than hydrophilic ones. SOURCES OF MATERIAL: The MEDLINE database. FINDINGS: According to the data reported thus far, statins may influence brain cholesterol metabolism directly (because they are able to penetrate BBB no matter whether they are hydrophilic or lipophilic) and also indirectly (by lowering plasma cholesterol). Although the definite mechanism is not known yet, it becomes obvious that statins do not only influence peripheral but also central cholesterol pool. CONCLUSION: Better understanding of the effects of statins on brain metabolism becomes more important because many studies bring evidence of a possible link between cholesterol and neurodegeneration.

The manifestation of systemic vasculitis in the central nervous system--a case report.

We present a case of a patient with systemic vasculitis suffering--besides heart, skin and gastrointestinal lesions--from the rarely reported involvement of the central nervous system. Even though the diagnosis could not be ascertained precisely, immunosuppressive therapy led to prompt regression of symptoms including initially present neurologic manifestations.

[Central hemiparesis as manifestation of systemic vasculitis]. / Centrální pravostranná hemiparéza jako dominující projev systémové vaskulitidy.

We present a case report of patient with systemic vasculitis with affection of heart, skin, gastrointestinal tract and rare involvement of central nervous system. Diagnosis of systemic vasculitis was based on clinical manifestations, blood hypereosinophilia and brain magnetic resonance imaging. Immunosuppressive therapy led to regression of symptoms including initially present neurologic manifestation.

Alendronate lowers cholesterol synthesis in the central nervous system of rats - a preliminary study.

Nitrogen-containing bisphosphonates were found to inhibit farnesyl diphosphate synthase - an essential enzyme in the cholesterol biosynthesis pathway, but their effect on cholesterol synthesis per se in the central nervous system (CNS) remains unknown. The aim of the present study was to examine possible influence of a representative agent alendronate on cholesterol synthesis rates in selected parts of rat CNS and on plasma cholesterol level. Two groups of rats were orally administered either alendronate (3 mg/kg b.w.) or vehicle for 9 days. At the end of experiment, brain (basal ganglia, frontal cortex and hippocampus) and spinal cord were isolated and cholesterol synthesis was determined using the technique of deuterium incorporation from deuterated water. In the alendronate group significant reductions of cholesterol synthesis rates were detected in frontal cortex, hippocampus and spinal cord (p<0.001). However, the experimental treatment did not produce a significant alteration in the levels of plasma cholesterol. In conclusion, this study brings the first experimental evidence of the inhibition of cholesterol biosynthesis with alendronate in central nervous system.

Cholesterol synthesis in central nervous system of rat is affected by simvastatin as well as by atorvastatin.

OBJECTIVE: There is evidence to suppose that cholesterol-lowering drugs such as statins might confer protection against dementia, probably via modulation of cholesterol synthesis in the brain. The aim of the present study was to investigate possible influence of two lipophilic statins (simvastatin and atorvastatin) on cholesterol synthesis in selected parts of rat central nervous system (CNS). METHODS: Three groups of rats were orally treated with simvastatin (10 mg/kg b.wt.), atorvastatin (10 mg/kg b.wt.) or vehicle (aqua) for 9 days. At the end of experiment, brains (for basal ganglia, frontal cortex and hippocampus) and spinal cord were isolated and cholesterol synthesis was determined using the incorporation of deuterium from deuterated water. ANOVA with Fisher's LSD Multiple-Comparison Test and Kruskal-Wallis test were applied for statistical evaluation. P < 0.05 was considered statistically significant. RESULTS: Significant reductions of cholesterol synthesis rate were detected in both experimental groups (vs. controls) in all studied localisations. Both drugs elicited comparable effects on cholesterol synthesis rate irrespective of the examined tissue. CONCLUSIONS: This study brings additional evidence of the role of statins in the CNS cholesterol synthesis. The finding that both statins were able to lower braincholesterol synthesis without altering plasma cholesterol supports the idea of their local action inthe brain. For comparison of the effects of statins in the spinal cord and selected parts of brain, the deuterium technique was utilised for the first time.

[Cognitive dysfunction in patients with systemic lupus erythemathosus with or without antiphospholipid antibodies]. / Kognitivní dysfunkce u pacientu se systémovým lupus erythematodes a antifosfolipidovými protilátkami.

INTRODUCTION: Impairment of cognitive functions is one of the neuropsychiatric symptoms of systemic lupus erythemathosus (SLE), the association of which with secondary antiphospholipid syndrome is often mentioned in the literature on the subject. Ethiology has not yet been fully clarified. PATIENTS AND METHODS: The aim of the study was to compare the "mini-mental state examination" (MMSE) outcomes in SLE patients with and without antiphospholipid antibodies (APA). RESULTS: Probands producing APA presented with significantly worse results in MMSE when compared to patients without these antibodies. There was no difference between patients with antisphospholipid syndrome and those with APA only. DISCUSSION AND CONCLUSION: Our study supports the notion that association of SLE with APA (not only with antiphospholipid syndrome) aggravates the deterioration of cognitive functions. MMSE test should not be omitted in the follow-up of SLE patients.

Cerebral toxoplasmosis in an allogeneic peripheral stem cell transplant recipient: case report and review of literature.

We present a patient who underwent allogeneic peripheral stem cell transplantation (PSCT) for chronic myelocytic leukemia. Twenty months after the PSCT he experienced status epilepticus. Magnetic resonance imaging (MRI) revealed a focus in the ventral thalamus-hypothalamus region. Using stereotactic biopsy with histology and specific polymerase chain reaction investigation from brain tissue, cerebral toxoplasmosis was diagnosed and treated with antiparasitic therapy. Early recognition of such serious and potentially lethal disease enabled prompt specific treatment. This case report emphasizes the role of stereotactic biopsy in diagnosis of cerebral toxoplasmosis. Other methods such as MRI are non-invasive but not sufficiently specific and sensitive.

Differential effects of statins and alendronate on cholinesterases in serum and brain of rats.

Acetylcholinesterase (AChE) inhibitors represent standard treatment of Alzheimer's disease. Cholesterol plays an important role in Alzheimer's disease development. Because cholesterol synthesis may be inhibited by statins or bisphosphonates, we hypothesized that these drugs might possibly have an influence on cholinesterases. Moreover, we also evaluated if the cholesterol-lowering agents that cross the blood-brain barrier (e.g. simvastatin) should be more effective than those which do not (e.g. atorvastatin). Four groups of rats were orally administered simvastatin, atorvastatin, alendronate or vehicle for seven days. Thereafter, blood samples were taken and the basal ganglia, septum, frontal cortex, and hippocampus were isolated from brains for measurement of acetylcholinesterase activity. In the blood, activities of neither acetyl- nor butyrylcholinesterase were influenced by any of the applied drugs. In the brain, no significant changes in AChE activity were observed after administration of atorvastatin. Both simvastatin and alendronate significantly suppressed the activity of AChE in the frontal cortex. In conclusion, our results confirmed the hypothesis that cholesterol-modifying drugs modulate AChE activity and it is more reasonable to use a blood-brain barrier penetrating drug.

[Use of sucrose permeability test (SaLM) for detection of lesions of upper gastrointestinal tract mucosa in upper dyspepsia patients--a pilot study]. / Vyuzití testu propustnosti pro sacharózu (SaLM) v detekci postizení sliznic horní cásti trávicí trubice u pacientu s horním dyspeptickým syndromem--pilotní studie.

INTRODUCTION: Endoscopy, a golden standard with its high diagnostic value, is an invasive and unpleasant method as far as patients are concerned. So far there has been no available non-invasive test in the Czech Republic capable of distinguishing between heavy (i.e. peptic ulcer) and light (i.e. portal gastropathy) lesions of upper gastrointestinal mucosa. AIMS: In this pilot study we decided to test our modification of sucrose permeability test (SaLM test) on upper dyspepsia patients in our conditions. We first needed to compare the results of intestinal permeability obtained from the studied test (containing sucrose, a so called SaLM test) with a formerly established intestinal permeability test (containing glucose, a so called LaMa test) to know, if the new test could replace the old one. Then we wanted to find normal values of sucrose permeability, find a relationship between sucrose permeability and endoscopically verified damage to upper gastrointestinal mucosa and calculate sensitivity and specificity of SaLM test using results of gastroduodenoscopy. After that we tried to suggest possible future benefits of the test for clinical praxis. MATERIALS AND METHODS: A group of 10 young healthy volunteers underwent both SaLM and LaMa tests, which were made methodically indentical to compare the tests as to the results of intestinal permeability. The probands ingested SaLM solution with the following composition: sucrose (25.0 g), lactulose (10.0 g), mannitol (2.0 g), xylose (2.0 g) and water (up to 100 ml). Urine was collected for five hours and the samples were analysed using gas chromatography. From the results normal value of sucrose permeability was calculated, too. After that, 28 patients with upper dyspepsia were included in the study. They were divided into two groups (a group of light lesions with 9 patients and a group of heavy lesions counting 19 patients) according to gastroscopical findings. We compared the results among the three groups. RESULTS: In our volunteers, the intestinal permeability values using LaMa and SaLM tests showed normal distributions. No statistically significant difference (p < 0.05) was found between the tests in regard to the intestinal permeability. The normal value of sucrose permeability was found to be up to 0.10% of the amount taken orally. The permeability for sucrose was significantly higher (p < 0.01) in patients with heavy lesions (0.527 +/- 0.414) versus those with light ones (0.178 +/- 0.090). Moreover, the latter had their sucrose permeability values significantly higher than healthy volunteers (0.088 +/- 0.067), (p < 0.05). Sensitivity and specificity of the test for heavy upper gastrointestinal mucosal damage was 0.95 and 0.33, respectively. CONCLUSION: SaLM test could replace LaMa test without having a significant effect on the intestinal permeability results. It is feasible to study SaLM test on bigger sets of patients and specify it in more detail, since the results of our pilot study (in accordance with many other studies) make it promising for various clinical applications (i.e. in upper dyspepsia patients it might help in deciding about urgency and reasonability of gastroduodenoscopy).