Bioavailability of Orally Administered Drugs After Bariatric Surgery.

PURPOSE OF REVIEW: Oral drug absorption after bariatric surgery is likely to be altered, but the impact of different bariatric surgery procedures on individual drugs is not uniform. The aim of this article is to describe factors influencing the bioavailability of orally administered drugs after bariatric surgery and to provide readers with practical recommendations for drug dosing. We also discuss the medications that may be harmful after bariatric surgery. RECENT FINDINGS: The fundamental factors for enteral drug absorption are the production of gastric acid; the preserved length of the intestine, i.e., the size of the absorption surface and/or the preserved enterohepatic circulation; and the length of common loop where food and drugs are mixed with digestive enzymes and bile acids. Bypassing of metabolizing enzymes or efflux pumps and changes in intestinal motility can also play an important role. Significant changes of drug absorption early after the anatomic alteration may also be gradually ameliorated due to gradual intestinal adaptation. The most affected drugs are those with low or variable bioavailability and those undergoing enterohepatic circulation. Attention should also be paid to oral drug formulations, especially in the early postoperative period, when immediate-release and liquid formulations are preferred. The changes in oral bioavailability are especially clinically meaningful in patients treated with drugs possessing narrow therapeutic index (e.g., oral anticoagulants, levothyroxine, and anticonvulsants) or in acute conditions (e.g., anti-infectives); nevertheless, it may also influence the therapeutic value of chronic therapy (e.g., antidepressants. antihypertensives, antiplatelets, statins, PPIs, contraceptives, and analgesics); therapeutic effect of chronic therapy is further influenced by pharmacokinetic alterations resulting from weight loss. Therapeutic drug monitoring, periodical clinical evaluation, and adequate dose adjustments are necessary. Due to safety reasons, patients should avoid oral bisphosphonates, regular use of non-steroidal anti-inflammatory drugs, and, if possible, corticosteroids after bariatric surgery.

Correction: Bariatric surgery and exercise: A pilot study on postural stability in obese individuals.

[This corrects the article DOI: 10.1371/journal.pone.0262651.].

Significant differences between two commonly used bioimpedance methods in hemodialysis patients.

INTRODUCTION: Bioimpedance methods are currently used abundantly in patients on chronic hemodialysis. In this population, their most important role is to determine the level of fluid volume, respectively its intra- and extracellular components. There are several bioimpedance devices on the market. In this project, we compared two frequently used devices: Body Composition Monitor and InBody S10. MATERIALS AND METHODS: We invited patients on chronic hemodialysis who are being treated in our institution. Inclusion criteria were: clinically stable condition, lack of artificial joints, pacemakers, or other implanted metal objects. The examinations were performed just prior to hemodialysis by both methods 5 minutes apart. Patients were examined in the supine position after 15 minutes at rest to stabilize body fluids. Studied parameters were those that are obtainable by both methods: total body water (TBW) (L), extracellular water (ECW) (L) and intracellular water (ICW) (kg), lean tissue mass (LTM) (L), and fat tissue mass (kg). RESULTS: We included 14 participants (aged 64.4 ± 18.0 years). Statistically and clinically significant differences between data from compared devices were observed for all variables. Inbody S10 overestimated TBW by 2.58 ± 2.73 L and ICW by 4.56 ± 2.27 L in comparison to BCM. The highest difference (27%) was measured for LTM and ICW 22%. LTM, fat, and ECW were higher when measured by BCM (LTM by 8.54 ± 6.43 kg, p < 0.001; fat by 3.41 ± 4.22, p = 0.01; ECW by 2.01 ± 0.89 L, p < 0.001). CONCLUSION: The differences between tested devices were significant not only statistically, but also clinically. These two devices cannot be used interchangeably for dry weight setting of hemodialysis patients.

Hypermetabolism and Substrate Utilization Rates in Pheochromocytoma and Functional Paraganglioma.

The overproduction of catecholamines in pheochromocytoma/paraganglioma (PPGL) induces a hypermetabolic state. The aim of this study was to evaluate the incidence of a hypermetabolic state and differences in substrate metabolism in consecutive PPGL patients divided by catecholamine phenotype. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured in 108 consecutive PPGL patients and 70 controls by indirect calorimetry. Hypermetabolic state was defined according to the Mifflin St. Jeor Equation as a ratio above 110%. Hypermetabolic state was confirmed in 70% of PPGL patients, regardless of phenotype. Older age, prevalence of diabetes mellitus and arterial hypertension were correlated with hypermetabolic PPGL as compared to normometabolic form. Analysis according to overproduced catecholamine showed differences in VCO2 (p < 0.05) and RQ (p < 0.01) and thus different substate metabolism between phenotypes in hypermetabolic form of PPGL. Lipid utilization was higher in the adrenergic phenotype (p = 0.001) and positively associated with the percentage of REE ratio (R = 0.48, p < 0.001), whereas the noradrenergic phenotype preferentially oxidizes carbohydrates (P = 0.001) and is correlated with the percentage of REE ratio (R = 0.60, p < 0.001). Hypermetabolic state in PPGL is a common finding in both catecholamine phenotypes. Hypermetabolic PPGL patients are older and suffer more from diabetes mellitus and arterial hypertension. Under basal conditions, the noradrenergic type preferentially metabolizes carbohydrates, whereas the adrenergic phenotype preferentially metabolizes lipids.

Catheter ablation versus antiarrhythmic drugs with risk factor modification for treatment of atrial fibrillation: a protocol of a randomised controlled trial (PRAGUE-25 trial).

INTRODUCTION: Atrial fibrillation (AF), with a prevalence of 2%, is the most common cardiac arrhythmia. Catheter ablation (CA) has been documented to be superior to treatment by antiarrhythmic drugs (AADs) in terms of sinus rhythm maintenance. However, in obese patients, substantial weight loss was also associated with AF reduction. So far, no study has compared the modern non-invasive (AADs combined with risk factor modification (RFM)) approach with modern invasive (CA) treatment. The aim of the trial is to compare the efficacy of modern invasive (CA) and non-invasive (AADs with risk factor management) treatment of AF. METHODS AND ANALYSIS: The trial will be a prospective, multicentre, randomised non-inferiority trial. Patients with symptomatic AF and a body mass index >30 will be enrolled and randomised to the CA or RFM arm (RFM+AAD) in a 1:1 ratio. In the CA arm, pulmonary vein isolation (in combination with additional lesion sets in non-paroxysmal patients) will be performed. For patients in the RFM+AAD arm, the aim will be a 10% weight loss over 6-12 months, increased physical fitness and a reduction in alcohol consumption. The primary endpoint will be an episode of AF or regular atrial tachycardia lasting >30 s. The secondary endpoints include AF burden, clinical endpoints associated with AF reoccurrence, changes in the quality of life assessed using dedicated questionnaires, changes in cardiorespiratory fitness and metabolic endpoints. An AF freedom of 65% in the RFM+AAD and of 60% in the CA is expected; therefore, 202 patients will be enrolled to achieve the non-inferiority with 80% power, 5% one-sided alpha and a non-inferiority margin of 12%. ETHICS AND DISSEMINATION: The PRAGUE-25 trial will determine if modern non-invasive AF treatment strategies are non-inferior to CA. The study was approved by the Ethics Committee of the University Hospital Kralovske Vinohrady. Results of the study will be disseminated on scientific conferences and in peer-reviewed scientific journals. After the end of follow-up, data will be available upon request to principal investigator. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04011800).

Bariatric surgery and exercise: A pilot study on postural stability in obese individuals.

This study aimed to analyze the changes in postural stability of individuals with obesity after bariatric surgery, and the effect of three months of regular exercise on the static postural stability. Twenty-two subjects (7 females and 15 males) aged 31 to 68 years (Body mass index 35-55 kg.m-2) completed the study. Participants were divided into two groups: one group participated in an exercise program after the bariatric surgery (n = 10; age 48.9 ± 7.5 years; Body mass index 42 ± 5.6 kg.m-2) while the second group did not exercise at all after bariatric surgery (n = 12; age 44.7 ± 13.6 years, Body mass index 42.6 ± 6.0 kg.m-2). Static postural stability was measured using a Tekscan MobileMat pressure plate before and 4 months after the bariatric surgery. The exercise program included exercising three times a week including: one hour of strengthening, one hour of aerobic group exercise and at least one session of individual exercise at home. There were no significant differences in Center of force sway, Center of force ranges and average speed before and 4 months after bariatric surgery. Also, no effect of exercise was found. Post-pre differences of some parameters were negatively related to age (r from-0.46 to-0.72). Further studies are needed to explore this topic in depth.

Implementation of the DSM-5 and ICD-11 Dimensional Models of Maladaptive Personality Traits Into Pre-bariatric Assessment.

Background: Personality pathology does not have to be a contraindication to a bariatric surgery if a proper pre-surgical assessment is done. Indicating subgroups of patients with their specific needs could help tailor interventions and improve surgical treatment outcomes. Objectives: Using the Alternative DSM-5 model for personality disorders (AMPD) and the ICD-11 model for PDs to detect subgroups of patients with obesity based on a specific constellation of maladaptive personality traits and the level of overall personality impairment. Methods: 272 consecutively consented patients who underwent a standard pre-surgical psychological assessment. The majority were women (58.0%), age range was 22-79 years (M = 48.06, SD = 10.70). Patients' average body mass index (BMI) was 43.95 kg/m2. All participants were administered the Personality Inventory for DSM-5 (PID-5) from which Level of Personality Functioning Scale-Self Report (LPFS-SR) and Standardized Assessment of Severity of Personality Disorder (SASPD) scores were gained using the "crosswalk" for common metric for self-reported severity of personality disorder. The k-means clustering method was used to define specific subgroups of patients with obesity and replicated for equality testing to the samples of non-clinical respondents and psychiatric patients. Results: The cluster analysis detected specific groups in the sample of patients with obesity, which differed quantitatively from the samples of non-clinical respondents and psychiatric patients. A vast majority of patients with obesity showed above-average values in most of the PID-5 facets compared to the United States representative general community sample. In two out of the three clusters defined, patients demonstrated moderate (> M + 1.5 × SD) to severe (> M + 2.0 × SD) personality psychopathology within the Detachment and Negative Affectivity domains according to PID-5, which in one of the clusters corresponded to the mild overall impairment in both, LPFS-SR (M = 2.18, SD = 0.27) and SASPD (M = 8.44, SD = 2.38). Moreover, higher levels of psychopathology prove to be associated with higher age and use of psychiatric medication. Conclusions: The dimensional DSM-5 and ICD-11 trait models are suitable procedures for defining specific "characters" of patients in a pre-bariatric setting. As such, they help to identify subgroups of patients with obesity who are different from general population and psychiatric patients. Implications for clinical practice and further research are discussed.

Real-time CGM Is Superior to Flash Glucose Monitoring for Glucose Control in Type 1 Diabetes: The CORRIDA Randomized Controlled Trial.

OBJECTIVE: The aim of this trial was to compare the efficacy of real-time and intermittently scanned continuous glucose monitoring (rtCGM and isCGM, respectively) in maintaining optimal glycemic control. RESEARCH DESIGN AND METHODS: In this randomized study, adults with type 1 diabetes (T1D) and normal hypoglycemia awareness (Gold score <4) used rtCGM (Guardian Connect Mobile) or isCGM (FreeStyle Libre) during 4 days of physical activity (exercise phase) and in the subsequent 4 weeks at home (home phase). Primary end points were time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) and time in range (3.9-10.0 mmol/L [70-180 mg/dL]). The isCGM group wore an additional masked Enlite sensor (iPro2) for 6 days to check for bias between the different sensors used by the rtCGM and isCGM systems. RESULTS: Sixty adults with T1D (mean age 38 ± 13 years; A1C 62 ± 12 mmol/mol [7.8 ± 1.1%]) were randomized to rtCGM (n = 30) or isCGM (n = 30). All participants completed the study. Percentage of time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) was lower among rtCGM versus isCGM participants in the exercise phase (6.8 ± 5.5% vs. 11.4 ± 8.6%, respectively; P = 0.018) and during the home phase (5.3 ± 2.5% vs. 7.3 ± 4.4%, respectively; P = 0.035). Hypoglycemia differences were significant and most notable during the night. rtCGM participants spent more time in range (3.9-10 mmol/L [70-180 mg/dL]) than isCGM participants throughout both the exercise (78.5 ± 10.2% vs. 69.7 ± 16%, respectively; P = 0.0149) and home (75.6 ± 9.7% vs. 67.4 ± 17.8%, respectively; P = 0.0339) phases. The results were robust to the insignificant bias between rtCGM and isCGM sensors that masked CGM found in the isCGM arm. CONCLUSIONS: rtCGM was superior to isCGM in reducing hypoglycemia and improving time in range in adults with T1D with normal hypoglycemia awareness, demonstrating the value of rtCGM alarms during exercise and in daily diabetes self-management.

Physical activity in the treatment of obesity in practice.

Physical activity is an integral part of the obesity treatment. Curiously, even among health professionals, the evaluation of obesity treatment persists only based on weight loss. However, the treatment of obesity is not only a simple weight loss, but above all the treatment of associated diseases such as hypertension, diabetes, dyslipidemia, etc. Physical fitness is very rarely assessed, although it best predicts the future and reduces mortality from all causes. It is mainly a cardiovascular disease, where it is shown that the parameter VO2Max is the strongest predictor of not only cardiovascular mortality. The specifics of the prescription of physical activity bring with it the presence not only of diabetes, hypertension and cardiovascular diseases, but also osteoarthritis, possibly undergoing bariatric surgery. To objectify physical activity, including subjective symptoms, it is appropriate to use modern methods of telemedicine, which is the future in the treatment of not only obesity.

Glycemic Outcomes in Adults With T1D Are Impacted More by Continuous Glucose Monitoring Than by Insulin Delivery Method: 3 Years of Follow-Up From the COMISAIR Study.

OBJECTIVE: This study assessed the clinical impact of four treatment strategies in adults with type 1 diabetes (T1D): real-time continuous glucose monitoring (rtCGM) with multiple daily insulin injections (rtCGM+MDI), rtCGM with continuous subcutaneous insulin infusion (rtCGM+CSII), self-monitoring of blood glucose with MDI (SMBG+MDI), and SMBG with CSII (SMBG+CSII). RESEARCH DESIGN AND METHODS: This 3-year, nonrandomized, prospective, real-world, clinical trial followed 94 participants with T1D (rtCGM+MDI, n = 22; rtCGM+CSII, n = 26; SMBG+MDI, n = 21; SMBG+CSII, n = 25). The main end points were changes in A1C, time in range (70-180 mg/dL [3.9-10 mmol/L]), time below range (<70 mg/dL [<3.9 mmol/L]), glycemic variability, and incidence of hypoglycemia. RESULTS: At 3 years, the rtCGM groups (rtCGM+MDI and rtCGM+CSII) had significantly lower A1C (7.0% [53 mmol/mol], P = 0.0002, and 6.9% [52 mmol/mol], P < 0.0001, respectively), compared with the SMBG+CSII and SMBG+MDI groups (7.7% [61 mmol/mol], P = 0.3574, and 8.0% [64 mmol/mol], P = 1.000, respectively), with no significant difference between the rtCGM groups. Significant improvements in percentage of time in range were observed in the rtCGM subgroups (rtCGM+MDI, 48.7-69.0%, P < 0.0001; and rtCGM+CSII, 50.9-72.3%, P < 0.0001) and in the SMBG+CSII group (50.6-57.8%, P = 0.0114). Significant reductions in time below range were found only in the rtCGM subgroups (rtCGM+MDI, 9.4-5.5%, P = 0.0387; and rtCGM+CSII, 9.0-5.3%, P = 0.0235). Seven severe hypoglycemia episodes occurred: SMBG groups, n = 5; sensor-augmented insulin regimen groups, n = 2. CONCLUSIONS: rtCGM was superior to SMBG in reducing A1C, hypoglycemia, and other end points in individuals with T1D regardless of their insulin delivery method. rtCGM+MDI can be considered an equivalent but lower-cost alternative to sensor-augmented insulin pump therapy and superior to treatment with SMBG+MDI or SMBG+CSII therapy.

FGF21 Levels in Pheochromocytoma/Functional Paraganglioma.

Fibroblast growth factor 21 (FGF21) is a hepatokine with beneficial effects on metabolism. Our aim was to evaluate the relationship between the serum FGF21, and energy and glucose metabolism in 40 patients with pheochromocytoma/functional paraganglioma (PPGL), in comparison with 21 obese patients and 26 lean healthy controls. 27 patients with PPGL were examined one year after tumor removal. Basic anthropometric and biochemical measurements were done. Energy metabolism was measured by indirect calorimetry (Vmax-Encore 29N). FGF21 was measured by ELISA. FGF21 was higher in PPGL than in controls (174.2 (283) pg/mL vs. 107.9 (116) pg/mL; p < 0.001) and comparable with obese (174.2 (283) pg/mL vs. 160.4 (180); p = NS). After tumor removal, FGF21 decreased (176.4 (284) pg/mL vs. 131.3 (225) pg/mL; p < 0.001). Higher levels of FGF21 were expressed, particularly in patients with diabetes. FGF21 positively correlated in PPGL with age (p = 0.005), BMI (p = 0.028), glycemia (p = 0.002), and glycated hemoglobin (p = 0.014). In conclusion, long-term catecholamine overproduction in PPGL leads to the elevation in serum FGF21, especially in patients with secondary diabetes. FGF21 levels were comparable between obese and PPGL patients, despite different anthropometric indices. We did not find a relationship between FGF21 and hypermetabolism in PPGL. Tumor removal led to the normalization of FGF21 and the other metabolic abnormalities.

[Physical activity - the Holy Grail of modern medicine?] / Pohybová aktivita - svatý grál moderní medicíny?

Movement is the basic attribute of life. It is not surprising that the return to regular physical activity is a very effective and cheap means of preventing and treating most non-cummunicable diseases. Therefore, every physician should be able to prescribe a suitable physical activity. The minimum amount of physical activity with proven effects in primary prevention of chronic diseases is relatively low: 150 minutes of moderate physical activity or 75 minutes of high intensity exercise per week or a combination of the two. The simplest and safe way of physical activity is walking (at least 10 000 steps/day or 6 000 steps/day on top of daily activities). The FITT model is a more sophisticated way of prescribing physical activity that already requires a stress test. Patients at risk of atherosclerosis or with any manifestation of atherosclerosis (patients with coronary artery disease, post-stroke, peripheral artery disease) benefit from exercise as well as patients with chronic heart failure. Physical activity also helps patients with lung disease (COPD, asthma), metabolic diseases (diabetes mellitus, obesity, osteoporosis) and also rheumatologic diseases. Regular exercise improves cognitive function, reduces depression and anxiety, and helps addicted people. Recently, it has been shown that exercise also changes the gut microbiome. One of the mechanisms that contribute to the beneficial effect of exercise is so-called "exercise factors" - myokines. Physical activity, when properly prescribed, is an inexpensive and universal medication with minimal side effects. It is our "home pharmacy" we always have with us.Key words: cancer - cardiovascular diseases - neuropsychiatric diseases - physical activity - type 2 diabetes.

Cardiovascular fitness in narcolepsy is inversely related to sleepiness and the number of cataplexy episodes.

OBJECTIVE: Cardiopulmonary fitness depends on daily energy expenditure or the amount of daily exercise. Patients with narcolepsy spent more time being sleepy or asleep than controls; thus we may speculate that they have a lower quantity and quality of physical activity. The aim of the present study was thus to test the hypothesis that exercise tolerance in narcolepsy negatively depends on sleepiness. PATIENTS AND METHODS: The cross-sectional study included 32 patients with narcolepsy with cataplexy, 10 patients with narcolepsy without cataplexy, and 36 age- and gender-matched control subjects, in whom a symptom-limited exercise stress test with expired gas analysis was performed. A linear regression analysis with multivariate models was used with stepwise variable selection. RESULTS: In narcolepsy patients, maximal oxygen uptake (VO2peak) was 30.1 ± 7.5 mL/kg/min, which was lower than 36.0 ± 7.8 mL/kg/min, p = 0.001, in controls and corresponded to 86.4% ± 20.0% of the population norm (VO2peak%) and to a standard deviation (VO2peakSD) of -1.08 ± 1.63 mL/kg/min of the population norm. VO2peak depended primarily on gender (p = 0.007) and on sleepiness (p = 0.046). VO2peak% depended on sleepiness (p = 0.028) and on age (p = 0.039). VO2peakSD depended on the number of cataplexy episodes per month (p = 0.015) and on age (p = 0.030). CONCLUSIONS: Cardiopulmonary fitness in narcolepsy and in narcolepsy without cataplexy is inversely related to the degree of sleepiness and cataplexy episode frequency.

"A Vegetarian vs. Conventional Hypocaloric Diet: The Effect on Physical Fitness in Response to Aerobic Exercise in Patients with Type 2 Diabetes." A Parallel Randomized Study.

It has been shown that it is possible to modify macronutrient oxidation, physical fitness and resting energy expenditure (REE) by changes in diet composition. Furthermore, mitochondrial oxidation can be significantly increased by a diet with a low glycemic index. The purpose of our trial was to compare the effects of a vegetarian (V) and conventional diet (C) with the same caloric restriction (-500 kcal/day) on physical fitness and REE after 12 weeks of diet plus aerobic exercise in 74 patients with type 2 diabetes (T2D). An open, parallel, randomized study design was used. All meals were provided for the whole study duration. An individualized exercise program was prescribed to the participants and was conducted under supervision. Physical fitness was measured by spiroergometry and indirect calorimetry was performed at the start and after 12 weeks Repeated-measures ANOVA (Analysis of variance) models with between-subject (group) and within-subject (time) factors and interactions were used for evaluation of the relationships between continuous variables and factors. Maximal oxygen consumption (VO2max) increased by 12% in vegetarian group (V) (F = 13.1, p < 0.001, partial η² = 0.171), whereas no significant change was observed in C (F = 0.7, p = 0.667; group × time F = 9.3, p = 0.004, partial η² = 0.209). Maximal performance (Watt max) increased by 21% in V (F = 8.3, p < 0.001, partial η² = 0.192), whereas it did not change in C (F = 1.0, p = 0.334; group × time F = 4.2, p = 0.048, partial η² = 0.116). Our results indicate that V leads more effectively to improvement in physical fitness than C after aerobic exercise program.

Comparison of Different Treatment Modalities for Type 1 Diabetes, Including Sensor-Augmented Insulin Regimens, in 52 Weeks of Follow-Up: A COMISAIR Study.

OBJECTIVE: To compare different treatment modalities for patients with type 1 diabetes (T1D) based on real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG) combined with multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS: Sixty-five T1D patients were followed up for a year. Of these, 27 started RT-CGM as part of a sensor-augmented insulin regimen (SAIR); within this SAIR group, 15 subjects started sensor-augmented pump (SAP) therapy and the remaining 12 continued with MDIs (MDIs + RT-CGM). A second group of 20 patients initiated CSII without RT-CGM, while a third group of 18 subjects continued on MDIs and SMBG. The main endpoints were reduction of HbA1c, glycemic variability (GV), and incidence of hypoglycemia. RESULTS: After a year, the baseline mean HbA1c in the SAIR group (8.3%) decreased to 7.1% (P < 0.0001); both SAIR subgroups, SAP and MDIs + RT-CGM, showed comparable improvement. The CSII group also had reduced HbA1c (8.4% ± 0.9% vs. 7.9% ± 0.7%; P < 0.05). Both SAIRs were superior to MDIs (P = 0.002) and CSII (P = 0.0032). GV was also lowered, both in the SAIR (P < 0.0001) and CSII (P < 0.05) groups. Reduced incidence of hypoglycemia was observed only with SAIR (8% ± 4% vs. 6% ± 3%; P < 0.01). CONCLUSION: Both SAIRs, SAP and MDIs + RT-CGM, provided significant and comparable decrease of HbA1c with concurrent reduction of hypoglycemia. This improvement was greater than that seen with CSII. The combination of RT-CGM and MDIs can be a suitable alternative to SAP for some patients.

Urine Levels of Phthalate Metabolites and Bisphenol A in Relation to Main Metabolic Syndrome Components: Dyslipidemia, Hypertension and Type 2 Diabetes. A Pilot Study.

AIM: Human exposure to organic pollutants (some of them also called endocrine disruptors) can be associated with adverse metabolic health outcomes including type 2 diabetes. The goal of this study was to compare the urine levels of bisphenol A and phthalate metabolites in subgroups of patients with metabolic syndrome composed of patients with and without three important components of metabolic syndrome (hypertension, dyslipidemia and diabetes). METHODS: We have investigated 24 hr urine samples of 168 patients with metabolic syndrome from the Metabolic Outpatient Department of General University Hospital in Prague. Using standard metabolic syndrome criteria, we classified patients as dyslipidemic (n=87), hypertensive (n=96), and type 2 diabetic (n=58). Bisphenol A and 15 metabolites of phthalates were evaluated in relation to creatinine excretion. Samples were analysed with enzymatic cleavage of glucuronide using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in one laboratory with external quality control. RESULTS: Four metabolites, mono-n-butyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-(2-ethyl-5-carboxypentyl) phthalate showed significantly higher levels in diabetic compared to non-diabetic patients (p<0.001, p=0.002, p=0.002, and p=0.005, respectively). The differences remained significant after adjustment to hypertension, dyslipidemia, age, and BMI. No difference was found between either the hypertensive and non-hypertensive or dyslipidemic and non-dyslipidemic patients. There was no significant relation of bisphenol A level to diabetes, hypertension, dyslipidemia, age, and BMI. CONCLUSIONS: Urine levels of four phthalate metabolites were significantly higher in type 2 diabetics independently on specified predictors. Phthalate levels can be in relation to beta cell dysfunction in type 2 diabetic patients but this study is not able to show if the relation is causal.

No difference in hypertension prevalence in smokers, former smokers and non-smokers after adjusting for body mass index and age: a cross-sectional study from the Czech Republic, 2010.

BACKGROUND: Several hypotheses suggest a temporary increase in blood pressure following smoking cessation. This may be the result of endocrine changes (e.g. alteration in adrenocorticotropic hormone and cortisol levels in post-cessation period) and/or post-cessation weight gain. Our aim was to identify factors that may be associated with the diagnosis of hypertension after quitting smoking. METHODS: In 2010, we conducted a cross-sectional survey in a sample of 2065 Czech adults, chosen by quota selection and representative according to age, gender, education, region of residence and the size of settlement, aged 18 to 94 years. We examined the association between age, gender, body mass index, smoking status, and education with the hypertension diagnosis in their personal history. Data were compiled and weighed by age categories. Statistical significance was measured by Pearson Chi-square test at the level of significance 95 %. RESULTS: Diagnosis of hypertension was reported in 461 (22 %) subjects, with no difference by gender. Based on univariate analysis, former smokers were more likely than non-smokers to be diagnosed for hypertension (OR 1.450 (1.110-1.900), p = 0.006). However, after adjusting for body mass index and age, the occurrence of hypertension diagnosis did not differ among non-smokers, smokers and former smokers (OR 0.760 for smokers, p = 0.082 and OR 1.020 for former smokers, p = 0.915). CONCLUSION: We did not find any differences in hypertension diagnosis prevalence according to smoking status.

Isoelectric Focusing of Serum Apolipoprotein C-III as a Sensitive Screening Method for the Detection of O-glycosylation Disturbances.

Apolipoprotein C-III (ApoC-III) is a glycoprotein carrying the most common O-linked glycan structure and is abundantly present in serum, what renders it a suitable marker for analysis of O-glycosylation abnormalities. Isoelectric focusing followed by a Western blot of ApoC-III, using PhastSystem™ Electrophoresis System (GE Healthcare), was introduced as a rather simple and rapid method for screening of certain subtypes of inherited glycosylation disorders. The study's aim was to establish this method in our laboratory, what included performing the analysis in a group of 170 healthy individuals to set the reference range of detected relative amounts of sialylated ApoC-III isoforms and to evaluate the gender- and age-dependent differences. A significant relative increase of asialo-ApoC-III with growing age was found. Secondly, we examined serum from patients with selected metabolic disorders and detected minor O-glycosylation changes in diseases such as Prader-Willi syndrome, PGM1 (phosphoglucomutase 1) or MAN1B (class 1B alpha-1,2-mannosidase) deficiency. Our results show that this method allows for a sensitive detection of ApoC-III O-glycosylation status, however this might be modulated by several factors (i.e. nutrition, medication) whose exact role remains to be determined.

[Physical activity in patients with microvascular complications of diabetes]. / Pohybová aktivita u pacientu s mikrovaskulárními komplikacemi diabetu.

Physical activity is often underestimated and little used in the treatment of diabetes. The fear of damage, especially in patients with diabetes complications is one of the reasons why it occurs. Physical activity plays an important role in prevention of the progression of peripheral neuropathy and its impact is primarily on the development of muscle strength and the ability to replace the function of nerve fibers damaged disabilities. Demonstrable effect on neuropathy is already recorded a few weeks of regular exercise, long-term programs then demonstrate the safety of occurrence of ulcers in compliance with basic foot care. Present autonomic neuropathy cannot predict response to cardiac respectively, heart rate and blood pressure. Due to other risks (silent ischemia, arrhythmia etc.), it is appropriate to stress test before a prescription of exercise programs. Monitoring of blood pressure, heart rate and blood glucose during the first hours of physical activity is necessary. In patients with autonomic neuropathy of the gastrointestinal tract may significantly affect the composition of the diet not only the ability of physical activity, but can also affect hypoglycaemia due to a slow carbohydrate absorption in these patients. Another risk in patients with autonomic neuropathy is orthostatic hypotension, which may potentiate antihypertensive drugs in "white coat" hypertension. Prescription of patients with retinopathy depends on the form and degree of retinopathy. Only proliferative retinopathy can significantly reduce exercise prescription, and it is always necessary to consult with ophthalmologist. In patients with nephropathy is an important stage of renal insufficiency for prescription of physical activity. Prescription is then influenced by the degree of renal insufficiency in addition to the presence of other associated diseases (anemia, hypertension, osteopathy etc.). Physical activity is essential in patients on dialysis respectively. After renal transplantation as maintaining peripheral muscle and its functions not only improves the prognosis, but also improves the quality of life and self-sufficiency is maintained.

[Perspective of obesity pharmacotherapy]. / Perspektivy farmakoterapie obezity.

Obesity is a very common disease with very difficult treatment. Most patients are not able to change their behaviour. Most hopeful for the future is a safe pharmacotherapy which could be widely used. In this review, old and potentially new drugs decreasing weight are mentioned (centrally acting anorectics, orlistat, incretine analogues and gliphlozines). Review of newly in U.S.A used antiobesitics is also mentioned. Finally potentially new principles of obesity pharmacotherapy are enumerated.