Levels of retinol and retinoic acid in pancreatic cancer, type-2 diabetes and chronic pancreatitis.

AIMS: Retinoids participate in multiple key processes in the human body e.g., vision, cell differentiation and embryonic development. There is growing evidence of the relationship between retinol, its active metabolite- all-trans retinoic acid (ATRA) - and several pancreatic disorders. Although low levels of ATRA in pancreatic ductal adenocarcinoma (PDAC) tissue have been reported, data on serum levels of ATRA in PDAC is still limited. The aim of our work was to determine serum concentrations of retinol and ATRA in patients with PDAC, type-2 diabetes mellitus (T2DM), chronic pancreatitis (CHP) and healthy controls. METHODS: High performance liquid chromatography with UV detection (HPLC) was used to measure serum levels of retinol and ATRA in 246 patients with different stages of PDAC, T2DM, CHP and healthy controls. RESULTS: We found a significant decrease in the retinol concentration in PDAC (0.44+/-0.18 mg/L) compared to T2DM (0.65+/-0.19 mg/L, P<0.001), CHP (0.60+/-0.18 mg/L, P< 0.001) and healthy controls (0.61+/-0.15 mg/L, P<0.001), significant decrease of ATRA levels in PDAC (1.14+/-0.49 ug/L) compared to T2DM (1.37+/-0.56 ug/L, P<0.001) and healthy controls(1.43+/-0.55 ug/L, P<0.001). Differences between early stages (I+II) of PDAC and non-carcinoma groups were not significant. We describe correlations between retinol, prealbumin and transferrin, and correlation of ATRA and IGFBP-2. CONCLUSION: Significant decrease in retinol and ATRA levels in PDAC compared to T2DM, healthy individuals and/or CHP supports existing evidence of the role of retinoids in PDAC. However, neither ATRA nor retinol are suitable for detection of early PDAC. Correlation of ATRA levels and IGFBP-2 provides new information about a possible IGF and retinol relationship.

Changes in the level of health literacy in Czechia between 2015 and 2020.

During the five years from 2015 to 2020, the proportion of people with limited health literacy decreased by 12%. This finding results from international research on the level of health literacy, which took place since 2019 till 2021 in 17 countries of the European region of the World Health Organization. In total, more than 42,000 respondents were interviewed, in Czechia there were 1,650 respondents. In 2020, however, we recorded a limited level of health literacy in 47% of the population over the age of 18. Respondents have the greatest problems with understanding health information from the media and with assessing different treatment options. Czechs (like Slovaks) have the biggest problem with following the instructions of a doctor or pharmacist. Health literacy is influenced by gender, age and education: women, older people and less educated people show higher levels of health literacy. The respondent's social gradient, primarily subjective social status has positive influence to health literacy while financial deprivation has negative influence. On the other hand, health literacy positively affects the physical activity of the respondent; subjectively perceived health and consumption of medical services are influenced as well. The Czech Health Literacy Institute is currently preparing monitoring in 2024-2025.

Professor Josef Charvát and Informatics.

Professor Josef Charvát, a prominent internist and endocrinologist, has been following the issues of cybernetics and computers from the very beginning. In the difficult times of the 1950s, he was heavily involved in the organization of seminars and meetings of workers in technical and medical fields interested in cybernetics. Later, in his books for the general public, he foresaw a significant application of computers in medicine. His predictions are quite accurate even 50 years after the publication of these ideas.

Novel biochemical markers for non-invasive detection of pancreatic cancer.

To identify non-invasive biomarkers of non-metastatic pancreatic cancer (PC), the blood from 186 patients (PC n=28; DM-diabetes mellitus n=60; ChP-chronic pancreatitis n=47; healthy controls n=51) was analyzed for 58 candidate biomarkers. Their effectiveness to identify PC was compared with CA19-9. Panel defined by Random-forest (RF) analysis (CA19-9, AAT, IGFBP2, albumin, ALP, Reg3A, HSP27) outperforms CA19-9 in discrimination of PC from DM (AUC 0.92 vs. 0.82). Panel (S100A11, CA72-4, AAT, CA19-9, CB, MMP-7, S100P-s, Reg3A) is better in discrimination PC from ChP than CA19-9 (AUC 0.90 vs. 0.75). Panel (MMP-7, Reg3A, sICAM1, OPG, CB, ferritin) is better in discrimination PC from healthy controls than CA19-9 (AUC 0.89 vs. 0.78). Panel (CA19-9, S100P-pl, AAT, albumin, adiponectin, IGF-1, MMP7, S100A11) identifies PC among other groups better than CA19-9 (AUC 0.91 vs. 0.80). Panel defined by logistic regression analysis (prealbumin, IGFBP-2, DJ-1, MIC-1, CA72-4) discriminates PC from DM worse than CA19-9 (AUC 0.80 vs. 0.82). Panel (IGF-1, S100A11, Reg1alfa) outperforms CA19-9 in discrimination PC from ChP (AUC 0.76 vs. 0.75). Panel (IGF-2, S100A11, Reg3A) outperforms CA19-9 in discrimination PC from healthy controls (AUC 0.95 vs. 0.78). Panel (albumin, AAT, S100P-serum, CRP, CA19-9, TFF1, MMP-7) outperforms CA19-9 in identification PC among other groups (AUC 0.89 vs. 0.8). The combination of biomarkers identifies PC better than CA19-9 in most cases. S100A11, Reg3A, DJ-1 were to our knowledge identified for the first time as possible serum biomarkers of PC.

Optimizing clinical approaches to COVID-19 patients in primary care.

There is insufficient evidence from medical studies for clinical approaches to patients with COVID-19 in primary care. Patients often urge the therapeutic use and preventive administration of various medicines, often controlled by studies insufficiently or completely unverified. The aim of the project, commissioned by the Committee of the Society of General Practice of the Czech Medical Association JEP, was to compensate for this deficiency by interdisciplinary consensus and thus provide general practitioners (GPs) with a basic support in accessing patients with COVID-19. Representatives of GPs identified the most common questionable diagnostic or therapeutic approaches and formulated 17 theses, taking into account their own experience, existing Czech and foreign professional recommendations. The RAND/UCLA Appropriateness Method, modified for the needs of pandemic situation, was chosen to seek consensus. Representatives of 7 medical specialties accepted the participation in the 20-member panel. The panel evaluated in 2 rounds, with the comments and opinions of others available to all panelists before the second round. The outcome of the evaluation was agreement on 10 theses addressing the administration of vitamin D, inhaled corticosteroids in patients with COPD and bronchial asthma, acetylsalicylic acid, indications for D-dimer levels examination, preventive administration of LMWH, importance of pulse oximetry, indication for emergency services, indication for antibiotics and rules for distant contact. The panel disagreed on 6 theses recommending the administration of ivermectin, isoprinosine, colchicine and corticosteroids in patients with COVID-19 in primary care. One thesis, taking into account the use of D-dimers in primary care was evaluated as uncertain. The most discussed theses, on which there was also no agreement, were outpatient administration of corticosteroids and the importance of elevation of D-dimers levels or their dynamic increase in a symptomatic patient with COVID-19 as an indication for referral to hospital. The results of the consensus identified topics that need to be further discussed and on which it is appropriate to focus further research.

Obesity and cardiovascular disease.

Obesity with no comorbidities probably carries no cardiovascular risk, and the so-called obesity paradox even comes into play, wherein obesity may improve the prognosis of cardiovascular disease. Cardiovascular complications primarily occur indirectly due to metabolic comorbidities of obesity. However, a thrombogenic potential of obesity has also been established. A very important question in contemporary obesitology is whether antidiabetics currently administered in obese non-diabetic individuals will have a positive cardiovascular effect similar to that in diabetics. Myokines, muscle tissue hormones, certainly have a protective effect on the cardiovascular system. Also of importance is the research into epicardial and pericardial fat. Its investigation and management will aid in finding additional options of diagnosing and treating cardiovascular disease.

Contemporary state and perspectives of obesity pharmacotherapy.

The history of obesity pharmacotherapy is controversial. Many drugs are not used more due to severe side effects. Today we have four effective antiobesity drugs. The effect of some of them is comparable with bariatric sugary. Weight loss induced by bariatric surgery is culminating in the first year. The effect of incretine analogues is progressive in several years and culminating later. There are many antiobesity drugs in development. Both centrally or peripherally acting new drugs will be available soon. Even targeted therapy using antibodies will be used in obesitology soon.

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.

Current views on metabolic syndrome.

The theory of metabolic syndrome originated 30 years ago. Several definitions try to explain the frequent common incidence of the risk factors for atherosclerosis. At first the syndrome of insulin resistance was involved. It was only later that the relation of the metabolic syndrome was described to what is known as systemic inflammation arising in adipose tissue and inflammatory diseases such as chronic bronchitis or psoriasis, or to degenerative diseases such as Alzheimers disease. The views on the metabolic syndrome are thus constantly changing. Key words: adipose tissue inflammation - definition of metabolic syndrome - insulin resistance - myokines - systemic inflammation.

A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss.

OBJECTIVE: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity. METHODS: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥  27 and ≤ 40 kg/m2 and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss. RESULTS: Gelesis100 treatment caused greater weight loss over placebo (6.4% vs. 4.4%, P = 0.0007), achieving 2.1% superiority but not 3% super-superiority. Importantly, 59% of Gelesis100-treated patients achieved weight loss of ≥ 5%, and 27% achieved ≥ 10% versus 42% and 15% in the placebo group, respectively. Gelesis100-treated patients had twice the odds of achieving ≥ 5% and ≥ 10% weight loss versus placebo (adjusted OR: 2.0, P = 0.0008; OR: 2.1, P = 0.0107, respectively), with 5% responders having a mean weight loss of 10.2%. Patients with prediabetes or drug-naive type 2 diabetes had six times the odds of achieving ≥ 10% weight loss. Gelesis100 treatment had no apparent increased safety risks. CONCLUSIONS: Gelesis100 is a promising new nonsystemic therapy for overweight and obesity with a highly desirable safety and tolerability profile.

[Treatment strategy of type 2 diabetes used in Czech Republic after metformin therapy failure]. / Strategie lécby diabetu 2. typu pri selhání lécby metforminem pouzívané ceskými lékari nebo v Ceské republice.

INTRODUCTION: Type 2 diabetes is an enormous medical problem caused by increasing prevalence of the disease and increasing prevalence of severe chronic complications of diabetes. New ADA/EASD guidelines and also Czech diabetes society guidelines enable effective individual approach to the patient. Goal of the therapy is optimal compensation of diabetes and prevention of acute and chronic complications of diabetes and decrease of mortality. Diabetes therapy is started by education in diet a regime combined with metformin. According to the progressive character of the disease it is usually necessary to intensify the therapy by adding antidiabetics from other groups. AIM: This study was proposed to analyse the use of therapy algorithm in Czech Republic in patients with insufficient metformin therapy. Secondary objectives were to describe level of compensation of diabetes in time and level of components of the metabolic syndrome in different treatment combinations.Methodic and results: In the sample of 1 516 patients, frequency of use of antidiabetic medication after metformin it was gliflozins 33% and gliptins 28% in the first phase of the study and the number increased later during the study. Median of HbA1c in the beginning of the study was 65 mmol/mol, greatest decrease was found in patents using combination of incretine analogs with metformin - 89 % of them had the HbA1c level < 60 mmol/mol. CONCLUSION: The study showed also that antidiabetic drugs used after metformin in Czech Republic are very effective in reducing weight, and improving blood pressure and lipid profile. Therapy using combination of metformin with gliflozins, gliptins or incretin analogs is most effective when metformin is not effective enough.Key words: diabetes type 2 - gliflozins - gliptins - incretine analogs - metformin therapy failure.

Phthalates exposure indicators determined by urinary phthalate metabolites in healthy non-obese Czech adults: FANTOM study.

It is assumed that human exposure to phthalates may be associated with adverse health effects. The indicators of urinary phthalate metabolite concentrations in healthy adults are limited. In this study, the phthalate metabolites concentrations were detected from 24-h urine collection in non-obese Czech adults (n = 201). Each participant filled in an 80-item questionnaire (FANTOM-SQ 2013) regarding the outdoor and indoor sources of phthalates, the use of personal care products and food intake sources. The concentrations of 15 phthalates metabolites were analysed following enzymatic cleavage of the glucuronide using ultra-high-performance liquid chromatography-electrospray ionisation tandem mass spectrometry (UHPLC-ESI-MS/MS). The indicators of chronic or acute exposure phthalate-containing materials were identified. It is shown that higher fruit consumption was positively and significantly associated with a higher level of total 15 urinary phthalates biomarkers (p < 0.001). Regular meat consumption showed a negative significant association with total 15 phthalates metabolites (p < 0.01). The use of personal care products was significantly and positively correlated with monoethyl phthalate urine concentrations (p < 0.05). The analysis of the dietary behaviour and personal care products use in the Czech non-obese population showed it to be a predictable tool in the level of phthalates exposure when high fruit consumption and personal care products use are linked to higher phthalate metabolite contents in the urine. However, this topic deserves more research.

[Alternative healing methods around us]. / Alternativní lécebné metody kolem nás.

This article gives information on selected alternative medicine methods (AMM) under conditions of the Czech health care system. They can be defined as contemporaneous diagnostic and therapeutic methods which differ in their theoretical fundaments as well as practices from the evidence based medicine. This definition is controversial because these methods are an intrinsically incompatible aggregate of modalities acting as a placebo above all. We can encounter many "therapeutic" and "examination" methods which are practiced namely by healers without formal medical education, and connected closely with esotericism. A general feature of the alternative methods is a void usage of scientific concepts and theories, e.g. the concept of energy.Motivations of patients and doctors are briefly introduced here. However, AMM is also an ethical problem because the doctor should help the patient with maximum efficiency hence excluding the methods with a questionable, small or negligible efficiency. The opinions how to find the way out from this situation are divergent. It could be a refusal or a very reserved attitude to AMM plus maximisation of the placebo effect enhancing the efficiency of a rational therapy. Furthermore, the methods most spread in the Czech Republic are subjected to elementary critics - the homoeopathy, acupuncture, the so-called "bioresonance" instrumental methods, psychic healing, and also some refused methods in cancer treatment. In our opinion medicine disposes of sufficient knowledge and experience to assess the efficiency of AMM and refuse them in causal therapy, eventually. Their use as a placebo should be carefully considered.Key words: alternative medicine, placebo, homeopathy, acupuncture.

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.

[Potential sources of phthalates and bisphenol A and their significance in the development of metabolic diseases]. / Potenciální zdroje ftalátu a bisfenolu A a jejich význam u metabolických onemocnení.

Nowadays, there is increasing evidence showing that the development of the metabolic syndrome combining obesity, type 2 diabetes mellitus, arterial hypertension and dyslipidemia involves except of traditional risk factors (overnutrition, lack of physical activity, genetic predisposition) also the effect of environmental organic substances called organic pollutants or endocrine disruptors. These chemicals can be found in plastic covers, paints, flame retardants, exhaust gases, fertilizers as well as diverse daily utensils. Phthalates, used primarily as plasticizers, and bisphenol A, are among the most wide-spread members of this group.The aim of this article is to provide a basic overview of the relationship between phthalates and bisphenol A and the etiopathogenesis of the metabolic syndrome and to highlight their potential sources. According to the analysis of materials used for parenteral nutrition and urinary excretion of phthalate metabolites and bisphenol A in subjects on long-term parenteral nutrition we suppose that currently used medical materials are safe with respect to the exposure to both phthalates and bisphenol A and that home environment, especially cosmetic products, might constitute a more probable source of these substances.

[A diet suitable for patients with dyslipidemia and metabolic syndrome]. / Dieta pri dyslipidemii a metabolickém syndromu.

Atherosclerosis or cardiovascular disease is the leading cause of mortality and morbidity in developed countries. Intervention of its risk factors is pharmacological but non-pharmacological intervention must be its integral part. Dietary recommendations for dyslipidemia are long known however it is necessary to emphasize the importance of their compliance. Presently, these recommendations for adult population to prevent from atherosclerosis are based on healthy nourishment, especially to have sufficient consumption of fish, fresh vegetable and fruit and to avoid consumption of secondary processed meat especially, i.e. smoked meat. Nowadays, there is a diverting trend from recommendation to strictly avoid cholesterol in the diet.Key works: atherosclerosis - cholesterol - diet intervention - dyslipidemia - fatty acids.

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.