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Background Hyperglycaemia was shown to be among the features of severe acute COVID-19 infection both in the acute and convalescence period. Mechanisms contributing to its development and/or maintenance in a post-COVID phase are still unclear. Materials and Methods Survivors of severe COVID-19 but without a known history of diabetes were examined at baseline (T0) and after 3 (T3) and 6 (T6) months: indirect calorimetry and OGTT. Insulin response and sensitivity (IS) were expressed as insulinogenic (IGI), disposition (DI), and Matsuda insulin sensitivity index (ISI), respectively. Resting energy expenditure (REE) was calculated using the Weir and Harris-Benedict equation and substrate preference using the respiratory quotient (RQ) and nitrogen losses. Results Thirty-two patients (12 women) were available for the analyses at T0 and 26 at T6. Baseline examination was within 21±6.5 days after COVID-19 diagnosis. Patients were hypermetabolic at baseline (30.7 ± 4.3 kcal/kg lean mass/day, ~120% predicted values) but REE declined over the 6 months (ΔT6-T0 mean difference (95% CI): -5.4 (-6.8, -4.1) kcal/kg lean mass/day, pH=3.07 ± 1.18, ISIN=3.23 ± 1.72, p=0.66), whereas insulin response was lower in the H group only (DIH=3.19 ± 2.16 vs DIN=8.78 ± 6.37, p=0.005). Over the 6 months, IS improved in the H group (ΔT6-T0 mean difference for ISI (95% CI): 1.84 (0.45, 3.24), p=0.01)), whereas IGI and DI did not improve in either group. Conclusions Severe COVID-19 infection was associated with hypermetabolism that did not persist over the follow-up. Patients were insulin resistant in the acute phase, but only those with insufficient insulin response developed hyperglycaemia. Insufficient beta cell response was a possible mechanism leading to hyperglycaemia.

Aims/Hypothesis: Beta-cell failure plays a fundamental role in type 2 diabetes mellitus (T2DM) development. It has been shown that the beta-cells are among the most sensitive to hypoxia. We aimed to analyze whether decrease in pancreatic perfusion relates to 1/decline in beta-cell function and 2/visceral fat accumulation in patients with T2DM. Methods: Fifteen women with T2DM on metformin therapy alone and fifteen women of comparable age and BMI without prediabetes/diabetes were cross-sectionally examined: clinical and anthropometric examination, fast sampled intravenous glucose tolerance test (FSIVGTT), dynamic contrast-enhanced magnetic resonance imaging to assess pancreatic perfusion (area under the curve of postcontrast saturation, AUCTSIC), and visceral adiposity (VAT, calculated from transverse sections at the level L2–L5 vertebrae). Results: Pancreatic blood perfusion (AUCTSIC) did not differ between groups (p = 0.273), but it negatively correlated with BMI (r = −0.434, p = 0.017), WHR (r = −0.411, p = 0.024), and VAT (r = −0.436, p = 0.016) in both groups. Moreover, AUCTSIC in the head of the pancreas negatively correlated with the level of fasting glycemia (r = −0.401, p = 0.028) and HOMA-IR (r = −0.376, p = 0.041). Discussion/Conclusion: We showed that decreased pancreatic perfusion did not relate to beta-cell dysfunction in early stages of T2DM development, but it was related to VAT, insulin resistance, and higher fasting glycemia. Furthermore, lower pancreatic perfusion was related to VAT, insulin resistance, and higher fasting glycemia.

Background Testing for autoantibodies against the zinc transporter ZnT8 (ZnTA) is becoming routine in pediatric diabetes. However, available data are inconclusive when focusing on adult-onset diabetes, including autoimmune diabetes, which does not require insulin at diagnosis (LADA). Basic procedures We examined the ZnTA prevalence and titers and matched them with the clinical phenotype and PTPN22 genotypes of Czech LADA patients who were positive for GADA and/or IA2A and had a fasting C-peptide level >200 pmol/L at diagnosis as well as HNF4A-, GCK- or HNF1A-MODY patients and healthy controls. Main findings Most LADA patients were negative for ZnTA, and the sensitivity of the assay was only 18–20% for patients with LADA-like progression to insulinotherapy compared to healthy controls. In LADA patients, there was no association between the ZnTA and PTPN22 risk genotypes. LADA patients positive for ZnTA had a lower BMI than those positive for other autoantibodies alone. Importantly, MODY patients were completely negative for ZnTA, and the levels of ZnTA in MODY patients were similar to those in healthy controls. Conclusions ZnTA quantification did not improve LADA diagnosis. However, positivity for ZnTA can be used as a negative MODY pre-diagnostic criterion even in the region of Central and East Europe, where other islet cell autoantibodies are common in MODY patients.

Objective: The aim of the study is to assess the risk of malnutrition among institutionalized elderly individuals in North Bohemia and compare it to the risk of malnutrition in the capital city of Prague, Czech Republic. In the Czech Republic, very few studies have been conducted with the goal of describing and evaluating the nutritional status of the institutionalized elderly. Methods: In this study, data was collected from 254 elderly individuals (aged ≥ 65) residing in retirement homes in North Bohemia and then compared with similar data for the elderly living in retirement homes in Prague (the data from Prague were previously published in 2013). The data included an Mini-Nutritional Assessment (MNA) test; anthropometric measurements - Body Mass Index (BMI), waist circumference, triceps skinfold thickness; and biochemical parameters - albumin, prealbumin, transferrin, urea, and creatinine. Results: Mean BMI values were 27.4 kg/m2 for females and 26.3 kg/m2 for males. According to the MNA questionnaire, 10.4% of all tested elderly were malnourished and 50.8% were at risk of malnutrition; lager proportion of females were found to be malnourished than males. Biochemical indicators supported the MNA results. MNA categories correlated positively with independence (r = 0.56; p < 0.001), mental status (r = 0.54; p < 0.001), mobility (r = 0.46; p < 0.001), calf circumference (r = 0.42; p < 0.001), BMI, and the ability to self-feed (both r = 0.37; p < 0.001). The percentage of institutionalized elderly with malnutrition living in North Bohemia and Prague were about the same; however, the percentage of those at risk of malnutrition was higher in North Bohemia (p = 0.006). Conclusion: Study results confirmed that the institutionalized elderly face issues that lower their nutritional status and put them at increased risk; clearly these issues need urgent attention.

As not much is known about the prevalence and predictors of nutritional deficiencies among vegans in the Czech Republic, we evaluated whether supplement use and duration of adherence to the vegan diet are associated with the risk of cobalamin and iron deficiencies. Associations between self-reported supplementation and duration of vegan diet with biomarkers of cobalamin (serum cobalamin, holotranscobalamin, homocysteine, folate) and iron status (serum ferritin, iron binding capacity, transferrin and saturation of transferrin) were assessed by cross-sectional analyses of medical data from a clinical nutrition center. Data from 151 (72 females) adult vegans (age 18–67 years), who were free of major chronic diseases and 85 (40 females) healthy non-vegans (age 21–47 years) were analyzed. Overall, vegans had significantly lower cobalamin, hemoglobin and ferritin levels, but higher folate and MCV values compared to non-vegans. Vegans not using cobalamin supplements were at higher risk of low plasma cobalamin than regularly supplementing vegans (OR: 4.41, 95% CI 1.2–16.16 for cobalamin, OR: 19.18, 95% CI 1.02–359.42 for holotranscobalamin), whereas no significant differences in cobalamin status related to duration of the vegan diet were observed. Regularly supplementing vegans had similar levels of cobalamin/holotranscobalamin as non-vegans. Despite lower ferritin and hemoglobin levels, there was no indication of a higher risk of iron-deficiency among vegans. To conclude cobalamin deficiency risk depends on supplementation status and not on the duration of an exclusive vegan diet, which underlines the need to integrate cobalamin status monitoring and counselling on supplement use in routine clinical care in the Czech Republic.

Background/Aims: Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Methods: Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Results: Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p < 0.0001). Oral and IV BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p < 0.0001) and GIP response (p < 0.0001) compared with the IV or placebo. Glucose levels declined significantly (p < 0.001) in the same pattern during both BCAA tests with no change in the placebo group. Conclusions: An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent.

Non-alcoholic fatty liver disease and its complications are frequent causes of liver-related morbidity and mortality. Incretin glucagon-like peptide-1 (GLP-1) affects liver functions and metabolism. Although GLP-1 analogues are widely used in clinical practice, information regarding their potential toxic effect on hepatocytes in vitro is missing. Therefore, we evaluated the effect of GLP-1 analogue liraglutide on activity of caspases 3/7, cell viability and oxidative stress in primary cultures of hepatocytes. Primary cultures isolated from male Wistar rats fed a standard (ST1-group, 10% energy from fat) or a high-fat diet (HF-group, 71% fat) for 10 weeks were incubated with liraglutide (0.1-1000 nmol/l) for 24 h. Activities of caspases 3/7 and cellular dehydrogenases (WST-1), lactate dehydrogenase (LDH) leakage and oxidative stress (malondialdehyde concentration and DCFDA assay) were evaluated. HF-groups vs. ST1-groups showed higher caspases activity, LDH leakage and MDA production (p < 0.001) and lower cellular dehydrogenases activity (p < 0.01). Liraglutide induced a dose-dependent decrease of caspases activity in both groups, reduction of oxidative stress in HF-animals and exerted no negative effects on other parameters. In conclusion, GLP-1 analogue liraglutide decreased activity of caspases 3/7, reduced ROS production and didn't exhibit negative effects on cell viability and oxidative stress in primary cultures of hepatocytes isolated from lean and steatotic livers.

Background: The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid tyrosine phosphatase (LYP), which is expressed primarily in lymphoid tissues. The functional but geographically highly variable PTPN22 single-nucleotide polymorphisms (SNPs), particularly c.1858C>T, contribute to the onset and progression of autoimmunity-associated diseases and facilitate the expression of disease-associated autoantibodies. In Central Europe, 17-25% of patients with monogenic diabetes (maturity-onset diabetes of the young, MODY) transiently express islet cell autoantibodies. Methods: We addressed the links between the functional and geographically variable PTPN22 SNPs with MODY manifestation and the expression of islet cell autoantibodies in 276 MODY patients who originated from four regions (the Czech Republic, Israel, Japan and Brazil). Results: The frequency of PTPN22 polymorphisms in the MODY patients was similar to those in geographically matched healthy populations, with the exception of c.788G>A, the minor allele frequency of which was significantly elevated in the Czech hepatocyte nuclear factor 1-α (HNF1A) MODY patients [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.2-10.7] and the Brazilian MODY patients (OR 8.4, 95% CI 1.8-39.1). A barely significant increase in the c.788G>A minor allele was also detected in the islet cell autoantibody-positive Czech MODY patients. However, c.788A behaves as a loss-of-function mutant in T cells, and thus protects against autoimmunity. Conclusions: MODY patients (including islet cell autoantibody-positive cases) do not display any increase in autoimmunity-associated PTPN22 alleles. The absence of autoimmunity-associated PTPN22 alleles was also demonstrated in latent autoimmune diabetes in adults, which suggests that the slow kinetics of the onset of autoantibodies is subject to a regulation that is different from that experienced in type 1 diabetes and other autoimmune disorders.

Objectives Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells. Design In vitro study on human skeletal muscle cells. Settings University research laboratories. Subjects Patients undergoing hip surgery and healthy volunteers. Interventions Vastus lateralis biopsies were processed to obtain cultured myotubes, which were exposed to a range of 1-10 μg/mL propofol for 96 hours. Measurements and main results Extracellular flux analysis was used to measure global mitochondrial functional indices, glycolysis, fatty acid oxidation, and the functional capacities of individual complexes of electron transfer chain. In addition, we used [1-C]palmitate to measure fatty acid oxidation and spectrophotometry to assess activities of individual electron transfer chain complexes II-IV. Although cell survival and basal oxygen consumption rate were only affected by 10 μg/mL of propofol, concentrations as low as 1 μg/mL reduced spare electron transfer chain capacity. Uncoupling effects of propofol were mild, and not dependent on concentration. There was no inhibition of any respiratory complexes with low dose propofol, but we found a profound inhibition of fatty acid oxidation. Addition of extra fatty acids into the media counteracted the propofol effects on electron transfer chain, suggesting inhibition of fatty acid oxidation as the causative mechanism of reduced spare electron transfer chain capacity. Whether these metabolic in vitro changes are observable in other organs and at the whole-body level remains to be investigated. Conclusions Concentrations of propofol seen in plasma of sedated patients in ICU cause a significant inhibition of fatty acid oxidation in human skeletal muscle cells and reduce spare capacity of electron transfer chain in mitochondria.

Our study compared total C-peptide secretion after administration of whey proteins and whey proteins in combination with glucose with results of classical tests assessing beta cell function in the pancreas of healthy individuals. Eight young, healthy (7 males, 1 female; aged 20-26 years), non-obese (BMI: 17-25.9 kg/m2) participants with normal glucose tolerance underwent six C-peptide secretion tests. Three secretion tests measured C-peptide response to orally administered substances: whey proteins only (OWT), whey proteins with glucose (OWGT) and glucose only (OGTT); while three secretion tests measured C-peptide response to intravenously administered substances: arginine (AST), glucagon (GST) and glucose (IVGTT). OWT stimulated a greater (93 %, p

It was recently suggested that routine islet cell autoantibody testing should be performed to discriminate maturity-onset diabetes of the young (MODY) from type 1 diabetes mellitus (T1DM). This is the first report ever to describe the familial manifestation of T1DM autoimmunity in nonobese HNF1A-MODY subjects and the presence of islet antigen-2 (IA-2) antibodies in MODY subjects. Three nonobese subjects in an age range of 14-35 years were diagnosed with HNF1A-MODY (p. Arg159Gln mutation). All the tested subjects had detectable (but varying) levels of islet cell autoantibodies (i.e., antibodies against glutamate decarboxylase or IA-2) in the absence of other T1DM characteristics. They displayed long-term expression of intermediate fasting C-peptide levels, ketoacidosis was absent even in periods of spontaneous insulin withdrawal, and full dependence on externally administered insulin was not detected in any of them although better glycemic control was achieved when insulin was supplemented. The course of the disease was similar to that of the autoantibody-negative HNF1A-MODY subjects. The case questions the selectivity of autoantibodies as a marker of T1DM or late-onset autoimmune diabetes of adulthood (LADA) over MODY and challenges the use of autoantibodies as a universal negative marker of MODY in an effort to decrease the cost of health care, as it may eventually lead to the wrong diagnosis and thus to the incorrect treatment. Further research should involve examination of the autoantibody titers and prevalence in large and geographically diverse cohorts of MODY subjects selected for genetic testing (regardless of their autoantibody titers) as well as determination of the islet cell autoantibody kinetics in the course of MODY onset and progression.

Recently, thousands of papers brought knowledge about effects of nutrients on cellular level, in experimental animals and in human experiments on one side, the results of epidemiological studies on the other side have suggested the nutrients and foods for healthy diet and nutrients and foods, which should be consumed only in limited amount. Among foods, which should be avoided, those with higher content of trans-fatty acids. Their daily intake should not exceed 1 % of total energy intake. Similar should be limited saturated fatty acid, added sugar and salt. On the contrary, the intake of monounsaturated and polyunsaturated fatty acids in foods should be basic part of fat intake. In these conditions the amount of consumed fat could create up to 35 % of all daily energy intake. Beneficial carbohydrates are those with low glycemic index, i.e. whole grain and brown rice products and legumes. The intake of salt is necessary to limit fewer than 6 g per day and alcohol intake should not exceed 10 g per day in women and 20 g per day in men. The recommendation in last years do not limit cholesterol daily intake. The food of animal origin with high content of saturated fatty acids, i.e. meat and milk products parallel contains also cholesterol. On the other hand, the oils of vegetable origin mostly from tropical oils, which contents high amount of saturated fatty acids represents the risk? On the contrary eggs and shellfish contents high amount of cholesterol and very low amounts of saturated fatty acids. Therefore, there is no reason for their strict limitation in the diet.carbohydrate - diabetes - dietary recommendation - energy intake - fat - healthy diet - iron - cholesterol - protein.

Branched chain amino acids (BCAA) are among nutrients strongly linked with insulin sensitivity (IS) measures. We investigated the effects of a chronic increase of BCAA intake on IS in two groups of healthy subjects differing in their basal consumption of BCAA, that is, vegans and omnivores. Eight vegans and eight matched omnivores (five men and three women in each group) received 15 g (women) or 20 g (men) of BCAA daily for 3 months. Anthropometry, blood analyses, glucose clamp, arginine test, subcutaneous abdominal adipose tissue (AT) and skeletal muscle (SM) biopsies (mRNA levels of selected metabolic markers, respiratory chain (RC) activity) were performed at baseline, after the intervention and after a 6 month wash-out period. Compared with omnivores, vegans had higher IS at baseline (GIR, glucose infusion rate: 9.6±2.4 vs 7.1±2.4 mg/kg/min, 95% CI for difference: 0.55 to 5.82) that declined after the intervention and returned to baseline values after the wash-out period (changes in GIR with 95% CI, 3–0 months: −1.64 [−2.5; −0.75] and 9-3 months: 1.65 [0.75; 2.54] mg/kg/min). No such change was observed in omnivores. In omnivores the intervention led to an increased expression of lipogenic genes (DGAT2, FASN, PPARγ, SCD1) in AT. SM RC activity increased in both groups. Negative impact of increased BCAA intake on IS was only detected in vegans, that is, subjects with low basal amino acids/BCAA intake, which appear to be unable to induce sufficient compensatory changes within AT and SM on a BCAA challenge.

Non-alcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome and is associated with insulin resistance, type 2 diabetes mellitus, obesity, hypertension, and dyslipidemia (T. Fukuhara et al. Hepatogastroenterology 2014; 61: 323–328). The current gold standard for the diagnosis of hepatic steatosis is a liver biopsy with a histopathological evaluation. However, less invasive and highly accurate diagnostic methods for the detection of fatty liver are currently being advocated, including abdominal ultrasound, CT, and MRI. Abdominal ultrasound may be the best and most available diagnostic modality for an initial fatty liver diagnosis (O.W. Hamer et al. Radiographics 2006; 26: 1637–1653). Based on diagnostic images, there are 3 established fatty liver patterns (O.W. Hamer et al. Radiographics 2006; 26: 1637–1653): i/ diffuse homogeneous fatty liver, ii/ diffuse fatty liver with focal fatty sparing (i. e., with areas without steatosis), and iii/ focal fatty lesions in an otherwise normal liver. The dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin, has been reported to improve or even reverse hepatic steatosis in patients with type 2 diabetes mellitus (T. Fukuhara et al. Hepatogastroenterology 2014; 61: 323–328).

he population of the Czech Republic (CR) is approximately 10 million inhabitants. It presents 2.3% of the extended EU population. In the Czech Republic the older population percentage is rapidly increasing due to the increase in life expectancy (M 73 yrs, F 79 yrs) and an extremely low birth rate, which has existed since the 1990 s (fertility rate increased slightly from minimum 1.13 in 1999 to 1.44 in 2006). In 2007, 15% of inhabitants were aged 65+ (more than 1.5 mil.), by 2030 the 65+ population is expected to reach 22.8%, and by 2050, it is expected to be 31.3%. The proportion of persons in the highest age group (85+) is growing the most rapidly and increases in life expectancy, in both sexes, is expected to continue, with estimated life expectancies of 84 years in males and 88 years in females by 2065. The relative share of seniors will unevenly increase in coming decades due to natural ageing of the early 1970 s “population boom,” which was a direct consequence of pro-birth measures linked to social policies of political “normalization”. The age structure in the CR, measured by the age preference index, is currently on par with the EU average, however, if present trends persist, the population of the CR will gradually become one of the oldest in Europe. Health insurance of pensioners, in the CR, is financed from the state budget. Traditionally, provision for health and social care was concentrated in modern institutions (hospitals, elderly homes, residential nursing homes, etc.). It is only recently that small steps, involving new trends of extramural care (e.g. home care) have been taken and political support for independent living and family care has only recently, been declared. Nonetheless, rising financial stress on the health care budget and persistent mental and organizational stereotypes and traditions T

To compare maternal health behaviors, maternal nutritional status, and infant size at birth of Romas and non-Romas in the Czech Republic.Maternal interviews and food frequency questionnaire, maternal blood samples, physical measurements of mothers and infants.Hospital, maternal/child care center; 2-4 days postpartum.76 Roma mothers and 151 mothers from the majority population.Infant length/weight; maternal height/weight; weight gain during pregnancy; duration of pregnancy; maternal smoking habits; dietary intake; use of food supplements during pregnancy; and maternal blood levels of folate, beta-carotene, retinol, and alpha-tocopherol.Comparison of ethnic groups by 2-sample Wilcoxon test, chi-square, Fischer's exact test, relative risk, and analysis of variance (ANOVA).Pregnancy duration was about 1 week shorter in Roma women (P.001), and their infants had lower birth weight (P.001) and shorter length (P.001). Prevalence of smoking was significantly higher among Roma mothers (P.001). Roma women used food supplements less frequently than non-Roma women (P.001) and had significantly lower mean blood concentrations of folate (P.001), beta-carotene (P.001), retinol (P.02), and alpha-tocopherol (P.02).The nutritional status of Roma mothers is worse than that of mothers from the majority Czech population. The dietary and smoking habits of pregnant Roma women should be of special concern to family doctors, obstetricians, nutrition educators, and social workers.

Our aim was to detect markers of Chlamydia pneumoniae (CPN) and human cytomegalovirus (HCMV) infection in patients with peripheral vascular occlusive disease and to follow markers of inflammation, endothelial dysfunction and lipid metabolism alteration in patients with active infection. CPN genome was detected in 9 (47.4 %) patients by at least one PCR method. Serological markers of acute CPN infection were found in 5 (26.3 %) subjects; each of them showed also positivity in at least one of the PCR methods. HCMV DNA were detected in 2 (10.5 %) patients; HCMV-specific antibodies were detected in 14 (73.7 %) subjects, however only in IgG subclass. Subjects with HCMV PCR positivity thus showed no serological markers of active HCMV infection. Laboratory findings of acute CPN infection were associated with increased plasma levels of Lp(a), triacylglycerols, atherogenic index of plasma and E-selectin (p < 0.05). No significant differences were found in the other markers, including plasma levels of total cholesterol, ferritin, homocysteine, oxidized LDL, IL-6, IL-8, IL-18, TNF-α, soluble forms of VCAM-1 and ICAM-1, von Willebrand factor, C-reactive protein, and plasma nitrites & nitrates. Frequent presence of chlamydial DNA in atheromatous plaques from patients with peripheral vascular disease was confirmed. HCMV DNA was detected only sporadically and with positivity in anamnestic anti-HCMV antibodies (IgG) only, indicating a rare presence of latent virus rather than active replication. Patients with laboratory markers of acute CPN infection exhibited more pronounced alterations in lipid metabolism and endothelial dysfunction.

Background/Objectives Our aim was to compare expressions of 6 microRNAs (miRNAs) in patients with pancreatic ductal adenocarcinoma (PAC) and non-cancer patients, moreover according to the presence or absence of diabetes mellitus. Methods Expressions of miRNA-192, -196, -200, -21, -30 and -423 were measured in 77 patients with PAC and 64 non-cancer patients (34 patients with type 2 DM and 30 control persons). 60 patients with PAC (78%) had DM or prediabetes and it was of new-onset (less than 2 years before the cancer diagnosis) in 44 out of them. Results The expressions of all microRNAs were 1.4–3.7 times higher (significantly) in the PAC group compared to non-cancer patients. No difference was found between PAC diabetic and PAC non-diabetic patients. MicroRNA-200 was significantly higher in PAC patients with significant body weight loss against those without weight loss. Adding miRNA-196 and -200 to the current marker CA 19-9 improved the discriminative ability of the test (compared to CA 19-9 alone). Conclusion MicroRNA-196 and -200 could be used as additional markers in PAC diagnosis.

Aim: The purpose of our study was to determine the content of trans fatty acids in early human breast milk as an indicator of dietary exposure in a sample of Roma breast-feeding women and in a sample of women from the general Czech population. Methods: We collected samples of early human milk from 43 Prague women from the general population and 21 Roma women. After lipid extraction, the fatty acids were converted into methyl esters (FAMEs). Finally, gas chromatography with flame ionization detector (GC-FID) analysis on a CP-Sil 88 column was used to determine C18:1 trans monoenic fatty acid levels and total trans isomers fatty acid levels in human milk. Results: A significantly higher content of C18:1 trans fatty acid isomers was detected in human milk fat from Roma mothers than in women of the general population (2.73 vs. 2.09%, p < 0.05). Both groups monitored did not differ in the representation of total fatty acid trans isomers. Differences in the frequency of consumption of certain TFA sources (butter, fried crisps) were established. Conclusions: The study proved a higher fatty acid trans isomers content in Roma breast-feeding mothers in the Czech Republic, and this is probably related to their bad eating habits.

Introduction Propofol infusion syndrome (PRIS) is a rare, but potentially lethal adverse effect of a commonly used drug. We aimed to review and correlate experimental and clinical data about this syndrome. Methods We searched for all case reports published between 1990 and 2014 and for all experimental studies on PRIS pathophysiology. We analysed the relationship between signs of PRIS and the rate and duration of propofol infusion causing PRIS. By multivariate logistic regression we looked at the risk factors for mortality. Results Knowledge about PRIS keeps evolving. Compared to earlier case reports in the literature, recently published cases describe older patients developing PRIS at lower doses of propofol, in whom arrhythmia, hypertriglyceridaemia and fever are less frequently seen, with survival more likely. We found that propofol infusion rate and duration, the presence of traumatic brain injury and fever are factors independently associated with mortality in reported cases of PRIS (area under receiver operator curve = 0.85). Similar patterns of exposure to propofol (in terms of time and concentration) are reported in clinical cases and experimental models of PRIS. Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose. Conclusion PRIS can develop with propofol infusion 95 %) missing and others (arrhythmia, electrocardiographic changes) occur late.

Pancreatic cancer is a disease with increasing incidence and high (and nearly unchanged) lethality that is caused mainly due to its late diagnosis. Risk factors for neoplastic transformation are especially chronic pancreatitis, diabetes mellitus, but also obesity and smoking. The search for suitable early markers becomes a key element of research in this area. Such markers could be microRNAs, short single-stranded RNA molecules functioning as regulators of translation. This article serves as a review of contemporary evidence of microRNA in diabetes mellitus and pancreatic cancer.

Sodium phosphate purgatives are used for bowel preparation before endoscopic or radiologic examination and occasionally for treatment of severe obstipation. Generally, they are well tolerated and effective; however, safety concerns exist regarding serious renal injury and electrolyte disturbances after administration of these drugs.The review presents complications associated with the use of agents containing sodium phosphate with regard to electrolyte disorders and renal impairment, namely acute phosphate nephropathy (APhN). This paper discusses the pathophysiology, histopathological findings, clinical symptoms, diagnosis and treatment of APhN. Additionally, it examines the epidemiology of adverse renal events and the safety of using sodium phosphate preparations prior to colonoscopy.Because of safety concerns, sodium phosphate purgatives are not recommended for routine bowel cleansing. Despite some serious and even fatal adverse events associated with these drugs when used with at-risk patients, available data suggest that administration of sodium phosphate purgatives is relatively safe in nonrisk individuals(i.e., in adequately hydrated, otherwise healthy adults, younger than 55 years with evidence of normal renal function).

Newly-onset diabetes mellitus (DM) in middle-aged and older people may be an early symptom of pancreatic cancer (PC). However, sensitive markers for PC are still missing. MicroRNAs (miRNAs) play an important role in a cell response regulation. Significant changes in miRNA expressions were observed in cancers. Our goal was to compare expressions of selected miRNAs in patients with PC, DM and controls.We enrolled 74 patients with PC (42/32, with/without DM), 29 type 2 diabetic patients and 17 controls. MicroRNA was determined in serum of all examined subjects. In 9 patients with PC the tumor was resected subsequently and after 3 months the measurements were repeated. We analyzed the expressions of 8 miRNAs that we had identified in a previous pilot study (miR-21, miR-30, miR-191, miR-192, miR-196, miR-200, miR-423, miR-454).MicroRNA expressions were significantly higher in patients with PC than in DM and controls: miR-192: 1.6 (1.2 to 2.0) vs 0.3 (0.2-0.4) vs 0.3 (0.2 to 0.5), p0.00001; miR-21: 1.4 (1.2-1.7) vs 0.3 (0.2 to 0.5) vs 0.5 (from 0.4 to 0.7), p0.00001, miR-200: 1.6 (1.1 to 2.3) vs 0.3 (0.3-0.4) vs 0.3 (0.2 to 0.4), p0.00001. No difference was observed between DM and controls, as well as between diabetic and non-diabetic patients within the PC group. There were no significant differences in miRNA expressions in 9 patients after pancreatic surgery. But there were significant interindividual differences.Our data shows that miR-21, miR-192 and miR-200 could be used as new diagnostic markers for pancreatic cancer. A dynamics of these miRNAs could serve as a prognostic marker in patients after cancer removal. Futher prospective studies with newly-onset diabetic patients with no signs of malignancy will be needed to validate if suggested miRNAs could be used as early markers as well.

Background The lipophilic positively charged moiety of triphenylphosphonium (TPP+) has been used to target a range of biologically active compounds including antioxidants, spin-traps and other probes into mitochondria. The moiety itself, while often considered biologically inert, appears to influence mitochondrial metabolism. Methodology/Principal Findings We used the Seahorse XF flux analyzer to measure the effect of a range of alkylTPP+ on cellular respiration and further analyzed their effect on mitochondrial membrane potential and the activity of respiratory complexes. We found that the ability of alkylTPP+ to inhibit the respiratory chain and decrease the mitochondrial membrane potential increases with the length of the alkyl chain suggesting that hydrophobicity is an important determinant of toxicity. Conclusions/Significance More hydrophobic TPP+ derivatives can be expected to have a negative impact on mitochondrial membrane potential and respiratory chain activity in addition to the effect of the biologically active moiety attached to them. Using shorter linker chains or adding hydrophilic functional groups may provide a means to decrease this negative effect.

The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid tyrosine phosphatase (LYP), which is expressed primarily in lymphoid tissues. The functional but geographically highly variable PTPN22 single-nucleotide polymorphisms (SNPs), particularly c.1858CT, contribute to the onset and progression of autoimmunity-associated diseases and facilitate the expression of disease-associated autoantibodies. In Central Europe, 17-25% of patients with monogenic diabetes (maturity-onset diabetes of the young, MODY) transiently express islet cell autoantibodies.We addressed the links between the functional and geographically variable PTPN22 SNPs with MODY manifestation and the expression of islet cell autoantibodies in 276 MODY patients who originated from four regions (the Czech Republic, Israel, Japan and Brazil).The frequency of PTPN22 polymorphisms in the MODY patients was similar to those in geographically matched healthy populations, with the exception of c.788GA, the minor allele frequency of which was significantly elevated in the Czech hepatocyte nuclear factor 1-α (HNF1A) MODY patients [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.2-10.7] and the Brazilian MODY patients (OR 8.4, 95% CI 1.8-39.1). A barely significant increase in the c.788GA minor allele was also detected in the islet cell autoantibody-positive Czech MODY patients. However, c.788A behaves as a loss-of-function mutant in T cells, and thus protects against autoimmunity.MODY patients (including islet cell autoantibody-positive cases) do not display any increase in autoimmunity-associated PTPN22 alleles. The absence of autoimmunity-associated PTPN22 alleles was also demonstrated in latent autoimmune diabetes in adults, which suggests that the slow kinetics of the onset of autoantibodies is subject to a regulation that is different from that experienced in type 1 diabetes and other autoimmune disorders.

Insulin secretion in patients with manifested diabetes mellitus tends to disappear months to decades after the diagnosis, which is a clear sign of a gradual loss of pancreatic islet beta-cells. In our sample of 30 type 2 diabetic patients, whose disease manifested between 30 and 45 years of age, about a half have retained or even increased insulin secretion 30 years later, while the other half exhibit a much diminished or lost insulin secretion. Factors that can damage or destroy beta-cells can be divided into the following groups: Metabolic factors: hyperglycemia and glucotoxicity, lipotoxicity, hypoxia, reactive oxygen species; Pharmacological factors: antimicrobial medication pentamidine, SSRI antidepressants; Factors related to impaired insulin secretion: MODY type diabetes; Environmental toxic factors: rat poison Vacor, streptozotocin, polychlorinated and polybrominated hydrocarbons; Disorders of the exocrine pancreas: tumor infiltration, fibrous infiltration, chronic pancreatitis, cystic fibrosis; Infections, inflammation, autoimmunity, viral factors: Coxsackie viruses, H1N1 influenza, enteroviruses. We are currently working on finding other factors leading to beta-cell damage, studying their effect on apoptosis and necrosis and looking for possible protective factors to prevent this damage. We our increasing knowledge about the mechanisms of beta-cell damage and destruction we come ever closer to suggest measures for their prevention. In this review we offer a brief and simplified summary of some of the findings related to this area.Key words: pancreatic islet beta-cells of Langerhans - factors damaging or destroying beta-cells - insulin secretion.

The aim of this study was to evaluate the effect of long-term administration of liquid nutritional supplement with increased amounts of whey protein and reduced amounts of lactose, produced in accordance with a new recipe "Nutrisen" on the elderly living in institutionalized care.The study was carried out from May to July, 2013, on 47 retirement home residents, living in Prague, all of which were 65 years or older. Supplemented group (n = 23) consumed (200 ml) milk drinks with three different flavours on a daily basis for eight weeks. The reference group was on a normal diet. There was no significant difference in baseline characteristics between participants in both groups. Anthropometric and biochemical indicators of nutritional status and tolerance of the nutritional supplement during long-term use were evaluated.Both compliance (daily intake program) and tolerance of the nutritionally defined supplement were very good. For the supplemented group, there was an average weight increased of 700 grams after the 8 week nutritional supplement test period. Average levels of albumin and prealbumin increased significantly (from the beginning to the end of the program), 35.5 ± 4.52 g/l vs 36.19 ± 4.1 g/l and 0.160 ± 0.05 vs 0.174 ± 0.04 g/l (p0.05), vitamin D levels increased from 31.2 ± 16.4 nmol/l to 36.8 ± 17.7 nmol/l (p0.001) and HDL-cholesterol levels increased from 1.29 ± 0.33 mmol/l to 1.35 ± 0.35 mmol/l (p0.001).The specific nutritionally defined milk drink (Nutrisen), used in this study, was well tolerated by the elderly study participants, over the eight-week clinical study. We observed a positive effect on the participants weight, serum albumin, prealbumin, vitamin D and HDL-cholesterol.

Both celiac disease and osteoporosis are common diseases which are considered an emerging problem in medicine. Celiac disease is a condition at high risk for secondary osteoporosis. Osteoporosis or osteopenia are typically present in untreated adult symptomatic celiac disease with an overt malabsorption syndrome, but is found in about 50 % in suboptimally treated celiac patients, subclinical patients and asymptomatic adult celiac patients, too. Etiology of pathologic bone alteration in celiac disease is multifactorial; however, two main mechanisms are involved: intestinal malabsorption and chronic inflammation. The evaluation of bone mineral metabolism (total calcium/albumin, 25-OH vitamin D3 and parathormone levels in serum) and bone mineral density (densitometry) is recommended in the clinical management of celiac patients. Many studies have demonstrated that bone mineral density values in adults show a good improvement in the first period after the institution of gluten-free diet, the improvement is then unsatisfactory and treatment with a mineral-active drug should probably be considered.

We investigated the contribution of impaired insulin secretion (observed as dynamics of C-peptide) and insulin resistance (measured by euglycemic clamps) to glucose dysregulation in 20 critically ill patients after severe trauma during feeding and intensive glucose control with intravenous insulin. Between the fourth and seventh day when insulin sensitivity is lowest, insulin secretion is highest and supranormal despite tight control of blood glucose by exogenous insulin. Afterward, plasma C-peptide decreases together with an improvement in insulin sensitivity. Multiple regression analysis revealed that plasma insulin is determined more by endogenous secretion than insulin infusion, even during the acute phase when exogenous insulin requirements are high.

The review article summarizes the principles of hedonic regulation of food intake which represents the food intake independent on the maintenance of homeostasis. The theory describing hedonic regulation, so called Incentive Salience Theory, comprises three major processes: liking (positive attribution to food stimulus), wanting (motivation to gain it) and learning (identification of these stimuli and distinguishing them from those connected with aversive reaction). Neuronal reward circuits are the anatomical and functional substrates of hedonic regulation. They react to gustatory and olfactory (or visual) stimuli associated with food intake. A food item is preferred in case its consumption is connected with a pleasant feeling thus promoting the behavioural reaction. The probability of this reaction after repetitive exposure to such a stimulus is increased (learned preference). On the contrary, learned aversion after repetitive exposure is connected with avoidance of a food item associated with a negative feeling. Main mediators of hedonic regulation are endocannabinoids, opioids and monoamines (dopamine, serotonin). Dopamine in dorsal striatum via D2 receptors generates food motivation as a key means of survival, however in ventral striatum (nucleus accumbens) is responsible for motivation to food bringing pleasure. Serotonin via its receptors 5-HT1A a T-HT2C decreases intake of palatable food. It plays a significant role in the pathogenesis of eating disorders, particularly mental anorexia. There, a food restriction represents a kind of automedication to constitutionally pathologically increased serotonin levels. Detailed understanding of processes regulating food intake is a key to new pharmacological interventions in eating disorders.

Isolated granulomatous noncaseating pancreatitis is a rare condition exceptionally described in human population. We demonstrate a case of the a 71-years-old female patient suffering from recent diabetes mellitus, generalized atherosclerosis and hypertension who died due to pulmonary embolism and terminal bronchopneumonia. Lipomatosis of pancreatic tissue was observed during the postmortem examination. Histological examination of pancreatic tissue discovered multiple small noncaseating epithelioid cell and giant cell granulomas, partly replacing the islets of Langerhans. To our knowledge, our case represents the first description of noninfectious granulomatous pancreatitis associated with acute manifested insulin-dependent diabetes mellitus.

Aims Islet cell autoantibodies are associated with autoimmune insulitis and belong to the diagnostic criteria of Type 1 diabetes mellitus. However, growing evidence suggests that autoantibodies are present in other types of diabetes. Here, we focus on the autoantibody incidence in Czech patients with maturity-onset diabetes of the young and analyse their functional relevance in terms of diabetes onset and control. Methods Autoantibodies against glutamic acid decarboxylase (GAD) 65 and protein tyrosine phosphatase islet antigen 2 (IA-2) were measured in a cohort of 28 Czech patients with maturity-onset diabetes of the young, all confirmed by genetic testing. Selected clinical data were correlated to the status and kinetics of autoantibodies. Results One quarter of patients with maturity-onset diabetes of the young examined (7/28; 25%) was positive for GAD or IA-2 autoantibodies. GAD autoantibodies were more prevalent (7/7) than IA-2 autoantibodies (1/7). The incidence of autoantibodies did not correlate with human leukocyte antigen status. The patients who were positive for the autoantibodies developed diabetes later than those who were autoantibody-negative, but had worse glycaemic control (increased HbA1c). Expression of autoantibodies decreased with any improvement of diabetes compensation. Only one patient did not correspond to the above and displayed signs of combined signs of maturity-onset diabetes of the young and Type 1 diabetes. Conclusions The data suggest transient but highly prevalent islet cell autoantibody expression in Czech patients with maturity-onset diabetes of the young. The autoantibodies were found in patients with delayed diabetes onset, and in times of insufficient diabetes control. As improvement of glycaemic control was associated with a decrease in levels of autoantibodies, their presence may reflect the kinetics of β-cell destruction induced by causes other than autoimmune ones.

Background: There are few studies in the Czech Republic describing and evaluating the nutritional status of institutionalized elderly. Methods: Data were collected from 659 women and 156 men aged 65 years and older and living in retirement homes in and around Prague. Data included: a Mini-Nutritional Assessment (MNA questionnaire), anthropometric measurements and biochemical evaluations. Results: According to the MNA questionnaire, 10.2% of these elderly individuals were malnourished and 39.4% were at risk of malnutrition. More women than men were malnourished (OR = 0.59 and 95% CI 0.42-0.86). Mean BMI values were 25.5 for females and 27.5 for males. MNA was positively correlated mostly with immobility (r = 0.63; p < 0.001), BMI (r = 0.57; p < 0.001) and mid-arm circumference (r = 0.56; p < 0.001). Serum albumin levels were Conclusion: The study results confirmed that institutionalized elderly, especially women, should be considered a nutritionally vulnerable population group that needs attention.

Background/Aims: Oxidized low-density lipoprotein (oxLDL) in complex with β2-glycoprotein I (β2GPI) has been associated with autoimmune diseases, diabetes mellitus, chronic renal disease and coronary atherosclerosis. The aim of our study was to determine whether plasma levels of oxLDL/β2GPI complexes are associated with insulin resistance, inflammation and markers of endothelial damage in obese middle-aged men and, if so, whether oxLDL/β2GPI correlates better with insulin resistance parameters than oxLDL, advanced oxidation protein products (AOPP) or thioredoxin. Methods: A total of 72 healthy men were recruited (41 obese and 31 nonobese individuals). Waist circumference >94 cm was used as the criterion for abdominal obesity. Results: The obese men demonstrated higher oxLDL/β2GPI levels (p < 0.001), homeostasis model assessment of insulin resistance (p < 0.01) and intima-media thickness of the common carotid artery (p < 0.01). oxLDL/β2GPI correlated with more insulin resistance parameters compared to AOPP, thioredoxin or oxLDL. Furthermore, oxLDL/β2GPI was associated with plasminogen activator inhibitor-I (PAI-I; r = 0.365, p < 0.001) and negatively with interleukin-8 (r = –0.297, p < 0.05). Conclusions: In summary, oxLDL/β2GPI reflects the criterion for abdominal obesity and markers of insulin resistance in our study. The independent positive correlation with PAI-I indicates that oxLDL/β2GPI may serve as an early marker of low-grade inflammation and atherosclerosis initiation.

Define the prevalence of protein-energy malnutrition (PEM) in a convenient sample of Prague's homeless population.The study was conducted in Prague over an 8 month period during 2003. Nutritional status was assessed using anthropometric measurements, biochemical and hematological indicators. Of the initial 217 subjects recruited, 201 participated actively. Thirteen percent of the participants were women. One hundred and thirty four participants were interviewed on the premises of Nadeje, a Czech charitable organization; the rest were interviewed in Bulovka University Hospital.Mean BMI values were within the normal range, with only 6 (3%) of the men and 2 (7%) of the women below 18.5kg/m2. Wasted muscle mass was found in only 1 (0.6%) man. Serum protein levels were within normal limits. Lymphocytopenia was reported in 3 (2%) of the men. Results of the CAGE questionnaire gave a strong indication of alcoholism in 24 (12%) and alcoholism in 32 (16%) of the participants.The data fails to demonstrate the existence of protein-energy malnutrition in Prague's homeless population.

To estimate the efficacy and metabolic effects of growth hormone substitution as intravenous pulses together with alanyl-glutamine supplementation and tight blood glucose control in prolonged critical illness.Prospective double-blind, randomized trial with open-label control arm.Intensive care unit of tertiary level hospital.Thirty multiple trauma patients (median Injury Severity Score 34).Patients were randomized, at day 4 after trauma, to receive intravenous alanyl-glutamine supplementation (0.3 g/kg x day(-1) from day 4 until day 17) and intravenous growth hormone (administered days 7-17, full dose 50 microg/kg x day(-1) from day 10 onward) (group 1, n = 10) or alanyl-glutamine and placebo (group 2, n = 10). Group 3 (n = 10) received isocaloric isonitrogenous nutrition (proteins 1.5 g/kg x day(-1)) without alanyl-glutamine.Cumulative nitrogen balance for the whole study period was -97 +/- 38 g of nitrogen for group 1, -193 +/- 50 g of nitrogen for group 2, and -198 +/- 77 g of nitrogen for group 3 (p.001). This represents a daily saving of 300 g of lean body mass in group 1. Insulin-mediated glucose disposal, during euglycemic clamp, as a measure of insulin sensitivity, significantly worsened between days 4 and 17 in group 1 but improved in groups 2 and 3. Group 1 required significantly more insulin to control blood glucose, resulting in higher insulinemia (approximately 70 mIU in group 1 vs. approximately 25 mIU in groups 2 and 3). Despite this, growth hormone treatment caused an increase in plasma nonesterified fatty acid (approximately 0.5-0.6 mM in group 1 in comparison with approximately 0.2-0.3 mM in groups 2 and 3) but did not influence lipid oxidation. There were no differences in morbidity, mortality, or 6-month outcome among the groups.Treatment with frequent intravenous pulses of low-dose growth hormone together with alanyl-glutamine supplementation improves nitrogen economy in patients with prolonged critical illness after multiple trauma but worsens insulin sensitivity. Tight blood glucose control is possible but requires higher doses of insulin.

Aim: In this study, we tested the impact of short-term intake of increased amounts of C18:1 trans fatty acids (TFAs) on parameters of cellular and humoral immunity in healthy young men. Methods: Twenty-seven healthy young men were subsequently exposed to a standard diet for 7 days and an experimental TFA-enriched diet for 4 days. The mean energy content of these diets was 2,453 and 2,455 kcal/day, with 10, 35 and 55% of energy from proteins, fats and carbohydrates, respectively. Standard diet contained about 0.8 g and experimental diet 10.4 g TFAs. Plasma levels of C18:1 TFAs and immunological parameters were measured. Results: The 4-day increased consumption of C18:1 TFAs led to a significant decrease in mitogen-induced CD69 expression on CD8+ T cells as well as decreased phagocytic activity on neutrophils. After returning to the participants’ habitual diet (1 week after the end of the experimental diet), we observed a significant decrease in the mean level of circulating immune complexes. Concentrations of plasma immunoglobulins remained unchanged throughout the study. Conclusions: Acute impact of higher dietary C18:1 TFA intake on phagocytosis and cell-mediated immunity seems to be suppressive. This finding differs from results describing proinflammatory effects associated with long-term exposure to TFAs.

Background Homeless people have higher morbidity and mortality rates than the general population. Research has shown that cardiovascular disease is the leading cause of death in older homeless adults. This study was undertaken to describe the prevalence of cardiovascular risk factors in the homeless population in Prague. Methods Data was obtained from a cross-sectional study carried out in 2003. Body mass index (BMI), waist circumference (WC), total cholesterol (TC), triacylglycerides (TAG) and smoking habits were assessed. The homeless participants in the study were recruited from a homeless center run by a Prague charitable organization called Naděje ("Hope") and at Prague's main railway station. Most participants were assessed at the Naděje center (134 persons) while the rest were assessed at Prague's Bulovka University Hospital (67 persons). Results A total of 201 homeless (174 males and 27 females) aged 19 – 70 years were examined. Mean values of BMI, WC, TC and TAG in homeless men and women were within normal limits. Compared with the majority of the Czech population, the homeless had significantly lower mean levels of TC and TAG and lower BMI and WC values. When compared to the majority of the Czech population, the incidence of smoking among the homeless was significantly higher. Among smokers in both populations, no differences were found in the number of cigarettes smoked per day. Conclusion Classical cardiovascular risk factors such as TC, TAG, BMI and WC, are significantly lower in Prague's homeless minority than in the majority of the Czech population. However, the prevalence of smoking is much higher in the homeless population.

Summary Background & aims Patients with type 2 diabetes (T2DM) tend to loose more lean body mass during both long-term weight reduction and short-term very-low-calorie diet. We ask what factors influence protein loss during acute starvation in T2DM. Methods In a prospective in-hospital observational study, we compared 10 subjects with T2DM and 10 age-weight-sex matched obese controls (OB) during 60 h of fasting and used frequent blood sampling and indirect calorimetry to describe metabolic and endocrine response. We analyzed factors influencing nitrogen balance using stepwise multiple regressions. Results Despite comparable pattern of plasma insulin, free fatty acid, 3-hydroxybutyrate and almost identical behavior of growth hormone axis, our T2DM subjects remained hyperglycaemic and in contrast to OB subjects they failed to reduce the rate of protein oxidation, even though muscle protein breakdown rate declined similarly in both groups. Regression analysis revealed that protein oxidation rate in T2DM group was enhanced by hyperglycemia and sympathetic activity and suppressed by circulating insulin and 3-hydroxybutyrate. Liver insulin resistance increases peripheral insulin concentrations and enhances the conversion of non-esterified fatty acids (NEFA) to ketones and thus it might be a protein-saving factor. Conclusion Relative deficiency of circulating insulin and hyperglycemia play a pivotal role in the impairment of protein sparing in T2DM during a short-term fasting.

Aim: The purpose of our study was to determine urinary iodine as an indicator of iodine supplementation in Roma (Gypsy) neonates compared to majority population neonates. Methods: The groups studied were formed by 30 full-term Roma neonates and 151 majority population neonates. Iodine was determined from samples of urine collected on the 4th day after delivery, after alkaline ashing, using the Sandell-Kolthoff method. Results: The median of urinary iodine in Roma neonates was 92.15 µg/l urine and in neonates from majority population mothers it was 109.20 µg/l urine. The mean of urinary iodine in Roma neonates was 114.55 µg/l urine (SD 71.68 µg/l) and in neonates from majority population mothers it was 141.86 µg/l urine (SD 87.42 µg/l). The difference was not statistically significant. Majority population mothers more frequently consumed nutrition supplements containing iodine as well as fish. Conclusions: Compared to older data, supplementation of neonates with iodine is higher. However, it does not reach optimum levels. The urinary iodine median in Roma neonates lies in the mild iodine deficiency band.

It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD.

Aim: To identify the total content of trans fatty acid (TFA) isomers and C18:1 trans isomers in subcutaneous fat samples from persons with atherosclerosis of the coronary arteries, as an indicator of dietary exposure. Methods: Using capillary gas chromatography, the authors determined total content of TFA isomers and C18:1 trans isomers in the subcutaneous fat of 34 patients with ischemic heart disease who had undergone aortocoronary bypass surgery and in 46 patients with no sign of coronary disease. Results: On average, the total TFAs in cardiac patients were 2.88 ± 1.19% of all fatty acids, in noncardiac patients 2.56 ± 0.89%. However, the difference is not statistically significant. The average concentration of C18:1 trans in cardiac patients (2.31 ± 1.09%) was statistically significantly higher (p = 0.05) than in the noncardiac group (1.95 ± 0.77%). Conclusions: The results obtained indicate a lower TFA load in comparison with previous studies in other countries. A higher concentration of 18:1 TFAs in the subcutaneous fat of patients with coronary disease might be an impulse to correct the dietary habits of this very high-risk population.

Background: Methionine loading test is commonly used to detect hyperhomocysteinemia in patients with arteriosclerosis and other conditions. As administration of methionine causes endothelial dysfunction in laboratory examinations, we explored whether loading with this compound leads to clinically relevant adverse effects, especially in vasculature. Methods and results: When studying genetic factors in arteriosclerosis we recorded acute complications during a standard methionine loading test (with a dose of 100 mg/kg bw) and assessed a 30-day mortality in a group of 296 patients with coronary artery or peripheral arterial disease and in 591 controls. Acute complications were observed in 33% of the women and 16.5% of the men. For each sex, the patients and controls exhibited the same proportion of complications. The most common symptom, dizziness, was attributable to methionine loading. In addition, isolated sleepiness, nausea, polyuria and decreased or increased blood pressure were observed in part of the subjects. None of the 887 individuals died within the 30-day period following the test. Conclusion: Our study suggests that although standard loading with L-methionine frequently causes transitory complications impairing perception and vigilance, the test does not have serious adverse effects on vasculature and may be considered a safe procedure.

The most important factors influencing drug need are disease prevalence and employed therapy. Our ability to predict future drug need is in most cases limited by the lack of adequate information on both these factors. One of the notable more favourable cases is diabetes though even here we are still far from the desired situation. A permanent rise in diabetes prevalence in most countries attracted much attention in recent years and epidemiological data about diabetes are gathered with a rapid pace. Even when these data are still rather imperfect, they can — together with the data about the demographic composition and characteristics of the studied population — form the necessary basis for building an epidemiological simulation model for the projection of the diabetic population. The second tiasic factor affecting the drug need is the employed therapy. Insulin therapy is indicated in a relatively well defined portion of diabetic patients and in Czechoslovakia the numbers of these patients are monitored by routine medical statistics.