Effect of the Drying Method and Storage Conditions on the Quality and Content of Selected Bioactive Compounds of Green Legume Vegetables.

This study aimed to determine the effect of the drying method (freeze-drying, air-drying), storage period (12 months), and storage conditions (2-4 °C, 18-22 °C) applied to two legume species: green beans and green peas. The raw and dried materials were determined for selected physical parameters typical of dried vegetables, contents of bioactive components (vitamin C and E, total chlorophyll, total carotenoids, ß-carotene, and total polyphenols), antioxidative activity against the DPPH radical, and sensory attributes (overall quality and profiles of color, texture, and palatability). Green beans had a significantly higher content of bioactive components compared to peas. Freeze-drying and cold storage conditions facilitated better retention of these compounds, i.e., by 9-39% and 3-11%, respectively. After 12 months of storage, higher retention of bioactive components, except for total chlorophyll, was determined in peas regardless of the drying method, i.e., by 38-75% in the freeze-dried product and 30-77% in the air-dried product, compared to the raw material.

Inhibitors of immune checkpoints-PD-1, PD-L1, CTLA-4-new opportunities for cancer patients and a new challenge for internists and general practitioners.

The treatment of cancer patients with immune checkpoint inhibitors (ICI) (anti-CTLA-4, anti-PD-1, anti-PD-L1, combined therapy anti-PD-1/PD-L1 with anti-CTLA-4) has without doubt been a significant breakthrough in the field of oncology in recent years and constitutes a major step forward as a novel type of immunotherapy in the treatment of cancer. ICIs have contributed to a significant improvement in the outcome of treatment and prognosis of patients with different types of malignancy. With the expansion of the use of ICIs, it is expected that caregivers will face new challenges, namely, they will have to manage the adverse side effects associated with the use of these drugs. New treatment options pose new challenges not only for oncologists but also for specialists in other clinical fields, including general practitioners (GPs). They also endorse the need for taking a holistic approach to the patient, which is a principle widely recognized in oncology and especially relevant in the case of the expanding use of ICIs, which may give rise to a wide variety of organ complications resulting from treatment. Knowledge and awareness of the spectrum of immune-related adverse events (irAEs) will allow doctors to qualify patients for treatment more appropriately, prevent complications, correctly recognize, and ultimately treat them. Additionally, patients with more non-specific symptoms would be expected, in the first instance, to consult their general practitioners, as complications may appear even after the termination of treatment and do not always proceed in line with disease progression. Dealing with any iatrogenic complications, will not only be the remit of oncologists but because of the likelihood that specific organs may be affected, is likely to extend also to specialists in various fields of internal medicine. These specialists, e.g., endocrinologists, dermatologists, pulmonologists, and gastroenterologists, are likely to receive referrals for patients suffering from specific types of adverse events or will be asked to provide care in cases requiring hospitalization of patients with complications in their field of expertise. In view of these considerations, we believe that there is an urgent need for multidisciplinary teamwork in the treatment of cancer patients undergoing immunotherapy and suffering the consequent adverse reactions to treatment.

Testing the Utility of Polygenic Risk Scores for Type 2 Diabetes and Obesity in Predicting Metabolic Changes in a Prediabetic Population: An Observational Study.

Prediabetes is an intermediate state of hyperglycemia during which glycemic parameters are above normal levels but below the T2D threshold. T2D and its precursor prediabetes affect 6.28% and 7.3% of the world's population, respectively. The main objective of this paper was to create and compare two polygenic risk scores (PRSs) versus changes over time (Δ) in metabolic parameters related to prediabetes and metabolic complications. The genetics of 446 prediabetic patients from the Polish Registry of Diabetes cohort were investigated. Seventeen metabolic parameters were measured and compared at baseline and after five years using statistical analysis. Subsequently, genetic polymorphisms present in patients were determined to build a T2D PRS (68 SNPs) and an obesity PRS (21 SNPs). Finally, the association among the two PRSs and the Δ of the metabolic traits was assessed. After a multiple linear regression with adjustment for age, sex, and BMI at a nominal significance of (p < 0.05) and adjustment for multiple testing, the T2D PRS was found to be positively associated with Δ fat mass (FM) (p = 0.025). The obesity PRS was positively associated with Δ FM (p = 0.023) and Δ 2 h glucose (p = 0.034). The comparison of genotype frequencies showed that AA genotype carriers of rs10838738 were significantly higher in Δ 2 h glucose and in Δ 2 h insulin. Our findings suggest that prediabetic individuals with a higher risk of developing T2D experience increased Δ FM, and those with a higher risk of obesity experience increased Δ FM and Δ two-hour postprandial glucose. The associations found in this research could be a powerful tool for identifying prediabetic individuals with an increased risk of developing T2D and obesity.

The Effect of Crataegus Fruit Pre-Treatment and Preservation Methods on the Extractability of Aroma Compounds during Liqueur Production.

The leaves, inflorescences, and fruits of hawthorn have long been known for their therapeutic properties. A wide range of hawthorn products, including liqueurs, are manufactured, due to the technological potential of the raw material as well as the richness of its volatile compounds. This study aimed to determine the effect of the liqueur production method and various methods of fruit preservation on the quantitative and qualitative composition of volatile compounds in the liqueurs produced. Hawthorn fruits saturated with sucrose and non-saturated with sucrose, fresh or preserved through one of three methods: freezing, air-drying, and freeze-drying, were used for liqueur preparation. The samples were analyzed using a gas chromatograph-mass spectrometer. They were found to contain 54 volatile compounds classified into 12 groups of chemicals. All 54 identified volatile compounds were detected in the liqueur made from hawthorn fruits non-saturated with sucrose and preserved by freeze-drying. In this liqueur type, 12 of the identified volatile compounds occurred in the highest concentration when compared to the other treatments. Among all volatiles, the following compounds were present in the analyzed liqueurs in the highest concentrations: dodecanoic acid ethyl ester (11.782 g/100 g), lactones (6.954 g/100 g), five monoterpenes (3.18 g/100 g), two aromatic hydrocarbons (1.293 g/100 g), isobensofuran (0.67 g/100 g), alcohol-2-methyl-2-propanol (0.059 g/100 g), and malonic ester (0.055 g/100 g). Among all analyzed liqueurs, the one made from the fruits non-saturated with sucrose and frozen was characterized by the smallest diversity of volatiles, which were present in the lowest concentrations in that liqueur.

An Association between Diet and MC4R Genetic Polymorphism, in Relation to Obesity and Metabolic Parameters-A Cross Sectional Population-Based Study.

The melanocortin-4 receptor (MC4R) gene harbours one of the strongest susceptibility loci for obesity and obesity-related metabolic consequences. We analysed whether dietary factors may attenuate the associations between MC4R genotypes and obesity and metabolic parameters. In 819 participants genotyped for common MC4R polymorphisms (rs17782313, rs12970134, rs633265, and rs135034), the anthropometric measurements, body fat content and distribution (visceral and subcutaneous adipose tissue, VAT and SAT, respectively), and blood glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides concentrations, and daily macronutrient intake were assessed. ANOVA or Kruskal-Wallis tests were used, and multivariate linear regression models were developed. We observed that the CC genotype carriers (rs17782313) presented higher VAT, VAT/SAT ratio, fasting blood glucose and triglyceride concentrations when they were stratified to the upper quantiles of protein intake. An increase in energy derived from proteins was associated with higher BMI (Est. 5.74, R2 = 0.12), body fat content (Est. 8.44, R2 = 0.82), VAT (Est. 32.59, R2 = 0.06), and VAT/SAT ratio (Est. 0.96, R2 = 0.05). The AA genotype carriers (rs12970134) presented higher BMI, body fat, SAT and VAT, fasting blood glucose, triglycerides and total cholesterol concentrations. An increase in energy derived from proteins by AA carriers was associated with higher VAT (Est.19.95, R2 = 0.06) and VAT/SAT ratio (Est. 0.64, R2 = 0.05). Our findings suggest that associations of the common MC4R SNPs with obesity and its metabolic complications may be dependent on the daily dietary intake, which may open new areas for developing personalised diets for preventing and treating obesity and obesity-related comorbidities.

The contamination of inland waters by microplastic fibres under different anthropogenic pressure: Preliminary study in Central Europe (Poland).

The contamination of freshwater ecosystems with microfibres has not yet been studied in Poland. We analysed samples from a river and three lakes located in central and northeastern Poland. A significantly higher number of fibres were reported in the river, which runs through large cities, compared with the lake situated within the Landscape Park. Fibres smaller than 1.0 mm dominated, especially in the river where they constituted 39% of all fibres detected. We found more microplastics (⩽ 4930 fibres·m-3) by using a mesh size of 20 µm compared with other studies of inland waters. The use of Raman spectroscopy allowed us to identify conventional plastic polymers: polyethylene terephthalate, polyester and polyurethane. We estimated that up to 25 g of microplastic in the form of fibres might be in the lake water under the surface. We found microplastic fibres in Majcz Lake situated within the Masurian Landscape Park. This suggests that microfibres are carried by the wind and rain and enter freshwater isolated from sewage outlets. By using the control sample and an air-test of microfibres in the laboratory, we observed that there is a high probability of contamination with microplastic in the field samples (up to 30% of all fibres detected). The contamination risk noted from the samples cannot be ignored; this could be particularly important for analysis of microplastic in remote freshwater ecosystems.

Metabolomics Reveal Altered Postprandial Lipid Metabolism After a High-Carbohydrate Meal in Men at High Genetic Risk of Diabetes.

BACKGROUND: The transcription factor 7-like 2 (TCF7L2) gene confers one of the strongest genetic predispositions to type 2 diabetes, but diabetes development can be modified by diet. OBJECTIVE: The aim of our study was to evaluate postprandial metabolic alterations in healthy men with a high genetic risk of diabetes, after two meals with varying macronutrient content. METHODS: The study was conducted in 21 homozygous nondiabetic men carrying the high-risk (HR, n = 8, age: 31.2 ± 6.3 y, body mass index (BMI, kg/m2) 28.5 ± 8.1) or low-risk (LR, n = 13, age: 35.2 ± 10.3 y, BMI: 28.1 ± 6.4) genotypes at the rs7901695 locus. During two meal challenge test visits subjects received standardized isocaloric (450 kcal) liquid meals: high-carbohydrate (HC, carbohydrates: 89% of energy) and normo-carbohydrate (NC, carbohydrates: 45% of energy). Fasting (0 min) and postprandial (30, 60, 120, 180 min) plasma samples were analyzed for metabolite profiles through untargeted metabolomics. Metabolic fingerprinting was performed on an ultra-high-performance liquid chromatography (UHPLC) system connected to an iFunnel quadrupole-time-of-flight (Q-TOF) mass spectrometer. RESULTS: In HR-genotype men, after the intake of an HC-meal, we noted a significantly lower area under the curves (AUCs) of postprandial plasma concentrations of most of the phospholipids (-37% to -53%, variable importance in the projection (VIP) = 1.2-1.5), lysophospholipids (-29% to -86%, VIP = 1.1-2.6), sphingolipids (-32% to -47%, VIP = 1.1-1.3), as well as arachidonic (-36%, VIP = 1.4) and oleic (-63%, VIP = 1.3) acids, their metabolites: keto- and hydoxy-fatty acids (-38% to -78%, VIP = 1.3-2.5), leukotrienes (-65% to -83%, VIP = 1.4-2.2), uric acid (-59%, VIP = 1.5), and pyroglutamic acid (-65%, VIP = 1.8). The AUCs of postprandial sphingosine concentrations were higher (125-832%, VIP = 1.9-3.2) after the NC-meal, AUCs of acylcarnitines were lower (-21% to -61%, VIP = 1.1-2.4), and AUCs of fatty acid amides were higher (51-508%, VIP = 1.7-3.1) after the intake of both meals. CONCLUSIONS: In nondiabetic men carrying the TCF7L2 HR genotype, subtle but detectable modifications in intermediate lipid metabolism are induced by an HC-meal. This trial was registered at www.clinicaltrials.gov as NCT03792685.

The MC4R genetic variants are associated with lower visceral fat accumulation and higher postprandial relative increase in carbohydrate utilization in humans.

PURPOSE: The interactions between lifestyle and genetic factors play an important role in obesity development. Mutations in melanocortin-4-receptor (MC4R) gene are one of the most common cause of monogenic obesity, however, the functional effects of polymorphic variants near MC4R gene in general populations remain uncertain. The aim of our study was to analyze whether the common single nucleotide polymorphisms (SNPs) of MC4R gene influence the food preferences, physical activity, body fat content and distribution, as well as fasting and postprandial energy expenditure and substrates utilization. METHODS: We genotyped previously identified MC4R SNPs: rs17782313, rs633265, rs1350341, rs12970134 in 927 subjects, who underwent anthropometric, total body fat content, visceral (VAT) and subcutaneous adipose tissue (SAT) measurements, and daily physical activity and dietary intake analysis. In randomly selected 47 subjects the energy expenditure, carbohydrate and lipid utilizations were evaluated in fasting state and after high-carbohydrate and control meals intake. RESULTS: We found the significant associations between studied SNPs of MC4R gene and VAT and VAT/SAT ratio. Moreover, the GG genotype carriers of rs1350341, who had the lowest VAT accumulation (p = 0.012), presented higher relative increase in postprandial carbohydrate utilization (p = 0.013, p = 0.024). CONCLUSIONS: We have observed that common SNPs of the MC4R gene influence the body fat content and distribution, as well as relative increase in postprandial carbohydrate utilization. We believe that our study may help to understand better the impact of MC4R gene on obesity development, and to help to provide personalized prevention/treatment strategies to fight against obesity and its metabolic consequences.

The relationship between the leptin/ghrelin ratio and meals with various macronutrient contents in men with different nutritional status: a randomized crossover study.

BACKGROUND: Hormones, which influence satiety and hunger, play a significant role in body energy balance regulation. Ghrelin is a peptide that plays an important role in short-term appetite regulation, whereas leptin is a factor that controls long-term energy balance and is considered as a satiety hormone. The aim of this study was to evaluate the leptin/ghrelin ratio in a fasting state and after the intake of meals with varying macronutrient contents and to assess the possible differences between normal body weight and overweight/obese men. METHODS: We examined 46 healthy adult men (23 with normal body weight and 23 overweight/obese) aged 21-58, who were divided into two groups. In the crossover study, participants received isocaloric (450 kcal) meals with different macronutrient contents: men from the first group received high-carbohydrate (HC) and normo-carbohydrate (NC) meals, and in the second group, participants received high-carbohydrate and high-fat (HF) meals. The ratio of leptin/ghrelin levels was calculated from leptin and total ghrelin serum concentrations in a fasting state and 30, 60, 120, 180 and 240 min after meal intake. One-way ANOVA and Wilcoxon signed-rank tests were carried out. The normality of the variable distribution was checked with the Shapiro-Wilk test, the homogeneity of variances was verified with the Levene test, and the false discovery rate p-value adjustment method was used. RESULTS: The leptin/ghrelin ratio was significantly higher in overweight/obese men than individuals with normal body weight in a fasting state, as well as postprandially. We observed trends towards a higher leptin/ghrelin ratio values from the 60 min after HC-meal intake compared to the NC- and HF-meals in normal body weight participants, while in overweight/obese men, we did not note any significant differences dependent on the meal type. CONCLUSIONS: We have observed a significantly different postprandial leptin/ghrelin ratio in normal body weight and overweight/obese men, and our results suggest that in men with normal body weight, a greater feeling of satiety may occur after high-carbohydrate meal intake, which was not noted in the overweight/obese individuals.

Serum irisin and its regulation by hyperinsulinemia in women with polycystic ovary syndrome.

Irisin is an adipokine/myokine which could be connected with insulin sensitivity. Polycystic ovary syndrome (PCOS) is characterized by oligo- or anovulation, polycystic ovary, hyperandrogenism and insulin resistance. The aim of the present study was to determine the relationship between serum irisin concentration and insulin sensitivity (Mffm) as well as the effect of insulin infusion on circulating irisin levels in PCOS women as compared with healthy controls. Seventy seven women were enrolled in the study - 57 with PCOS and 20 healthy controls matched for BMI and age. Hyperinsulinemic euglycemic clamps were performed in all of the study participants. The serum concentrations of irisin at baseline and after the clamp, as well as changes of serum irisin concentration in response to insulin supplied during the clamp (Δ irisin), were estimated. The mean serum concentrations of irisin at baseline and after hyperinsulinemia were higher in PCOS women in comparison to the control group (p=0.01; p=0.006, respectively). Insulin infusion resulted in a decrease of serum irisin concentration only in the PCOS group (p=0.007). In the control group, Δ irisin positively correlated with Mffm (r=0.56, p=0.009). In the entire group, multiple regression analysis showed that Δ irisin (ß=0.70, p=0.0002), FFAs 60' during the clamp study (ß=-0.22, p=0.01), SHBG (ß=0.54, p<0.0001) and the interaction between Δ irisin and PCOS (ß=-0.67, p=0.0004) were significantly associated with Mffm. The higher serum irisin concentrations at baseline and in response to insulin infusion might be secondary to insulin resistant conditions in PCOS women.

CE-MS-based serum fingerprinting to track evolution of type 2 diabetes mellitus.

Development of type 2 diabetes mellitus (T2DM) is preceded by insulin resistance (IR), which may evolve to impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). IFG and IGT are considered as prediabetic states (PD). Prediabetes indicates the high risk for the future development of diabetes, it is estimated that up to 70% of prediabetics eventually develop T2DM. The risk of T2DM development is increased in overweight (OW) and obese (OB) people; however normal weight (NW) individuals also suffer from T2DM. The present study was designed to evaluate whether changes in polar metabolites induced by T2DM evolution are different between NW, overweight and obese individuals. CE-MS serum fingerprinting was performed on 197 serum samples obtained from OW, OB, and NW humans whom were IR, prediabetics, diabetics or with normal glucose homeostasis. Metabolic changes evoked by the progression of T2DM differ between obese, overweight, and normal weight subjects. Based on obtained results several metabolites can be proposed as a promising target to track T2DM evolution; BCAA in OW and NW humans, lysine in OB, while acetylcarnitine and methionine independently on body mass index. Validation of obtained results on larger population is required.

Disturbances of modulating molecules (FOXP3, CTLA-4/CD28/B7, and CD40/CD40L) mRNA expressions in the orbital tissue from patients with severe graves' ophthalmopathy.

Purpose. To evaluate the relationship between the expression of orbital tissue mRNA for FOXP3, CTLA-4/CD28/CD80/CD86, and CD40/CD40 and the severity of Graves' orbitopathy (GO). Material and Methods. Orbital tissue was obtained from 26 patients with GO, with mild (n = 6) or severe GO (n = 20), and 7 healthy controls. The expression of mRNA of FOXP3, CTLA-4/CD28/CD80/CD86, CD40/CD40L was measured by RT-PCR. TCR and CD3 were evaluated by immunohistochemistry. Results. Higher mRNA for FoxP3 (relative expression: 1.4) and CD40 (1.27) and lower expression of CTLA-4 (0.61) were found in the GO tissues versus controls. In severe GO as compared to mild GO higher mRNA expression for FoxP3 (1.35) and CD40 (1.4) and lower expression for CTLA-4 (0.78), CD28 (0.62), and CD40L (0.56) were found. A positive correlation was found between FOXP3 mRNA and CD3 infiltration (R = 0.796, P = 0.0000001). Conclusions. The enhanced FOXP3 mRNA expression in GO samples may suggest the dysfunction of FOXP3 cells in the severe GO. The diminished mRNA expression of CTLA-4 in severe GO may indicate inadequate T regulatory function. The enhanced mRNA expression of CD40 in severe GO and negative correlation to CRP mRNA may suggest their role in the active and inactive GO.

Potential first trimester metabolomic biomarkers of abnormal birth weight in healthy pregnancies.

OBJECTIVE: Macrosomia and low birth weight (LBW) can be associated with pregnancy complications and may affect the long-term health of the child. The aim of this study was to evaluate the metabolomic serum profiles of healthy pregnant women to identify early biomarkers of macrosomia and LBW and to understand mechanisms leading to abnormal fetal growth not related to mother's body mass index or presence of gestational diabetes. METHOD: Serum samples from 770 women were collected between the 12th and 14th gestational week. Delivery samples were divided into three groups according to the infant birth weight as follows: low, <2500 g; normal, 2500-4000 g; and high >4000 g. Samples from women with any complications of pregnancy were excluded. Serum fingerprinting was performed by LC-QTOF-MS. RESULTS: Lower levels of phospholipids, lysophospholipids, and monoacylglycerols; low vitamin D3 metabolites; and increased bilirubin level were associated with macrosomia. Because most changes involved lipids, as a concept of validation, adipocyte fatty acid-binding protein (A-FABP) levels were measured and found correlated with the studied lipids and birth weight. CONCLUSION: Serum fingerprinting in early pregnancy can predict the risk of macrosomia. Serum levels of A-FABP and several lipids are promising prognostic markers for macrosomia in healthy pregnancies.

Serum irisin concentration in women with gestational diabetes.

Irisin is a novel myokine and adipokine which induces an increase in total body energy expenditure, improving insulin sensitivity and glucose tolerance in experimental animals. In the present study, serum irisin concentration was measured by an enzyme immunoassay in 130 women with gestational diabetes mellitus (GDM) and 140 BMI-matched patients with normal glucose tolerance (NGT). Median irisin level was significantly lower in the patients with GDM than in the NGT subjects (1703.3 [1354.8-2097.9 ng/ml] versus 1873.8 [1519.8-2294.8 ng/ml], p = 0.01); however, 3 months after childbirth its concentrations did not differ markedly between the two groups (1165.9 [872.1-1497.5] ng/ml versus 1139.0 [984.0-1376.7] ng/ml). In the whole group, irisin concentration correlated negatively with 2 h glucose level (R = -0.14, p = 0.03). In the women with NGT, irisin concentration correlated positively with IS(OGTT) (R = 0.22, p = 0.04) and the disposition index (DI(120)) (R = 0.24, p = 0.03), as well as negatively with 2 h insulin level (R = -0.23, p = 0.03) and HOMA-IR (R = -0.24, p = 0.02). Multiple regression analysis revealed that 2 h glucose and DI(120) were the only variables significantly influencing serum irisin (ß = 0.158, p = 0.03 and ß = 0.159, p = 0.02, respectively). Our results suggest that serum irisin concentration increases markedly in pregnant women, but this increase seems to be significantly lower in patients with GDM.

The BDNF protein is associated with glucose homeostasis and food intake in carriers of common BDNF gene variants.

CONTEXT: The brain-derived neurotrophic factor (BDNF) concentrations may differ between BDNF gene genotype carriers. These changes occur in individuals with metabolic and mental disorders. OBJECTIVE: The aim of this study was to assess the associations of glucose homeostasis parameters and the frequency of food consumption with BDNF protein concentrations based on the BDNF single-nucleotide polymorphisms (SNPs). METHODS: Among the 439 participants, some common rs10835211 BDNF gene variants were analyzed. We evaluated BDNF concentration, fasting glucose and insulin concentrations and during oral glucose tolerance tests. Anthropometric measurements, body composition, and body fat distribution were assessed, and 3-day food intake diary and food frequency questionnaire were completed. RESULTS: We noticed significant differences in concentration of BDNF between AA and AG genotype rs10835211 carriers (p=0.018). The group of AA genotype holders were older, and positive correlation was found between age and BDNF in the whole study population (p=0.012) and in the GG genotype carriers (p=0.023). Moreover, BDNF protein correlated with fasting insulin (p=0.015), HOMA-IR (p=0.031), HOMA-B (p=0.010) , and the VAT/SAT ratio (p=0.026) in the GG genotype individuals. Presence of the GG genotype was negatively correlated with nut and seed (p=0.047), lean pork consumption (p=0.015) and the BDNF protein. Moreover, we observed correlations between the frequency of chicken (p=0.028), pasta (p=0.033) and sweet food intake (p=0.040) and BDNF concentration in the general population. Among carriers of the AA genotype, we observed a positive correlation between the consumption of rice (p=0.048) and sweet food (p=0.028) and the BDNF protein level. CONCLUSION: Peripheral BDNF may be associated with visceral fat content and insulin concentrations in the GG genotype carriers and may depend on variable food intake, which warrants further investigation.

Circulating interleukin 6 and soluble forms of its receptors in relation to resting energy expenditure in women with anorexia nervosa.

CONTEXT: Anorexia nervosa (AN) is an eating disorder, resulting in sustained low weight and marked decrease in fat mass. Interleukin 6 (IL-6) may play a role in appetite, energy expenditure and body weight control. IL-6 acts through binding with membrane receptor (IL-6R) and activates glycoprotein 130 (gp130) signalling. Both IL-6R and gp130 are present in the blood in the soluble forms (sIL-6R and sgp130 respectively). sIL-6R sensitizes cells towards IL-6, whereas sgp130 inhibits gp130 signalling. OBJECTIVE: To estimate circulating IL-6/sIL-6R/sgp130 system and its relationships with body weight and resting energy expenditure (REE) in AN women. PATIENTS: We examined 19 women with AN and 27 healthy normal-weight female controls. MEASUREMENTS: Indirect calorimetry and the measurement of serum IL-6, sIL-6R and sgp130 concentrations were performed in all the subjects. RESULTS: REE was decreased in AN women (P < 0·001). Serum IL-6 was higher in AN women in comparison with control group (P = 0·005). Serum sIL-6R was lower (P = 0·009) and serum sgp130 was higher (P = 0·004) in AN women in comparison with controls. IL-6 and sIL-6R were related to REE in the entire study population (r = -0·54, P < 0·001 and r = 0·48, P = 0·001 respectively) and in AN group (r = -0·54, P = 0·024 and r = 0·60, P = 0·011 respectively). CONCLUSIONS: Increased IL-6 in AN seems to be compensated by the changes in sIL-6R and sgp130, which are directed towards inhibition of IL-6 action. The balance between these factors might play a role in the regulation of energy expenditure in AN.

Decreased CD127 expression on CD4+ T-cells and elevated frequencies of CD4+CD25+CD127- T-cells in children with long-lasting type 1 diabetes.

Pathobiology of type 1 diabetes (T1D) is predominantly associated with T-cell-related actions. Homeostasis of majority of T-cells is critically dependent on signals mediated by CD127 (interleukin-7 receptor, IL-7R). In contrast, regulatory T-cells express very little CD127 and thereby may be delineated by CD4+CD25+CD127- phenotype. Here we aimed to analyze CD127 expression on CD4+ and CD8+ T-cells and enumerate CD4+CD25+CD127- T-cells in long-lasting T1D. T-cells were analyzed by flow cytometry and immunologic data were correlated with vascular, metabolic, and inflammatory parameters. We demonstrated significantly decreased CD127 levels on CD4+, but not CD8+, T cells in T1D pediatric patients. Interestingly, frequencies of CD4+CD25+CD127- T-cells were significantly enhanced in T1D children and correlated well with frequencies of CD34+CD144+ endothelial progenitor cells and CD4+CD25- T-cells. Levels of CD127 on both CD4+ and CD8+ T-cells in T1D patients were not correlated to each other or HbA1C. Interestingly, however, CD127 levels on CD4+ T-cells were significantly correlated to frequencies of CD4+CD25+CD127- T-cells, whereas CD127 levels on CD8+ T-cells were significantly correlated to concentrations of VEGF and triglycerides. Our data indicate that CD127 expression is differentially modulated on CD4+ and CD8+ T-cells in the course of T1D. Moreover, we demonstrated that, in contrast to recent-onset T1D, long-lasting T1D is associated with enhancement of T-cells with regulatory phenotype.

Normal metabolic flexibility despite insulin resistance women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder, where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. Insulin resistance (IR) is connected with disturbances in switching between lipid and carbohydrate oxidation in response to insulin, called "metabolic inflexibility". The aim of the present study was to estimate the whole-body insulin sensitivity, lipid and carbohydrate oxidation, metabolic flexibility in lean and obese PCOS women. The study group consisted of 92 women with PCOS, 40 lean (BMI<25 kg/m²) and 52 overweight or obesity (BMI>25 kg/m²), and 30 healthy normally menstruating women (14 lean and 16 overweight/obese) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Both the presence of PCOS (P<0.001) and obesity (P=0.005) were independently characterized by lower insulin sensitivity. PCOS (P=0.002) and obesity (P=0.001) independently predisposed to the lower non-oxidative glucose metabolism. Obese women had lower glucose oxidation (P=0.005) and higher lipid oxidation (P<0.001) in insulin-stimulated conditions in comparison to lean subject whereas PCOS had no effect on these parameters (P=0.29 and P=0.43; respectively). Metabolic flexibility was impaired in the obese (P=0.001) but it was not influenced by the presence of PCOS (P=0.78). Our data indicate that PCOS women have normal metabolic flexibility, which could suggest a distinct pathophysiological mechanism for insulin resistance in this group.

The influence of insulin infusion on the metabolism of amyloid ß peptides in plasma.

BACKGROUND: Accumulating body of evidence suggests pathophysiologic links between Alzheimer's disease and diabetes mellitus (DM). For example, the two crucial peptides playing a role in both degenerative disorders, amyloid ß (Aß) and insulin, are metabolized by the same enzyme, insulin degrading enzyme. Euglycemic hyperinsulinemic clamp is a method of estimating insulin sensitivity, based on the assumption that during steady-state hyperinsulinemic euglycemia, glucose infusion rate equals tissue glucose uptake, that is, the higher the glucose infusion rate, the higher the insulin sensitivity. OBJECTIVE: The aim of this study was to analyze the influence of insulin on the plasma concentrations of Aß peptides. METHODS: Blood samples were collected from 20 healthy young male volunteers before insulin infusion (clamp) and then at 120 and 360 minutes. In the second protocol, insulin was accompanied by Intralipid, which is mainly a mixture of triacylglycerols, and heparin, given as an activator of lipoprotein lipase, inducing insulin resistance. Analyses of plasma Aß1-42, Aßx-42, Aß1-40, and Aßx-40 were performed with multiplexing technology. Furthermore, concentrations of the Aß peptides in healthy persons were compared with those in 16 type 1 DM patients receiving chronic insulin therapy. RESULTS: When applied alone (i.e., without Intralipid), insulin infusion increased concentrations of Aß42 (full length and N-terminally shortened) but not of Aß40. When combined with Intralipid, infusion of insulin resulted in increased concentrations of all peptides (nonsignificant tendency in case of Aßx-40). We did not observe differences between Aß peptide concentrations in healthy subjects and those in type 1 DM patients. CONCLUSION: Infusion of insulin in nonphysiologic high doses increases plasma concentrations of Aß peptides; in case of Aß40, only when applied together with Intralipid, which perhaps might be explained by hypothetical shift of insulin degrading enzyme activity from degradation of Aß peptides to the degradation of insulin.

Obesity-related parameters in carriers of some BDNF genetic variants may depend on daily dietary macronutrients intake.

Some common single-nucleotide polymorphisms of the brain-derived neurotrophic factor (BDNF) gene have been associated not only with the neurodegenerative diseases but also with some eating disorders. The aim of this study was to assess the possible differences in the obesity-related and glucose metabolism parameters between some BDNF genotypes', that may depend on the daily energy and macronutrients intake. In 484 adult participants we performed the anthropometric measurements, body composition analysis, and body fat distribution. The daily dietary intake was assessed using the 3-day food intake diaries. Blood glucose and insulin concentrations were measured at fasting and during oral glucose tolerance tests. Moreover, the visceral adipose tissue/subcutaneous adipose tissue (VAT/SAT) ratio and homeostatic model assessment of insulin resistance were calculated. We noted that participants carrying the GG genotype had lower skeletal muscle mass and fat free mass (FFM) when carbohydrate intake was > 48%, whereas they presented higher fat-free mass (FFM), and surprisingly higher total cholesterol and LDL-C concentrations when daily fiber intake was > 18 g. Moreover, in these subjects we noted higher waist circumference, BMI, and fasting glucose and insulin concentrations, when > 18% of total daily energy intake was delivered from proteins, and higher VAT content and HDL-C concentrations when > 30% of energy intake was derived from dietary fat. Our results suggest that glucose homeostasis and obesity-related parameters in carriers of some common variants of BDNF gene, especially in the GG (rs10835211) genotype carriers, may differ dependently on daily energy, dietary macronutrients and fiber intake.