Isoflavonoids and lignans in legumes : Nutritional and health aspects in humans

Peer reviewe

Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

<p>Abstract</p> <p>Background</p> <p>We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4⁺CD25^HIFoxp3⁺regulatory T cells and expanded melanoma-specific CD8⁺T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients.</p> <p>Methods</p> <p>In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[¹⁸F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging.</p> <p>Results</p> <p>After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; <it>p </it>value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year.</p> <p>Conclusions</p> <p>These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00299689">NCT00299689</a></p

Insulin-stimulated glucose uptake in skeletal muscle, adipose tissue and liver: A positron emission tomography study

Objective: Insulin resistance is reflected by the rates of reduced glucose uptake (GU) into the key insulin-sensitive tissues, skeletal muscle, liver and adipose tissue. It is unclear whether insulin resistance occurs simultaneously in all these tissues or whether insulin resistance is tissue specific. Design and methods: We measured GU in skeletal muscle, adipose tissue and liver and endogenous glucose production (EGP), in a single session using 18F-fluorodeoxyglucose with positron emission tomography (PET) and euglycemic–hyperinsulinemic clamp. The study population consisted of 326 subjects without diabetes from the CMgene study cohort. Results: Skeletal muscle GU less than 33 µmol/kg tissue/min and subcutaneous adipose tissue GU less than 11.5 µmol/kg tissue/min characterized insulin-resistant individuals. Men had considerably worse insulin suppression of EGP compared to women. By using principal component analysis (PCA), BMI inversely and skeletal muscle, adipose tissue and liver GU positively loaded on same principal component explaining one-third of the variation in these measures. The results were largely similar when liver GU was replaced by EGP in PCA. Liver GU and EGP were positively associated with aging. Conclusions: We have provided threshold values, which can be used to identify tissue-specific insulin resistance. In addition, we found that insulin resistance measured by GU was only partially similar across all insulin-sensitive tissues studied, skeletal muscle, adipose tissue and liver and was affected by obesity, aging and gender.</p

The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double-Blind, Placebo-Controlled Study With 8-Week Treatment in Type 2 Diabetes Patients

OBJECTIVE The aim of this study was to investigate tissue-specific effects of dapagliflozin on insulin sensitivity and liver and body fat in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This randomized, double-blind, parallel group, placebo-controlled study recruited 32 patients with type 2 diabetes. Enrolled patients were to have HbA(1c) 6.5-10.5% (48-91 mmol/mol) and >= 3 months of stable treatment with metformin, dipeptidyl peptidase 4 inhibitor, or their combination. Patients were randomized 1:1 to receive 10 mg dapagliflozin or placebo daily for 8 weeks. Before and after the intervention, tissue insulin sensitivity was measured using [F-18]-fluorodeoxyglucose and positron emission tomography during hyperinsulinemic-euglycemic clamp. Liver proton density fat fraction (PDFF) and adipose tissue volumes were assessed using MRI, and blood biomarkers were analyzed. RESULTS After 8 weeks, glycemic control was improved by dapagliflozin (placebo-corrected change in HbA(1c) -0.39%, P < 0.01), but whole-body glucose uptake was not increased (P = 0.90). Tissue-specific insulin-stimulated glucose uptake did not change in skeletal muscle, liver, myocardium, or white and brown adipose tissue, and endogenous glucose production remained unaffected. However, there were significant placebo-corrected decreases in liver PDFF (-3.74%, P < 0.01), liver volume (-0.10 L, P < 0.05), visceral adipose tissue volume (-0.35 L, P < 0.01), interleukin-6 (-1.87 pg/mL, P < 0.05), and N-terminal prohormone of brain natriuretic peptide (-96 ng/L, P = 0.03). CONCLUSIONS In this study, 8 weeks of treatment with dapagliflozin reduced liver PDFF and the volume of visceral adipose tissue in obese patients with type 2 diabetes. Although glycemic control was improved, no effect on tissue-level insulin sensitivity was observed

Predicting Skeletal Muscle and Whole-Body Insulin Sensitivity Using NMR-Metabolomic Profiling

Purpose: Abnormal lipoprotein and amino acid profiles are associated with insulin resistance and may help to identify this condition. The aim of this study was to create models estimating skeletal muscle and whole-body insulin sensitivity using fasting metabolite profiles and common clinical and laboratory measures.Material and Methods: The cross-sectional study population included 259 subjects with normal or impaired fasting glucose or type 2 diabetes in whom skeletal muscle and whole-body insulin sensitivity (M-value) were measured during euglycemic hyperinsulinemic clamp. Muscle glucose uptake (GU) was measured directly using [F-18]FDG-PET. Serum metabolites were measured using nuclear magnetic resonance (NMR) spectroscopy. We used linear regression to build the models for the muscle GU (Muscle-insulin sensitivity index [ISI]) and M-value (whole-body [WB]-ISI). The models were created and tested using randomly selected training (n = 173) and test groups (n = 86). The models were compared to common fasting indices of insulin sensitivity, homeostatic model assessment-insulin resistance (HOMA-IR) and the revised quantitative insulin sensitivity check index (QUICKI).Results: WB-ISI had higher correlation with actual M-value than HOMA-IR or revised QUICKI (rho = 0.83 vs -0.67 and 0.66; P < 0.05 for both comparisons), whereas the correlation of Muscle-ISI with the actual skeletal muscle GU was not significantly stronger than HOMA-IR's or revised QUICKI's (rho = 0.67 vs -0.58 and 0.59; both nonsignificant) in the test dataset.Conclusion: Muscle-ISI and WB-ISI based on NMR-metabolomics and common laboratory measurements from fasting serum samples and basic anthropometrics are promising rapid and inexpensive tools for determining insulin sensitivity in at-risk individuals. (C) Endocrine Society 2020

Stress ocupacional no ensino : um estudo com professores dos 3º ciclo e ensino secundário

Este trabalho foi realizado com 689 professores portugueses, a leccionarem nos terceiro ciclo e ensino secundário. Foram avaliados indicadores de stress, “burnout”, saúde física e satisfação profissional. Observaram-se valores significativos de stress ocupacional (perto de 40%), e de “burnout” (10% na exaustão emocional, 3% na baixa realização pessoal e 1% na despersonalização), vários problemas de saúde física e valores de insatisfação profissional perto dos 20%. As análises de regressão múltipla apontaram diferentes variáveis preditoras para as três dimensões do “burnout” (62% de variância explicada na exaustão emocional, 16% na realização pessoal e 13% na despersonalização). As análises discriminantes e “t-test” para amostras independentes demonstraram maior stress ocupacional nas mulheres, nos professores mais velhos, nos profissionais com vínculos profissionais mais precários, nos professores com mais horas de trabalho e com mais alunos em sala de aula. No final, apresentam-se as limitações do estudo e as implicações para a investigação futura.(undefined

A partial loss-of-function variant in AKT2 is associated with reduced insulin-mediated glucose uptake in multiple insulin-sensitive tissues: A genotype-based callback positron emission tomography study

Rare fully penetrant mutations in AKT2 are an established cause of monogenic disorders of glucose metabolism. Recently, a novel partial loss-of-function AKT2 coding variant (p.Pro50Thr) was identified that is nearly specific to Finns (frequency 1.1%), with the low-frequency allele associated with an increase in fasting plasma insulin level and risk of type 2 diabetes. The effects of the p.Pro50Thr AKT2 variant (p.P50T/AKT2) on insulin-stimulated glucose uptake (GU) in the whole body and in different tissues have not previously been investigated. We identified carriers (N = 20) and matched noncarriers (N = 25) for this allele in the population-based Metabolic Syndrome in Men (METSIM) study and invited these individuals back for positron emission tomography study with [18F]-fluorodeoxyglucose during euglycemic hyperinsulinemia. When we compared p.P50T/AKT2 carriers to noncarriers, we found a 39.4% reduction in whole-body GU (P = 0.006) and a 55.6% increase in the rate of endogenous glucose production (P = 0.038). We found significant reductions in GU in multiple tissues—skeletal muscle (36.4%), liver (16.1%), brown adipose (29.7%), and bone marrow (32.9%)—and increases of 16.8–19.1% in seven tested brain regions. These data demonstrate that the p.P50T substitution of AKT2 influences insulin-mediated GU in multiple insulin-sensitive tissues and may explain, at least in part, the increased risk of type 2 diabetes in p.P50T/AKT2 carriers

Both sedentary time and physical activity are associated with cardiometabolic health in overweight adults in a 1 month accelerometer measurement

The aim of this study was to examine the associations of cardiometabolic health markers with device-measured sedentary behavior (SB) duration and different intensities of physical activity (PA) among overweight working-aged adults with low self-reported PA levels. This cross-sectional analysis included 144 subjects (42 men) with mean age of 57 (SD 6.5) years and mean BMI of 31.7 (SD 4) kg/m2. SB and standing time, breaks in sedentary time, light PA (LPA) and moderate-to-vigorous PA (MVPA) were measured for 4 consecutive weeks (mean 25 days, SD 4) with hip-worn accelerometers. Fasting plasma glucose, insulin, HbA1c, triglycerides and total cholesterol, HDL and LDL were measured from venous blood samples. HOMA-IR index was calculated as a surrogate of insulin resistance. The associations were examined using linear models. LPA, MVPA, and daily steps associated with better insulin sensitivity and favorable plasma lipid profile, when adjusted for age, sex and BMI, whereas greater proportion of SB associated with insulin resistance and unfavorable lipid profile. As all PA intensities associated with better cardiometabolic health, the total daily duration of PA may be more relevant than intensity in maintaining metabolic health in overweight adults, if the current guidelines for PA are not met.</p

Sense of coherence and intentions to retire early among Finnish women and men

Peer reviewe

Individual and contextual covariates of burnout: a cross-sectional nationwide study of French teachers

<p>Abstract</p> <p>Background</p> <p>Limited information on the covariates of burnout syndrome in French teachers is available. The aim of this study was to evaluate the relative contributions of individual and contextual factors on the three burnout dimensions: emotional exhaustion, depersonalization, and reduced personal accomplishment.</p> <p>Methods</p> <p>The source data come from an epidemiological postal survey on physical and mental health conducted in 2005 among 20,099 education workers (in activity or retired) selected at random from the health plan records of the national education system. The response rate was 52.4%. Teachers in activity currently giving classes to students who participated in the survey (n = 3,940) were invited to complete a self-administered questionnaire including the Maslach Burnout Inventory. 2,558 teachers provided complete data (64.9%). Variables associated with high emotional exhaustion (highest quartile of score), high depersonalization (highest quartile), and reduced personal accomplishment (lowest quartile) were evaluated using multivariate logistic regression. Studied variables referred to demographic characteristics, socio-professional environment, job dissatisfaction, experienced difficulties at work, and teaching motivations.</p> <p>Results</p> <p>Different variables were associated with each burnout dimension. Female teachers were more susceptible to high emotional exhaustion and reduced personal accomplishment, whereas male teachers were more susceptible to high depersonalization. Elementary school teachers were more susceptible to high emotional exhaustion, but less susceptible to high depersonalization and reduced personal accomplishment than their higher school level counterparts. Experienced difficulties with pupils were associated with all three dimensions. A socio-economically underprivileged school neighbourhood was also related to high emotional exhaustion and high depersonalization.</p> <p>Conclusion</p> <p>Programs to enhance teaching environment might be an interesting approach to try to prevent burnout. It would be useful to take the different dimensions into account in planning the intervention.</p