Calorie restriction-induced leptin reduction and T-lymphocyte activation in blood and adipose tissue in men with overweight and obesity.

BACKGROUND: T-Lymphocyte activation is modulated by the adipokine leptin and serum concentrations of this hormone can be reduced with short-term calorie restriction. The aim of this study was to understand whether leptin per se is important in determining levels of T-lymphocyte activation in humans, by investigating whether the reduction in leptin concentration following calorie restriction is associated with a decrease in T-Lymphocyte activation in blood and adipose tissue. METHODS: Twelve men with overweight and obesity (age 35-55 years, waist circumference 95-115 cm) reduced their calorie intake by 50% for 3 consecutive days. Blood and subcutaneous adipose tissue were obtained for isolation of immune cells and cytokine analysis. CD4+ and CD8 + T-Lymphocytes were identified and characterised according to their expression of activation markers CD25 and CD69 by flow cytometry. RESULTS: Serum leptin was reduced by (mean ± SEM) 31 ± 16% (p < 0.001) following calorie restriction. The percentage of blood CD4 + CD25 + T-lymphocytes and level of CD25 expression on these lymphocytes were significantly reduced by 8 ± 10% (p = 0.016) and 8 ± 4% (p = 0.058), respectively. After calorie restriction, ex vivo leptin secretion from abdominal subcutaneous adipose tissue explants was not changed, and this corresponded with a lack of change in adipose tissue resident T-Lymphocyte activation. CONCLUSIONS: Serum leptin was reduced after calorie restriction and this was temporally associated with a reduction in activation of blood CD4 + CD25 + T-Lymphocytes. In abdominal subcutaneous adipose tissue, however, leptin secretion was unaltered, and there were no observed changes in adipose resident T-Lymphocyte activation.

Nonlinear association between atherogenic index of plasma and type 2 diabetes mellitus in overweight and obesity patients: evidence from Chinese medical examination data.

BACKGROUND: The atherogenic index of plasma (AIP) is closely associated with the onset of diabetes, with obesity being a significant risk factor for type 2 diabetes mellitus (T2DM). However, the association between the AIP and T2DM in overweight and obese populations has been infrequently studied. Therefore, this study aimed to explore this association in overweight and obese individuals with T2DM. METHODS: This cross-sectional analysis utilized data from 40,633 participants with a body mass index (BMI) ≥ 24 kg/m2 who were screened from January 2018 to December 2023 at Henan Provincial People's Hospital. Participants were categorized into groups of overweight and obese individuals with and without diabetes according to the T2DM criteria. The AIP, our dependent variable, was calculated using the formula log10 [(TG mol/L)/HDL-C (mol/L)]. We investigated the association between the AIP and T2DM in overweight and obese individuals using multivariate logistic regression, subgroup analysis, generalized additive models, smoothed curve fitting, and threshold effect analysis. Additionally, mediation analysis evaluated the role of inflammatory cells in AIP-related T2DM. RESULTS: Overweight and obese patients with T2DM exhibited higher AIP levels than those without diabetes. After adjusting for confounders, our results indicated a significant association between the AIP and the risk of T2DM in overweight and obese individuals (odds ratio (OR) = 5.17, 95% confidence interval (CI) 4.69-5.69). Notably, participants with a high baseline AIP (Q4 group) had a significantly greater risk of T2DM than those in the Q1 group, with an OR of 3.18 (95% CI 2.94-3.45). Subgroup analysis revealed that the association between the AIP and T2DM decreased with increasing age (interaction P < 0.001). In overweight and obese populations, the association between AIP and T2DM risk displayed a J-shaped nonlinear pattern, with AIP > - 0.07 indicating a significant increase in T2DM risk. Various inflammatory cells, including neutrophils, leukocytes, and monocytes, mediated 4.66%, 4.16%, and 1.93% of the associations, respectively. CONCLUSION: In overweight and obese individuals, the AIP was independently associated with T2DM, exhibiting a nonlinear association. Additionally, the association between the AIP and T2DM decreased with advancing age. Multiple types of inflammatory cells mediate this association.

Weight-Reducing Dietary Intervention Increases the Ability of Hyperinsulinemia to Suppress Serum Ghrelin Concentration in Individuals with Obesity.

BACKGROUND: Ghrelin is an orexigenic peptide secreted mainly by the stomach. Serum ghrelin concentrations are suppressed after a meal, probably due to insulin release. Individuals with obesity are characterized by a lower fasting serum ghrelin and a lower ghrelin decrease after a meal. The effect of weight loss on the ability of insulin to suppress serum ghrelin concentration remains unknown. OBJECTIVE: The aim of the present study was to analyze the effect of weight-reducing dietary intervention on the ability of hyperinsulinemia to suppress serum ghrelin concentration in young individuals with uncomplicated obesity. METHODS: We examined 38 individuals with marked overweight or obesity, who underwent a 12-wk dietary intervention program. Serum ghrelin concentration was measured before and after a 2-h hyperinsulinemic-euglycemic clamp, both pre- and post-intervention. Twenty normal-weight individuals served as a control group and were examined at baseline only. RESULTS: Individuals with overweight/obesity were characterized by a lower fasting serum ghrelin concentration than normal-weight individuals (P = 0.006). Insulin decreased serum ghrelin concentration in both groups (P < 0.001); however, this decrease was markedly lower in individuals with overweight/obesity than in normal-weight individuals (99.70 ± 136.37 vs. 215.45 ± 250.28 pg/mL; P = 0.026). Fasting serum ghrelin concentration increased after the intervention. After weight-reducing dietary intervention, the decrease in serum ghrelin concentration after the clamp was significantly greater than the pre-intervention value (99.70 ± 136.37 vs. 221.82 ± 228.75 pg/mL; P = 0.002). CONCLUSIONS: Weight-reducing dietary intervention restores the ability of hyperinsulinemia to suppress serum ghrelin concentration. It may suggest an enhanced feeling of satiety after moderate weight loss in individuals with overweight/obesity.

The intake of ultra-processed foods and homocysteine levels in women with(out) overweight and obesity: The Rotterdam Periconceptional Cohort.

PURPOSE: Today's diet consists of a substantial proportion of ultra-processed foods (UPF), especially in women with overweight and obesity in the reproductive period. High UPF intake results in an inadequate and unbalanced diet leading to derangements of several metabolic pathways detrimental to pregnancy and birth outcomes. Therefore, we aim to investigate whether UPF intake in the periconceptional period affects total homocysteine plasma levels (tHcy). METHODS: 1532 participants were included from the prospective Rotterdam Periconceptional Cohort. UPF intake was calculated using Food Frequency Questionnaires including items classified as 4 in the Nova classification, and tHcy was measured by using liquid chromatography-tandem mass spectrometry system, with an interassay coefficient of variation of < 5.5%. Multivariable linear regression modeling was used and adjusted for covariates and significant interaction terms. RESULTS: Women with overweight or obesity showed significantly higher percentage of UPF intake (respectively, 50.3 and 51.3%) and higher tHcy (respectively, 6.6 and 6.3 µmol/L, Kruskal-Wallis test; respectively, p < 0.001 and p = 0.04) compared to women with normal BMI (UPF intake: 46.8%, tHcy: 6.1 µmol/L). A 10% higher intake of UPF was associated with an increase in tHcy (adjusted: ß = 1.31, 95% CI = 0.38-2.23). Analysis stratified for BMI classification showed comparable associations in normal weight participants (adjusted: ß = 1.07, 95% CI = 0.06-2.07); however, no significant association in participants with overweight (adjusted: ß = 0.06, 95% CI = - 0.95-1.07) and obesity (adjusted: ß = 1.70, 95% CI = - 0.52-3.92) was shown. CONCLUSION: This study showed that a higher intake of UPF is associated with increased tHcy. Better knowledge and awareness of the nutritional quality of the diet in the periconceptional period may contribute to 1-CM and subsequently improve pregnancy course and outcome. TRIAL REGISTRATION NUMBER AND DATE: NTR4356, November 2010.

U-shaped association between 25-hydroxyvitamin D concentration and the prevalence of asthma in the overweight and obese U.S. population.

INTRODUCTION: Vitamin D supplementation has shown promise in averting asthma. However, the association between 25(OH)D levels and asthma prevention in various demographic groups remains inconclusive. Here, we explore this relationship in the context of overweight and obese individuals in the United States. METHODS: We scrutinized cross-sectional data derived from the National Health and Nutrition Examination Survey conducted between 2007 and 2018. This dataset encompasses comprehensive information about asthma patients with a body mass index greater than 25 kg/m2, in addition to data regarding 25(OH)D concentration and other pertinent variables. Among the 3889 participants, 16.2% (631/3889) reported a history of asthma, constituting 1765 (45.4%) males and 2124 (54.6%) females. The median age was 56.0 years, with a standard deviation of 16.0 years. We conducted restricted cubic spline (RCS) regression analysis to assess the correlation between 25(OH)D levels and asthma. RESULTS: After adjusting for confounders, compared to individuals with lower 25-hydroxyvitamin D concentration (group1 ≤ 46.6 nmol/L), the adjusted odds ratios (OR) for asthma in group2 (46.7-62 nmol/L), group3 (62.1-78.2 nmol/L), and group4 (≥78.3 nmol/L) were 0.68 (95% CI: 0.49-0.94, p < 0.021), 0.65 (95% CI: 0.47-0.88, p < 0.006), and 0.83 (95% CI: 0.61-1.12, p < 0.22), respectively. Restricted cubic spline (RCS) regression analysis revealed a nonlinear U-shaped curve (p = 0.017) with an inflection point at approximately 84.95 nmol/L. CONCLUSIONS: High levels of 25(OH)D are correlated with a diminished prevalence of asthma among overweight and obese individuals in the United States.

Vitamin D supplementation may reduce the incidence of asthma in the overweight and obese individuals.A u-shaped association was observed between 25-hydroxyvitamin D levels and asthma, with an inflection point of 84.95 nmol/L.Presenting supportive evidence for vitamin D supplementation in the overweight and obese individuals.

The influence of maternal prepregnancy weight and gestational weight gain on the umbilical cord blood metabolome: a case-control study.

BACKGROUND: Maternal overweight/obesity and excessive gestational weight gain (GWG) are frequently reported to be risk factors for obesity and other metabolic disorders in offspring. Cord blood metabolites provide information on fetal nutritional and metabolic health and could provide an early window of detection of potential health issues among newborns. The aim of the study was to explore the impact of maternal prepregnancy overweight/obesity and excessive GWG on cord blood metabolic profiles. METHODS: A case control study including 33 pairs of mothers with prepregnancy overweight/obesity and their neonates, 30 pairs of mothers with excessive GWG and their neonates, and 32 control mother-neonate pairs. Untargeted metabolomic profiling of umbilical cord blood samples were performed using UHPLC‒MS/MS. RESULTS: Forty-six metabolites exhibited a significant increase and 60 metabolites exhibited a significant reduction in umbilical cord blood from overweight and obese mothers compared with mothers with normal body weight. Steroid hormone biosynthesis and neuroactive ligand‒receptor interactions were the two top-ranking pathways enriched with these metabolites (P = 0.01 and 0.03, respectively). Compared with mothers with normal GWG, in mothers with excessive GWG, the levels of 63 metabolites were increased and those of 46 metabolites were decreased in umbilical cord blood. Biosynthesis of unsaturated fatty acids was the most altered pathway enriched with these metabolites (P < 0.01). CONCLUSIONS: Prepregnancy overweight and obesity affected the fetal steroid hormone biosynthesis pathway, while excessive GWG affected fetal fatty acid metabolism. This emphasizes the importance of preconception weight loss and maintaining an appropriate GWG, which are beneficial for the long-term metabolic health of offspring.

Plasma irisin and the brain-derived neurotrophic factor levels in sedentary subjects: effect of 8-weeks lifestyle intervention.

Objectives. Sedentary lifestyle increasingly observed in the population contributes to the incremental incidence of obesity, cardiovascular diseases, mental disorders, type 2 diabetes, hyper-tension, dyslipidemia, and others. Physical inactivity together with an imbalance in caloric intake and expenditure leads to a loss of muscle mass, reduced insulin sensitivity, and accumulation of the visceral fat. Organokines (adipokines, myokines, hepatokines, etc.) serve in the organism for inter-organ communication. However, human studies focused on the exercise-related changes in plasma levels of certain myokines have produced contradictory results. In the present study, we verified a hypothesis that myokine irisin, which is expected to increase in response to physical activity, induces brain-derived neurotrophic factor (BDNF) production and by this way mediates the beneficial effect of exercise on several brain functions. Subjects and Methods. Women (n=27) and men (n=10) aged 44.5±12.0 years, who were sedentary and overweight/obese (men ≥25%, women ≥28% body fat), participated in the study. The effect of an 8-week intensive lifestyle intervention (150 minutes of moderate physical activity per week, diet modification, and reduction of caloric intake) on the selected organokines (irisin, BDNF) in the context of an expected improvement in cardiometabolic status was examined. Results. The 8-week lifestyle intervention resulted in a significant (p<0.05) reduction in body mass index, body fat, blood pressure, insulin resistance, lipid and liver parameters, and irisin levels (p<0.001). However, BDNF increase in the whole group did not reach statistical significance. After the improvement of cardiometabolic parameters, a significant decrease in irisin and increase in BDNF levels were also observed in the subgroup with unsatisfactory (≤5%) body weight reduction. Neither relationship between irisin and BDNF levels, nor effect of age or sex on their levels was observed. Conclusions. We cannot confirm the hypothesis that exercise-induced irisin may increase the BDNF levels, whereas, the organokine levels in the periphery may not completely reflect the processes in the brain compartments. The observed decrease in irisin levels after 8-week intensive lifestyle intervention program, which was in contrary to its supposed mechanisms of action and dynamics, suggests the presence of several yet undiscovered impacts on the secretion of irisin.

Biochemical and Anthropometric Indices of Insulin Resistance in Obese and Overweight Children with Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND The prevalence of metabolic (dysfunction)-associated fatty liver disease (MAFLD) increases together with the epidemic of childhood obesity. An important mechanism in the phenomenon appears to be insulin resistance (IR), the assessment of which in children is problematic. The homeostatic model assessment of IR (HOMA-IR), commonly used for this, is not standardized and appears not to correlate with IR in the pediatric population. Therefore, our study aimed to evaluate potential substitute indices of IR, including the triglyceride-glucose index (TyG), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), modified TyG indices: TyG-waist circumference (TyG-WC) and TyG-body mass index (TyG-BMI) as surrogate markers of MAFLD in obese children suspected to have liver disease. MATERIAL AND METHODS The retrospective study included 264 obese children admitted to the Department to diagnose suspected liver disease. MAFLD was diagnosed according to the International Expert Consensus Statement. Anthropometric measurements and laboratory tests were made and the indices were calculated. Receiver operating characteristics analysis was performed to calculate the power of the indices. RESULTS MAFLD was diagnosed in 184 patients (70%). Obese children with MAFLD showed significantly higher activity of liver enzymes and concentration of total cholesterol, TG, WC, and waist-to-hip ratio compared to non-hepatopathic obese controls (n=80). The most important indices in identifying MAFLD were: TyG (AUC=0.641, p<0.001, cut-off =8.41, sensitivity=57.4%, specificity=68.8%), and TG/HDL-C (AUC=0.638, p<0.001, cut-off=2.5, sensitivity=48.6%, specificity=76.3%). TyG-BMI and HOMA-IR were not useful predictors. CONCLUSIONS TyG and TG/HDL-C can be considered as potential surrogate biomarkers in predicting MAFLD in obese children.

Associations between non-insulin-based insulin resistance indices and heart failure prevalence in overweight/obesity adults without diabetes mellitus: evidence from the NHANES 2001-2018.

BACKGROUND: The triglyceride glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio are recognized as simple non-insulin-based insulin resistance indices. Our study aimed to explore the relationship between these two indicators and heart failure (HF) in overweight or obesity individuals without diabetes. METHODS: This cross-sectional study selected 13,473 participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018 dataset. Weighted multivariable logistic regression and subgroup analysis were employed to evaluate the relationships between TyG index, TG/HDL-C ratio, and HF prevalence, respectively. Additionally, smooth curve fitting was utilized to analyze the dose-response relationships. RESULTS: A total of 13,473 obesity or overweight people without diabetes were included in this study through screening, among whom 291 (2.16%) had comorbid HF. The results of multivariable logistic regression suggested that the highest TyG index (OR = 2.4, 95% CI = 1.4-4.2, p = 0.002) and the highest TG/HDL-C ratio (OR = 1.2, 95% CI = 1.1-1.3, p < 0.001) both increased the prevalence of HF, especially in the non-Hispanic population. Dose-response relationships suggested nonlinear relationships between these two indicators and HF. CONCLUSION: Our study demonstrated that elevated TyG index and TG/HDL-C ratio were closely associated with the prevalence of HF, and both exhibited nonlinear relationships with HF prevalence in overweight/obesity adults without diabetes. Based on these findings, additional prospective studies are needed for further validation.

Effect of body mass index on progesterone level on trigger day in gonadotropin-releasing hormone antagonist cycles.

OBJECTIVE: To investigate the effect of body mass index (BMI) on progesterone (P) level on trigger day in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles. METHODS: This study was a retrospective cohort study. From October 2017 to April 2022, 412 in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) patients who were treated with GnRH-ant protocol for controlled ovarian hyperstimulation (COH) in the reproductive center of our hospital were selected as the research objects. Patients were divided into three groups according to BMI level: normal weight group (n = 230):18.5 kg/m2≤BMI < 24 kg/m2; overweight group (n = 122): 24 kg/m2≤BMI < 28 kg/m2; Obesity group (n = 60): BMI ≥ 28 kg/m2. Variables with p < .10 in univariate analysis (BMI, basal FSH, basal P, FSH days, Gn starting dose and E2 level on trigger day) and variables that may affect P level on trigger day (infertility factors, basal LH, total FSH, HMG days and total HMG) were included in the multivariate logistic regression model to analyze the effect of BMI on P level on trigger day of GnRH-ant protocol. RESULTS: After adjustment for confounding factors, compared with that in normal weight patients, the risk of serum P elevation on trigger day was significantly lower in overweight and obese patients (OR = 0.434 and 0.199, respectively, p < .05). CONCLUSION: The risk of P elevation on trigger day in GnRH-ant cycles decreased with the increase of BMI, and BMI could be used as one of the predictors of P level on trigger day in GnRH-ant cycles.

A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.

Dietary choline and betaine intake, cardio-metabolic risk factors and prevalence of metabolic syndrome among overweight and obese adults.

BACKGROUND: Choline is an important metabolite involved in phospholipids synthesis, including serum lipids, and is the immediate precursor of betaine. There are numerous studies with inconsistent results that evaluated the association between dietary choline intakes with cardiovascular risk factors. In addition, the association between dietary betaine and choline intakes with cardio-metabolic risk factors is not well studied. In the current study, our aim was to evaluate dietary choline and betaine intakes in the usual diet of obese individuals and to assess its association with serum lipids, blood pressure and glycemic markers among obese individuals. METHODS: We recruited a total number of 359 obese people aged between 20 and 50 years in the present study. A semi-quantitative food frequency questionnaire (FFQ) was used for dietary assessment; dietary choline and betaine intakes were calculated using the United States Department of Agriculture (USDA) database. National cholesterol education program adult treatment panel (NCEP-ATP)-III criteria was used metabolic syndrome (MetS) definition. Enzymatic methods were used to assess biochemical variables. Body composition was measured with the bioelectrical impedance analysis (BIA) method. RESULTS: Higher body mass index (BMI), waist to hip ratio (WHR), fat-free mass (FFM) and basal metabolic rate (BMR) were observed in higher tertiles of dietary choline intake (P < 0.01). There was no significant difference in terms of biochemical parameters among different tertiles of dietary choline intake, while systolic blood pressure (SBP) and diastolic blood pressure (DBP) were reduced in higher betaine tertiles (P < 0.05). For total dietary choline and betaine intakes, there was a reduction in DBP and low density lipoprotein (LDL) concentrations (P < 0.05). Also, a non-significant reduction in serum total cholesterol (TC), triglyceride (TG) and MetS prevalence was observed in higher tertiles of dietary choline and betaine intakes. After classification of the study population according to MetS status, there was no significant difference in biochemical variables in subjects with MetS (P > 0.05), while in the non-MetS group, SBP, DBP, TG and insulin levels reduced in higher tertiles of dietary betaine and choline (P > 0.05). CONCLUSION: According to our findings, higher dietary intakes of choline and betaine were associated with lower levels of blood pressure and LDL concentrations among obese individuals. Further studies are warranted to confirm the results of the current study.

Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10-7, range P = 9.2 × 10-8 to 6.0 × 10-46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10-6, range P = 5.5 × 10-6 to 6.1 × 10-35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.

Marginal Impact of Brown Seaweed Ascophyllum nodosum and Fucus vesiculosus Extract on Metabolic and Inflammatory Response in Overweight and Obese Prediabetic Subjects.

The objective of the present study was to test whether a brown seaweed extract rich in polyphenols combined with a low-calorie diet would induce additional weight loss and improve blood glucose homeostasis in association with a metabolic and inflammatory response in overweight/obese prediabetic subjects. Fifty-six overweight/obese, dysglycemic, and insulin-resistant men and women completed a randomized, placebo-controlled, double-blind, and parallel clinical trial. Subjects were administrated 500 mg/d of either brown seaweed extract or placebo combined with individualized nutritional advice for moderate weight loss over a period of 12 weeks. Glycemic, anthropometric, blood pressure, heart rate, body composition, lipid profile, gut integrity, and oxidative and inflammatory markers were measured before and at the end of the trial. No effect was observed on blood glucose. We observed significant but small decreases in plasma C-peptide at 120 min during 2 h-OGTT (3218 ± 181 at pre-intervention vs. 2865 ± 186 pmol/L at post-intervention in the brown seaweed group; 3004 ± 199 at pre-intervention vs. 2954 ± 179 pmol/L at post-intervention in the placebo group; changes between the two groups, p = 0.002), heart rate (72 ± 10 at pre-intervention vs. 69 ± 9 (n/min) at post-intervention in the brown seaweed group; 68 ± 9 at pre-intervention vs. 68 ± 8 (n/min) at post-intervention in the placebo group; changes between the two groups, p = 0.01), and an inhibition in the increase of pro-inflammatory interleukin-6 (IL-6) (1.3 ± 0.7 at pre-intervention vs. 1.5 ± 0.7 pg/L at post-intervention in the brown seaweed group; 1.4 ± 1.1 at pre-intervention vs. 2.2 ± 1.6 pg/L at post-intervention in the placebo group; changes between the two groups, p = 0.02) following brown seaweed consumption compared with placebo in the context of moderate weight loss. Although consumption of brown seaweed extract had no effect on body weight or blood glucose, an early attenuation of the inflammatory response was observed in association with marginal changes in metabolic parameters related to the prevention of diabetes type 2.

The effects of dapagliflozin, metformin or exercise on glycaemic variability in overweight or obese individuals with prediabetes (the PRE-D Trial): a multi-arm, randomised, controlled trial.

AIMS/HYPOTHESIS: We aimed to investigate the short-term efficacy and safety of three glucose-lowering interventions in overweight or obese individuals with prediabetes defined by HbA1c. METHODS: The PRE-D Trial was a randomised, controlled, parallel, multi-arm, open-label, non-blinded trial performed at Steno Diabetes Center Copenhagen, Gentofte, Denmark. One hundred and twenty participants with BMI ≥25 kg/m2, 30-70 years of age, and prediabetes (HbA1c 39-47 mmol/mol [5.7-6.4%]) were randomised 1:1:1:1 to dapagliflozin (10 mg once daily), metformin (1700 mg daily), interval-based exercise (5 days/week, 30 min/session) or control (habitual lifestyle). Participants were examined at baseline and at 6, 13 and 26 weeks after randomisation. The primary outcome was the 13 week change in glycaemic variability (calculated as mean amplitude of glycaemic excursions [MAGE]) determined using a continuous glucose monitoring system (pre-specified minimal clinically important difference in MAGE ∼30%). RESULTS: One hundred and twelve participants attended the examination at 13 weeks and 111 attended the follow-up visit at 26 weeks. Compared with the control group, there was a small decrease in MAGE in the dapagliflozin group (17.1% [95% CI 0.7, 30.8], p = 0.042) and a small, non-significant, reduction in the exercise group (15.3% [95% CI -1.2, 29.1], p = 0.067), whereas MAGE was unchanged in the metformin group (0.1% [95% CI -16.1, 19.4], p = 0.991)). Compared with the metformin group, MAGE was 17.2% (95% CI 0.8, 30.9; p = 0.041) lower in the dapagliflozin group and 15.4% (95% CI -1.1, 29.1; p = 0.065) lower in the exercise group after 13 weeks, with no difference between exercise and dapagliflozin (2.2% [95% CI -14.8, 22.5], p = 0.815). One serious adverse event occurred in the control group (lung cancer). CONCLUSIONS/INTERPRETATION: Treatment with dapagliflozin and interval-based exercise lead to similar but small improvements in glycaemic variability compared with control and metformin therapy. The clinical importance of these findings in prediabetes is uncertain. TRIAL REGISTRATION: ClinicalTrials.gov NCT02695810 FUNDING: The study was funded by the Novo Nordisk Foundation, AstraZeneca AB, the Danish Innovation Foundation, the University of Copenhagen and Ascensia Diabetes Care Denmark ApS Graphical abstract.

Associations between ghrelin and leptin and neural food cue reactivity in a fasted and sated state.

Food cue exposure can trigger eating. Food cue reactivity (FCR) is a conditioned response to food cues and includes physiological responses and activation of reward-related brain areas. FCR can be affected by hunger and weight status. The appetite-regulating hormones ghrelin and leptin play a pivotal role in homeostatic as well as hedonic eating. We examined the association between ghrelin and leptin levels and neural FCR in the fasted and sated state and the association between meal-induced changes in ghrelin and neural FCR, and in how far these associations are related to BMI and HOMA-IR. Data from 109 participants from three European centers (age 50±18 y, BMI 27±5 kg/m2) who performed a food viewing task during fMRI after an overnight fast and after a standardized meal were analyzed. Blood samples were drawn prior to the viewing task in which high-caloric, low-caloric and non-food images were shown. Fasting ghrelin was positively associated with neural FCR in the inferior and superior occipital gyrus in the fasted state. This was partly attributable to BMI and HOMA-IR. These brain regions are involved in visual attention, suggesting that individuals with higher fasting ghrelin have heightened attention to food cues. Leptin was positively associated with high calorie FCR in the medial prefrontal cortex (PFC) in the fasted state and to neural FCR in the left supramarginal gyrus in the fasted versus sated state, when correcting for BMI and HOMA-IR, respectively. This PFC region is involved in assessing anticipated reward value, suggesting that for individuals with higher leptin levels high-caloric foods are more salient than low-caloric foods, but foods in general are not more salient than non-foods. There were no associations between ghrelin and leptin and neural FCR in the sated state, nor between meal-induced changes in ghrelin and neural FCR. In conclusion, we show modest associations between ghrelin and leptin and neural FCR in a relatively large sample of European adults with a broad age and BMI range. Our findings indicate that people with higher leptin levels for their weight status and people with higher ghrelin levels may be more attracted to high caloric foods when hungry. The results of the present study form a foundation for future studies to test whether food intake and (changes in) weight status can be predicted by the association between (mainly fasting) ghrelin and leptin levels and neural FCR.

Effects of Totum-63 on glucose homeostasis and postprandial glycemia: a translational study.

Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg·m-2] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5 g·day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.

The correlation between serum inflammatory, antioxidant, glucose handling biomarkers, and Dietary Antioxidant Index (DAI) and the role of DAI in obesity/overweight causation: population-based case-control study.

BACKGROUND: Obesity is a multifactorial disease, and about 40% of world adults are overweight, and about 20% are obese. Diet is one of the most important factors in the causality of obesity. The interactions between the diet and gut microbiota or chronic inflammation pathways highlight the importance of its various aspects in the incidence and prevalence of obesity. At the same time, diet is a combination of several antioxidants that are needed together for the body's antioxidant system. The Dietary Antioxidant Index (DAI) is a valid nutritional tool, and its correlation has been studied concerning total antioxidant capacity and malondialdehyde. The study aimed to examine the relationship between the DAI and the odds of obesity. We hypothesized that a higher DAI score indicating a predominantly antioxidant diet has a protective effect against odds of obesity. METHODS: In this population-based case-control study, 812 participants with a higher body mass index (BMI) than 25 were selected as the case group. Also, 793 participants with BMI in the range of 17.9-24.9 were selected as the control group. A valid and reliable 124-item food frequency questionnaire (FFQ) was used to assess dietary intake. Based on FFQ data, we summed up the standardized intake of the major dietary antioxidants, including vitamin A, E, C, selenium, zinc, and manganese, to calculate DAI. RESULTS: In a multivariable adjusting model, there was a significant association between DAI (as a continuous variable) and BMI (odds ratio (OR) = 0.95; 95% CI: 0.92-0.99; P value = 0.02). Also, there was a significant association between DAI (as a categorized variable) and body surface area with multivariable adjusting model (OR = 0.79; 95% CI: 0.64-0.98; P value = 0.04). CONCLUSION: In conclusion, the DAI can accurately predict some serum antioxidant and anti-inflammatory levels along with glucose handling markers.

Walking Initiated 20 Minutes before the Time of Individual Postprandial Glucose Peak Reduces the Glucose Response in Young Men with Overweight or Obesity: A Randomized Crossover Study.

BACKGROUND: Although a single bout of postmeal exercise can lower postprandial glucose (PPG), its optimal timing remains unclear. OBJECTIVE: This study aimed to investigate the effect of exercise timing using an individualized approach on PPG in overweight or obese young men. METHODS: Twenty men [age: 23.0 ± 4.3 y; BMI (kg/m2): 27.4 ± 2.8] each completed three 240-min trials in a randomized order separated by 6-14 d: 1) sitting (SIT), 2) walking initiated at each participant's PPG-peak time (PPGP) (iP), and 3) walking initiated 20 min before the PPGP (20iP). For each participant, PPGP was predetermined using continuous glucose monitoring. Walking was performed at 50% maximal oxygen consumption for 30 min. Venous blood was collected at 15- and 30-min intervals for 0-120 min and 120-240 min, respectively. The primary outcome was plasma PPG. Generalized estimating equations were used for comparison between trials. RESULTS: Compared with SIT, the 4-h incremental AUCs (iAUCs) for plasma PPG (-0.6 mmol · L-1 · h; P = 0.047) and insulin (-28.7%, P < 0.001) were reduced in 20iP only, and C-peptide concentrations were lower after iP (-14.9%, P = 0.001) and 20iP (-28.7%, P < 0.001). Plasma insulin (-11.1%, P = 0.006) and C-peptide (-8.3%, P = 0.012) were lower due to the 20iP compared with iP treatment. Finally, PPG reductions due to iP and 20iP occurred only in men with a BMI > 27.5 kg/m2 (iP, -11.2%; 20iP, -14.7%; P = 0.047) and higher glucose iAUC values during SIT (iP, -25.5%; 20iP, -25.7%; P < 0.001). CONCLUSIONS: Walking initiated 20 min before PPGP lowered PPG and plasma insulin and C-peptide concentrations in young men with overweight or obesity, in particular in those with high BMI or glucose iAUC values during SIT; it also lowered plasma insulin and C-peptide concentrations more effectively than did exercise initiated at PPGP. This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) as ChiCTR1900023175.

Overweight with HBV infection limited the efficacy of TACE in hepatocellular carcinoma by inhibiting the upregulated HMGB1.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective treatment for patients with hepatocellular carcinoma (HCC). However, the impact of hepatitis B viral (HBV) infection and body mass index (BMI) on TACE is controversial. The present study aimed to compare the influence of HBV and high BMI on TACE outcomes in advanced HCC. METHODS: Based on HBV infection history and BMI, patients were assigned to different subgroups. Blood samples were collected and analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. The primary endpoint was progression-free survival (PFS) and the overall survival (OS) in the population. RESULTS: Compared to overweight combined HBV patients who received TACE, people with normal weight or no viral infection had significantly better OS and PFS. Sex, age, portal vein tumor thrombus, BCLC, ECOG, and tumor diameter are the main risk factors affecting PFS and OS. Except for the postoperative fever, no significant difference was detected in adverse reactions. Irrespective of TACE, the average expression of HMGB1 in hepatitis or obesity patients was higher than that in normal individuals and did not show upregulation after TACE. Patients without overweight or HBV infection had a low expression of serum HMGB1 that was substantially upregulated after TACE. CONCLUSIONS: In this study, overweight combined HBV infection patients had shorter PFS and OS than other HCC patients. Thus, HBV and BMI maybe two factors affecting the efficacy of TACE via upregulated HMGB1.