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Effects of 12-Week Combined Strength and Endurance Circuit Training Program on Insulin Sensitivity and Retinol-Binding Protein 4 in Women with Insulin-Resistance and Overweight or Mild Obesity: A Randomized Controlled Trial.
Ratajczak, M, Krzywicka, M, Szulińska, M, Musiałowska, D, Kusy, K, Karolkiewicz, J
Diabetes, metabolic syndrome and obesity : targets and therapy. 2024;:93-106
Abstract
BACKGROUND Circuit training is an exercise mode, that may include both endurance and resistance components. There are premises that a combination of these two modalities brings additional benefits, particularly in improving insulin sensitivity. The retinol-binding protein 4 (RBP4) may inhibit signaling from insulin metabolic pathways in skeletal muscles, thus developing insulin resistance. This study aimed to evaluate whether moderate intensity circuit training combining strength and endurance exercise induces changes in tissue insulin sensitivity, carbohydrate and lipid metabolism, and serum RBP4 levels in insulin-resistant women. METHODS In this clinical controlled trial women diagnosed with insulin-resistance were randomly divided into two groups. The training group (T) performed circuit training combining strength (50%-80%1RM) and endurance (50%-75%HRR) exercise on five weight and two cardio machines, for 33 minutes, three times per week, for 3 months. Women from the control non-training group (NT) did not change their previous physical activity. At the beginning of the study and after the intervention period, a one-repetition maximum, body mass, and composition, resting heart rate (HR), blood pressure, glucose, insulin, blood lipids, thyroid-stimulating hormone (TSH), insulin-like growth factor-1 (IGF-1), RBP4, and insulin resistance (HOMA-IR) were measured. The results of 27 patients were analyzed using a two-way repeated measures ANOVA. RESULTS Significant differences in the pattern of change over time between the groups for resting HR (p < 0.010) and total lean mass (p < 0.039) were found. No differences in HOMA-IR, and RBP4 were observed post-study compared to pre-study in the T group. A significant correlation between RBP4 and TSH concentration was found. CONCLUSION Twelve-week circuit training combining strength and endurance exercise has minor effects on HOMA-IR, glucose and lipid metabolism, IGF-1, TSH, and RBP4. Although moderate-intensity circuit training is considered safe, its effectiveness in patients with overweight and mild obesity may be insufficient to reduce insulin resistance. TRIAL REGISTRATION ClinicalTrials.gov: NCT04528693, registered August 23, 2020.
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The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.
Wang, M, Luan, R, Liu, B, Gong, Y, Zhao, J, Chen, X, Yang, Q, Liu, J, Liu, J, Shao, Y, et al
Diabetes, metabolic syndrome and obesity : targets and therapy. 2024;:1199-1213
Abstract
PURPOSE To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). METHODS This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. RESULTS The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). CONCLUSION Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. CLINICAL TRIAL REGISTRATION This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).
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Deep learning-based BMI inference from structural brain MRI reflects brain alterations following lifestyle intervention.
Finkelstein, O, Levakov, G, Kaplan, A, Zelicha, H, Meir, AY, Rinott, E, Tsaban, G, Witte, AV, Blüher, M, Stumvoll, M, et al
Human brain mapping. 2024;(3):e26595
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Abstract
Obesity is associated with negative effects on the brain. We exploit Artificial Intelligence (AI) tools to explore whether differences in clinical measurements following lifestyle interventions in overweight population could be reflected in brain morphology. In the DIRECT-PLUS clinical trial, participants with criterion for metabolic syndrome underwent an 18-month lifestyle intervention. Structural brain MRIs were acquired before and after the intervention. We utilized an ensemble learning framework to predict Body-Mass Index (BMI) scores, which correspond to adiposity-related clinical measurements from brain MRIs. We revealed that patient-specific reduction in BMI predictions was associated with actual weight loss and was significantly higher in active diet groups compared to a control group. Moreover, explainable AI (XAI) maps highlighted brain regions contributing to BMI predictions that were distinct from regions associated with age prediction. Our DIRECT-PLUS analysis results imply that predicted BMI and its reduction are unique neural biomarkers for obesity-related brain modifications and weight loss.
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Probiotics and Prebiotics in Subclinical Hypothyroidism of Pregnancy with Small Intestinal Bacterial Overgrowth.
Ouyang, Q, Xu, Y, Ban, Y, Li, J, Cai, Y, Wu, B, Hao, Y, Sun, Z, Zhang, M, Wang, M, et al
Probiotics and antimicrobial proteins. 2024;(2):579-588
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Evaluating efficacy of probiotics combined with prebiotics in small intestinal bacterial overgrowth (SIBO) in subclinical hypothyroidism (SCH) in the second trimester. We collected data from 78 pregnant women with SCH (SCH group) and 74 normal pregnant women (control group) in second trimester, compare the differences in high sensitivity C-reactive protein (hsCRP), result of lactulose methane-hydrogen breath test and gastrointestinal symptoms assessed by GSRS scale between two groups. In SCH group, 32 patients with SIBO were selected as intervention group. Treatment with probiotics + prebiotics for 21 days; The differences of lipid metabolism, hsCRP, thyroid function level, methane-hydrogen breath test results and GSRS scores before and after treatment were compared to evaluate the therapeutic effect. (1) The positive rate of SIBO and methane, hsCRP levels in SCH group were higher than those in control group (P < 0.05), the total score of GSRS scale, mean score of indigestion syndrome, and constipation syndrome in SCH group were higher (P < 0.05). (2) The mean abundance of hydrogen and methane were higher in SCH group. (3) After treatment, serum levels of thyrotropin(TSH), total cholesterol(TC), triglyceride(TG), low-density lipoprotein (LDL), and hsCRP in intervention group were decreased, and high-density lipoprotein (HDL) was increased compared with before treatment (P < 0.05). (4) After treatment, methane positive rate, total score of GSRS scale, mean score of diarrhea syndrome, dyspepsia syndrome, and constipation syndrome were decreased (P < 0.05). (5) The average abundance of methane and hydrogen were lower. Probiotics combined with prebiotics are effective in the treatment of SIBO in pregnant SCH patients.Clinical Trial Registration Number: ChiCTR1900026326.
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The Efficacy of Chaihu-Guizhi-Ganjiang Decoction on Chronic Non-Atrophic Gastritis with Gallbladder Heat and Spleen Cold Syndrome and Its Metabolomic Analysis: An Observational Controlled Before-After Clinical Trial.
Wen, T, Liu, X, Pang, T, Li, M, Jiao, G, Fan, X, Tang, J, Zhang, C, Wang, Z, Yue, X, et al
Drug design, development and therapy. 2024;:881-897
Abstract
PURPOSE The aim of this study was to verify the effectiveness and explore the mechanism of Chaihu-Guizhi-Ganjiang decoction (CGGD) in the treatment of chronic non-atrophic gastritis (CNAG) with gallbladder heat and spleen cold syndrome (GHSC) by metabolomics based on UHPLC-Q-TOF/MS. PATIENTS AND METHODS An observational controlled before-after study was conducted to verify the effectiveness of CGGD in the treatment of CNAG with GHSC from January to June 2023, enrolling 27 patients, who took CGGD for 28 days. 30 healthy volunteers were enrolled as the controls. The efficacy was evaluated by comparing the traditional Chinese medicine (TCM) syndrome and CNAG scores, and clinical parameters before and after treatment. The plasma levels of hormones related to gastrointestinal function were collected by ELISA. The mechanisms of CGGD in the treatment of CNAG with GHSC were explored using a metabolomic approach based on UHPLC-Q-TOF/MS. RESULTS Patients treated with CGGD experienced a statistically significant improvement in TCM syndrome and CNAG scores (p < 0.01). CGGD treatment evoked the concentration alteration of 15 biomarkers, which were enriched in the glycerophospholipid metabolism, and branched-chain amino acids biosynthesis pathways. Moreover, CGGD treatment attenuated the abnormalities of the gastrointestinal hormone levels and significantly increased the pepsinogen level. CONCLUSION It was the first time that this clinical trial presented detailed data on the clinical parameters that demonstrated the effectiveness of CGGD in the treatment of CNAG with GHSC patients. This study also provided supportive evidence that CNAG with GHSC patients were associated with disturbed branched-chain amino acid metabolism and glycerophospholipid levels, suggesting that CNAG treatment based on TCM syndrome scores was reasonable and also provided a potential pharmacological mechanism of action of CGGD.
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Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial.
Sethi, S, Wakeham, D, Ketter, T, Hooshmand, F, Bjornstad, J, Richards, B, Westman, E, Krauss, RM, Saslow, L
Psychiatry research. 2024;:115866
Abstract
The ketogenic diet (KD, also known as metabolic therapy) has been successful in the treatment of obesity, type 2 diabetes, and epilepsy. More recently, this treatment has shown promise in the treatment of psychiatric illness. We conducted a 4-month pilot study to investigate the effects of a KD on individuals with schizophrenia or bipolar disorder with existing metabolic abnormalities. Twenty-three participants were enrolled in a single-arm trial. Results showcased improvements in metabolic health, with no participants meeting metabolic syndrome criteria by study conclusion. Adherent individuals experienced significant reduction in weight (12 %), BMI (12 %), waist circumference (13 %), and visceral adipose tissue (36 %). Observed biomarker enhancements in this population include a 27 % decrease in HOMA-IR, and a 25 % drop in triglyceride levels. In psychiatric measurements, participants with schizophrenia showed a 32 % reduction in Brief Psychiatric Rating Scale scores. Overall Clinical Global Impression (CGI) severity improved by an average of 31 %, and the proportion of participants that started with elevated symptomatology improved at least 1-point on CGI (79 %). Psychiatric outcomes across the cohort encompassed increased life satisfaction (17 %) and enhanced sleep quality (19 %). This pilot trial underscores the potential advantages of adjunctive ketogenic dietary treatment in individuals grappling with serious mental illness.
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Predictors of long-term absence of coronary artery calcium in individuals with high blood pressure: results from the MESA study.
You, S, Gao, JW, Zhang, HF, Xiong, ZC, Hao, QY, Han, JJ, Wang, JF, Zhang, SL, Liu, PM
Annals of medicine. 2023;(1):2209334
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BACKGROUND & AIMS Individuals with high blood pressure (BP) have varying risks of cardiovascular events due to other coexisting factors. We aimed to identify the predictors of long-term absence of coronary artery calcium (CAC) in individuals with high BP, which is an indicator of healthy arterial aging and can guide preventive strategies. METHODS We analyzed data from participants with high BP (≥120/80 mm Hg) in the Multi-Ethnic Study of Atherosclerosis who had baseline CAC = 0 and underwent a second CAC scanning after 10 years. We used multivariable logistic regression to evaluate the association between various risk factors for atherosclerotic cardiovascular disease (ASCVD) and long-term CAC = 0. We also calculated the area under the receiver operating characteristic curve (AUC) to predict the phenotype of healthy arterial aging in this population. RESULTS We included 830 participants (37.6% male, mean ± SD age of 59.4 ± 8.7 years). During follow-up, 46.5% of participants (n = 386) had CAC = 0, and they were younger and had fewer metabolic syndrome components. Adding ASCVD risk factors to the demographic model (age, sex, and ethnicity) moderately increased the predictive value for long-term CAC = 0 (AUC: demographic model + ASCVD risk factors vs. demographic model alone, 0.653 vs. 0.597, p < .001; category net reclassification improvement = 0.104, p = .044; integrated discrimination improvement = 0.040, p < .001). CONCLUSION In individuals with high BP and initial CAC = 0, over 40% maintained CAC = 0 during a 10-year follow-up, which was associated with fewer ASCVD risk factors. These findings may have implications for preventive strategies in individuals with high BP.Clinical Trial registration number: The MESA was registered at clinical trials. gov as NCT00005487.KEY MESSAGESNearly half (46.5%) of individuals with high blood pressure (BP) maintained a long-term absence of coronary artery calcium (CAC) during a 10-year follow-up, and this was associated with a 66.6% lower risk of atherosclerotic cardiovascular disease (ASCVD) events compared to those who developed incident CAC.Individuals with high BP, who are usually assumed to have an increased risk of ASCVD, exhibit significant heterogeneity in their ASCVD risk; those who maintain CAC = 0 have a lower ASCVD risk.Adding overall ASCVD risk factors to demographic information resulted in a moderate improvement in predicting long-term CAC = 0.
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Serum, Urine, and Fecal Metabolome Alterations in the Gut Microbiota in Response to Lifestyle Interventions in Pediatric Obesity: A Non-Randomized Clinical Trial.
Lee, Y, Cho, JY, Cho, KY
Nutrients. 2023;15(9)
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Paediatric obesity is linked to an increased risk of type 2 diabetes, hypertension, dyslipidaemia, and metabolic syndrome. Diverse evidence suggests that obesity is associated with alterations in the gut microbiota and its metabolites. The aim of this study was to understand the metabolic pathways underlying paediatric obesity and the effect of intervention, which could provide guidance for the treatment of obesity. This study was a non-randomised clinical trial which enrolled 50 children with obesity and 22 normal-weight children aged 7–18 years. Results showed that imbalances in microbiota and metabolites were associated with both obesity and response to the intervention. The most distinct metabolic alterations in the obese group were branched-chain amino acid and purine changes. Authors conclude that the findings of their study could be valuable for identifying novel targets and biomarkers for the treatment of obesity.
Abstract
Pediatric obesity is associated with alterations in the gut microbiota and its metabolites. However, how they influence obesity and the effect of lifestyle interventions remains unknown.. In this non-randomized clinical trial, we analyzed metabolomes and microbial features to understand the associated metabolic pathways and the effect of lifestyle interventions on pediatric obesity. Anthropometric/biochemical data and fasting serum, urine, and fecal samples were collected at baseline and after an eight-week, weight-reduction lifestyle modification program. Post-intervention, children with obesity were classified into responder and non-responder groups based on changes in total body fat. At baseline, serum L-isoleucine and uric acid levels were significantly higher in children with obesity compared with those in normal-weight children and were positively correlated with obesogenic genera. Taurodeoxycholic and tauromuricholic α + β acid levels decreased significantly with obesity and were negatively correlated with obesogenic genera. Branched-chain amino acid and purine metabolisms were distinguished metabolic pathways in the obese group. Post-intervention, urinary myristic acid levels decreased significantly in the responder group, showing a significant positive correlation with Bacteroides. Fatty acid biosynthesis decreased significantly in the responder group. Thus, lifestyle intervention with weight loss is associated with changes in fatty acid biosynthesis, and myristic acid is a possible therapeutic target for pediatric obesity.
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Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis.
Gómez-Pérez, AM, Ruiz-Limón, P, Salas-Salvadó, J, Vioque, J, Corella, D, Fitó, M, Vidal, J, Atzeni, A, Torres-Collado, L, Álvarez-Sala, A, et al
Gut microbes. 2023;15(1):2223339
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Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease. The aim of this study was to evaluate the changes in the microbiota associated with changes in biochemical markers of NAFLD/NASH after an intervention. This substudy was conducted in the frame of the PREDIMED-Plus study, a 6-year, multicentre, randomised clinical trial for primary prevention of cardiovascular disease (CVD) conducted in men aged 55–75 years and women aged 60–75 years with overweight or obesity and metabolic syndrome. Results showed a relationship between liver disease biochemical indexes changes and gut microbiota changes within a context of a Mediterranean lifestyle. In fact, two noninvasive scores for liver steatosis and liver fibrosis, usually used in clinical practice, could differentiate gut microbiota populations. Authors conclude that their findings highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.
Abstract
To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations. What You Need to KnowWhat is the context:Obesity and metabolic syndrome have been associated with nonalcoholic fatty liver disease (NAFLD). Gut microbiota and its interaction with the environment may play a key role in NAFLD.What is new:Mediterranean diet and physical activity can modify the scores for liver steatosis (HSI) and liver fibrosis (FIB−4) in only one year. A relation between the changes in these scores and gut microbiota changes was found.What is the impact:The discovery of microbiota-based biomarkers for NAFLD and the development of strategies to modulate gut microbiota in the treatment of NAFLD.
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An insight into the functional alterations in the gut microbiome of healthy adults in response to a multi-strain probiotic intake: a single arm open label trial.
Rodenes-Gavidia, A, Lamelas, A, Bloor, S, Hobson, A, Treadway, S, Haworth, J, Vijayakumar, V, Naghibi, M, Day, R, Chenoll, E
Frontiers in cellular and infection microbiology. 2023;13:1240267
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The human gut microbiota is a key mediator of host health and is known to affect many physiological processes, such as digestion, metabolism, immune function and inhibition of pathogen colonisation. The gut microbiome can be impacted by many extrinsic factors. The aim of this study was to assess both compositional and functional changes in the microbiome of healthy individuals using shotgun metagenomics following 8-weeks of daily multi-strain probiotic intake. This study was a single-arm open-label study which enrolled a total of 41 healthy adult males and females between 18 to 40 years old. Results showed that alpha- and beta-diversity of the faecal microbiota structure was not significantly altered in response to probiotic intake. However, significant changes were observed when functional genes were assessed. Abundance of certain genes involved in several functional pathways were also significantly altered. Additionally, there were no significant changes in stool frequency or consistency, faecal biochemistry, or breath tests of methane and hydrogen observed. Authors conclude that the findings of their study have the potential to provide insights into the underlying mechanisms of action of the 14-strain probiotic blend in healthy adults.
Abstract
BACKGROUND Probiotic supplements, by definition, provide a benefit to the host, but few studies have investigated the effect of probiotic supplements in healthy adult populations. PURPOSE The present, single arm, open label clinical trial, evaluated compositional and functional changes in the fecal microbiome of healthy adults after supplementation with a 14-strain probiotic. METHODS We analysed the effect of a 14-strain probiotic blend (Bacillus subtilis NCIMB 30223, Bifidobacterium bifidum NCIMB 30179, B. breve NCIMB 30180, B. infantis NCIMB 30181, B. longum NCIMB 30182, Lactobacillus helveticus NCIMB 30184, L. delbrueckii subsp. bulgaricus NCIMB 30186, Lacticaseibacillus paracasei NCIMB 30185, Lactiplantibacillus plantarum NCIMB 30187, Lacticaseibacillus rhamnosus NCIMB 30188, L. helveticus NCIMB 30224, Lactobacillus salivarius NCIMB 30225, Lactococcus lactis subsp. lactis NCIMB 30222, and Streptococcus thermophilus NCIMB 30189), on the faecal microbiota of healthy young adults (n=41) in a single arm study. The adults consumed 4 capsules daily of the 14 strain blend(8 billion colony forming units/day) for 8 weeks. Compositional and functional changes in faecal microbiota before and after supplementation were assessed using shotgun metagenomic sequencing. Fasting breath analysis, faecal biochemistry and bowel habits were also assessed. RESULTS In healthy adult participants, no significant changes to the overall alpha- or beta-diversity was observed after 8 weeks of multi-strain probiotic supplementation. However, in a simplified model that considered only time and individual differences, significant decreases (p < 0.05) in family Odoribacteraceae and Bacteroidaceae abundance and a significant increase (p < 0.05) in genus Megamonas abundance were observed. At a functional level, there were significant changes in functional gene abundance related to several functional pathways, including phenylalanine metabolism, O-antigen nucleotide sugar biosynthesis, bacterial chemotaxis, and flagellar assembly. No significant changes in stool form or frequency, fecal biochemistry, or methane and hydrogen breath tests were observed. CONCLUSION In healthy young adults, overall alpha- and beta-diversity did not change in response to probiotic intake even though modest compositional changes at the family and genus level were observed. However, at functional level, results identified changes in gene abundance for several functional pathways.