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Adverse Effects of Selected Markers on the Metabolic and Endocrine Profiles of Obese Women With and Without PCOS.
Daghestani, MH, Daghestani, MH, Warsy, A, El-Ansary, A, Omair, MA, Omair, MA, Hassen, LM, Alhumaidhi, EM, Al Qahtani, B, Harrath, AH
Frontiers in endocrinology. 2021;:665446
Abstract
The aim of the present study, is to investigate the influence of obesity, with and without polycystic ovarian syndrome (PCOS), on the levels of kisspeptin, vitamin D (Vit D), and vascular endothelial growth factor (VEGF) and to explore the relationship between these parameters and endocrine and metabolic variables. The study group included 126 obese Saudi females. Of these 63 were suffering from PCOS while the rest were normo-ovulatory obese women (non-PCOS obese). In the obese PCOS, VEGF was almost four times as high as in the non-PCOS obese, while kisspeptin and Vit D did not differ. A highly significant elevation was recorded in the waist/hip (WHR), cholesterol, LDL-C, fasting glucose, LH, LH/FSH ratio, estradiol (E2), and testosterone, while hip circumference, leptin, progesterone, and sex hormone binding globulin (SHBG) were lower in the obese PCOS subjects. BMI, HDL-C, ghrelin, insulin, and FSH levels did not differ significantly between the two groups. The obese PCOS had the same level of insulin resistance as the non-PCOS group, as judged by QUICK Index. Correlation studies showed a significant negative correlation between kisspeptin and glucose and LH levels, and a positive correlation with LH/FSH ratio in obese PCOS while in the non-PCOS obese, the kisspeptin correlated positively with glucose, and there was no correlation with LH or LH/FSH. VEGF negatively correlated with FSH and positively with LH/FSH ratio in the non-PCOS obese but this was lost in the obese PCOS. PCOS had no effect on the correlation between Vit D and all studied parameters. Multiple regression analysis showed triglyceride as predictor variable for kisspeptin as a dependent variable, while, leptin is a predictor variable for VEGF as a dependent variable. ROC studies showed the highest sensitivity and specificity for VEGF (AOC=1.00), followed by LH/FSH ratio (AOC=0.979). In conclusion, our study shows that PCOS results in significant elevation of VEGF in obese females, while kisspeptin and Vit D levels are not affected. It also leads to elevation in several of the lipid and hormonal abnormalities in the obese females. In addition, PCOS influences relationship between Kisspeptin and VEGF and some parameters such as glucose, LH or FSH and LH/FSH ratio in obese females, but does not affect Vit D relationship with other parameter.
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The use of anti-obesity medications in people with mental illness as an adjunct to lifestyle interventions - Effectiveness, tolerability and impact on eating behaviours: A 52-week observational study.
Tham, M, Chong, TWH, Jenkins, ZM, Castle, DJ
Obesity research & clinical practice. 2021;(1):49-57
Abstract
OBJECTIVE The increasing prevalence of obesity and metabolic syndrome in people with mental illness (MI) is a global health priority. Anti-obesity medications (AOMs) may help with reducing medication induced hunger and weight gain when lifestyle changes are insufficient. Our aim is to evaluate the effectiveness, tolerability, impact on eating behaviours and psychiatric safety of AOMs in this population. METHODS We conducted an observational study of 244 adults with MI with at least two risk factors for metabolic syndrome attending an obesity management clinic. Participants received standardised diet, exercise and psychological care, in addition to AOMs tailored to each participant's circumstances. Baseline and 12-month assessments encompassing physical, metabolic and psychological parameters were compared. RESULTS Over the course of the study, the average weight loss was 11.79 kg (12.1%), decrease in BMI was 3.90 kg/m2 and reduction in waist circumference was 12.6 cm. Participants with good glycaemic control increased from 28.6% to 80.7%, hypercholesterolaemia reduced from 85.2%-29.9% and hypertension rates reduced from 88.9%-52.0%. Depression, anxiety and stress levels for the sample decreased significantly (all p < .01). Eating behaviours improved (all p < .001) at follow-up. Psychiatric side effects including deterioration of mood (28.2%) and suicidality (30.8%) were primarily experienced by those on topiramate. CONCLUSIONS AOMs can be effective in achieving clinically meaningful weight loss, improved metabolic co-morbidities and eating behaviours in people living with MI, when combined with a comprehensive lifestyle program. The majority of AOMs are well tolerated but topiramate appears more likely to negatively impact mental health.
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Linking the Endocannabinoidome with Specific Metabolic Parameters in an Overweight and Insulin-Resistant Population: From Multivariate Exploratory Analysis to Univariate Analysis and Construction of Predictive Models.
Depommier, C, Flamand, N, Pelicaen, R, Maiter, D, Thissen, JP, Loumaye, A, Hermans, MP, Everard, A, Delzenne, NM, Di Marzo, V, et al
Cells. 2021;(1)
Abstract
The global obesity epidemic continues to rise worldwide. In this context, unraveling new interconnections between biological systems involved in obesity etiology is highly relevant. Dysregulation of the endocannabinoidome (eCBome) is associated with metabolic complications in obesity. This study aims at deciphering new associations between circulating endogenous bioactive lipids belonging to the eCBome and metabolic parameters in a population of overweight or obese individuals with metabolic syndrome. To this aim, we combined different multivariate exploratory analysis methods: canonical correlation analysis and principal component analysis, revealed associations between eCBome subsets, and metabolic parameters such as leptin, lipopolysaccharide-binding protein, and non-esterified fatty acids (NEFA). Subsequent construction of predictive regression models according to the linear combination of selected endocannabinoids demonstrates good prediction performance for NEFA. Descriptive approaches reveal the importance of specific circulating endocannabinoids and key related congeners to explain variance in the metabolic parameters in our cohort. Analysis of quartiles confirmed that these bioactive lipids were significantly higher in individuals characterized by important levels for aforementioned metabolic variables. In conclusion, by proposing a methodology for the exploration of large-scale data, our study offers additional evidence of the existence of an interplay between eCBome related-entities and metabolic parameters known to be altered in obesity.
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Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial.
Neeland, IJ, Marso, SP, Ayers, CR, Lewis, B, Oslica, R, Francis, W, Rodder, S, Pandey, A, Joshi, PH
The lancet. Diabetes & endocrinology. 2021;(9):595-605
Abstract
BACKGROUND Visceral and ectopic fat are key drivers of adverse cardiometabolic outcomes in obesity. We aimed to evaluate the effects of injectable liraglutide 3·0 mg daily on body fat distribution in adults with overweight or obesity without type 2 diabetes at high cardiovascular disease risk. METHODS In this randomised, double-blind, placebo-controlled, phase 4, single centre trial, we enrolled community-dwelling adults, recruited from the University of Texas Southwestern Medical Center, with BMI of at least 30 kg/m2 or BMI of at least 27 kg/m2 with metabolic syndrome but without diabetes and randomly assigned them, in a 1:1 ratio, to 40 weeks of treatment with once-daily subcutaneous liraglutide 3·0 mg or placebo, in addition to a 500 kcal deficient diet and guideline-recommended physical activity counselling. The primary endpoint was percentage reduction in visceral adipose tissue (VAT) measured with MRI. All randomly assigned participants with a follow-up imaging assessment were included in efficacy analyses and all participants who received at least one dose of study drug were included in the safety analyses. The trial is registered on ClinicalTrials.gov: NCT03038620. FINDINGS Between July 20, 2017 and Feb 21, 2020 from 235 participants assessed for eligibility, 185 participants were randomly assigned (n=92 liraglutide, n=93 placebo) and 128 (n=73 liraglutide, n=55 placebo) were included in the final analysis (92% female participants, 37% Black participants, 24% Hispanic participants, mean age 50·2 years (SD 9·4), mean BMI 37·7 kg/m2). Mean change in VAT over median 36·2 weeks was -12·49% (SD 9·3%) with liraglutide compared with -1·63% (SD 12·3%) with placebo, estimated treatment difference -10·86% (95% CI -6·97 to -14·75, p<0·0001). Effects seemed consistent across subgroups of age, sex, race-ethnicity, BMI, and baseline prediabetes. The most frequently reported adverse events were gastrointestinal-related (43 [47%] of 92 with liraglutide and 12 [13%] of 93 with placebo) and upper respiratory tract infections (10 [11%] of 92 with liraglutide and 14 [15%] of 93 with placebo). INTERPRETATION In adults with overweight or obesity at high cardiovascular disease risk, once-daily liraglutide 3·0 mg plus lifestyle intervention significantly lowered visceral adipose tissue over 40 weeks of treatment. Visceral fat reduction may be one mechanism to explain the benefits seen on cardiovascular outcomes in previous trials with liraglutide among patients with type 2 diabetes. FUNDING NovoNordisk.
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Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome.
Kaur, V, Dimitriadis, GK, Pérez-Pevida, B, Bansi, DS, Jayasena, C, Bate, D, Houghton, R, Fielding, BA, Balfoussia, D, Webber, L, et al
Metabolism: clinical and experimental. 2021;:154908
Abstract
BACKGROUND Duodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans. METHODS Thirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention. RESULTS A small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion. CONCLUSIONS These findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.
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Effects of macronutrient intake in obesity: a meta-analysis of low-carbohydrate and low-fat diets on markers of the metabolic syndrome.
Willems, AEM, Sura-de Jong, M, van Beek, AP, Nederhof, E, van Dijk, G
Nutrition reviews. 2021;(4):429-444
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Abstract
The metabolic syndrome (MetS) comprises cardiometabolic risk factors frequently found in individuals with obesity. Guidelines to prevent or reverse MetS suggest limiting fat intake, however, lowering carbohydrate intake has gained attention too. The aim for this review was to determine to what extent either weight loss, reduction in caloric intake, or changes in macronutrient intake contribute to improvement in markers of MetS in persons with obesity without cardiometabolic disease. A meta-analysis was performed across a spectrum of studies applying low-carbohydrate (LC) and low-fat (LF) diets. PubMed searches yielded 17 articles describing 12 separate intervention studies assessing changes in MetS markers of persons with obesity assigned to LC (<40% energy from carbohydrates) or LF (<30% energy from fat) diets. Both diets could lead to weight loss and improve markers of MetS. Meta-regression revealed that weight loss most efficaciously reduced fasting glucose levels independent of macronutrient intake at the end of the study. Actual carbohydrate intake and actual fat intake at the end of the study, but not the percent changes in intake of these macronutrients, improved diastolic blood pressure and circulating triglyceride levels, without an effect of weight loss. The homeostatic model assessment of insulin resistance improved with both diets, whereas high-density lipoprotein cholesterol only improved in the LC diet, both irrespective of aforementioned factors. Remarkably, changes in caloric intake did not play a primary role in altering MetS markers. Taken together, these data suggest that, beyond the general effects of the LC and LF diet categories to improve MetS markers, there are also specific roles for weight loss, LC and HF intake, but not reduced caloric intake, that improve markers of MetS irrespective of diet categorization. On the basis of the results from this meta-analysis, guidelines to prevent MetS may need to be re-evaluated.
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Global pandemics interconnected - obesity, impaired metabolic health and COVID-19.
Stefan, N, Birkenfeld, AL, Schulze, MB
Nature reviews. Endocrinology. 2021;(3):135-149
Abstract
Obesity and impaired metabolic health are established risk factors for the non-communicable diseases (NCDs) type 2 diabetes mellitus, cardiovascular disease, neurodegenerative diseases, cancer and nonalcoholic fatty liver disease, otherwise known as metabolic associated fatty liver disease (MAFLD). With the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), obesity and impaired metabolic health also emerged as important determinants of severe coronavirus disease 2019 (COVID-19). Furthermore, novel findings indicate that specifically visceral obesity and characteristics of impaired metabolic health such as hyperglycaemia, hypertension and subclinical inflammation are associated with a high risk of severe COVID-19. In this Review, we highlight how obesity and impaired metabolic health increase complications and mortality in COVID-19. We also summarize the consequences of SARS-CoV-2 infection for organ function and risk of NCDs. In addition, we discuss data indicating that the COVID-19 pandemic could have serious consequences for the obesity epidemic. As obesity and impaired metabolic health are both accelerators and consequences of severe COVID-19, and might adversely influence the efficacy of COVID-19 vaccines, we propose strategies for the prevention and treatment of obesity and impaired metabolic health on a clinical and population level, particularly while the COVID-19 pandemic is present.
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Effects of Whole-Body Vibration Training on Body Composition, Cardiometabolic Risk, and Strength in the Population Who Are Overweight and Obese: A Systematic Review With Meta-analysis.
Rubio-Arias, JÁ, Martínez-Aranda, LM, Andreu-Caravaca, L, Sanz, G, Benito, PJ, Ramos-Campo, DJ
Archives of physical medicine and rehabilitation. 2021;(12):2442-2453
Abstract
OBJECTIVES To assess the effects of whole-body vibration training (WBVT) on body composition, metabolic and cardiovascular risk variables, and lower limb strength in participants who are overweight/obese. DATA SOURCES A systematic review with meta-analysis was conducted in 3 databases (PubMed-MEDLINE, Web of Science, and Cochrane Library) from inception through to January 26, 2020. STUDY SELECTION Studies analyzing the effect of WBVT on body composition variables, metabolic profile, blood pressure, heart rate, and lower limb strength in the population who are overweight/obese, with interventions of a minimum length of 2 weeks were included. DATA EXTRACTION After applying the inclusion and exclusion criteria, 23 studies involving 884 participants who were obese/overweight (experimental group: 543; weight=79.9 kg; body mass index (BMI) =31.3 kg/m2, obesity class I according to World Health Organization) were used in the quantitative analysis. The sex of the participants involved in the studies were as follows: (1) 17 studies included only female participants; (2) 1 study included only boys, and (3) 5 studies included both sexes. Meta-analysis, subgroup analysis, and meta-regression methods were used to calculate the mean difference and standardized mean difference (SMD; ± 95% confidence intervals [CIs]) as well as to analyze the effects of pre-post intervention WBVT and differences from control groups. DATA SYNTHESIS WBVT led to a significant decrease in fat mass (-1.07 kg, not clinically significant). In addition, WBVT reduced systolic blood pressure (-7.01 mmHg, clinically significant), diastolic blood pressure (-1.83 mmHg), and heart rate (-2.23 bpm), as well as increased the lower extremity strength (SMD=0.63; range, 0.40-0.86). On the other hand, WBVT did not modify the weight, BMI, muscle mass, cholesterol, triglycerides, or glucose. CONCLUSIONS WBVT could be an effective training modality to reduce blood pressure (clinically relevant) and resting heart rate. In addition, WBVT led to improved lower limb strength. However, these findings were not consistent with significant improvements on other variables associated with metabolic syndrome (body composition, cholesterol, triglycerides, glucose).
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A Review of the Increasing Prevalence of Metabolic-Associated Fatty Liver Disease (MAFLD) in Children and Adolescents Worldwide and in Mexico and the Implications for Public Health.
Ramírez-Mejía, MM, Díaz-Orozco, LE, Barranco-Fragoso, B, Méndez-Sánchez, N
Medical science monitor : international medical journal of experimental and clinical research. 2021;:e934134
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects almost a quarter of the world's population and is the most common cause of chronic liver disease in children and adolescents. The recent proposal to replace the terminology of NAFLD with metabolic-associated fatty liver disease (MAFLD) aims to reflect the pathophysiology and risk factors for this disease. Importantly, the risk factors for MAFLD may be prenatal, such as genetic factors, or postnatal, such as obesity and insulin resistance. MAFLD is increasingly recognized in children and adolescents. Early diagnosis and identification of high-risk individuals with type 2 diabetes mellitus and metabolic syndrome is important. The diagnosis and management of MAFLD in children and adolescents should follow international clinical guidelines, such as those from the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD). Current guidelines recommend lifestyle and dietary modifications, exercise, screening, individualized patient assessment, and multidisciplinary patient management. This review assesses the revised terminology and discusses the epidemiology, risk factors, pathophysiology, diagnosis, and prevention of MAFLD in children and adolescents worldwide and in Mexico, and also considers the implications for public health.
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Telemonitoring-Supported Exercise Training in Employees With Metabolic Syndrome Improves Liver Inflammation and Fibrosis.
Haufe, S, Hupa-Breier, KL, Bayerle, P, Boeck, HT, Rolff, S, Sundermeier, T, Kerling, A, Eigendorf, J, Kück, M, Hanke, AA, et al
Clinical and translational gastroenterology. 2021;(6):e00371
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Abstract
INTRODUCTION Metabolic syndrome (MetS) is a major health problem worldwide and the main risk factor for metabolic-associated fatty liver disease (MAFLD). Established treatment options are lifestyle interventions facilitating dietary change and increased physical activity. Here, we tested the effect of a telemonitoring-supported intervention on liver parameter of inflammation and fibrosis in individuals with MetS. METHODS This was a prospective, randomized, parallel-group, and assessor-blind study performed in workers of the main Volkswagen factory (Wolfsburg, Germany). Volunteers with diagnosed MetS were randomly assigned (1:1) to a 6-month lifestyle intervention focusing on supervised, activity-tracker-guided exercise or to a waiting-list control group. This secondary analysis assessed the effect of the intervention on liver enzymes and MAFLD-related parameters. RESULTS We screened 543 individuals between October 10, 2017, and February 27, 2018, of whom 314 were randomly assigned to the intervention group (n = 160) or control group (n = 154). Liver transaminases, alkaline phosphatase, and gamma-glutamyl transferase significantly decreased after 6 months in the intervention group compared with the CG. Furthermore, an aspartate aminotransferase-to-platelet ratio index score as a marker for liver fibrosis significantly decreased in the intervention group. These improvements were associated with changes in obesity and exercise capacity. DISCUSSION A 6-month lifestyle intervention based on exercise training with individualized telemonitoring-based supervision led to improvements of liver inflammation and fibrosis in employees with MetS. Therefore, this intervention shows therapeutic potential for individuals at high risk of MAFLD (ClinicalTrials.gov Identifier: NCT03293264).