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Effectiveness and tolerability of orlistat and liraglutide in patients with obesity in a real-world setting: The XENSOR Study.
Gorgojo-Martínez, JJ, Basagoiti-Carreño, B, Sanz-Velasco, A, Serrano-Moreno, C, Almodóvar-Ruiz, F
International journal of clinical practice. 2019;(11):e13399
Abstract
AIMS: To evaluate in a real-world setting the effectiveness of two drugs, orlistat and liraglutide, in patients with overweight or obesity and insufficient weight loss (WL) after a lifestyle modification programme. METHODS Retrospective, observational cohort study comparing clinical outcomes of orlistat 120 mg three times a day and liraglutide (up to 3 mg daily) in adult patients with BMI ≥30 kg/m2 or ≥27 kg/m2 with at least a weight-related comorbidity who had failed to lose at least 5% of their weight after 6 months of lifestyle modification. The co-primary end-points, assessed at 3-6 months and at the end of the follow-up, were weight change from baseline, proportion of patients who lost at least 5% of their baseline weight and adjusted differences in WL between both drugs. RESULTS Five hundred patients, 400 in the group of orlistat (age 47.0, weight 107.8 kg) and 100 in the group of liraglutide (age 51.9 years, weight 105.1 kg), were included. Treatment with both drugs significantly reduced weight, fasting plasma glucose, systolic BP, low-density lipoprotein-cholesterol and alanine transaminase over a median follow-up period of 7 months. WL with liraglutide (-7.7 kg) was significantly greater than that observed with orlistat (-3.3 kg), and more individuals lost at least 5% of their baseline weight with liraglutide (64.7%) than with orlistat (27.4%). Rates of prediabetes significantly decreased with liraglutide in comparison to orlistat. CONCLUSIONS In this real-world study, liraglutide showed a greater effectiveness in WL compared with orlistat and improved several obesity-associated metabolic and cardiovascular risk factors.
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Effects of Weight-Loss Interventions on Short-Chain Fatty Acid Concentrations in Blood and Feces of Adults: A Systematic Review.
Sowah, SA, Riedl, L, Damms-Machado, A, Johnson, TS, Schübel, R, Graf, M, Kartal, E, Zeller, G, Schwingshackl, L, Stangl, GI, et al
Advances in nutrition (Bethesda, Md.). 2019;(4):673-684
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Abstract
Short-chain fatty acids (SCFAs, mainly acetate, propionate, and butyrate), which are primarily derived from the gut microbiome, may exert anti-inflammatory and immunomodulatory effects, and regulate energy homeostasis. It has been suggested that weight loss may affect SCFA metabolism, but a systematic review of intervention studies is lacking. We aimed to systematically assess the effects of dietary, physical activity-based, and surgical weight-loss interventions among overweight [body mass index (BMI) 25-29.9 kg/m2)] or obese (BMI ≥30 kg/m2) adults (≥18 y) on concentrations of acetate, propionate, butyrate, and total SCFAs in blood, urine, or feces. We conducted a systematic literature search in PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 30, 2018 for randomized and nonrandomized weight-loss trials among overweight or obese adults, in which the concentrations of individual and total SCFAs were assessed. A total of 9 studies consisting of 2 randomized parallel-arm trials, 4 crossover trials, and 3 nonrandomized clinical or surgical trials were included. In the majority of studies, changes in fecal SCFA concentrations were assessed, whereas changes in serum SCFAs were reported from 1 trial. Individual and total SCFA concentrations either remained unchanged or decreased significantly following weight loss. Three of the dietary interventions that resulted in decreased SCFA concentrations were low (≤5% of energy) in total carbohydrates. Most of the studies had a high risk of bias. Decreases in SCFA concentrations may accompany weight loss induced by bariatric surgery or dietary restriction among overweight or obese adults, particularly when carbohydrate intake is reduced. However, findings were inconsistent and based on studies with high to unclear risk of bias, and small sample sizes. Because measurements of fecal SCFAs may not be ideal due to limited sample standardization, well-powered trials with repeated blood measurements of SCFAs are required. This review was registered at PROSPERO as CRD42018088716.
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The relationship between dietary restraint and deficits in reasoning about causes of obesity.
Husted, M, Seiss, E, Banks, AP
Psychology & health. 2019;(12):1504-1522
Abstract
Objective: Increased levels of dietary restraint are associated with deficits on many cognitive tasks. Less is known about how individual differences in restraint influences complex cognition such as reasoning which is the focus of this research.Design: Two experimental studies are reported. In study 1, participants (n = 158) completed a causal conditional reasoning task with statements about weight-related and general causal relationships. Study 2 replicated and extended study 1. Participants (n = 108) completed a causal conditional reasoning task focusing on behavioural causes of weight change or general statements.Main outcome measure: Causal conditional reasoning task performance.Results: In study 1, levels of dietary restraint were negatively associated with reasoning abilities for weight-related statements only. Study 2 replicated the negative association between dietary restraint and reasoning finding the effect in both weight-related, and general, causal judgements.Conclusion: The novel findings show that individual differences in dietary restraint have a wider relationship with cognition than previously demonstrated. Results tentatively support theoretical explanations of a reduction in cognitive capacity, rather than differences in belief, explaining reasoning deficits. These findings open an interesting avenue for research and might have implications for effective decision making about personal health behaviours, such as food choice.
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Obesity survival paradox in cancer patients: Results from the Physical Frailty in older adult cancer patients (PF-EC) study.
Pamoukdjian, F, Aparicio, T, Canoui-Poitrine, F, Duchemann, B, Lévy, V, Wind, P, Ganne, N, Sebbane, G, Zelek, L, Paillaud, E
Clinical nutrition (Edinburgh, Scotland). 2019;(6):2806-2812
Abstract
BACKGROUND & AIMS the obesity survival paradox is an emergent issue in oncology, but its existence remains unclear particularly in older cancer patients. We aimed to assess the obesity survival paradox in older cancer patients. METHODS all consecutive cancer outpatients 65 years and older referred for geriatric assessment (GA) before a decision on cancer treatment between November 2013 and September 2016 were enrolled in the PF-EC cohort study. The main outcome was 6-month mortality. A Cox univariate and multivariate proportional hazard regression models were performed with baseline GA, oncological variables (cancer site, extension and treatment modalities) and C-reactive protein (CRP). We assessed the prognostic value of body mass index categories (i.e. malnutrition <21, 21 ≤ normal weight ≤24.9, 25 ≤ overweight ≤29.9 and obesity ≥30 kg/m2) in the whole study population and according to the metastatic status. RESULTS 433 patients with a mean age of 81.2 ± 6.0 years were included, 51% were women, 44.3% had digestive cancers, 18% breast cancer and 14.5% lung cancer and 45% metastatic cancers. Eighty-eight of these patients (20.3%) were obese at baseline. Mortality rate was 17% during the 6-month follow-up period. After adjustment for sex, gait speed, Mini-Mental State Examination, cancer site and exclusive supportive care, obesity (compared to normal weight) was independently and negatively associated with 6-month mortality only in metastatic patients (aHR 0.17, 95% CI [0.03-0.92], P = 0.04). CONCLUSION our study confirms the obesity survival paradox in older cancer patients only in the metastatic group.
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Effect of Roux-en-Y gastric surgery on ciprofloxacin pharmacokinetics: an obvious effect?
Rivas, AB, Lopez-Picado, A, Salas-Butrón, MDR, Terleira, A, Sanchez Pernaute, A, Torres Garcia, AJ, Moreno Lopera, C, Chicharro, LM, Bandrés, F, Rubio Herrera, MA, et al
European journal of clinical pharmacology. 2019;(5):647-654
Abstract
PURPOSE To evaluate pharmacokinetic parameters of ciprofloxacin in patients undergoing Roux-en-Y gastric surgery (RYGS). METHODS Controlled, single-dose, open-label study in patients undergoing RYGS. Healthy overweight/obese patients 18-60 years old were included. The assessment was performed once in control patients and three times in case patients (before surgery and 1 and 6 months after surgery). In each visit, the subjects received a single oral dose of ciprofloxacin 500 mg. Venous blood samples were obtained at baseline and 0.5, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 8 and 14 h after ciprofloxacin intake. Pre- and post-surgery variables were compared using paired ANOVA or the Wilcoxon tests and control vs cases using ANOVA or Mann Whitney. Given the post-surgery change in body weight, the parameters were corrected by dose (mg)/body weight (kg). The analysis was performed using SPSS. RESULTS Ciprofloxacin Cmax was significantly reduced 1 month after surgery (1840.9 ± 485.2 vs 1589.6 ± 321.8 ng/ml; p = 0.032) but not 6 months after. Cmax on the sixth month was lower than Cmax in control group (2160.4 ± 408.6 vs 1589.6 ± 321.8 ng/ml; p < 0.001). After correcting by the dose (mg)/patient's body weight, both Cmax and AUClast showed significant decrease 1 and 6 months after surgery: Cmax, 289.1 ± 65.3 and 263.5 ± 52.1 (ng/ml)/(dose (mg)/weight (kg)) respectively vs 429.3 ± 127.6 (ng/ml)/(dose (mg)/weight (kg)) at baseline; AUC, 1340.6 ± 243.0 and 1299.2 ± 415.4 (h × ng/ml)/(dose (mg)/weight (kg)) respectively vs 1896.7 ± 396.8 (h × ng/ml)/(dose (mg)/weight (kg)) at baseline. Cmax 1 month post-surgery showed lower values than the control group (375.4 ± 77.4 vs 263.5 ± 52.1 ng/ml; p < 0.001). CONCLUSION Ciprofloxacin absorption is impaired 1 month and 6 months after RYGS. The effect on Cmax and AUClast faded on the sixth month due to weight loss. It is no necessary to modify the doses of ciprofloxacin in these patients.
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Sympathetic Neural Overdrive in the Obese and Overweight State.
Grassi, G, Biffi, A, Seravalle, G, Trevano, FQ, Dell'Oro, R, Corrao, G, Mancia, G
Hypertension (Dallas, Tex. : 1979). 2019;(2):349-358
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Abstract
Nerve traffic recordings (muscle sympathetic nerve traffic [MSNA]) have shown that sympathetic activation may occur in obesity. However, the small sample size of the available studies, presence of comorbidities, heterogeneity of the subjects examined represented major weaknesses not allowing to draw definite conclusions. This is the case for the overweight state. The present meta-analysis evaluated 1438 obese or overweight subjects recruited in 45 microneurographic studies. The analysis was primarily based on MSNA quantification in obesity and overweight, excluding as concomitant conditions hypertension, metabolic syndrome, and other comorbidities. Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as plasma norepinephrine and heart rate, anthropometric variables, as body mass index, waist-to-hip ratio, presence/absence of obstructive sleep apnea, and metabolic profile. Compared with normoweights MSNA was significantly greater in overweight and more in obese individuals (37.0±4.1 versus 43.2±3.5 and 50.4±5.0 burts/100 heartbeats, P<0.01). This was the case even in the absence of obstructive sleep apnea. MSNA was significantly directly related to body mass index and waist-to-hip ratio ( r=0.41 and r=0.64, P<0.04 and <0.01, respectively), clinic blood pressure ( r=0.68, P<0.01), total cholesterol, LDL (low-density lipoprotein) cholesterol, and triglycerides ( r=0.91, r=0.94, and r=0.80, respectively, P<0.01) but unrelated to plasma insulin, glucose, and homeostatic model assessment for insulin resistance. No significant correlation was found between MSNA, heart rate, and norepinephrine. Thus, obesity and overweight are characterized by sympathetic overactivity which mirrors the severity of the clinical condition and reflects metabolic alterations, with the exclusion of glucose/insulin profile. Neither heart rate nor norepinephrine appear to represent faithful markers of the muscle sympathetic overdrive.
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The association between obesity and cardiovascular disease mortality in different strata of socioeconomic position: evidence from pooled Norwegian health surveys.
Kjøllesdal, M, Degerud, E, Næss, Ø
European journal of public health. 2019;(6):1160-1166
Abstract
BACKGROUND Socioeconomic position (SEP) is related to both obesity and cardiovascular disease (CVD). There is little evidence on whether SEP modifies the relation between obesity and CVD. The aim of the study was to investigate whether the association between obesity and CVD mortality is stronger among people with disadvantaged than among people with advantaged life course SEP. METHODS Data from Norwegian population-based cardiovascular health surveys (1985-2003), including body mass index and CVD risk factors (cholesterol, blood pressure, smoking, current treatment for hypertension) were linked to socioeconomic indicators from register and census data (1960-90), and to the Cause of Death Registry (up until 2014). The total number of participants was 398 297. RESULTS In comparison with normal weight, the age-adjusted hazard ratios and 95% confidence intervals of CVD mortality among obese participants were 2.39 (2.07-2.75) and 2.08 (1.70-2.53) among men and women with high SEP, respectively and 1.88 (1.60-2.21) and 1.75 (1.43-2.14) among men and women with low SEP. Adjustment for CVD risk factors attenuated the results in a similar manner in all SEP groups, and among both women and men. CONCLUSION Obesity was consistently associated with a higher risk of CVD mortality, with only minor variation according to SEP. This means that preventing or treating obesity is, for the purpose of reducing CVD risk, equally important for an individual with high or low SEP.
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Maternal and Infant Lipid-Based Nutritional Supplementation Increases Height of Ghanaian Children at 4-6 Years Only if the Mother Was Not Overweight Before Conception.
Kumordzie, SM, Adu-Afarwuah, S, Arimond, M, Young, RR, Adom, T, Boatin, R, Ocansey, ME, Okronipa, H, Prado, EL, Oaks, BM, et al
The Journal of nutrition. 2019;(5):847-855
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BACKGROUND Few studies have evaluated the long-term effects of nutritional supplementation during the first 1000 d of life. We previously reported that maternal and child lipid-based nutrient supplements (LNS) increased child length by 18 mo. OBJECTIVE The aim of this study was to examine the effects of LNS on later growth and body composition at 4-6 y of age. DESIGN This was a follow-up of children in the International Lipid-based Nutrient Supplements (iLiNS)-DYAD trial in Ghana. Women (n = 1320) at ≤20 weeks of gestation were randomly assigned to: 1) iron and folic acid during pregnancy and 200 mg calcium/d for 6 mo postpartum, 2) multiple micronutrients (1-2 RDA of 18 vitamins and minerals) during both periods, or 3) maternal LNS during both periods plus child LNS from 6 to 18 mo. At 4-6 y, we compared height, height-for-age z score (HAZ), and % body fat (deuterium dilution method) between the LNS group and the 2 non-LNS groups combined. RESULTS Data were available for 961 children (76.5% of live births). There were no significant differences between LNS compared with non-LNS groups in height [106.7 compared with 106.3 cm (mean difference, MD, 0.36; P = 0.226)], HAZ [-0.49 compared with -0.57 (MD = 0.08; P = 0.226)], stunting (< -2 SD) [6.5 compared with 6.3% (OR = 1.00; P = 0.993)], or % body fat [15.5 compared with 15.3% (MD = 0.16; P = 0.630)]. However, there was an interaction with maternal prepregnancy BMI (kg/m2) (P-interaction = 0.046 before correction for multiple testing): among children of women with BMI < 25 , LNS children were taller than non-LNS children (+1.1 cm, P = 0.017), whereas there was no difference among children of women with BMI ≥ 25 (+0.1 cm; P = 0.874). CONCLUSIONS There was no overall effect of LNS on height at 4-6 y in this cohort, which had a low stunting rate, but height was greater in the LNS group among children of nonoverweight/obese women. There was no adverse impact of LNS on body composition. This trial was registered at clinicaltrials.gov as NCT00970866.
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Bioactive compounds in plant materials for the prevention of diabetesand obesity.
Kato, E
Bioscience, biotechnology, and biochemistry. 2019;(6):975-985
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Plant materials have been widely studied for their preventive and therapeutic effects for type 2 diabetes mellitus (T2DM) and obesity. The effect of a plant material arises from its constituents, and the study of these bioactive compounds is important to achieve a deeper understanding of its effect at the molecular level. In particular, the study of the effects of such bioactive compounds on various biological processes, from digestion to cellular responses, is required to fully understand the overall effects of plant materials in these health contexts. In this review, I summarize the bioactive compounds we have recently studied in our research group that target digestive enzymes, dipeptidyl peptidase-4, myocyte glucose uptake, and lipid accumulation in adipocytes. Abbreviations: AC: adenylyl cyclase; AMPK AMP-activated protein kinase; βAR: β-adrenergic receptor; CA: catecholamine; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; DPP-4: dipeptidyl peptidase-4; ERK: extracellular signal-regulated kinase; GC: guanylyl cyclase; GH: growth hormone; GLP-1: glucagon-like peptide-1; GLUT glucose transporter; HSL: hormone-sensitive lipase; IR: insulin receptor; IRS: insulin receptor substrate; MAPK mitogen-activated protein kinase; MEK: MAPK/ERK kinase; MG: maltase-glucoamylase; NP: natriuretic peptide; NPR: natriuretic peptide receptor; mTORC2: mechanistic target of rapamycin complex-2; PC: proanthocyanidin; PI3K: phosphoinositide 3-kinase; PKA: cAMP-dependent protein kinase; PKB (AKT): protein kinase B; PKG: cGMP-dependent protein kinase; PPARγ: peroxisome proliferator-activated receptor-γ; SGLT1: sodium-dependent glucose transporter 1; SI: sucrase-isomaltase; T2DM: type 2 diabetes mellitus; TNFα: tumor necrosis factor-α.
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Lorcaserin treatment decreases body weight and reduces cardiometabolic risk factors in obese adults: A six-month, randomized, placebo-controlled, double-blind clinical trial.
Tuccinardi, D, Farr, OM, Upadhyay, J, Oussaada, SM, Mathew, H, Paschou, SA, Perakakis, N, Koniaris, A, Kelesidis, T, Mantzoros, CS
Diabetes, obesity & metabolism. 2019;(6):1487-1492
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Lorcaserin is a serotonin 2c receptor agonist that promotes weight loss while contributing to the prevention and improvement of type 2 diabetes and improvement of atherogenic lipid profiles, without higher rates of major cardiovascular events. The full spectrum of possible lorcaserin-induced improvements in cardiometabolic health remains to be clarified. Thus, we investigated the way in which lorcaserin treatment may alter cardiovascular disease risk, either independently or through changes in body weight. We measured, for the first time, lipid particle quantification, lipid peroxidation, appetite-regulating hormones and mRNA expression of the 5-hydroxytryptamine 2c receptor (5-HT2c receptor). A total of 48 obese participants were enrolled in this six-month, randomized (1:1), placebo-controlled, double-blinded clinical trial. Lorcaserin treatment reduced fat mass (P < 0.001), the fatty liver index (P < 0.0001) and energy intake (P < 0.03) without affecting energy expenditure or lean mass. Total low-density lipoprotein (LDL) (P < 0.04) and small LDL particles (P < 0.03) decreased, while total high-density lipoprotein (HDL) P < 0.02) increased and heart rate significantly decreased with lorcaserin treatment. No mRNA expression of the 5-HT2c receptor was observed in peripheral organs. These data suggest that lorcaserin treatment for six months improves cardiometabolic health in obese individuals, acting mainly through the brain.