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1.
Obesity (Silver Spring) ; 28(4): 724-732, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32202075

RESUMO

OBJECTIVE: This study aimed to evaluate ertugliflozin in patients with overweight and obesity with type 2 diabetes mellitus. METHODS: Data from three placebo-controlled, randomized, Phase 3 studies were pooled. Patients with baseline BMI ≥ 25 (1,377/1,544; 89%) were assessed with a stratification by BMI subgroup. RESULTS: At week 26, reductions from baseline in glycated hemoglobin A1c (HbA1c), fasting plasma glucose, body weight (BW), and systolic blood pressure (SBP) were greater with ertugliflozin versus placebo. For placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively, least squares mean change was 0.1%, -0.8%, and -0.9% for HbA1c and -1.2 kg, -3.1 kg, and -3.2 kg for BW. HbA1c reductions were consistent across BMI subgroups. For ertugliflozin 5 mg and 15 mg, least squares mean change (placebo adjusted) in absolute BW was -1.4 kg and -1.2 kg for BMI 25 to < 30, -1.8 kg and -1.9 kg for BMI 30 to < 35, and -2.5 kg and -2.9 kg for BMI ≥ 35. Percent BW changes were similar across BMI subgroups. Incidence of adverse events was 52.5%, 44.6%, and 50.1% with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively. CONCLUSIONS: Meaningful reductions in HbA1c, fasting plasma glucose, BW, and SBP were observed with ertugliflozin in patients with overweight and obesity with type 2 diabetes mellitus. Ertugliflozin improved HbA1c and SBP and reduced BW across BMI subgroups. Ertugliflozin was generally well tolerated.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
2.
Obesity (Silver Spring) ; 28(5): 870-881, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32187881

RESUMO

OBJECTIVE: The aim of this study was to explore the dose response of licogliflozin, a dual inhibitor of sodium/glucose cotransporter 1 (SGLT1) and 2 (SGLT2), by evaluating change in body weight in adults with overweight or obesity. METHODS: This dose-response analysis evaluated change in body weight following 24 weeks with four once-daily and twice-daily licogliflozin doses (2.5-150 mg) versus placebo (primary end point). A further 24-week analysis evaluated the efficacy and safety of two once-daily licogliflozin doses in maintaining initial weight reduction. RESULTS: Licogliflozin once daily or twice daily produced a significant dose-response signal for weight loss versus placebo (P < 0.0001). However, mean adjusted percent changes in body weight after 24 weeks were modest, ranging from -0.45% to -3.83% (in the 50 mg twice daily group [95% CI: -5.26% to -2.48%]; n = 75). Responder analysis of ≥ 5% weight loss at week 24 revealed significant differences versus placebo, which were most pronounced with highest doses of 50 mg twice daily (45.3%) and 150 mg once daily (42.9%) (both P < 0.01). While weight loss was greater at higher doses, gastrointestinal adverse events were also more frequent. The 50-mg once-daily dose had perhaps the best balance between efficacy and tolerability. CONCLUSIONS: Licogliflozin produced significant reductions in body weight versus placebo. However, the magnitude of weight reduction was modest.


Assuntos
Anidridos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sorbitol/análogos & derivados , Perda de Peso/efeitos dos fármacos , Adolescente , Adulto , Idoso , Anidridos/farmacologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Sorbitol/farmacologia , Sorbitol/uso terapêutico , Adulto Jovem
3.
Acta Diabetol ; 57(6): 715-723, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32020414

RESUMO

PURPOSE: To determine the separated and combined effects of metformin and exercise on insulin sensitivity and free-living glycemic control in overweight individuals with prediabetes/type 2 diabetes (T2DM). METHODS: We recruited 16 adults with BMI of 32.7 ± 4.3 kg m-2 and insulin resistance (HOMA-IR 3.2 ± 0.4) under chronic metformin treatment (1234 ± 465 g day-1) enrolled in a high-intensity interval training (HIIT) program. Participants underwent four 72-h experimental trials in a random-counterbalanced order: (1) maintaining their habitual metformin treatment (MET); (2) replacing metformin treatment by placebo (CON); (3) placebo plus two HIIT sessions (EX + CON), and (4) metformin plus two HIIT sessions (MET + EX). We used intermittently scanned continuous glucose monitoring (isCGM) during 72 h in every trial to obtain interstitial fluid glucose area under the curve (IFGAUC) and the percentage of measurements over 180 mg dL-1 (% IFGPEAKS). Insulin sensitivity was assessed on the last day of each trial with HOMA-IR index and calculated insulin sensitivity (CSI) from intravenous glucose tolerance test. RESULTS: IFGAUC was lower in MET + EX and MET than in CON (P = 0.011 and P = 0.025, respectively). In addition, IFGAUC was lower in MET + EX than in EX + CON (P = 0.044). %IFGPEAKS were only lower in MET + EX in relation to CON (P = 0.028). HOMA-IR and CSI were higher in CON in comparison with MET + EX (P = 0.011 and P = 0.022, respectively) and MET (P = 0.006 and P < 0.001, respectively). IFGAUC showed a significant correlation with HOMA-IR. CONCLUSION: Intense aerobic exercise in patients with diabetes and prediabetes under metformin treatment reduces free-living 72-h blood hyperglycemic peaks. This may help to prevent the development of cardiovascular complications associated with diabetes.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/terapia , Exercício Físico/fisiologia , Intolerância à Glucose/terapia , Hiperglicemia/prevenção & controle , Metformina/farmacologia , Sobrepeso/terapia , Glicemia/metabolismo , Automonitorização da Glicemia , Terapia Combinada , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Terapia por Exercício/métodos , Líquido Extracelular/química , Líquido Extracelular/efeitos dos fármacos , Líquido Extracelular/metabolismo , Feminino , Glucose/análise , Glucose/metabolismo , Intolerância à Glucose/sangue , Intolerância à Glucose/tratamento farmacológico , Teste de Tolerância a Glucose , Treinamento Intervalado de Alta Intensidade , Humanos , Hiperglicemia/sangue , Resistência à Insulina/fisiologia , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Sobrepeso/sangue , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Estado Pré-Diabético/sangue , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/terapia
4.
Am J Clin Nutr ; 111(4): 757-768, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31950134

RESUMO

BACKGROUND: Obese children are vulnerable to vitamin D deficiency and impaired cardiovascular health; vitamin D replenishment might improve their cardiovascular health. OBJECTIVES: The aims were to determine, in vitamin D-deficient overweight and obese children, whether supplementation with vitamin D3 1000 or 2000 IU/d is more effective than 600 IU/d in improving arterial endothelial function, arterial stiffness, central and systemic blood pressure (BP), insulin sensitivity (1/fasting insulin concentration), fasting glucose concentration, and lipid profile and to explore whether downregulation of adipocytokines and markers of systemic inflammation underlies vitamin D effects. METHODS: We conducted a randomized, double-masked, controlled clinical trial in 225 10- to 18-y-old eligible children. Change in endothelial function at 6 mo was the primary outcome. RESULTS: Dose-response increases in serum 25-hydroxyvitamin D concentrations were significant and tolerated without developing hypercalcemia. Changes at 3 and 6 mo in endothelial function, arterial stiffness, systemic-systolic BP, lipids, and inflammatory markers did not differ between children receiving 1000 or 2000 IU vitamin D and children receiving 600 IU. Some secondary outcomes differed between groups. Compared with the 600-IU group, central-systolic, central-diastolic, and systemic-diastolic BP was lower at 6 mo in the 1000-IU group [-2.66 (95% CI: -5.27, -0.046), -3.57 (-5.97, -1.17), and -3.28 (-5.55, -1.00) mm Hg, respectively]; insulin sensitivity increased at 3 and 6 mo and fasting glucose concentration declined at 6 mo (-2.67; 95% CI: -4.88, -0.46 mg/dL) in the 2000-IU group. CONCLUSIONS: Correction of vitamin D deficiency in overweight and obese children by vitamin D3 supplementation with 1000 or 2000 IU/d versus 600 IU/d did not affect measures of arterial endothelial function or stiffness, systemic inflammation, or lipid profile, but resulted in reductions in BP and fasting glucose concentration and in improvements in insulin sensitivity. Optimization of children's vitamin D status may improve their cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01797302.


Assuntos
Colecalciferol/administração & dosagem , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Adipocinas/metabolismo , Adolescente , Glicemia , Pressão Sanguínea , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Criança , Suplementos Nutricionais/análise , Feminino , Coração/fisiopatologia , Humanos , Insulina/metabolismo , Resistência à Insulina , Masculino , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , Sobrepeso/genética , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia , Rigidez Vascular
6.
Medicine (Baltimore) ; 98(47): e18060, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764835

RESUMO

OBJECTIVE: A retrospective chart review was conducted to explore the effect of Gambisan, a granular extract of novel herbal medicine, for short-term (≤16 weeks) weight loss in adults who are overweight and those with obesity. METHODS: Outpatients of Kyung Hee University Korean Medicine Hospital (Seoul, Korea) who took Gambisan and underwent bioelectric impedance analysis were selected (Jan 2011 to Dec 2015); their electronic medical records and clinical charts were retrospectively reviewed. The effectiveness of Gambisan was primarily evaluated by comparing body weight (BW) at baseline and endpoint, using paired t tests; the safety of Gambisan was evaluated on the basis of adverse events (AEs) experienced by patients. RESULTS: Two hundred five patients were included in this study. The study population exhibited a significant reduction in BW (73.69 ±â€Š14.49 kg to 69.01 ±â€Š13.20 kg, P < .001) as well as percentage body fat (37.38 ±â€Š5.38% to 34.50 ±â€Š5.83%, P < .001). Moreover, 111 (54.1%) patients achieved modest weight loss (≥5%), while 35 (17.1%) achieved ≥10% weight loss. Furthermore, Gambisan induced significant reduction of BW in all subgroups (body mass index, sex, prescribed duration, and dosage). Among 139 patients with available data, 79 (56.8%) reported loss-of-appetite. In addition, 120 (mostly mild) AEs were reported in 69 (49.6%) patients, and the most frequent AEs were nausea, palpitation, and insomnia. DISCUSSION: Despite limitations in interpreting the results of this retrospective medical record review, Gambisan induced statistically and clinically meaningful weight loss with a tolerable level of AEs. Based on the findings of this review, further well-designed clinical trials are warranted.


Assuntos
Sobrepeso/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Perda de Peso/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Estudos Retrospectivos , Fatores de Tempo
7.
Medicine (Baltimore) ; 98(45): e17922, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702673

RESUMO

BACKGROUND: The prevalence of excessive body weight has rapidly increased worldwide over the past decades; however, medications are intended for moderately and severely obese patients and are associated with side effects. As an alternative approach, the use of traditional herbal medicines has gained increasing popularity among overweight individuals in recent years in East Asia. HT048 is an herbal extract of Citrus unshiu and Crataegus pinnatifida, and HT077 is an herbal extract of Nelumbo nucifera and Prunus persica. These 4 herbs have been used widely for body weight reduction in China and Korea. The aims of this trial are to investigate whether HT048 and HT077 are effective at reducing body fat and weight in overweight adults, and to determine the safety of HT048 and HT077. METHODS/DESIGN: A double-blind, randomized, placebo-controlled, 3-arm parallel group trial will be conducted in adults with a body mass index (BMI) of 25 to <30 kg/m. A total of 120 eligible participants will be randomized in a 1:1:1 ratio to receive either HT048 (1000 mg), HT077 (400 mg), or matching placebo twice daily for 12 weeks, and will be monitored for an additional 4-week follow-up period after the treatment. All participants will be assessed for efficacy and safety of the investigational product at baseline and weeks 4, 8, 12, and 16. The primary endpoint is the change in body fat mass and percent body fat measured by dual-energy X-ray absorptiometry at week 12 from the baseline. The secondary efficacy variables are abdominal fat area measured by computed tomography, body fat mass and percent body fat measured by bioelectrical impedance analysis, body weight, BMI, and serum lipids and adipocytokines concentrations. Safety will be evaluated on the basis of reported adverse events, abnormal laboratory results, vital signs, and physical examination findings. DISCUSSION: This is a first-in-human trial of HT048 and HT077 to assess the efficacy and safety in overweight subjects. The results will provide high-quality evidence of the therapeutic benefits of HT048 and HT077 for weight management and the prevention of obesity. TRIAL REGISTRATION: Korean Clinical Research Information Service (KCT0004271) Registered September 2, 2019.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Sobrepeso/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Adulto , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , República da Coreia
8.
Trials ; 20(1): 633, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747930

RESUMO

BACKGROUND: People with severe mental illness (SMI) are two to three times more likely to be overweight and obese than the general population and this is associated with significant morbidity and premature mortality. Although lifestyle interventions can support people with SMI to lose weight, some are unable to make the necessary lifestyle changes or, despite making the changes, continue to gain weight. OBJECTIVE: To assess the feasibility and acceptability of delivering a full-scale trial evaluating whether liraglutide 3.0 mg, a once-daily injectable therapy, may be an effective treatment of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis. METHODS: Design: a single-centre, double-blind, randomised, placebo-controlled trial. SETTING: mental health facilities within Southern Health NHS Trust. PARTICIPANTS: 60 adults with schizophrenia, schizoaffective or first-episode psychosis prescribed antipsychotic medication will be recruited. Participants will be overweight or obese, defined by their baseline BMI which will be: • BMI ≥ 30 kg/m2 or • BMI ≥ 27 kg/m2 to < 30 kg/m2 in the presence of at least one weight-related consequence. This is in concordance with the current EU licence for liraglutide (maximum dosage 3.0 mg). INTERVENTION: participants will be allocated in a 1:1 ratio using a computer-based randomisation programme to either once-daily subcutaneously administered liraglutide or placebo, titrated to 3.0 mg daily, for 6 months. All participants will receive standardised written information about healthy eating and exercise at their randomisation visit. OUTCOMES: the main aim of the study is to gather data on recruitment, consent, retention and adherence. Qualitative interviews with a purposive sub-sample of participants and healthcare workers will provide data on intervention feasibility and acceptability. Secondary clinical outcome measurements will be assessed at 3 and 6 months and will include: weight, fasting plasma glucose, lipid profile, HbA1c level; and the Brief Psychiatric Rating Scale. DISCUSSION: This study should provide evidence of the potential benefits of liraglutide (maximum dosage 3.0 mg daily) on body weight and metabolic variables in people with schizophrenia, schizoaffective disorder and first-episode psychosis. It will also address the feasibility and acceptability of the use of liraglutide in mental health settings. This will inform the design of a longer outcome study that will be needed to determine whether any weight loss can be maintained in the long term. TRIAL REGISTRATION: Universal Trial Number (UTN), ID: U1111-1203-0068. Registered on on 2/10/2017. European Clinical Trials Database (EudraCT), ID: 2017-004064-35. Registered on 3/10/2017.


Assuntos
Transtornos Psicóticos Afetivos/complicações , Liraglutida/administração & dosagem , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Transtornos Psicóticos/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/complicações , Adolescente , Adulto , Idoso , Método Duplo-Cego , Humanos , Liraglutida/efeitos adversos , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
9.
Nutrients ; 11(10)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615016

RESUMO

Platycodon grandiflorus root extract (PGE) has shown various properties, such as anti-hyperlipidemia, anti-diabetic, and anti-obesity, but mostly in animal studies. Therefore, we conducted a preliminary study on the anti-obesity effect of PGE in 108 Korean adults (aged 20-60 years, 30 kg/m2 ≥ body mass index ≥ 23 kg/m2). The participants were randomly assigned to four groups and were administered the placebo, PGE571 (571 mg as PGE), PGE1142 (1142 mg as PGE), and PGE2855 (2855 mg as PGE), independently, for 12 weeks. Body composition, nutrient intake, computed tomography scan, and plasma adipokines, as well as hepatic/renal function markers, were assessed. The PGE571 group revealed a significant decrease in body fat mass and body fat percentage when compared with the placebo group. Moreover, the total abdominal and subcutaneous fat areas were significantly decreased following PGE (PGE2855 group) supplementation. These results provide useful information on the anti-obesity effect of PGE for overweight and obese adult humans.


Assuntos
Sobrepeso/tratamento farmacológico , Extratos Vegetais/farmacologia , Platycodon/química , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/química , Adulto Jovem
10.
Acta Diabetol ; 56(12): 1333-1339, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31506721

RESUMO

AIMS: This study aimed to evaluate the effect of pioglitazone on brown adipose tissue function and hypothalamic gliosis in humans. Brown adipose tissue and the hypothalamus are regarded as important potential pharmacological targets to metabolic diseases, and defining the impact of current therapies on their structure and/or function could provide therapeutic advance in this field. METHODS: Six patients with type 2 diabetes were treated for 24 weeks with pioglitazone 30 mg/day as an add-on therapy. Brown adipose tissue glucose uptake and volume were determined using 18F-FDG PET/CT scans; hypothalamic gliosis was determined using MRI scans; blood was collected for hormone and biochemistry measurements. All tests were performed at inclusion and six months after pioglitazone introduction. RESULTS: Pioglitazone treatment led to a significant 3% body mass increase. There were neither changes in cold-induced brown adipose tissue glucose uptake and volume nor changes in hypothalamic gliosis. CONCLUSIONS: This is a proof-of-concept study that provides clinical evidence for a lack of action of a thiazolidinedione, pioglitazone, to promote homogeneous and measurable changes in brown adipose tissue volume and also in hypothalamic gliosis after 6 months of treatment.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gliose/prevenção & controle , Hipotálamo/efeitos dos fármacos , Hipotálamo/patologia , Pioglitazona/farmacologia , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Marrom/patologia , Adulto , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patologia , Quimioterapia Combinada , Feminino , Fluordesoxiglucose F18 , Gliose/diagnóstico , Gliose/patologia , Humanos , Hipotálamo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Obesidade/patologia , Tamanho do Órgão/efeitos dos fármacos , Sobrepeso/complicações , Sobrepeso/diagnóstico , Sobrepeso/tratamento farmacológico , Sobrepeso/patologia , Pioglitazona/administração & dosagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudo de Prova de Conceito , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/farmacologia
11.
Trials ; 20(1): 512, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31420057

RESUMO

BACKGROUND: Obesity is a major public health problem in recent decades. The accumulation of excessive fat promotes inflammatory status. Meanwhile, herbal products are marketed for their weight-loss properties, such as Nigella sativa (N. Sativa) which has been used for centuries to treat rheumatoid arthritis, diabetes, and asthma; recently, the anti-obesity characteristics of N. sativa have also been indicated. However, the exact mechanisms and cellular-related pathways are still unclear. Thus, we will aim to assess the effects of oral N. sativa on the gene expression of inflammatory and adipogenesis-related factors, including TNF-α, PPAR-γ, and adiponectin as well as assessing their serum concentrations among obese and overweight individuals. METHODS: Obese and overweight women aged 25-55 years with a body mass index (BMI) of 25-35 kg/m2 will be recruited from the Obesity Clinic in Shahid Sadoughi University of Medical Sciences and will be assessed for eligibility against inclusion criteria. They will be randomly assigned into two groups to receive either two capsules of N. sativa or two capsules of placebo per day for eight weeks (each capsule contains 1000 mg of N. sativa or placebo). There will be a four-week wash-out period and then participants will receive the reverse supplements for another eight weeks. Biochemical assessments and gene expressions (using real-time polymerase chain reaction) will be conducted at the beginning and at the end of every intervention period. DISCUSSION: The present study will investigate the probable cellular pathways for the anti-obesity effects of N. sativa in overweight/obese women. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20180528039884N1 . Registered on 2nd of July, 2018.


Assuntos
Adiponectina/sangue , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , PPAR gama/sangue , Óleos Vegetais/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/sangue , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/sangue , Sobrepeso/sangue , Óleos Vegetais/uso terapêutico
12.
Genes (Basel) ; 10(8)2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398921

RESUMO

A dose of proanthocyanidins with satiating properties proved to be able to limit body weight increase several weeks after administration under exposure to a cafeteria diet. Here we describe some of the molecular targets and the duration of the effects. We treated rats with 500 mg grape seed proanthocyanidin extract (GSPE)/kg BW for ten days. Seven or seventeen weeks after the last GSPE dose, while animals were on a cafeteria diet, we used reverse transcriptase-polymerase chain reaction (RT-PCR) to measure the mRNA of the key energy metabolism enzymes from the liver, adipose depots and muscle. We found that a reduction in the expression of adipose Lpl might explain the lower amount of adipose tissue in rats seven weeks after the last GSPE dose. The liver showed increased expression of Cpt1a and Hmgs2 together with a reduction in Fasn and Dgat2. In addition, muscle showed a higher fatty oxidation (Oxct1 and Cpt1b mRNA). However, after seventeen weeks, there was a completely different gene expression pattern. At the conclusion of the study, seven weeks after the last GSPE administration there was a limitation in adipose accrual that might be mediated by an inhibition of the gene expression of the adipose tissue Lpl. Concomitantly there was an increase in fatty acid oxidation in liver and muscle.


Assuntos
Adiposidade/efeitos dos fármacos , Depressores do Apetite/farmacologia , Dieta da Carga de Carboidratos/efeitos adversos , Dieta Ocidental/efeitos adversos , Sobrepeso/prevenção & controle , Proantocianidinas/farmacologia , Tecido Adiposo/metabolismo , Animais , Depressores do Apetite/uso terapêutico , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Coenzima A-Transferases/genética , Coenzima A-Transferases/metabolismo , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Feminino , Leptina/genética , Leptina/metabolismo , Fígado/metabolismo , Músculo Esquelético/metabolismo , Sobrepeso/tratamento farmacológico , Proantocianidinas/uso terapêutico , Ratos , Vitis/química
13.
Int J Clin Pract ; 73(11): e13399, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31397946

RESUMO

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.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Liraglutida/uso terapêutico , Obesidade/tratamento farmacológico , Orlistate/uso terapêutico , Adulto , Estudos de Coortes , Feminino , Humanos , Lactonas/uso terapêutico , Estilo de Vida , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Orlistate/efeitos adversos , Sobrepeso/tratamento farmacológico , Estudos Retrospectivos , Perda de Peso/efeitos dos fármacos
14.
Med Hypotheses ; 131: 109308, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443779

RESUMO

Adiposity is a chronic disease and one of the major modifiable risk factors for the development of type 2 diabetes mellitus (T2DM). Its prevalence in the world could be considered epidemic with 80% of patients with T2DM being obese. Novel antidiabetic drugs, such as glucagone-like peptide-1 (GLP-1) agonists have demonstrated benefitial effect on weight reduction. Nevertheless, in the last decades the need for new therapeutic strategies in the management of adiposity have emerged. Both adiposity and T2DM have negative effect on hypothalamic-pituitary-gonadal axis. Conversely, it has been known that sex hormone replacement therapy improves metabolic parameters in hypogonadal subjects. Recent research has found potential therapeutic effect of combination therapies with sex hormones and GLP-1 agonists in reducing body weight. Based on the aforementioned, we hypothesize that there is a possible synergistic effect of GLP-1 agonists and sex hormones on body mass reduction in patients with type 2 diabetes. The possible additional effect of sex hormones on weight loss could contribute to more effective treatment of T2DM and its complications.


Assuntos
Adiposidade/fisiologia , Fármacos Antiobesidade/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Hormônios Esteroides Gonadais/farmacologia , Hipoglicemiantes/farmacologia , Modelos Biológicos , Perda de Peso , Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/farmacologia , Depressores do Apetite/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/prevenção & controle , Sinergismo Farmacológico , Estradiol/sangue , Feminino , Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Hormônios Esteroides Gonadais/fisiologia , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Masculino , Ciclo Menstrual/fisiologia , Sobrepeso/sangue , Sobrepeso/tratamento farmacológico , Sobrepeso/epidemiologia , Pâncreas/efeitos dos fármacos , Pâncreas/embriologia , Fatores de Risco , Taxa Secretória/efeitos dos fármacos , Testosterona/sangue , Perda de Peso/efeitos dos fármacos
15.
Phytother Res ; 33(8): 2015-2022, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31206225

RESUMO

INTRODUCTION: It is well known that there is a strong linkage between obesity, systemic low-grade inflammation, and oxidative stress in the pediatric population. Possible strategies that might control obesity and its relevant problems in this crucial group are of utmost importance. Therefore, the aim of this study was to evaluate the effects of curcumin supplements on inflammation, oxidative stress, and chemerin levels in adolescent girls. METHODS: Totally, 60 overweight and obese adolescent girls were randomly assigned to either placebo or intervention group in a randomized placebo-controlled parallel trial design. Adolescents consumed one 500-mg curcumin or placebo per day along with a slight weight loss diet for 10 weeks. High-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), total antioxidant capacity (TAC), malondialdehyde (MDA), chemerin levels, and anthropometric measurements were assessed at the beginning and end of the trial. RESULTS: Curcumin supplementation had a significant effect on IL-6 levels and oxidative stress markers including TAC and MDA in crude model. After controlling the effects of confounders, curcumin supplementation had a substantial effect on inflammation (hs-CRP and IL-6) and oxidative stress (TAC) marker of adolescents. DISCUSSION: Ten weeks of curcumin supplementation had beneficial effects on inflammation and oxidative stress markers among postpubescent overweight and obese girl adolescents.


Assuntos
Curcumina/uso terapêutico , Inflamação/tratamento farmacológico , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Adolescente , Curcumina/farmacologia , Feminino , Humanos
16.
Clin Obes ; 9(4): e12324, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172667

RESUMO

The prevalence of pre-diabetes and of type 2 diabetes mellitus is increasing. Preventing disease progression is important to improve outcomes. Natural products are becoming popular alternatives to pharmaceutical products for preventative health and treatment of disease; however, the evidence to support the use of natural alternatives for pre-diabetes and type 2 diabetes is lacking. Two such natural medicines include alpha-cyclodextrin (marketed as FBCx), a fibre derived from corn starch that has been found to bind triglycerides in the intestines to prevent its absorption, aiding weight maintenance and lipid control, and hydrolysed ginseng extract (marketed as GINST15), a formula containing high amounts of Compound K, a metabolite of ginsenosides thought to be an active ingredient contributing to the anti-hyperglycaemic effects of ginseng. This paper describes the rationale and design of a 12-month randomized controlled trial to investigate the metabolic effects of these two products in people with pre-diabetes and overweight or obesity. A total of 400 participants will be randomized to one of four groups (FBCx + GINST15, FBCx + placebo, placebo + GINST15, placebo + placebo) for 6 months, followed by 6 months of follow-up. Participants will also receive lifestyle advice for healthy eating and weight loss. Data collected during the trial will include weight, waist circumference, body composition and blood pressure. Blood samples will also be collected to measure lipid profile and glycaemia. If the products are found to improve lipid and glucose levels, it will provide evidence for their use in people with pre-diabetes to help reduce the risk of progression to type 2 diabetes.


Assuntos
Colesterol/metabolismo , Ginsenosídeos/administração & dosagem , Estado Pré-Diabético/tratamento farmacológico , alfa-Ciclodextrinas/administração & dosagem , Adulto , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/metabolismo , Sobrepeso/tratamento farmacológico , Sobrepeso/metabolismo , Estado Pré-Diabético/metabolismo , Triglicerídeos/metabolismo
17.
Complement Ther Med ; 44: 269-276, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126565

RESUMO

BACKGROUND & AIMS: Existing evidence on the possible effects of pro-/synbiotics on overweight or obese children and adolescents has not been fully established. Therefore, the present review was undertaken to evaluate the overall effects of pro-/synbiotics supplementation on anthropometric indices and metabolic indices in overweight or obese children and adolescents. METHODS: A systematic computerized literature search of PubMed, Scopus, ISI Web of science and Google Scholar databases was conducted up to November 2018. All RCTs using pro-/synbiotics supplements in overweight or obese children and adolescents included in this systematic review and meta-analysis. RESULTS: Overall 9 randomized trials including 410 subjects were identified for the present meta-analysis. Pooled analysis did not illustrate any significant changes in BMI z-score, waist circumference, weight, body fat, fasting blood sugar and lipid profiles (triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) after supplementation with pro-/synbiotics for 4-16 weeks. However, subgroup analysis by intervention type revealed a significant reduction of BMI z-score in synbiotic subgroups. CONCLUSION: Based on our findings, modulation of gut microbiota composition through pro-/ synbiotic supplements did not have favorable effects to manage overweight or obese children and adolescents. Further large-scale studies are warranted to confirm present findings.


Assuntos
Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Probióticos/administração & dosagem , Simbióticos/administração & dosagem , Adolescente , Criança , Suplementos Nutricionais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Complement Ther Med ; 44: 296-300, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126570

RESUMO

OBJECTIVES: To evaluate the antihypertensive efficacy and safety of a standardized Vaccinium arctostaphylos (V. arctostaphylos) berry hydro-alcoholic extract in the overweight/obese hypertensive patients. DESIGN: Randomized placebo-controlled trial. SETTING: Baqiyatallah hospital (Tehran, Iran). INTERVENTIONS: The antihypertensive efficacy and safety of 3-month intake of 400 mg extract capsule three times daily alongside standardized anti-hypertensive regimen in the treatment of 50 patients was compared with the placebo (n = 50). MAIN OUTCOME MEASURES: SBP (systolic blood pressure), DBP (diastolic blood pressure), body mass index, waist circumference, CBC (complete blood count), blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), BUN (blood urea nitrogen) and creatinine. RESULTS: SBP decreased from 152.1 ± 7.7 to 140.5 ± 10.7 in the V. arctostaphylos group and from 152.9 ± 8.1 to 150.8 ± 9.3 in the placebo group (P < 0.001). DBP decreased from 90.3±8 to 82.1±8.8 in the V. arctostaphylos group and from 89.6 ± 7.8 to 87.6 ± 7.9 in the placebo group (P < 0.001). The extract capsule had no significant effect on the other parameters (P > 0.05). Moreover, no drug side effect and adverse interaction with other antihypertensive drugs was observed in the patients. CONCLUSIONS: V. arctostaphylosberry extract improves blood pressure control and has safety and tolerability in the overweight/obese hypertensive patients taking standard antihypertensive drugs.


Assuntos
Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Arctostaphylos/química , Hipertensão/tratamento farmacológico , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vaccinium/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Arctostaphylos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Frutas/química , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Vaccinium/efeitos adversos , Circunferência da Cintura/efeitos dos fármacos
19.
Psychooncology ; 28(8): 1640-1646, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31140202

RESUMO

OBJECTIVE: Breast cancer survivors experience problems with cognition that interfere with daily life and can last for years. In the general population, obesity and diabetes are risk factors for cognitive decline, and weight loss can improve cognition; however, the impact of intentional weight loss on cancer survivors' cognition has not been tested. We investigated the impact of weight loss and metformin on changes in cognitive function in a sample of breast cancer survivors. METHODS: Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomized to a weight loss intervention versus control and metformin versus placebo in a 2 × 2 factorial design. Outcomes were changes in five cognitive domains from baseline to 6 months measured by objective neurocognitive tests. RESULTS: There were no statistically significant intervention effects for the metformin or weight loss interventions in five neurocognitive domains. Baseline body mass index (BMI) was a significant effect modifier of the changes in verbal functioning for the weight loss (P = 0.009) and metformin interventions (P = 0.0125). These effect modifications were independent of percent weight loss achieved during the 6-month study period. CONCLUSIONS: This randomized controlled trial of weight loss and metformin interventions that examined changes to cognition among breast cancer survivors suggests that these interventions may not improve cognitive functioning among breast cancer survivors in general. However, weight loss may improve verbal functioning among individuals with a higher BMI.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Disfunção Cognitiva/terapia , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Sobrepeso/terapia , Perda de Peso , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Terapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/terapia , Avaliação de Resultados em Cuidados de Saúde , Sobrepeso/tratamento farmacológico
20.
Mar Drugs ; 17(5)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067674

RESUMO

Low-fat diets, lipid-modifying nutraceuticals and a higher level of physical activity are often recommended to reduce dyslipidemia. A double-blind, randomized, crossover, controlled trial was designed to evaluate the independent and synergistic effects of Arthrospira (Spirulina) maxima supplementation (4.5 g·day-1) with or without performing a physical exercise program (PEP: aerobic exercise (3 days·week-1) + high-intensity interval training (2 days·week-1)) on blood lipids and BMI of 52 sedentary men with excess body weight. During six weeks, all participants were assigned to four intervention treatments (Spirulina maxima with PEP (SE), placebo with PEP (Ex), Spirulina maxima without PEP (Sm), placebo without PEP (C; control)) and plasma lipids were evaluated spectrophotometrically pre- vs. post intervention in stratified subgroups (overweight, obese and dyslipidemic subjects). Pre/post comparisons showed significant reductions in all plasma lipids in the SE group, particularly in those with dyslipidemia (p ≤ 0.043). Comparing the final vs. the initial values, BMI, total cholesterol, triglycerides and low-density lipoprotein cholesterol were decreased. High-density lipoprotein cholesterol increased in all treatment groups compared to C. Changes were observed mostly in SE interventions, particularly in dyslipidemic subjects (p < 0.05). Spirulina maxima supplementation enhances the hypolipidemic effect of a systematic PEP in men with excess body weight and dyslipidemia.


Assuntos
Dislipidemias/tratamento farmacológico , Exercício Físico , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Spirulina , Adulto , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Colesterol/metabolismo , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Estudos Cross-Over , Dieta , Suplementos Nutricionais , Método Duplo-Cego , Dislipidemias/sangue , Humanos , Lipídeos/sangue , Masculino , Obesidade/sangue , Sobrepeso/sangue , Triglicerídeos/sangue , Triglicerídeos/metabolismo
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