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1.
Value Health ; 23(7): 842-850, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762985

RESUMO

OBJECTIVES: To quantify patients' maximum acceptable risk (MAR) of urinary and genital tract infections (UGTI) in exchange for benefits associated with treatments for managing type 2 diabetes mellitus (T2DM). METHODS: In a discrete choice experiment, adult patients with T2DM and currently on metformin and/or sulphonylurea (first-line treatments) were asked to choose between 2 hypothetical medications defined by 6 attributes: years of medication effectiveness in controlling blood glucose, weight reduction, UGTI risk, risk of hospitalization from heart failure, all-cause mortality risk, and out-of-pocket medication cost. We used latent class logistic regression parameters to estimate the conditional relative importance of treatment attributes and MAR of UGTI for various treatment benefits. RESULTS: A 2-class latent class model was identified as the best fit for the responses from 147 patients. The first class (49% of sample), termed as "survival-conscious," stated that they were willing to accept 46% (95% confidence interval [CI]: 2%-90%) UGTI risk in exchange for a reduction from 6% to 1% in all-cause mortality risk. The second class (51% of sample), termed as "UGTI/cost-conscious" were willing to accept significantly lower (6%; CI: 2%-11%, and 5%; CI: 2%-8%) UGTI risk in exchange for the same reduction in all-cause mortality and hospitalization risks, respectively. CONCLUSIONS: On average, patients were willing to trade higher UGTI risk for a more effective medication. Our findings suggest that physicians should present the benefits and potential side effects of all available treatments and consider patient preferences in their treatment recommendations.


Assuntos
Comportamento de Escolha , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Preferência do Paciente , Idoso , Glicemia/efeitos dos fármacos , Feminino , Gastos em Saúde , Hospitalização/estatística & dados numéricos , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infecções do Sistema Genital/epidemiologia , Infecções Urinárias/epidemiologia , Perda de Peso/efeitos dos fármacos
2.
Complement Ther Med ; 51: 102423, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32507436

RESUMO

BACKGROUND: Obesity is a global health problem and its incidence is on the rise. Euiiyin-tang is an herbal medicinal formula that is often used in the clinical treatment of obesity. The purpose of the present study was to evaluate the efficacy and safety of Euiiyin-tang in obesity treatment. METHODS: A randomized, double-blind, placebo-controlled, multicenter trial was conducted. Participants with obesity were randomly assigned to receive Euiiyin-tang or placebo 3 times daily for 12-weeks. The primary outcome was weight reduction between the baseline and 12 weeks. The secondary outcomes included the rate of weight loss compared to baseline, and changes in body mass index, lipid profiles, and questionnaires related to the quality of life and diet. Safety factors, such as vital signs and laboratory parameters, were also measured. RESULTS: A total of 149 participants were randomly distributed to either the Euiiyin-tang group (n = 76) or the placebo group (n = 73). Weight reduction in the Euiiyin-tang group was significantly greater than that in the placebo group (2.50 kg in the Euiiyin-tang group vs. 0.82 kg in the placebo group). The participant response rates of ≥3% weight loss compared to baseline was 36.8 % in the Euiiyin-tang group and 17.8 % in the placebo group. Body mass index, waist circumference, and hip circumference showed a greater change in the Euiiyin-tang group than in the placebo group (1.00, 3.23, and 2.00 in the Euiiyin-tang group vs. 0.33, 1.96, and 0.86 in the placebo group). Questionnaires, lipid profiles, and safety factors did not show significant differences between groups. CONCLUSION: The results of this study suggest that Euiiyin-tang has beneficial effects on weight loss. TRIAL REGISTRATION: Clinicaltrials.gov NCT01724099.


Assuntos
Medicina Tradicional Coreana/métodos , Obesidade/tratamento farmacológico , Preparações de Plantas/uso terapêutico , Perda de Peso/efeitos dos fármacos , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Medicina Herbária , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , República da Coreia , Inquéritos e Questionários , Adulto Jovem
3.
Life Sci ; 257: 118025, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32598933

RESUMO

BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) co-agonists have emerged as treatment options for reversing diabetes and obesity. Here, we screened the high potency receptor-biased GLP-1R agonists via a newly designed high-throughput GLP-1R extracellular domain (ECD)-based system and demonstrated its in vitro and in vivo therapeutic characters. METHODS: Twelve 9-mer peptides (named XEL1-XEL12) which were screened from a large phage-displayed peptide library were fused to the N-terminus of GIP (3-30) to generate another twelve fusion peptides, termed XEL13-24. Using the six lysine-altered XEL17 as leading sequences, eighteen fatty chain modified fusion peptides were further assessed via in vitro GLP-1R/GIPR-based cell assay. Moreover, the acute and long-acting in vivo effects of selected candidate on diabetic db/db mice and diet-induced obesity (DIO) rats were both carefully evaluated. RESULTS: XEL17 exhibited balanced activation potency on GLP-1R/GIPR in stable cell lines, and further assessment was performed to evaluate the XEL32, a fatty chain modified XEL17 derivative. Preclinical pharmacodynamic results in diabetic db/db mice demonstrated that XEL32 held outstanding insulinotropic and glucose-lowering activities. In addition, protracted antidiabetic effects of XEL32 were also proved by the hypoglycemic test and multiple oral glucose tolerance test. Furthermore, chronic treatment of XEL32 in DIO rats exhibited outstanding beneficial effects on body weight control, fat loss, food intake control, hemoglobin A1C (HbA1C) reduction as well as the glucose tolerance. CONCLUSIONS: XEL32, as a novel GLP-1/GIP dual receptor agonist, may supply efficient glycemic control and weight loss.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Peptídeos/farmacologia , Receptores dos Hormônios Gastrointestinais/metabolismo , Perda de Peso/efeitos dos fármacos , Animais , Glicemia/metabolismo , China , Diabetes Mellitus/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/efeitos dos fármacos , Teste de Tolerância a Glucose , Células HEK293 , Ensaios de Triagem em Larga Escala/métodos , Humanos , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Obesidade/metabolismo , Ratos , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/efeitos dos fármacos
4.
Obesity (Silver Spring) ; 28(7): 1254-1262, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32568464

RESUMO

OBJECTIVE: The aim of this study was to determine the effects of empagliflozin on glycerol-derived hepatic gluconeogenesis in adults with obesity without type 2 diabetes mellitus (T2DM) using oral carbon 13 (13 C)-labeled glycerol. METHODS: A randomized, double-blind, placebo-controlled trial was performed in participants with magnetic resonance imaging assessment of body fat and measurement of glycerol-derived 13 C enrichment in plasma glucose by nuclear magnetic resonance spectroscopy following ingestion of [U-13 C3 ]glycerol. Participants were randomized to oral empagliflozin 10 mg once daily or placebo for 3 months. Glycerol-derived 13 C enrichment studies were repeated, and treatment differences in the mean percentage of 13 C glycerol enrichment in glucose were compared using mixed linear models. RESULTS: Thirty-five participants completed the study. Empagliflozin increased glycerol-derived 13 C enrichment between baseline and follow-up by 6.5% (P = 0.005), consistent with less glycerol from visceral adipose tissue (VAT). No difference was found with placebo. Glycerol-derived 13 C enrichment was lower in participants with high VAT compared with low VAT by 12.6% (P = 0.04), but there was no heterogeneity of the treatment effect by baseline VAT. Glycerol-derived 13 C enrichment was inversely correlated with VAT but was not correlated with weight loss. CONCLUSIONS: VAT is associated with endogenous glycerol-derived hepatic gluconeogenesis, and empagliflozin reduces endogenous glycerol gluconeogenesis in adults with obesity without T2DM. These findings suggest a mechanism by which sodium-glucose cotransporter 2 inhibitors may prevent T2DM in obesity.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gluconeogênese/efeitos dos fármacos , Glucosídeos/uso terapêutico , Glicerol/metabolismo , Fígado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Adulto , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Método Duplo-Cego , Feminino , Humanos , Gordura Intra-Abdominal , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Placebos , Perda de Peso/efeitos dos fármacos
5.
Clin Drug Investig ; 40(8): 695-713, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32583294

RESUMO

Polycystic ovary syndrome is a complex and heterogenous disorder involving multiple organ systems and different molecular pathways. It is tightly associated with obesity and especially abdominal obesity. As body weight reduction is the main modifiable risk factor for polycystic ovary syndrome, therapeutic approaches in overweight or obese women with polycystic ovary syndrome have been developed. Liraglutide is a glucagon-like peptide-1 receptor agonist that promotes sustained weight loss, as well as abdominal fat reduction, in individuals with obesity, prediabetes, and type 2 diabetes mellitus. The majority of current clinical studies have demonstrated that liraglutide therapy achieved significant reductions in body weight, body mass index, and abdominal circumference in overweight and obese women with polycystic ovary syndrome. Liraglutide therapy promoted significant improvements in free testosterone and sex hormone-binding globulin levels in some studies. Important metabolic and hormonal improvements were also reported after the combination of liraglutide with metformin. Increased menstrual frequency, as well as potential positive effects in reproduction, were described. However, the small number of participants, short duration, and low daily liraglutide dose are some of the main limitations of these studies. Larger and longer, multi-centred, double-blind, placebo-controlled trials of liraglutide monotherapy or combination therapy, with prolonged post-interventional monitoring, are crucially anticipated. Metabolic, hormonal, and reproductive primary outcomes should be uniformly addressed, to tailor future targeted treatment approaches, according to the patient phenotype and needs. This will improve long-term therapeutic outcomes in this population.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Síndrome do Ovário Policístico/complicações , Adulto , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Metformina/administração & dosagem , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/tratamento farmacológico , Sobrepeso/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/fisiopatologia , Perda de Peso/efeitos dos fármacos
6.
BMC Health Serv Res ; 20(1): 386, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381084

RESUMO

BACKGROUND: Ideally situated within the community, pharmacists can be involved in a broad range of health promotion campaigns including prevention of obesity. Limited evidence is available regarding their involvement in weight management in Lebanon, a country with escalating prevalence rate of obesity. OBJECTIVE: To examine the role of community pharmacists in weight management in Lebanon, specifically studying their beliefs, current practices, services, and knowledge. METHODS: Using a stratified random sampling approach, a cross sectional national survey of community pharmacists was conducted (n = 341, response rate 89%). At the pharmacy, and through a face-to-face interview, pharmacists completed a multi-component questionnaire that addressed, in addition to socio-demographic and work characteristics, their beliefs, practices, knowledge in relation to weight management. Frequencies and proportions were used to describe the data. Simple and multiple linear regression analyses were used to examine the determinants of knowledge in the study population. RESULTS: Over 80% of study participants agreed that they have an important role to play in weight management. However, 50% of pharmacists did not agree that weight loss products are well regulated and 81.1% thought that companies marketing weight loss products are making false promises. The majority of pharmacists always/often sold weight loss products (84.7%) and counseled their patients for diet (86.3%) and physical activity (91.7%). Despite taking weight and height measurements, 50% of pharmacists rarely/never calculated BMI. Among the pharmacists who reported side effects of weight loss products (46.5%), the majority (91.3%) did so to the pharmaceutical company. The knowledge of pharmacists was better for the use of weight loss products as opposed to their side effects and interactions. Significant predictors of knowledge were holding a Masters/ PhD degree in Pharmacy, graduating from a university inside Lebanon, obtaining weight management training within the academic degree, and receiving inquiries about weight management in the pharmacy more than once daily. CONCLUSIONS: The results of the study provided important insights on the beliefs, practices and knowledge of community pharmacists in weight management in Lebanon. These findings could be used to inform the development of future evidence-based community pharmacists led weight management service provision nationally and internationally.


Assuntos
Obesidade/prevenção & controle , Farmacêuticos/psicologia , Papel Profissional/psicologia , Adulto , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/economia , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Líbano , Masculino , Farmacêuticos/estatística & dados numéricos , Inquéritos e Questionários , Perda de Peso/efeitos dos fármacos
7.
J Nutr ; 150(8): 2101-2111, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32470979

RESUMO

BACKGROUND: Dietary polyphenols including anthocyanins target multiple organs. OBJECTIVE: We aimed to assess the involvement of glucagon-like peptide 1 (GLP-1), leptin, insulin and fibroblast growth factor 21 (FGF21) in mediating metabolic beneficial effects of purified anthocyanin cyanidin-3-glucoside (Cy3G). METHODS: Intestinal proglucagon gene (Gcg; encoding GLP-1) and liver Fgf21 expression were assessed in 6-wk-old male C57BL-6J mice fed a low-fat-diet (LFD; 10% of energy from fat), alone or with 1.6 mg Cy3G/L in drinking water for 3 wk [experiment (Exp.) 1; n = 5/group]. Similar mice were fed the LFD or a high-fat diet (HFD; 60% energy from fat) with or without Cy3G for 20 wk. Half of the mice administered Cy3G also received 4 broad-spectrum antibiotics (ABs) in drinking water between weeks 11 and 14, for a total of 6 groups (n = 8/group). Metabolic tolerance tests were conducted between weeks 2 and 16. Relevant hormone gene expression and plasma hormone concentrations were assessed mainly at the end of 20 wk (Exp. 2). RESULTS: In Exp. 1, Cy3G administration increased ileal but not colonic Gcg level by 2-fold (P < 0.05). In Exp. 2, Cy3G attenuated HFD-induced body-weight gain (20.3% at week 16), and improved glucose tolerance (26.5% at week 15) but not insulin tolerance. Although Cy3G had no effect on glucose tolerance in LFD mice, LFD/Cy3G/AB mice showed better glucose tolerance than LFD/Cy3G mice (23%). In contrast, HFD/Cy3G/AB mice showed worse glucose tolerance compared with HFD/Cy3G mice (15%). Beneficial effects of Cy3G in HFD mice were not associated with changes in plasma leptin, insulin or GLP-1 concentrations. However, Cy3G increased hepatic Fgf21 expression in mice in Exp. 1 by 4-fold and attenuated Fgf21 overexpression in HFD mice (Exp. 2, 22%), associated with increased expression of genes that encode FGFR1 and ß-klotho (>3-fold, P < 0.05). CONCLUSIONS: Dietary Cy3G may reduce body weight and exert metabolic homeostatic effects in mice via changes in hepatic FGF21.


Assuntos
Antocianinas/farmacologia , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/administração & dosagem , Fatores de Crescimento de Fibroblastos/metabolismo , Intolerância à Glucose , Glucosídeos/farmacologia , Ganho de Peso/efeitos dos fármacos , Animais , Gorduras na Dieta/efeitos adversos , Fatores de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Incretinas/genética , Incretinas/metabolismo , Leptina/metabolismo , Fígado , Masculino , Camundongos , Distribuição Aleatória , Perda de Peso/efeitos dos fármacos
8.
Pediatr Blood Cancer ; 67(7): e28379, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32383818

RESUMO

BACKGROUND: Hypothalamic obesity causes unrelenting weight gain for childhood brain tumor survivors. No single therapy has proven effective for treatment. We aimed to evaluate effectiveness of long-term methylphenidate therapy on body mass index (BMI) change in children with hypothalamic obesity. METHODS: A retrospective analysis included children with a history of brain tumor and hypothalamic obesity receiving methylphenidate (10-60 mg/day) for hypothalamic obesity. Subjects were evaluated for BMI trajectory before and after methylphenidate start. Given that z-scores can be skewed in severely obese children, we calculated BMI as a percent of the BMI at the 95th percentile for the child's age and gender (BMI% 95th). RESULTS: Twelve patients with hypothalamic obesity completed methylphenidate therapy for at least 6 months (median 3.1 years, range 1.0-5.8 years). All subjects had a suprasellar tumor (nine [75%] with craniopharyngioma) and pituitary dysfunction. Pretreatment median BMI percent of the 95th percentile was 125.6% (interquartile range [IQR] 25-75: 115.3-138.3%) with BMI z-score of 2.4 (IQR 25-75: 2.1-2.6). Following methylphenidate treatment, there was a 69.9% reduction in the median slope of BMI change. Eleven of 12 patients (92%) had a reduction in the slope of their BMI change on methylphenidate treatment. Postmethylphenidate median BMI percent of the 95th percentile decrease to 115.2% (IQR 25-75: 103.6-121.2%) with median BMI z-score of 2.1 (IQR 25-75: 1.8-2.2). Mild side effects were noted in six patients. CONCLUSIONS: Methylphenidate use reduced and sustained BMI change in children with hypothalamic obesity. Stimulant therapy is an effective first-line agent for treatment of hypothalamic obesity.


Assuntos
Neoplasias Encefálicas/complicações , Sobreviventes de Câncer/estatística & dados numéricos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Doenças Hipotalâmicas/tratamento farmacológico , Metilfenidato/uso terapêutico , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Doenças Hipotalâmicas/diagnóstico , Doenças Hipotalâmicas/etiologia , Masculino , Obesidade/diagnóstico , Obesidade/etiologia , Prognóstico , Estudos Retrospectivos
9.
Res Vet Sci ; 131: 194-205, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32388022

RESUMO

One option for controlled weight loss for dogs and cats in overweight condition could be to modestly restrict caloric intake using a reduced-energy ('light') maintenance diet, but there is no prior research on the safety and efficacy of such an approach. A prospective observational cohort study was performed in 67 overweight dogs and 17 overweight cats undergoing weight loss using reduced-energy maintenance diets from one manufacturer. Diets were fed at approximately 80% of maintenance energy requirements for ideal bodyweight for a period of 8 weeks. Essential nutrient intake was estimated for each dog and cat and compared with minimum requirement (MR) or adequate intake (AI, when no MR had been demonstrated) as set by the National Research Council in 2006. Weight loss was seen in 56/67 dogs (84%), losing a median of 4.7% (range 15.2% loss to 10.0% gain) of their starting body weight (SBW). Weight loss was also seen in all 17 cats, losing a median of 6.4% (range 2.0 loss to 15.2% loss) of SBW. Of the essential nutrients examined, only selenium, choline, potassium, and riboflavin were less than NRC recommendations in a minority of animals. However, no signs of any nutrient deficiency were observed in any of the dogs or cats during the study. In summary, modestly energy restricting overweight dogs and cats when feeding a low-energy maintenance diet can induce weight loss and might be a useful initial step for weight management. Although no adverse effects were seen, borderline intake of some micronutrients warrants further consideration.


Assuntos
Ração Animal/análise , Restrição Calórica/veterinária , Doenças do Gato/dietoterapia , Dieta Redutora/veterinária , Doenças do Cão/dietoterapia , Sobrepeso/veterinária , Animais , Gatos , Estudos de Coortes , Cães , Ingestão de Energia , Feminino , Sobrepeso/dietoterapia , Estudos Prospectivos , Selênio , Perda de Peso/efeitos dos fármacos
10.
Obesity (Silver Spring) ; 28(6): 1040-1049, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32441474

RESUMO

OBJECTIVE: This study aimed to perform a preliminary investigation of the impact of combined hormonal contraceptive (CHC) use on weight loss during an 18-month behavioral weight-loss trial. METHODS: Adults (n = 170; 18-55 years; BMI 27-42 kg/m2 ) received a weight-loss intervention that included a reduced-calorie diet, a progressive exercise prescription, and group-based behavioral support. Premenopausal women (n = 110) were classified as CHC users (CHC, n = 17) or non-CHC users (non-CHC, n = 93). Changes in weight were examined within groups using a linear mixed model, adjusted for age and randomized group assignment. RESULTS: At 6 M, weight was reduced from baseline in both CHC (mean, -6.7 kg; 95% CI: -9.8 to -3.7 kg) and non-CHC (-9.1 kg; -9.1 to -6.4 kg). Between 6 and 18 M, CHC regained weight (4.9 kg; 0.9 to 8.9 kg), while weight remained relatively unchanged in non-CHC (-0.1 kg; -1.8 to 1.6 kg). At 18 M, weight was relatively unchanged from baseline in CHC (-1.8 kg; -7.3 to 3.6 kg) and was reduced from baseline in non-CHC (-7.9 kg; -10.2 to -5.5 kg). CONCLUSIONS: In this secondary data analysis, CHC use was associated with weight regain after initial weight loss. Prospective studies are needed to further understand the extent to which CHC use influences weight loss and maintenance.


Assuntos
Anticoncepcionais/uso terapêutico , Perda de Peso/efeitos dos fármacos , Adulto , Anticoncepcionais/farmacologia , Feminino , Humanos , Masculino , Estudos Prospectivos
11.
Aliment Pharmacol Ther ; 51(11): 1067-1075, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32319111

RESUMO

BACKGROUND: An association between bariatric surgery and development of de-novo inflammatory bowel disease (IBD) has been observed. AIM: To evaluate further the association among bariatric surgery, weight loss medications, obesity and new-onset IBD. METHODS: Using Explorys, a population-based Health Insurance Portability and Accountability Act compliant database, we estimated the prevalence of de-novo IBD among patients treated with bariatric surgery (Roux-en-Y gastrojejunostomy, laparoscopic sleeve gastrectomy or gastric banding) (n = 60 870) or weight loss medications (orlistat, phentermine/topiramate, lorcaserin, bupropion/naltrexone and liraglutide) (n = 193 790) compared with obese controls (n = 5 021 210), between 1999 and 2018. RESULTS: The prevalence of de-novo IBD was lower among obese patients exposed to bariatric surgery (7.72 per 1000 patients) or weight loss medications (7.22 per 1000 patients) compared with patients with persistent obesity not exposed to these interventions (11.66 per 1000 patients, P < 0.0001). The risk reduction for de-novo IBD was consistent across bariatric surgeries and weight loss medications with the exception of orlistat which was not associated with a reduction in risk for de-novo IBD compared with the persistent obese control cohort. CONCLUSION: Obese patients undergoing treatment with bariatric surgery or weight loss medications are at a lower risk for developing de-novo IBD compared with persistently obese controls not exposed to these interventions. These data suggest that obesity and ineffective management of obesity are risk factors for de-novo IBD. Further research is needed to confirm these observations and understand potential mechanisms.


Assuntos
Fármacos Antiobesidade/efeitos adversos , Cirurgia Bariátrica/efeitos adversos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/etiologia , Obesidade Mórbida/cirurgia , Perda de Peso/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cirurgia Bariátrica/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Perda de Peso/efeitos dos fármacos , Adulto Jovem
12.
Life Sci ; 253: 117651, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32304764

RESUMO

AIMS: To investigate the combination of dimerization and PEGylation to enhance the receptor activation and in vivo stability of Oxyntomodulin (OXM). MAIN METHODS: All LDM peptides were produced by using standard method of solid phase synthesis. The in vitro effects of LDM peptides were assessed by glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GcgR) binding test and Proteolytic stability test. Subsequently, saline, Liraglutide and three doses of LDM-3 treated groups were subjected to the evaluation of aute and long-term efficacy. KEY FINDINGS: Five long-acting OXM conjugates, termed LDM-1 to LDM-5, were designed using cysteine (Cys)-specific modification reaction including the activated PEG, bisMal-NH2, and OXM-Cys, and all prepared with high purity. LDM-3 exhibited greater GLP-1R and GcgR activation and ameliorative serum stability. In addition, LDM-3 was identified with enhanced insulinotropic and glycemic abilities in the gene knockout mice. The prolonged glucose-lowering effects of the LDM-3 were proved by hypoglycemic duration test and multiple oral glucose tolerance tests (OGTTs) in the diet-induced obesity (DIO) mice. Furthermore, the pharmacokinetic tests in Sprague Dawley (SD) rat and cynomolgus monkey exhibited the lifespans of LDM-3 at 90 nmol·kg-1 were 101.5 h and 119.4 h, respectively. Nevertheless, consecutive 8-week administration of LDM-3 improved the cumulative body weight gain, food intake, % HbA1c, glucose tolerance and the pancreatic of the obese mice. SIGNIFICANCE: LDM-3, as a dual GLP-1R and GcgR agonist, holds potential to be developed as a promising therapeutic candidate for both diabetes and obesity.


Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hipoglicemiantes/química , Oxintomodulina/química , Receptores de Glucagon/metabolismo , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus/metabolismo , Dimerização , Glucagon/metabolismo , Teste de Tolerância a Glucose , Hipoglicemiantes/farmacocinética , Macaca fascicularis , Masculino , Camundongos , Camundongos Knockout , Camundongos Obesos , Obesidade/metabolismo , Oxintomodulina/farmacocinética , Polietilenoglicóis/química , Ratos Sprague-Dawley , Técnicas de Síntese em Fase Sólida , Perda de Peso/efeitos dos fármacos
13.
Expert Opin Pharmacother ; 21(11): 1319-1328, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32292094

RESUMO

INTRODUCTION: Pharmacotherapy is a useful adjunct when patients with obesity are unable to achieve adequate benefit from lifestyle interventions. AREAS COVERED: This review covers the history of antiobesity drugs, efficacy, and risks of currently approved drugs, limits of their usefulness in clinical practice, gaps in knowledge, methodological limitations of clinical trials, and reasons for underutilization. EXPERT OPINION: In randomized controlled trials, currently approved antiobesity drugs have yielded an average weight loss ranging from approximately 3% to 9% relative to placebo at 1 year. Inadequate inclusion of racial and ethnic minorities and men, and high dropout rates in clinical trials limit generalizability of these findings to clinical practice. Weight loss achieved with antiobesity drugs is generally associated with lowered glycemia, but improvements in blood pressure and lipid measures tend to be marginal. There is limited evidence for sustained weight loss beyond 1 year and for safety and efficacy of antiobesity drugs in children and adolescents, and in post-bariatric surgery patients. None have demonstrated reduction in major adverse cardiovascular events or other significant disease outcomes. Limited health insurance coverage and negative perceptions of physicians have hindered the utilization of antiobesity drugs.


Assuntos
Fármacos Antiobesidade , Obesidade/tratamento farmacológico , Perda de Peso/efeitos dos fármacos , Adolescente , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Pressão Sanguínea/efeitos dos fármacos , Criança , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Uso de Medicamentos , Humanos , Estilo de Vida , Resultado do Tratamento
14.
Rev Med Interne ; 41(5): 335-338, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-32334861

RESUMO

INTRODUCTION: This case report signifies the need to systemically assess antimalarial toxicity in those undergoing long-term treatment. CASE REPORT: A 59-year-old man with a history of ischemic-labeled heart disease revealed by conduction disorders and cutaneous lupus treated initially with hydroxychloroquine followed by chloroquine consulted for asthenia and weight loss. Clinically, he had a muscular atrophy, a motor deficit, and an abolition of the osteo-tendinous reflexes in the lower limbs. Adverse drug effects of the antimalarial therapy were suspected-specifically, muscular and cardiac toxicity. The diagnosis was confirmed with a muscle biopsy, which showed typical and florid vacuolar myopathy. Cessation of the drug resulted in a slow regression of symptoms. CONCLUSION: Cardiac and muscular toxicity related to antimalarials are rare and sometimes fatal; thus, they must be systematically assessed in a patient with several years of exposure. A muscle biopsy could be sufficient to allow for the diagnosis.


Assuntos
Antimaláricos/efeitos adversos , Astenia , Cardiotoxicidade/diagnóstico , Doenças Musculares/induzido quimicamente , Doenças Musculares/diagnóstico , Perda de Peso , Astenia/induzido quimicamente , Astenia/diagnóstico , Biópsia , Cardiotoxicidade/etiologia , Cardiotoxicidade/patologia , Diagnóstico Diferencial , Humanos , Hidroxicloroquina/efeitos adversos , Assistência de Longa Duração , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/diagnóstico , Doenças por Armazenamento dos Lisossomos/induzido quimicamente , Doenças por Armazenamento dos Lisossomos/diagnóstico , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Doenças Musculares/patologia , Perda de Peso/efeitos dos fármacos
15.
PLoS One ; 15(4): e0231815, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32348327

RESUMO

Reducing carbohydrates digestion by having a low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107 (Slimming Plus), an eight-herb formula that is modified from RCM-104, indicated significant weight-loss action in clinical trials. However, no published research has studied its mechanism of action on reducing carbohydrate absorption via suppressing the activities of porcine pancreatic alpha-amylase (PPA). In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact. Therefore, our data has provided new knowledge on the mechanisms of action of the RCM-107 formula and its individual herbal ingredients for weight loss, in terms of decreasing carbohydrate digestion via the inhibition of pancreatic alpha-amylase.


Assuntos
Fármacos Antiobesidade/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Obesidade/tratamento farmacológico , alfa-Amilases Pancreáticas/antagonistas & inibidores , Perda de Peso/efeitos dos fármacos , Animais , Fármacos Antiobesidade/química , Metabolismo dos Carboidratos/efeitos dos fármacos , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Colestenonas/química , Colestenonas/farmacologia , Medicamentos de Ervas Chinesas/química , Ensaios Enzimáticos , Flavanonas/química , Flavanonas/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Obesidade/metabolismo , alfa-Amilases Pancreáticas/química , alfa-Amilases Pancreáticas/metabolismo , Suínos
17.
Toxicol Appl Pharmacol ; 394: 114956, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32171571

RESUMO

Proper enterocytic proliferation/differentiation, besides providing adequate adherens junctions (AJ) integrity, are responsible for strengthening of the gut barrier that acts as a first line defense against endotoxemia. However, the preferential role of the underlying PI3K/Akt (PKB) axis in triggering enterocytic proliferation/differentiation signaling and AJ assembly is still obscure in sepsis. Additionally, the potential involvement of dipeptidyl peptidase (DPP)-IV in cholestatic sepsis has not yet been reported. Common bile duct ligation (CBDL) insult was performed in adult male Sprague-Dawley rats except for sham operated animals; three doses of vildagliptin (VLD3, 10 and 30 mg/kg/d; p.o) were administered for 10 consecutive days post CBDL. VLD3/10/30 dose-dependently decreased DPP-IV and elevated GLP-1, IGF-1, PI3K, pS473-Akt (PKB), pS9-GSK-3ß, pS133-CREB and cyclin-D1. VLD3/10 reduced fever, portal/aortic endotoxin and IgG, body weight loss as well as ileal NF-κB, TNF-α, MPO, TBARS, subepithelial/pericryptal and submucosal collagen deposition, vimentin immunoreactivity, N-cadherin, Zeb1 and pY654-ß-catenin but increased E-cadherin, NPSH and colon/spleen indices - effects that were quite the opposite of VLD30. Accordingly, maintaining proper enterocytic proliferation/differentiation and phosphorylation inputs consequent to adequate DPP-IV inhibition is integral to AJ assembly in cholestatic sepsis; however, perturbed signals by excessive suppression of the enzyme activity induce toxic effects manifested as AJ disassembly and EMT, hence gut leakage and overt endotoxemia.


Assuntos
Colestase/patologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Enterócitos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Sepse/patologia , Animais , Diferenciação Celular/efeitos dos fármacos , Colestase/tratamento farmacológico , Ducto Colédoco/lesões , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Íleo/patologia , Ligadura , Masculino , Ratos , Ratos Sprague-Dawley , Sepse/tratamento farmacológico , Vildagliptina/farmacologia , Vimentina/metabolismo , Perda de Peso/efeitos dos fármacos
18.
Open Heart ; 7(1): e001003, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32201580

RESUMO

Spirulina, a cyanobacteria commonly referred to as a blue-green algae, is one of the oldest lifeforms on Earth. Spirulina grows in both fresh and saltwater sources and is known for its high protein and micronutrient content. This review paper will cover the effects of spirulina on weight loss and blood lipids. The currently literature supports the benefits of spirulina for reducing body fat, waist circumference, body mass index and appetite and shows that spirulina has significant benefits for improving blood lipids.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Obesidade/tratamento farmacológico , Spirulina , Perda de Peso/efeitos dos fármacos , Animais , Fármacos Antiobesidade/efeitos adversos , Biomarcadores/sangue , Suplementos Nutricionais/efeitos adversos , Dislipidemias/sangue , Dislipidemias/diagnóstico , Humanos , Hipolipemiantes/efeitos adversos , Obesidade/diagnóstico , Obesidade/fisiopatologia , Resultado do Tratamento
19.
Obes Facts ; 13(2): 279-291, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32114568

RESUMO

Obesity is a chronic metabolic disease resulting from excessive fat accumulation and/or abnormal distribution caused by multiple factors. As a major component of metabolic syndrome, obesity is closely related to many diseases such as type 2 diabetes mellitus, hyperlipidemia, hypertension, coronary heart disease, stroke and cancer. Hence, the problem of obesity cannot be ignored, and recent studies have shown that grape seed proanthocyanidin extract (GSPE) has an antiobesity effect. This paper systematically reviews the research progress and potential mechanism of GSPE emphasizing on obesity prevention and treatment.


Assuntos
Extrato de Sementes de Uva/farmacologia , Extrato de Sementes de Uva/uso terapêutico , Obesidade/tratamento farmacológico , Proantocianidinas/farmacologia , Proantocianidinas/uso terapêutico , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Síndrome Metabólica/tratamento farmacológico , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Perda de Peso/efeitos dos fármacos
20.
Complement Ther Med ; 49: 102337, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32147051

RESUMO

OBJECTIVE: Despite controversies, no study has systematically summarized findings from earlier studies on the effect of berberine and barberry on anthropometric measures. Therefore, the current systematic review and meta-analysis was conducted on the effect of berberine and barberry on body mass index (BMI), body weight (BW), waist circumference (WC) and waist-hip ratio (WHR) in adults. METHODS: Relevant studies, published up to August 2019, were searched through PubMed/Medline, Scopus, ISI Web of Science, Embase and Google Scholar. All randomized clinical trials investigating the effect of berberine and barberry on the anthropometric measures including BMI, BW, WC or/and WHR were included. RESULTS: Out of 252 citations, 12 trials that enrolled 849 subjects were included. Berberine and barberry resulted in no significant change in BMI (Weighted mean differences (WMD): -0.16 kg/m2; 95 % CI: -0.43 to 0.11, P = 0.247), BW (WMD: -0.11 kg; 95 % CI: -0.13 to 0.91, P = 0.830), and berberine resulted in not significant in WC (WMD: -0.58 cm; 95 % CI: -1.89 to 0.72, P = 0.379) and significant reduction in WHR (WMD: -0.03; 95 % CI: -0.04 to -0.01, P < 0.0001). CONCLUSION: We found a significant reduction in WHR following berberine consumption in adults. Further clinical trials with high quality according to challenges mentioned seem to be helpful to use berberine and barberry as a supplement for certain health conditions, efficiently.


Assuntos
Berberina/uso terapêutico , Berberis , Perda de Peso/efeitos dos fármacos , Antropometria , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
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