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1.
Nutrients ; 13(8)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34445049

RESUMO

Vitamin D deficiency is highly prevalent in patients with overweight/obesity and type 2 diabetes (T2DM). Herein, we investigated the relationship between vitamin D status and overweight/obesity status, insulin resistance (IR), systemic inflammation as well as oxidative stress (OS). Anthropometric and laboratory assessments of 25-hydroxyvitamin D (25(OH)D) and glycemic, pro-inflammatory and OS biomarkers were performed in a sample of 47 patients with T2DM who were divided into categories based on overweight and degree of obesity. The main findings were: the overweight/obesity status correlated negatively with the degree of serum 25(OH)D deficiency (ρ = -0.27) with a trend towards statistical significance (p = 0.069); the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly different (p = 0.024) in patients with 25(OH)D deficiency, as was total oxidant status (TOS) and oxidative stress index (OSI) in patients with severe serum 25(OH)D deficiency as compared to those with 25(OH)D over 20 ng/mL (TOS: p = 0.007, OSI: p = 0.008); and 25(OH)D had a negative indirect effect on TOS by body mass index (BMI), but BMI was not a significant mediator of the studied relationship. In a setting of overweight and increasing degree of obesity, patients with T2DM did not display decreasing values of 25(OH)D. Subjects with the lowest values of 25(OH)D presented the highest values of BMI. Patients with 25(OH)D deficiency were more insulin resistant and showed increased OS but no elevated systemic inflammation. The negative effect of 25(OH)D on TOS did not seem to involve BMI as a mediator.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Estado Nutricional/fisiologia , Obesidade/sangue , Sobrepeso/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Antropometria , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Inflamação , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicações , Estresse Oxidativo , Prevalência , Estudos Prospectivos , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia
2.
Nutrients ; 13(7)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34371884

RESUMO

The dietary supplement, trans-resveratrol and hesperetin combination (tRES-HESP), induces expression of glyoxalase 1, countering the accumulation of reactive dicarbonyl glycating agent, methylglyoxal (MG), in overweight and obese subjects. tRES-HESP produced reversal of insulin resistance, improving dysglycemia and low-grade inflammation in a randomized, double-blind, placebo-controlled crossover study. Herein, we report further analysis of study variables. MG metabolism-related variables correlated with BMI, dysglycemia, vascular inflammation, blood pressure, and dyslipidemia. With tRES-HESP treatment, plasma MG correlated negatively with endothelial independent arterial dilatation (r = -0.48, p < 0.05) and negatively with peripheral blood mononuclear cell (PBMC) quinone reductase activity (r = -0.68, p < 0.05)-a marker of the activation status of transcription factor Nrf2. For change from baseline of PBMC gene expression with tRES-HESP treatment, Glo1 expression correlated negatively with change in the oral glucose tolerance test area-under-the-curve plasma glucose (ΔAUGg) (r = -0.56, p < 0.05) and thioredoxin interacting protein (TXNIP) correlated positively with ΔAUGg (r = 0.59, p < 0.05). Tumor necrosis factor-α (TNFα) correlated positively with change in fasting plasma glucose (r = 0.70, p < 0.001) and negatively with change in insulin sensitivity (r = -0.68, p < 0.01). These correlations were not present with placebo. tRES-HESP decreased low-grade inflammation, characterized by decreased expression of CCL2, COX-2, IL-8, and RAGE. Changes in CCL2, IL-8, and RAGE were intercorrelated and all correlated positively with changes in MLXIP, MAFF, MAFG, NCF1, and FTH1, and negatively with changes in HMOX1 and TKT; changes in IL-8 also correlated positively with change in COX-2. Total urinary excretion of tRES and HESP metabolites were strongly correlated. These findings suggest tRES-HESP counters MG accumulation and protein glycation, decreasing activation of the unfolded protein response and expression of TXNIP and TNFα, producing reversal of insulin resistance. tRES-HESP is suitable for further evaluation for treatment of insulin resistance and related disorders.


Assuntos
Hesperidina/administração & dosagem , Resistência à Insulina , Obesidade/terapia , Sobrepeso/terapia , Resveratrol/administração & dosagem , Adulto , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Proteínas de Transporte/sangue , Correlação de Dados , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Quimioterapia Combinada , Dislipidemias/sangue , Dislipidemias/terapia , Feminino , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/terapia , Glicosilação/efeitos dos fármacos , Humanos , Inflamação , Mediadores da Inflamação/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Obesidade/sangue , Sobrepeso/sangue , Aldeído Pirúvico/sangue , Fator de Necrose Tumoral alfa/sangue
3.
Nutrients ; 13(6)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34200027

RESUMO

In 2015, the Dietary Guidelines for Americans (DGA) eliminated the historical upper limit of 300 mg of dietary cholesterol/day and shifted to a more general recommendation that cholesterol intake should be limited. The primary aim of this secondary analysis of the Diet Intervention Examining the Factors Interacting With Treatment Success (DIETFITS) weight loss diet trial was to evaluate the associations between 12-month changes in dietary cholesterol intake (mg/day) and changes in plasma lipids, particularly low-density lipoprotein (LDL) cholesterol for those following a healthy low-carbohydrate (HLC) diet. Secondary aims included examining high-density lipoprotein (HDL) cholesterol and triglycerides and changes in refined grains and added sugars. The DIETFITS trial randomized 609 healthy adults aged 18-50 years with body mass indices of 28-40 kg/m2 to an HLC or healthy low-fat (HLF) diet for 12 months. Linear regressions examined the association between 12-month change in dietary cholesterol intake and plasma lipids in 208 HLC participants with complete diet and lipid data, adjusting for potential confounding variables. Baseline dietary cholesterol intake was 322 ± 173 (mean ± SD). At 12 months, participants consumed an average of 460 ± 227 mg/day of dietary cholesterol; 76% consumed over the previously recommended limit of 300 mg/day. Twelve-month changes in cholesterol intake were not significantly associated with 12-month changes in LDL-C, HDL-C, or triglycerides. Diet recall data suggested participants' increase in dietary cholesterol was partly due to replacing refined grains and sugars with eggs. An increase in daily dietary cholesterol intake to levels substantially above the previous 300 mg upper limit was not associated with a negative impact on lipid profiles in the setting of a healthy, low-carbohydrate weight loss diet.


Assuntos
Colesterol na Dieta/administração & dosagem , Dieta com Restrição de Carboidratos , Dieta Saudável , Dieta Redutora , Lipídeos/sangue , Adolescente , Adulto , Colesterol na Dieta/efeitos adversos , LDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/dietoterapia , Triglicerídeos/sangue , Adulto Jovem
4.
Nutrients ; 13(7)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206539

RESUMO

The association between vitamin D deficiency and metabolic syndrome (MS) in severe obesity is unclear and controversial. We analyzed serum and dietary vitamin D and their association with MS in 150 adults with class II and III obesity (BMI ≥ 35 kg/m2) from the DieTBra Trial (NCT02463435). MS parameters were high fasting blood glucose, low HDL cholesterol, high triglycerides, elevated waist circumference, and hypertension. Vitamin D deficiency was considered as a level < 20 ng/mL. We performed multivariate Poisson regression adjusted for sociodemographic and lifestyle variables. The prevalence of serum vitamin D deficiency was 13.3% (mean 29.9 ± 9.4 ng/mL) and dietary vitamin D median was 51.3 IU/day. There were no significant associations between vitamin D, serum, and diet and sociodemographic variables, lifestyle, and class of obesity. Serum vitamin D deficiency was associated with age ≥ 50 years (p = 0.034). After a fully adjusted multivariate Poisson regression, MS and its parameters were not associated with serum or dietary vitamin D, except for lower HDL, which was associated with serum vitamin D deficiency (PR = 0.71, 95% CI 0.52-0.97; p = 0.029). Severe obese individuals had a low prevalence of vitamin D deficiency, which was not associated with MS.


Assuntos
Dieta/estatística & dados numéricos , Síndrome Metabólica/epidemiologia , Obesidade/complicações , Deficiência de Vitamina D/epidemiologia , Vitamina D/análise , Adolescente , Adulto , Fatores Etários , Idoso , Dieta/efeitos adversos , Inquéritos sobre Dietas , Feminino , Humanos , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/classificação , Distribuição de Poisson , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Fatores de Risco , Deficiência de Vitamina D/etiologia , Adulto Jovem
5.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209561

RESUMO

Obesity is one of the major health problems worldwide. Following healthy dietary patterns can be difficult in some countries due to the lack of availability of certain foods; thus, alternative foods are needed. Our aim was to evaluate the effect of a dietary pattern consisting of fruit, avocado, whole grains, and trout (FAWGT) on postprandial insulinemia and lipemia in obese Colombian subjects. A randomized controlled crossover study was conducted, in which 44 subjects with BMI ≥ 30 kg/m2 followed either a FAWGT diet or a diet high in saturated fat and rich in processed carbohydrates. Levels of lipids and carbohydrates were measured during the postprandial state. The FAWGT diet reduced fasting insulin, VLDL, and HOMA-IR after 8 weeks (p < 0.05), while there was a lower postprandial increase in TG, VLDL, and insulin levels after both acute and chronic intake of FAWGT diet (p < 0.05). The intake of FAWGT-diet was characterized by high consumption of foods rich in fiber, MUFAs, and vitamins C and E (p < 0.05). The consumption of a diet composed of fruit, avocado, whole grains, and trout has emerged as a valid alternative to the foods included in other heart-healthy diets since it improves postprandial lipemia and insulinemia in obese people and has similar beneficial effects to these healthy models.


Assuntos
Dieta Saudável/métodos , Ingestão de Alimentos/fisiologia , Hiperinsulinismo/dietoterapia , Hiperlipidemias/dietoterapia , Obesidade/dietoterapia , Animais , Glicemia/análise , Índice de Massa Corporal , VLDL-Colesterol/sangue , Estudos Cross-Over , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Jejum/sangue , Feminino , Frutas , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/etiologia , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Insulina/sangue , Resistência à Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Persea , Período Pós-Prandial/fisiologia , Alimentos Marinhos , Triglicerídeos/sangue , Truta , Grãos Integrais
6.
Biomed Pharmacother ; 139: 111668, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243630

RESUMO

Metabolic Syndrome (MetS) is a complex and multifactorial condition often characterised by obesity, hypertension, hyperlipidaemia, insulin resistance, glucose intolerance and fasting hyperglycaemia. Collectively, MetS can increase the risk of atherosclerotic-cardiovascular disease, which is the leading cause of death worldwide. However, no animal model currently exists to study MetS in the context of atherosclerosis. In this study we developed a pre-clinical mouse model that recapitulates the spectrum of MetS features while developing atherosclerosis. When BPHx mice were placed on a western type diet for 16 weeks, all the classical characteristics of MetS were observed. Comprehensive metabolic analyses and atherosclerotic imaging revealed BPHx mice to be obese and hypertensive, with elevated total plasma cholesterol and triglyceride levels, that accelerated atherosclerosis. Altogether, we demonstrate that the BPHx mouse has all the major components of MetS, and accelerates the development of atherosclerosis.


Assuntos
Aterosclerose/patologia , Dieta/efeitos adversos , Hipertensão/patologia , Síndrome Metabólica/patologia , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , Glicemia/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hiperlipidemias/sangue , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Hipertensão/sangue , Hipertensão/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/metabolismo , Obesidade/patologia , Triglicerídeos/sangue
7.
Nutrients ; 13(6)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073344

RESUMO

BACKGROUND: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. METHODS: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27-60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m2; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. RESULTS: The VLCKD program resulted in a significant decrease of body weight and BMI (-14.6%) and waist circumference (-12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (-3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. CONCLUSIONS: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.


Assuntos
Dieta Cetogênica , Coração , Obesidade/dietoterapia , Sobrepeso/dietoterapia , Adiposidade , Adulto , Idoso , Pressão Sanguínea , Índice de Massa Corporal , HDL-Colesterol , LDL-Colesterol , Dieta , Feminino , Humanos , Resistência à Insulina , Estilo de Vida , Fígado , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/urina , Sobrepeso/sangue , Sobrepeso/urina , Estudos Prospectivos , Triglicerídeos , Circunferência da Cintura , Perda de Peso
8.
Nat Med ; 27(6): 1079-1087, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34127852

RESUMO

Agonism of the glucagon-like peptide-1 receptor (GLP-1R) results in glycemic lowering and body weight loss and is a therapeutic strategy to treat type 2 diabetes (T2D) and obesity. We developed danuglipron (PF-06882961), an oral small-molecule GLP-1R agonist and found it had comparable efficacy to injectable peptidic GLP-1R agonists in a humanized mouse model. We then completed a placebo-controlled, randomized, double-blind, multiple ascending-dose phase 1 study ( NCT03538743 ), in which we enrolled 98 patients with T2D on background metformin and randomized them to receive multiple ascending doses of danuglipron or placebo for 28 d, across eight cohorts. The primary outcomes were assessment of adverse events (AEs), safety laboratory tests, vital signs and 12-lead electrocardiograms. Most AEs were mild, with nausea, dyspepsia and vomiting most commonly reported. There were no clinically meaningful AEs in laboratory values across groups. Heart rate generally increased with danuglipron treatment at day 28, but no heart-rate AEs were reported. Systolic blood pressure was slightly decreased and changes in diastolic blood pressure were similar with danuglipron treatment at day 28, compared with placebo. There were no clinically meaningful electrocardiogram findings. In this study in T2D, danuglipron was generally well tolerated, with a safety profile consistent with the mechanism of action of GLP-1R agonism.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Hipoglicemiantes/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/administração & dosagem , Camundongos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/genética , Obesidade/patologia
9.
Medicine (Baltimore) ; 100(26): e26529, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190188

RESUMO

ABSTRACT: We aimed to evaluate sarcopenia and sarcopenic obesity (SO) in patients with type 2 diabetes mellitus (T2DM), possible relationships with serum irisin and myostatin levels, and the effect of glycemic control on SO.Ninety T2DM patients were included in this a cross-sectional study. Sarcopenia was determined by evaluating muscle mass (bioelectrical impedance analysis), muscle strength (HGS), and gait speed (GS). Patients with muscle mass loss with functionally reduced muscle strength and/or performance were considered sarcopenic. In addition, participants were divided into 3 groups according to the FM (fat mass)/FFM (fat-free mass) ratio [group 1:5th-50th percentiles; group 2:50th-95th percentiles and group 3: ≥95 percentiles (sarcopenic obese)]. Irisin, myostatin levels and metabolic parameters were measured in all patients.The prevalence of sarcopenia and SO was 25.6% and 35.6%, respectively. Irisin levels were lower in sarcopenic patients, while glycosylated hemoglobin (A1c), body mass index (BMI), FM, and FM index were higher (P < .05). From group 1 to group 3, BMI, FM, FM index, GS, myostatin, and A1c increased, and muscle mass percentage, HGS, and irisin decreased (P < .05). A positive correlation was found between FM/FFM and myostatin and a negative correlation between FM/FFM and irisin (r = 0.303, P = .004 vs. r = -0.491, P < .001). Irisin remained an important predictor of SO, even after adjusting for confounding variables (OR:1.105; 95% CI:0.965-1.338, P = .002). The optimal cut-off value for irisin to predict SO was 9.49 ng/mL (specificity = 78.1%, sensitivity = 75.8%). In addition, A1c was an independent risk factor for SO development (OR:1.358, P = .055).This study showed that low irisin levels (<9.49ng/mL) and poor glycemic control in T2DM patients were an independent risk factor, especially for SO.


Assuntos
Diabetes Mellitus Tipo 2 , Fibronectinas/sangue , Miostatina/sangue , Obesidade , Sarcopenia , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Obesidade/sangue , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/fisiopatologia , Desempenho Físico Funcional , Valor Preditivo dos Testes , Prevalência , Fatores de Risco , Sarcopenia/sangue , Sarcopenia/diagnóstico , Sarcopenia/fisiopatologia , Velocidade de Caminhada
10.
Nutrients ; 13(5)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34067098

RESUMO

Low-grade inflammation is often present in people living with obesity. Inflammation can impact iron uptake and metabolism through elevation of hepcidin levels. Obesity is a major public health issue globally, with pregnant women often affected by the condition. Maternal obesity is associated with increased pregnancy risks including iron deficiency (ID) and iron-deficiency anaemia (IDA)-conditions already highly prevalent in pregnant women and their newborns. This comprehensive review assesses whether the inflammatory state induced by obesity could contribute to an increased incidence of ID/IDA in pregnant women and their children. We discuss the challenges in accurate measurement of iron status in the presence of inflammation, and available iron repletion strategies and their effectiveness in pregnant women living with obesity. We suggest that pre-pregnancy obesity and overweight/obese pregnancies carry a greater risk of ID/IDA for the mother during pregnancy and postpartum period, as well as for the baby. We propose iron status and weight gain during pregnancy should be monitored more closely in women who are living with overweight or obesity.


Assuntos
Anemia Ferropriva/epidemiologia , Fenômenos Fisiológicos da Nutrição Materna , Obesidade/complicações , Sobrepeso/complicações , Complicações na Gravidez/epidemiologia , Adulto , Anemia Ferropriva/etiologia , Feminino , Ganho de Peso na Gestação , Humanos , Incidência , Ferro/sangue , Obesidade/sangue , Sobrepeso/sangue , Gravidez , Complicações na Gravidez/etiologia , Fatores de Risco
11.
Int J Biol Macromol ; 183: 2074-2087, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34097961

RESUMO

Lycium barbarum polysaccharides (LBPs) are known for their beneficial effects on diabetes, NAFLD and related chronic metabolic diseases induced by high-fat diet (HFD). However, the relevant researches are mainly about the whole crude polysaccharides, the specific active ingredient of LBPs and its bioactivity have been rarely explored. Herein, a homogeneous polysaccharide (LBP-W) was isolated and purified from crude LBPs. Structure characterizations indicated that LBP-W contained a main chain consisting of a repeated unit of →6)-ß-Galp(1 â†’ residues with branches composed of α-Araf, ß-Galp and α-Rhap residues at position C-3. The objective of this study was to evaluate the anti-obesogenic effect of LBP-W and figure out the underlying mechanisms. In vivo efficacy trial illustrated that LBP-W supplements can alleviate HFD-induced mice obesity significantly. Gut microbiota analysis showed that LBP-W not only improved community diversity of intestinal flora, but also regulated their specific genera. Moreover, LBP-W can increase the content of short-chain fatty acids (SCFAs), a metabolite of the intestinal flora. In summary, all these results demonstrated that the homogeneous polysaccharide purified from L. barbarum could be used as a prebiotic agent to improve obesity by modulating the composition of intestinal flora and the metabolism of SCFAs.


Assuntos
Fármacos Antiobesidade/farmacologia , Bactérias/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Prebióticos , Animais , Fármacos Antiobesidade/química , Arabinose/química , Arabinose/farmacologia , Bactérias/crescimento & desenvolvimento , Bactérias/metabolismo , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Disbiose , Ácidos Graxos/sangue , Galactose/química , Galactose/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Estrutura Molecular , Obesidade/sangue , Obesidade/microbiologia , Ramnose/química , Ramnose/farmacologia , Relação Estrutura-Atividade
12.
Ther Adv Cardiovasc Dis ; 15: 17539447211012803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34120532

RESUMO

BACKGROUND: Rates of obesity continue to rise worldwide as evidenced in the 2017 Centers for Disease Control and Prevention (CDC) report that indicated over 35% of United States (US) citizens are obese, with Louisiana ranked as the fifth most obese state in America. Since large clinical trials tend to exclude obese patients, health care providers are faced with concerns of under- or overdosing these patients on warfarin. METHODS: This retrospective chart review evaluated patients who reported to a community anticoagulation clinic for warfarin management between 1 June 2017 and 30 September 2017. Along with baseline demographics, chronic use of drugs that have clinically significant interactions with warfarin, social activity such as tobacco use and alcohol consumption, were collected. Body mass indexes (BMI) were collected and categorized according to the World Health Organization definitions as follows: Normal (BMI 18-24.9 kg/m2), Overweight (25-29.9 kg/m2), Obesity Class I (30-34.9 kg/m2), Obesity Class II (35-39.9 kg/m2), Obesity Class III (⩾40 kg/m2). The primary outcome was the mean 90-day warfarin dose required to maintain "intermediate control" or "good control" of international normalized ratio (INR), stratified by BMI classifications. The secondary outcome was the time in therapeutic range (TTR) stratified by BMI classifications. RESULTS: A total of 433 patient encounters were included in this study. There was a total of 43 encounters in the Normal BMI category, 111 Overweight encounters, 135 Obesity Class I encounters, 45 Obesity Class II encounters, and 99 Obesity Class III encounters. Approximately 63% of the study population were male, and over 90% the patients were African American. The Obesity Class I and Obesity Class II class required an average of 11.47 mg and 17.10 mg more warfarin, respectively, to maintain a therapeutic INR when compared with the Normal BMI category. These findings were statistically significant with p values of 0.007 and <0.001, respectively. Additionally, upon comparing the Overweight BMI category with the Obesity Class II category, there was a mean warfarin dose difference of 11.22 mg (p = 0.010) more in Obesity Class II encounters to maintain a therapeutic INR. In the secondary analysis of TTR, Overweight category encounters had the highest TTR, whereas encounters in the Normal BMI category had the lowest TTR. CONCLUSION: As BMI increases, there is an increased chronic warfarin requirement to maintain "intermediate control" or "good control" of INR between 2 and 3 in an ambulatory care setting.


Assuntos
Anticoagulantes/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Obesidade/diagnóstico , Varfarina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/sangue , Cálculos da Dosagem de Medicamento , Interações Medicamentosas , Monitoramento de Medicamentos , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Registros Médicos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Tempo , Varfarina/sangue
13.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067683

RESUMO

The global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to use several host receptors for viral entry, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the lung and other organs. However, ACE2 could be shed from the surface to be soluble ACE2 (sACE2) in the circulation. The epigenetic factors affecting ACE2 expression include a type of small non-coding RNAs called microRNAs (miRNAs). In this study, we aimed at exploring the status of the sACE2 as well as serum levels of several upstream novel miRNAs as non-invasive biomarkers that might have a potential role in T2DM patients. Serum samples were collected from 50 T2DM patients and 50 healthy controls, and sACE2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Also, RNA was extracted, and TaqMan miRNA reverse transcription quantitative PCR (RT-qPCR) was performed to measure serum miRNA levels. Our results revealed that sACE2 is decreased in the T2DM patients and is affected by age, gender, and obesity level. Additionally, 4 miRNAs, which are revealed by in silico analysis to be potentially upstream of ACE2 were detectable in the serum. Among them, miR-421 level was found to be decreased in the serum of diabetic patients, regardless of the presence or absence of diabetic complications, as well as being differential in various body mass index (BMI) groups. The other 3 miRNAs (miR-3909, miR-212-5p, and miR-4677-3p) showed associations with multiple factors including age, gender, BMI, and serum markers, in addition to being correlated to each other. In conclusion, our study reveals a decline in the circulating serum levels of sACE2 in T2DM patients and identified 4 novel miRNAs that were associated with T2DM, which are influenced by different clinical and demographic factors.


Assuntos
Enzima de Conversão de Angiotensina 2/sangue , Complicações do Diabetes/sangue , Diabetes Mellitus Tipo 2/sangue , MicroRNAs/sangue , Adulto , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Biomarcadores/sangue , Índice de Massa Corporal , COVID-19/sangue , COVID-19/complicações , COVID-19/genética , Complicações do Diabetes/genética , Complicações do Diabetes/virologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/virologia , Regulação para Baixo , Feminino , Regulação da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/genética
14.
Clin Nutr ; 40(5): 2707-2715, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33933736

RESUMO

BACKGROUND & AIMS: Human beings are often driven to exhibit dietary preference according to their hedonic characteristics. Though previous studies proposed that the fat taste preference of an obese individual was associated with BMI, the perception of fat taste differs for every individual. The genetic variation among populations in taste receptor genes such as CD36 may be a contributing factor for this difference. Satiety peptides can also play a role in the regulation of fat taste perception. Generally, this hormone helps us to feel the sense of satiety. METHODS: We have analysed the relationship among oro-gustatory perception of dietary lipids, salivary peptide-YY and genetic polymorphism in CD36. Oral fatty acid sensitivity analysis was performed by alternative forced choice method. Salivary peptide-YY concentration was analysed by ELISA and single nucleotide polymorphism (SNP) in CD36 gene was determined by Real-Time PCR experiments. RESULTS: We observed that the SNP at rs1761667 of CD36 and oral detection threshold for linoleic acid (LA) are associated with choice of food, lipid profiles, peptide-YY as well as adiposity parameters in obese population. Obese peoples had significantly low levels of peptide YY than people with BMI less than 25. These factors possibly play a role in preference for energy rich diets, development of obesity and associated complications. CONCLUSION: This study provides a solid foundation for understanding the alterations in the dietary fat intake and levels of peptide-YY, which are associated with polymorphism in fat taste receptor. This is the first report that shows a significant relationship between the satiety hormone level, SNP in CD36 gene and oral fat detection threshold in human subjects.


Assuntos
Antígenos CD36/genética , Obesidade/metabolismo , Peptídeo YY/sangue , Polimorfismo de Nucleotídeo Único , Regulação da Expressão Gênica , Variação Genética , Humanos , Obesidade/sangue , Obesidade/genética , Peptídeo YY/genética , Peptídeo YY/metabolismo
15.
Biomed Pharmacother ; 140: 111738, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34029949

RESUMO

BACKGROUND: Diabetes and obesity contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). However, how diabetes and obesity accelerate liver tumorigenesis remains to be fully understood. Moreover, to verify the therapeutic potential of anti-diabetic drugs, there exists a strong need for appropriate animal models that recapitulate human pathophysiology of NASH and HCC. METHODS: We established a novel murine model of NASH-associated liver tumors using genetically obese melanocortin 4 receptor-deficient mice fed on Western diet in combination with a chemical procarcinogen, and verified the validity of our model in evaluating drug efficacy. FINDINGS: Our model developed multiple liver tumors together with obesity, diabetes, and NASH within a relatively short period (approximately 3 months). In this model, sodium glucose cotransporter 2 inhibitor Tofogliflozin prevented the development of NASH-like liver phenotypes and the progression of liver tumors. Tofogliflozin attenuated p21 expression of hepatocytes in non-tumorous lesions in the liver. INTERPRETATION: Tofogliflozin treatment attenuates cellular senescence of hepatocytes under obese and diabetic conditions. This study provides a unique animal model of NASH-associated liver tumors, which is applicable for assessing drug efficacy to prevent or treat NASH-associated HCC.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Glucosídeos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Animais , Compostos Benzidrílicos/farmacologia , Glicemia/análise , Senescência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Dieta Ocidental , Modelos Animais de Doenças , Progressão da Doença , Glucosídeos/farmacologia , Hepatócitos/efeitos dos fármacos , Insulina/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/sangue , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/patologia , Receptor Tipo 4 de Melanocortina/genética , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
16.
Medicine (Baltimore) ; 100(21): e26049, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032731

RESUMO

BACKGROUND: This study aims to assess the therapeutic effects of a well-known component (puerarin) obtained from a Chinese herb root in patients with polycystic ovary syndrome (PCOS). METHODS: Women with premature ovarian failure (POF) were assigned to the obese group (body mass index [BMI] ≥24 kg/m2 and waist hip ratio [WHR] >0.85) or non-obese group (group 3, n = 21). Obese patients were further randomly assigned to the obese treatment group (group 1, n = 15) and obese control group (group 1, n = 15). All patients received standard treatment (Diane-35, 1 tablet/d, orally, plus metformin, 1.5 g/d, orally). In addition to the standard modality, patients in group 1 and group 3 also orally received 150 mg/d of puerarin tablets for 3 months. Venous blood was drawn before and after treatment. Then, the metabolic and antioxidant biomarkers were measured. The normality of distribution of the data was tested using the Kolmogorov-Smirnov method. The baseline characteristics were analyzed using one-factor analysis of variance (ANOVA), and post-hoc was performed using the least significance difference (LSD)-t test. RESULTS: Significantly improved blood levels of sex hormone binding globulin (SHBG) and superoxide dismutase (SOD) were observed in patients who received the additional treatment of puerarin, regardless of their lean or obese status, while these were not observed in patients who did not receive puerarin. Furthermore, obese patients with PCOS had significantly lower systolic blood pressure, total cholesterol, and testosterone blood levels, when compared with before treatment. CONCLUSION: The addition of puerarin to the present treatment protocol can be considered for the management of metabolic disorders and hyperandrogenism in PCOS patients.


Assuntos
Isoflavonas/administração & dosagem , Obesidade/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Insuficiência Ovariana Primária/tratamento farmacológico , Administração Oral , Adolescente , Adulto , China , Colesterol/sangue , Acetato de Ciproterona/administração & dosagem , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Etinilestradiol/administração & dosagem , Feminino , Humanos , Metformina/administração & dosagem , Obesidade/sangue , Obesidade/complicações , Obesidade/metabolismo , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Insuficiência Ovariana Primária/sangue , Insuficiência Ovariana Primária/etiologia , Insuficiência Ovariana Primária/metabolismo , Globulina de Ligação a Hormônio Sexual/análise , Superóxido Dismutase/sangue , Comprimidos , Testosterona/sangue , Resultado do Tratamento , Adulto Jovem
17.
Medicine (Baltimore) ; 100(21): e26107, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032752

RESUMO

ABSTRACT: Evidence from trials demonstrating the benefits and risks of low-glycemic index and fat-restricted diets in weight loss and blood lipid profile changes is unclear. This study aimed to assess the implemented and effects of a fat-restricted low-glycemic index diet on weight control and blood lipid profile changes in in overweight/obese Southwest Chinese individualst.This prospective pilot study enrolled overweight/obese subjects at the People's Hospital of Sichuan Province between February and July 2019. The daily energy intake was reduced by 300 to 500 kcal according to the participant's weight and activity level, with low-glycemic index carbohydrate- and fat-energy ratios < 45% and 25% to 30%, respectively. Participants received guidance for 3 months by telephone follow-up, internet interaction, or WeChat. Changes in weight, body composition, and blood profile were measured.A total of 254 patients were finally analyzed, including 101 males and 153 females. After adjusting for potential confounders, weight (P < .001), body mass index (P < .001), waist circumference (P < .001), waist-hip ratio (P < .001), body fat percentage (P < .001), visceral fat area (P < .001), basal metabolism (P = .002), cholesterol (P < .001), and triglycerides (P < .001) were significantly reduced after the 3-month intervention. The above indexes showed no significant differences between men and women.Regardless of gender, fat-restricted low-glycemic index diet might be helpful for controlling weight and lowering blood cholesterol and triglycerides in overweight/obese individuals in Southwest China.


Assuntos
Dieta com Restrição de Gorduras , Índice Glicêmico , Lipídeos/sangue , Obesidade/dietoterapia , Sobrepeso/dietoterapia , Adulto , Composição Corporal , China , Dieta com Restrição de Gorduras/efeitos adversos , Feminino , Humanos , Masculino , Obesidade/sangue , Sobrepeso/sangue , Projetos Piloto , Estudos Prospectivos , Fatores Sexuais , Perda de Peso
18.
Nutr Metab Cardiovasc Dis ; 31(6): 1879-1889, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33992509

RESUMO

BACKGROUND AND AIMS: Breaking up sedentary periods, particularly with light activity, increases total energy expenditure (EE), and helps provide better glycemic control. However, the effects of activities of various intensities to interrupt prolonged sedentary time are unclear. The purpose of the present study was to examine potential differences in glycemic control and EE from breaking up sedentary time with short exercise bouts of different intensities. METHODS AND RESULTS: Nine overweight/obesity young men underwent whole body indirect calorimetry at 19:00 on day 1 and stayed overnight. After awakening on day 2, they performed short duration jogging every 30 min over 8 h (16-time bouts in total) under 3 different conditions with the same running distance: (1) lactate threshold (LT) for 2 min, (2) 60% LT for 200 s, and (3) onset of blood lactate accumulation (OBLA) for 75 s. The 24-h EE and interstitial glucose concentration (from 8:00 to 19:00 on day 2) was continuously measured throughout the trials. The standard deviation during intervention and indexes of postprandial of the interstitial glucose concentration was significantly lower at LT and OBLA than at 60% LT (p < 0.05). The 24-h EE was not significantly different among conditions, but EE at OBLA during intervention was slightly but significantly higher than at 60% LT and LT. CONCLUSION: Breaking up sedentary time with short-duration jogging at LT and with OBLA intensities may have better glycemic control and increased use of carbohydrate as a fuel, while short-duration a jogging at OBLA intensity may increase EE. TRIAL REGISTRATION: UMIN000041361.


Assuntos
Metabolismo Energético , Obesidade/terapia , Condicionamento Físico Humano , Corrida , Comportamento Sedentário , Biomarcadores/sangue , Glicemia/metabolismo , Calorimetria Indireta , Estudos Cross-Over , Ingestão de Energia , Humanos , Japão , Ácido Láctico/sangue , Masculino , Refeições , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Fatores de Tempo , Adulto Jovem
19.
Medicine (Baltimore) ; 100(20): e26061, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011124

RESUMO

BACKGROUND: The aim of this study is to evaluate the alterations in bone mineral density and other surrogate markers for osteoporosis in obese patients with type 2 diabetes mellitus (T2DM) who received Roux-en-Y gastric bypass (RYGB) versus medical treatment as control. METHODS: We searched 4 electronic databases and reference lists of relevant studies for eligible research published before December, 2019. After quality assessment, eligible studies were synthesized for relevant outcomes, including lumbar spine bone mineral density (L-spine BMD) change, total hip BMD change, osteocalcin level, C-terminal telopeptide level, and parathyroid hormone level. RESULTS: Three randomized clinical trials and 2 observational studies concerning 307 total obese T2DM patients were included. Follow-up ranged from 12 to 60 months. Patients underwent RYGB surgery were associated with both higher L-spine BMD loss (mean difference: -2.90, 95% CI: -2.99∼-2.81, P < .00001) and total hip BMD loss (mean difference: -5.81, 95% CI: -9.22∼-2.40, P = .0008). As to biochemical markers of bone metabolism, we found significantly higher osteocalcin level in medical treatment (control) group compared with RYGB group (mean difference: 11.16, 95% CI: 8.57-13.75, P < .00001). However, higher C-terminal telopeptide level and parathyroid hormone level were noted in medical treatment group (control) compared with RYGB group (mean difference: 0.29, 95% CI: 0.11-0.48, P = .002; mean difference: 1.56, 95% CI: 0.84-2.27, P < .0001). CONCLUSIONS: RYGB surgery is associated with negative impact on bone metabolism and increase the risk of osteoporosis in obese patients with T2DM. We suggest that clinicians acknowledge the adverse effects of surgery and keep monitoring bone mineral components in post-RYGB populations. Further studies regarding the optimal amount of perioperative and postsurgical supplementation should be evaluated.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Obesidade/sangue , Obesidade/cirurgia , Osteoporose/sangue , Biomarcadores/sangue , Densidade Óssea , Humanos , Obesidade/complicações , Osteoporose/complicações , Osteoporose/diagnóstico
20.
PLoS One ; 16(5): e0250956, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33956870

RESUMO

Clinical and laboratory predictors of COVID-19 severity are now well described and combined to propose mortality or severity scores. However, they all necessitate saturable equipment such as scanners, or procedures difficult to implement such as blood gas measures. To provide an easy and fast COVID-19 severity risk score upon hospital admission, and keeping in mind the above limits, we sought for a scoring system needing limited invasive data such as a simple blood test and co-morbidity assessment by anamnesis. A retrospective study of 303 patients (203 from Bordeaux University hospital and an external independent cohort of 100 patients from Paris Pitié-Salpêtrière hospital) collected clinical and biochemical parameters at admission. Using stepwise model selection by Akaike Information Criterion (AIC), we built the severity score Covichem. Among 26 tested variables, 7: obesity, cardiovascular conditions, plasma sodium, albumin, ferritin, LDH and CK were the independent predictors of severity used in Covichem (accuracy 0.87, AUROC 0.91). Accuracy was 0.92 in the external validation cohort (89% sensitivity and 95% specificity). Covichem score could be useful as a rapid, costless and easy to implement severity assessment tool during acute COVID-19 pandemic waves.


Assuntos
COVID-19/epidemiologia , Idoso , COVID-19/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Comorbidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Paris/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
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