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1.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281282

RESUMO

Urinary acrolein adduct levels have been reported to be increased in both habitual smokers and type-2 diabetic patients. The impairment of glucose transport in skeletal muscles is a major factor responsible for glucose uptake reduction in type-2 diabetic patients. The effect of acrolein on glucose metabolism in skeletal muscle remains unclear. Here, we investigated whether acrolein affects muscular glucose metabolism in vitro and glucose tolerance in vivo. Exposure of mice to acrolein (2.5 and 5 mg/kg/day) for 4 weeks substantially increased fasting blood glucose and impaired glucose tolerance. The glucose transporter-4 (GLUT4) protein expression was significantly decreased in soleus muscles of acrolein-treated mice. The glucose uptake was significantly decreased in differentiated C2C12 myotubes treated with a non-cytotoxic dose of acrolein (1 µM) for 24 and 72 h. Acrolein (0.5-2 µM) also significantly decreased the GLUT4 expression in myotubes. Acrolein suppressed the phosphorylation of glucose metabolic signals IRS1, Akt, mTOR, p70S6K, and GSK3α/ß. Over-expression of constitutive activation of Akt reversed the inhibitory effects of acrolein on GLUT4 protein expression and glucose uptake in myotubes. These results suggest that acrolein at doses relevant to human exposure dysregulates glucose metabolism in skeletal muscle cells and impairs glucose tolerance in mice.


Assuntos
Acroleína/toxicidade , Transportador de Glucose Tipo 4/antagonistas & inibidores , Glucose/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Acroleína/administração & dosagem , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Glicemia/metabolismo , Linhagem Celular , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Humanos , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
2.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281287

RESUMO

Diabetic retinopathy (DR) is a common complication of diabetes that causes severe visual impairment globally. The pathogenesis of DR is related to oxidative stress and chronic inflammation. The fibroblast growth factor type 1 (FGF-1) mitogen plays crucial roles in cell function, development, and metabolism. FGF-1 is involved in blood sugar regulation and exerts beneficial antioxidative and anti-inflammatory effects on various organ systems. This study investigated the antioxidative and anti-inflammatory neuroprotective effects of FGF-1 on high-glucose-induced retinal damage. The results revealed that FGF-1 treatment significantly reversed the harmful effects of oxidative stress and inflammatory mediators in retinal tissue in a streptozotocin-induced diabetic rat model. These protective effects were also observed in the in vitro model of retinal ARPE-19 cells exposed to a high-glucose condition. We demonstrated that FGF-1 attenuated p38 mitogen-activated protein kinase and nuclear factor-κB pathway activation under the high-glucose condition. Our results indicated that FGF-1 could effectively prevent retinal injury in diabetes. The findings of this study could be used to develop novel treatments for DR that aim to reduce the cascade of oxidative stress and inflammatory signals in neuroretinal tissue.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/prevenção & controle , Fator 1 de Crescimento de Fibroblastos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Glicemia/metabolismo , Linhagem Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Fator 1 de Crescimento de Fibroblastos/deficiência , Glucose/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
3.
J Cardiothorac Surg ; 16(1): 198, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284809

RESUMO

BACKGROUND: Poor glycemic control has been associated with an increased risk of wound complications after various types of operations. However, it remains unclear how hemoglobin A1c (HbA1c) and preoperative glycemia can be used in clinical decision-making to prevent sternal wound complications (SWC) following off-pump coronary artery bypass grafting (OPCAB). METHODS: We conducted a retrospective study of 1774 consecutive patients who underwent OPCAB surgery between January 2010 and November 2016. A new four-grade classification for SWC was used. The associations of HbA1c and preoperative glycemia with incidence and grade of SWC were analysed using logistic regression analysis and proportional odds models, respectively. RESULTS: During a median follow-up of 326 days (interquartile range (IQR) 21-1261 days), SWC occurred in 133/1316 (10%) of non-diabetes and 82/458 (18%) of diabetes patients (p < 0.001). Higher HbA1c was significantly associated with a higher incidence of SWC (odds ratio, OR 1.24 per 1% increase, 95% confidence interval, CI 1.04;1.48, p = 0.016) as well as a higher grade of SWC (OR 1.25, 95% CI 1.06;1.48, p = 0.010). There was no association between glycemia and incidence (p = 0.539) nor grade (p = 0.607) of SWC. Significant modifiers of these effects were found: HbA1c was associated with SWC in diabetes patients younger than 70 years (OR 1.41, 95% CI 1.17;1.71, p < 0.001), whereas it was not in those older than 70 years. Glycemia was associated with SWC in patients who underwent non-urgent surgery (OR 2.48, 95% CI 1.26;4.88, p = 0.009), in diabetes patients who received skeletonised grafts (OR 4.83, 95% CI 1.28;18.17, p = 0.020), and in diabetes patients with a BMI < 30 (OR 2.19, 95% CI 1.01;4.76, p = 0.047), whereas it was not in the counterparts of these groups. CONCLUSIONS: Under certain conditions, HbA1c and glycemia are associated SWC following OPCAB. These findings are helpful in planning the procedure with minimal risk of SWC.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Tomada de Decisões , Diabetes Mellitus/epidemiologia , Hemoglobina A Glicada/metabolismo , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Comorbidade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus/sangue , Feminino , Humanos , Incidência , Masculino , Razão de Chances , Período Pré-Operatório , Estudos Retrospectivos , Resultado do Tratamento
4.
Medicine (Baltimore) ; 100(27): e26590, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232208

RESUMO

ABSTRACT: Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, accounting for around 90% of all cases worldwide. One means to strengthen the prevention and treatment of diabetes is via changes in self-management and lifestyle behaviors. However, lifestyle and personal health behaviors are strongly influenced by personality traits, and thus personality may play a significant role in such aspects as medication compliance, exercise habits, blood glucose monitoring, diet control, and maintenance of an ideal body weight.In this study, we examined whether certain personality traits of patients with T2DM are correlated with higher glycohemoglobin (HbA1c) levels.A total of 214 participants with T2DM were recruited from an outpatient setting. χ2 test and logistic regression analyses with 5 models were employed.The OR for the "neuroticism" trait was 3.199 (95% CI = 1.228-8.331, P = .017), and those with this trait were 3.199 times more likely to have higher HbA1c levels than those with the "openness-extraversion" personality trait. This strong relationship between neuroticism and a higher HbA1c level was also evident in models 2, 3, 4, and 5. One-way ANOVA also indicated that the group with the neuroticism personality trait had significantly different mean fasting glucose, HbA1c, triglyceride, and high-density lipoprotein cholesterol levels.We found that a personality characterized by neuroticism is an independent predictor of higher HbA1c level in this study. We also found that people in the pre-contemplation and contemplation stages of exercise have higher HbA1c levels.


Assuntos
Automonitorização da Glicemia/métodos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/metabolismo , Estilo de Vida , Personalidade , Autogestão/métodos , Adulto , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
5.
Nutrients ; 13(6)2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34203025

RESUMO

Clinical decision support systems (CDSS) are data aggregation tools based on computer technology that assist clinicians to promote healthy weight management and prevention of cardiovascular diseases. We carried out a randomised controlled 3-month trial to implement lifestyle modifications in breast cancer (BC) patients by means of CDSS during the COVID-19 pandemic. In total, 55 BC women at stages I-IIIA were enrolled. They were randomly assigned either to Control group, receiving general lifestyle advice (n = 28) or the CDSS group (n = 27), to whom the CDSS provided personalised dietary plans based on the Mediterranean diet (MD) together with physical activity guidelines. Food data, anthropometry, blood markers and quality of life were evaluated. At 3 months, higher adherence to MD was recorded in the CDSS group, accompanied by lower body weight (kg) and body fat mass percentage compared to control (p < 0.001). In the CDSS arm, global health/quality of life was significantly improved at the trial endpoint (p < 0.05). Fasting blood glucose and lipid levels (i.e., cholesterol, LDL, triacylglycerols) of the CDSS arm remained unchanged (p > 0.05) but were elevated in the control arm at 3 months (p < 0.05). In conclusion, CDSS could be a promising tool to assist BC patients with lifestyle modifications during the COVID-19 pandemic.


Assuntos
Neoplasias da Mama , COVID-19 , Sistemas de Apoio a Decisões Clínicas , Dieta Mediterrânea , Estilo de Vida , Obesidade/prevenção & controle , Pandemias , Tecido Adiposo/metabolismo , Adulto , Terapia Comportamental , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal , LDL-Colesterol/sangue , Feminino , Nível de Saúde , Humanos , Pessoa de Meia-Idade , Obesidade/etiologia , Cooperação do Paciente , Qualidade de Vida , SARS-CoV-2 , Triglicerídeos/sangue
6.
Nutrients ; 13(6)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201185

RESUMO

High-protein diets (HPDs) are widely accepted as a way to stimulate muscle protein synthesis when combined with resistance training (RT). However, the effects of HPDs on adipose tissue plasticity and local inflammation are yet to be determined. This study investigated the impact of HPDs on glucose control, adipocyte size, and epididymal adipose inflammatory biomarkers in resistance-trained rats. Eighteen Wistar rats were randomly assigned to four groups: normal-protein (NPD; 17% protein total dietary intake) and HPD (26.1% protein) without RT and NPD and HPD with RT. Trained groups received RT for 12 weeks with weights secured to their tails. Glucose and insulin tolerance tests, adipocyte size, and an array of cytokines were determined. While HPD without RT induced glucose intolerance, enlarged adipocytes, and increased TNF-α, MCP-1, and IL1-ß levels in epididymal adipose tissue (p < 0.05), RT diminished these deleterious effects, with the HPD + RT group displaying improved blood glucose control without inflammatory cytokine increases in epididymal adipose tissue (p < 0.05). Furthermore, RT increased glutathione expression independent of diet (p < 0.05). RT may offer protection against adipocyte hypertrophy, pro-inflammatory states, and glucose intolerance during HPDs. The results highlight the potential protective effects of RT to mitigate the maladaptive effects of HPDs.


Assuntos
Glicemia/metabolismo , Dieta Rica em Proteínas , Inflamação/sangue , Gordura Intra-Abdominal/patologia , Treinamento de Força , Adipócitos/patologia , Animais , Tamanho Celular , Dieta , Epididimo/patologia , Glutationa/metabolismo , Resistência à Insulina , Masculino , Tamanho do Órgão , Ratos Wistar , Ganho de Peso
7.
Nutrients ; 13(7)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201703

RESUMO

Global protein consumption has been increasing for decades due to changes in demographics and consumer shifts towards higher protein intake to gain health benefits in performance nutrition and appetite regulation. Plant-derived proteins may provide a more environmentally sustainable alternative to animal-derived proteins. This study, therefore, aimed to investigate, for the first time, the acute effects on glycaemic indices, gut hormones, and subjective appetite ratings of two high-quality, plant-derived protein isolates (potato and rice), in comparison to a whey protein isolate in a single-blind, triple-crossover design study with nine male participants (30.8 ± 9.3 yrs). Following a 12 h overnight fast, participants consumed an equal volume of the three isocaloric protein shakes on different days, with at least a one-week washout period. Glycaemic indices and gut hormones were measured at baseline, then at 30, 60, 120, 180 min at each visit. Subjective palatability and appetite ratings were measured using visual analogue scales (VAS) over the 3 h, at each visit. This data showed significant differences in insulin secretion with an increase in whey (+141.8 ± 35.1 pmol/L; p = 0.011) and rice (-64.4 ± 20.9 pmol/L; p = 0.046) at 30 min compared to potato protein. A significantly larger total incremental area under the curve (iAUC) was observed with whey versus potato and rice with p < 0.001 and p = 0.010, respectively. There was no significant difference observed in average appetite perception between the different proteins. In conclusion, this study suggests that both plant-derived proteins had a lower insulinaemic response and improved glucose maintenance compared to whey protein.


Assuntos
Biomarcadores/metabolismo , Glicemia/metabolismo , Ingestão de Alimentos , Oryza/química , Proteínas de Plantas/farmacologia , Solanum tuberosum/química , Proteínas do Soro do Leite/farmacologia , Adulto , Aminoácidos/análise , Apetite , Hormônios/sangue , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Peptídeos/sangue , Saciação , Escala Visual Analógica , Adulto Jovem
8.
Nutrients ; 13(6)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204055

RESUMO

Lately, matcha green tea has gained popularity as a beverage and food additive. It has proved to be effective in preventing obesity and related metabolic syndromes. However, the underlying mechanisms of its control effects against non-alcoholic fatty liver disease (NAFLD) are complicated and remain elusive. In the present study, we performed an in vivo experiment using male C57BL/6 mice fed with a high-fat diet and simultaneously treated with matcha for six weeks. Serum biochemical parameters, histological changes, lipid accumulation, inflammatory cytokines, and relevant indicators were examined. Dietary supplementation of matcha effectively prevented excessive accumulation of visceral and hepatic lipid, elevated blood glucose, dyslipidemia, abnormal liver function, and steatosis hepatitis. RNA sequencing analyses of differentially expressed genes in liver samples indicated that matcha treatment decreased the activity of lipid droplet-associated proteins and increased the activity of cytochrome P450 enzymes, suggesting improved metabolic capacity and liver function. The current study provided evidence for new dietary strategies based on matcha supplementation to ameliorate lipotoxicity-induced obesity and NALFD.


Assuntos
Antioxidantes/administração & dosagem , Metabolismo dos Lipídeos/fisiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Obesidade/terapia , Chá , Animais , Glicemia/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Dislipidemias/metabolismo , Inflamação , Fígado/metabolismo , Testes de Função Hepática , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/etiologia
9.
Nutrients ; 13(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34208914

RESUMO

Based on several randomized clinical trials, it has been suggested that baseline glucose homeostasis interacts with the influence of diet composition on weight loss and weight loss maintenance. In this secondary analysis of the YoYo study, a study investigating predictors of weight loss maintenance, we tested the hypothesis that (self-selected) dietary carbohydrate and/or fibre intake interact with the glucose homeostasis parameters for weight loss maintenance. Sixty-one overweight or obese individuals lost around 10 kg of body weight on an energy-restricted diet and were then followed for 9 months. During this period, participants were advised to maintain their body weight and eat a healthy diet without further recommendations on calorie intake or diet composition. Contrary to our hypothesis, carbohydrate intake showed no positive association with weight regain after weight loss, and no interaction with baseline fasting glucose concentration was found. There was a non-significant negative association between fibre intake and weight regain (B = -0.274, standard error (SE) 0.158, p = 0.090), but again, no interaction with fasting plasma glucose was found. In conclusion, the data from the YoYo study do not support a role for baseline glucose homeostasis in determining the association between self-reported carbohydrate and/or fibre intake and weight regain after weight loss.


Assuntos
Glicemia/metabolismo , Dieta Redutora , Homeostase , Ganho de Peso/fisiologia , Carboidratos da Dieta/farmacologia , Fibras na Dieta , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade
10.
Nutrients ; 13(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209137

RESUMO

D-Pinitol (DPIN) is a natural occurring inositol capable of activating the insulin pathway in peripheral tissues, whereas this has not been thoroughly studied in the central nervous system. The present study assessed the potential regulatory effects of DPIN on the hypothalamic insulin signaling pathway. To this end we investigated the Phosphatidylinositol-3-kinase (PI3K)/Protein Kinase B (Akt) signaling cascade in a rat model following oral administration of DPIN. The PI3K/Akt-associated proteins were quantified by Western blot in terms of phosphorylation and total expression. Results indicate that the acute administration of DPIN induced time-dependent phosphorylation of PI3K/Akt and its related substrates within the hypothalamus, indicating an activation of the insulin signaling pathway. This profile is consistent with DPIN as an insulin sensitizer since we also found a decrease in the circulating concentration of this hormone. Overall, the present study shows the pharmacological action of DPIN in the hypothalamus through the PI3K/Akt pathway when giving in fasted animals. These findings suggest that DPIN might be a candidate to treat brain insulin-resistance associated disorders by activating insulin response beyond the insulin receptor.


Assuntos
Hipotálamo/metabolismo , Inositol/análogos & derivados , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Administração Oral , Animais , Glicemia/metabolismo , Ativação Enzimática/efeitos dos fármacos , Glucagon/sangue , Homeostase , Hipotálamo/efeitos dos fármacos , Inositol/administração & dosagem , Inositol/sangue , Inositol/química , Inositol/farmacologia , Insulina/sangue , Insulina/metabolismo , Resistência à Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Fosforilação/efeitos dos fármacos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
11.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068151

RESUMO

Severe burns represent an important challenge for patients and medical teams. They lead to profound metabolic alterations, trigger a systemic inflammatory response, crush the immune defense, impair the function of the heart, lungs, kidneys, liver, etc. The metabolism is shifted towards a hypermetabolic state, and this situation might persist for years after the burn, having deleterious consequences for the patient's health. Severely burned patients lack energy substrates and react in order to produce and maintain augmented levels of glucose, which is the fuel "ready to use" by cells. In this paper, we discuss biological substances that induce a hyperglycemic response, concur to insulin resistance, and determine cell disturbance after a severe burn. We also focus on the most effective agents that provide pharmacological modulations of the changes in glucose metabolism.


Assuntos
Glicemia/metabolismo , Queimaduras/complicações , Hiperglicemia/etiologia , Resistência à Insulina , Animais , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/patologia
12.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34074061

RESUMO

BACKGROUND: Erythritol, a sugar alcohol, is widely used as a substitute for sugar in diets for patients with diabetes or obesity. METHODS: In this study, we aimed to investigate the effects of erythritol on metabolic disorders induced by a high-fat diet in C57BL/6J mice, while focusing on changes in innate immunity. RESULTS: Mice that were fed a high-fat diet and administered water containing 5% erythritol (Ery group) had markedly lower body weight, improved glucose tolerance, and markedly higher energy expenditure than the control mice (Ctrl group) (n = 6). Furthermore, compared with the Ctrl group, the Ery group had lesser fat deposition in the liver, smaller adipocytes, and significantly better inflammatory findings in the small intestine. The concentrations of short-chain fatty acids (SCFAs), such as acetic acid, propanoic acid, and butanoic acid, in the serum, feces, and white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. In flow cytometry experiments, group 3 innate lymphoid cell (ILC3) counts in the lamina propria of the small intestine and ILC2 counts in the white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. Quantitative real-time reverse transcription polymerase chain reaction analyses showed that the Il-22 expression in the small intestine of the Ery group was markedly higher than that in the Ctrl group. CONCLUSIONS: Erythritol markedly decreased metabolic disorders such as diet-induced obesity, glucose intolerance, dyslipidemia, and fat accumulation in the mouse liver by increasing SCFAs and modulating innate immunity.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Eritritol/farmacologia , Intolerância à Glucose/dietoterapia , Imunidade Inata/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Metabolismo Energético/efeitos dos fármacos , Eritritol/administração & dosagem , Ácidos Graxos Voláteis/sangue , Ácidos Graxos Voláteis/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Intolerância à Glucose/metabolismo , Imunidade Inata/genética , Inflamação/dietoterapia , Inflamação/genética , Inflamação/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Linfócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/metabolismo , Obesidade/genética , Obesidade/metabolismo
13.
Molecules ; 26(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064815

RESUMO

Men with early-onset androgenetic alopecia are characterized by hormonal profiles similar to those observed in women with polycystic ovary syndrome. The purpose of this research was to investigate levels of cardiometabolic risk factors in 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)-treated men with early-onset androgenic alopecia. We studied two matched rosuvastatin-treated groups of men with mixed dyslipidemia: subjects with early-onset androgenic alopecia (group A) and subjects with normal hair growth (group B). Plasma lipids, glucose homeostasis markers, and levels of sex hormones, uric acid, hsCRP, homocysteine, fibrinogen, and 25-hydroxyvitamin D were measured before entering the study and six months later. Both groups differed in insulin sensitivity and levels of calculated bioavailable testosterone, dehydroepiandrosterone-sulfate, uric acid, hsCRP, fibrinogen, and 25-hydroxyvitamin D. Though observed in both study groups, treatment-induced reductions in total cholesterol, LDL cholesterol, hsCRP, and fibrinogen were more pronounced in group B than group A. Moreover, only in group A did rosuvastatin deteriorate insulin sensitivity, and only in group B did the drug affect uric acid, homocysteine, and 25-hydroxyvitamin D. The impact of rosuvastatin on cardiometabolic risk factors correlated with insulin sensitivity, calculated bioavailable testosterone, and dehydroepiandrosterone-sulfate. The obtained results suggest that men with early-onset androgenic alopecia may benefit to a lesser degree from rosuvastatin treatment than their peers.


Assuntos
Alopecia/complicações , Fatores de Risco Cardiometabólico , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Rosuvastatina Cálcica/efeitos adversos , Rosuvastatina Cálcica/uso terapêutico , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Humanos , Lipídeos/sangue , Masculino
14.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070765

RESUMO

Heart failure (HF) affects up to over 20% of patients with type 2 diabetes (T2DM), even more in the elderly. Although, in T2DM, both hyperglycemia and the proinflammatory status induced by insulin resistance are crucial in cardiac function impairment, SGLT2i cardioprotective mechanisms against HF are several. In particular, these beneficial effects seem attributable to the significant reduction of intracellular sodium levels, well-known to exert a cardioprotective role in the prevention of oxidative stress and consequent cardiomyocyte death. From a molecular perspective, patients' exposure to gliflozins' treatment mimics nutrient and oxygen deprivation, with consequent autophagy stimulation. This allows to maintain the cellular homeostasis through different degradative pathways. Thus, since their introduction in the clinical practice, the hypotheses on SGLT2i mechanisms of action have changed: from simple glycosuric drugs, with consequent glucose lowering, erythropoiesis enhancing and ketogenesis stimulating, to intracellular sodium-lowering molecules. This provides their consequent cardioprotective effect, which justifies its significant reduction in CV events, especially in populations at higher risk. Finally, the updated clinical evidence of SGLT2i benefits on HF was summarized. Thus, this review aimed to analyze the cardioprotective mechanisms of sodium glucose transporter 2 inhibitors (SGLT2i) in patients with HF, as well as their clinical impact on cardiovascular events.


Assuntos
Cardiotônicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Resistência à Insulina/genética , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Transportador 2 de Glucose-Sódio/genética , Idoso , Autofagia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/patologia , Eritropoese/efeitos dos fármacos , Eritropoese/genética , Regulação da Expressão Gênica , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Hospitalização/estatística & dados numéricos , Humanos , Sódio/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Análise de Sobrevida
15.
J Ayub Med Coll Abbottabad ; 33(2): 188-191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34137526

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive disease due to multiple pathophysiological defects. Monotherapy alone cannot achieve adequate glycemic control and can lead to treatment failure. Empagliflozin, a sodium-glucose cotransporter2 (SGLT2) inhibitor improves glycemic control in patients with T2DM. There were limited studies to determine efficacy and safety profile of empagliflozin with conventional oral antidiabetic drugs (OADs) in Pakistan. So we investigated the efficacy and safety profile of empagliflozin as add-on therapy to metformin and sitagliptin in T2DM patients. METHODS: In this comparative randomized placebo-controlled trial, 240 obese type 2 diabetic patients with inadequate glycaemic control (i.e, HbA1c ≥7%) with metformin and sitagliptin were allocated in to two groups. Patients in group B were given tab empagliflozin 10mg twice a day while patients in group A were given tab placebo for a period of 24 weeks. Changes in body weight, HbA1c, blood pressure were analysed pre and post treatment by using SPSS v23. RESULTS: Empagliflozin caused a significant reduction in body weight -6.9±2.4 kg as compared to placebo -3.1±0.8 kg with p-value <0.001. This body weight reduction was further accompanied by reduction in systolic blood pressure -10.1±2.6 mmHg in empagliflozin group versus -5.3±2.5 mmHg in placebo group with p-value <0.001, and HbA1c -1.68±0.45 in empagliflozin group versus -0.1±0.06 in placebo group with p-value <0.001. There were 28.3% patients in empagliflozin group in whom HbA1c levels reduced <7% as compared to only 13.3% patients in placebo group (p-value 0.04). However no significant adverse effects were recorded in both study groups. CONCLUSIONS: Empagliflozin as a combination therapy has good efficacy and safety profile in obese type 2 diabetic patients.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Obesidade/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adulto , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/farmacologia , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/farmacologia , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Placebos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Resultado do Tratamento , Perda de Peso/efeitos dos fármacos
16.
Metabolism ; 121: 154814, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34119537

RESUMO

Diabetes, one of the most prevalent chronic diseases in the world, is strongly associated with a poor prognosis in COVID-19. Scrupulous blood sugar management is crucial, since the worse outcomes are closely associated with higher blood sugar levels in COVID-19 infection. Although recent observational studies showed that insulin was associated with mortality, it should not deter insulin use in hospitalized patients requiring tight glucose control. Back and forth dilemma in the past with regards to continue/discontinue certain medications used in diabetes have been mostly resolved. The initial fears of consequences related to continuing certain medications have been largely dispelled. COVID-19 also necessitates the transformation in diabetes care through the integration of technologies. Recent advances in health-related technologies, notably telemedicine and remote continuous glucose monitoring, have become essential in the management of diabetes during the pandemic. Today, these technologies have changed the landscape of medicine and become more important than ever. Being a high-risk population, patients with type 1 or type 2 diabetes, should be prioritized for vaccination. In the future, as the pandemic fades, the prevalence of non-communicable diseases is expected to rise due to lifestyle changes and medical issues/dilemma encountered during the pandemic.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Glicemia/metabolismo , Automonitorização da Glicemia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/mortalidade , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suscetibilidade a Doenças , Humanos , Hipoglicemiantes/uso terapêutico , Pandemias , SARS-CoV-2/isolamento & purificação
17.
Phytomedicine ; 87: 153582, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34091150

RESUMO

BACKGROUND AND PURPOSE: Diosmetin (Dios), a flavonoid compound with multiple pharmacological activities. However, fewer studies have reported its effects on type 2 diabetic mellitus (T2DM). Here, we address the effect of Dios on glucose metabolism and gut microbiota in KK-Ay diabetic mice. METHOD: Wild type C57BL/6 J mice or diabetic KK-Ay mice were treated with vehicle or Dios for one month. The ELISA kit and fluorescence microscope system were respectively employed to the evaluation of serum biochemical indicators and histopathological changes. Liver RNA-Seq and western blot were used to reveal the key signaling pathway. The effects of Dios on gut microbiota was investigated by the 16S rRNA gene sequencing, as well as the relationship between Dios and C. glu on glucose metabolism was explored with the C. glu transplantation. RESULTS: Dios treatment significantly decreased blood glucose and increased serum insulin concentrations. RNA-Seq analysis found that the underlying action mechanism of Dios on T2DM was via modulating glucose metabolism, which was proved by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. Besides, Dios treatment reshaped the unbalanced gut microbiota by suppressing the ratio of Firmicutes/Bacteroidetes and markedly increasing the richness of C. glu. Moreover, treatment with C. glu and Dios together could markedly ameliorate glucose metabolism by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. CONCLUSIONS: Dios treatment remarkably ameliorated glucose metabolism in KK-Ay diabetic mice by the regulation of C. glu via IRS/PI3K/AKT signaling pathway and reshaped the unbalanced gut microbiota. Our study provided evidence for the application of Dios to the treatment of T2DM.


Assuntos
Corynebacterium glutamicum/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Animais , Glicemia/metabolismo , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Glicogênio/metabolismo , Insulina/sangue , Insulina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Ribossômico 16S , Fatores de Transcrição/metabolismo
18.
Nutrients ; 13(5)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063109

RESUMO

Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of ß-cell function and prevent cardiovascular complications. Most of the metabolic processes involved in PPHG, i.e., ß-cell secretory function, GLP-1 secretion, insulin sensitivity, muscular glucose uptake, and hepatic glucose production, are controlled by the circadian clock and display daily oscillation. Consequently, postprandial glycemia displays diurnal variation with a higher glycemic response after meals with the same carbohydrate content, consumed at dusk compared to the morning. T2D and meal timing schedule not synchronized with the circadian clock (i.e., skipping breakfast) are associated with disrupted clock gene expression and is linked to PPHG. In contrast, greater intake in the morning (i.e., high energy breakfast) than in the evening has a resetting effect on clock gene oscillations and beneficial effects on weight loss, appetite, and reduction of PPHG, independently of total energy intake. Therefore, resetting clock gene expression through a diet intervention consisting of meal timing aligned to the circadian clock, i.e., shifting most calories and carbohydrates to the early hours of the day, is a promising therapeutic approach to improve PPHG in T2D. This review will focus on recent studies, showing how a high-energy breakfast diet (Bdiet) has resetting and synchronizing actions on circadian clock genes expression, improving glucose metabolism, postprandial glycemic excursions along with weight loss in T2D.


Assuntos
Desjejum/fisiologia , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos/métodos , Ingestão de Energia/fisiologia , Apetite/fisiologia , Glicemia/metabolismo , Relógios Circadianos/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Comportamento Alimentar/fisiologia , Humanos , Hiperglicemia , Refeições/fisiologia , Período Pós-Prandial/fisiologia , Fatores de Tempo , Perda de Peso/fisiologia
19.
Nutrients ; 13(6)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063822

RESUMO

Vitamin D has been implicated in the regulation of glucose metabolism and insulin resistance. We designed this study to provide evidence that insulin resistance is dependent on the concentration of vitamin D in the body. Forty observational studies of both type 2 diabetes mellitus patients and healthy subjects were included in this meta-analysis. Related articles were searched from Embase, PubMed, and Medline through January 2021. Filters for search were used to obtain more focused results. We used Comprehensive Meta-Analysis Version 3 for the construction of forest plots. RevMan software version 5.3 was used to build the risk of bias tables and summary plots. The observational studies included in this systematic review and meta-analysis showed an inverse relationship of insulin resistance with the status of vitamin D both in non-diabetic (r = -0.188; 95% CI = -0.141 to -0.234; p = 0.000) and diabetic (r = -0.255; 95% CI = -0.392 to -0.107, p = 0.001) populations. From the meta-analysis we concluded that hypovitaminosis D is related to increased levels of insulin resistance in both type 2 diabetes patients and the healthy population all over the world.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Resistência à Insulina/fisiologia , Estado Nutricional , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Humanos , Insulina/sangue , Estudos Observacionais como Assunto , Vitamina D/sangue , Deficiência de Vitamina D/complicações
20.
Nutrients ; 13(6)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063900

RESUMO

Short-chain fatty acids (SCFAs) are the product of the anaerobic intestinal bacterial fermentation of dietary fiber and resistant starch. An abnormal intestinal microbiota may cause a reduction in the production of SCFAs, which stimulate the development of intestinal epithelial cells, nourish enterocytes, influence their maturation and proper differentiation, reduce the pH, and are an additional source of energy for the host. There have been reports of the special role of SCFAs in the regulation of glucose and lipid metabolism during pregnancy. AIM: The aim of the study was to analyze the correlation of SCFAs with lipid and hepatic metabolism during pregnancy in relation to the body weight of pregnant women. MATERIAL AND METHODS: This study was conducted in pregnant women divided into two groups: Obese (OW-overweight and obese women; n = 48) and lean (CG-control group; n = 48) individuals. The biochemical plasma parameters of lipid metabolism (TG, CH, LDL, HDL), inflammation (CRP), and liver function (ALT, AST, GGT) were determined in all of the subjects. SCFA analysis was performed in the stool samples to measure acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0 i), butyric acid (C 4:0 n), isovaleric acid (C 5:0 i) valeric acid (C 5:0 n), isocaproic acid (C 6:0 i), caproic acid (C 6:0 n), and heptanoic acid (C 7:0). RESULTS: Statistically significant differences in the concentrations of C 3:0 and C 6:0 n were found between women in the OW group compared to the CG group. The other SCFAs tested did not differ significantly depending on BMI. The C 2:0, C 3:0, and C 4:0 n ratios showed differences in both OW and CG groups. In the OW group, no relationship was observed between the concentrations of the SCFAs tested and CRP, ALT, AST. A surprising positive relationship between C 5:0 n and all fractions of the tested lipids and branched C 5:0 with CHL, HDL, and LDL was demonstrated. In the OW group, HDL showed a positive correlation with C 3:0. However, lower GGT concentrations were accompanied by higher C 4:0 and C 5:0 values, and this tendency was statistically significant. CONCLUSIONS: The results of our research show that some SCFAs are associated with hepatic lipid metabolism and CRP concentrations, which may vary with gestational weight. Obesity in pregnancy reduces the amount of SCFAs in the stool, and a decrease in the level of butyrate reduces liver function.


Assuntos
Ácidos Graxos Voláteis/metabolismo , Metabolismo dos Lipídeos/fisiologia , Obesidade/metabolismo , Sobrepeso/metabolismo , Complicações na Gravidez/metabolismo , Ácidos Acíclicos/análise , Adulto , Glicemia/metabolismo , Fezes/química , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Mediadores da Inflamação/sangue , Lipídeos/sangue , Fígado/metabolismo , Testes de Função Hepática , Gravidez , Estudos Prospectivos
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