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1.
Nutrients ; 13(8)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34444986

RESUMO

Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.


Assuntos
Pressão Sanguínea , Polipeptídeo Inibidor Gástrico/sangue , Fármacos Gastrointestinais/farmacologia , Peptídeo 1 Semelhante ao Glucagon/sangue , Hipotensão , Período Pós-Prandial , Somatostatina/sangue , Acarbose/farmacologia , Acarbose/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Fármacos Gastrointestinais/uso terapêutico , Glucagon/sangue , Receptor do Peptídeo Semelhante ao Glucagon 1/sangue , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/fisiopatologia , Insulina/sangue , Peptídeos , Circulação Esplâncnica
2.
Nutrients ; 13(7)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34371890

RESUMO

The impact of glucose fluctuation on intracranial artery stenosis remains to be elucidated. This study aimed to investigate the association between glucose fluctuation and intracranial artery stenosis. This was a cross-sectional study of type 2 diabetes mellitus (T2DM) patients equipped with the FreeStyle Libre Pro continuous glucose monitoring system (Abbott Laboratories) between February 2019 and June 2020. Glucose fluctuation was evaluated according to the standard deviation (SD) of blood glucose, coefficient of variation (%CV), and mean amplitude of glycemic excursions (MAGE). Magnetic resonance angiography was used to evaluate the degree of intracranial artery stenosis. Of the 103 patients, 8 patients developed severe internal carotid artery (ICA) siphon stenosis (≥70%). SD, %CV, and MAGE were significantly higher in the severe stenosis group than in the non-severe stenosis group (<70%), whereas there was no significant intergroup difference in the mean blood glucose and HbA1c. Multivariable logistic regression analysis adjusted for sex showed that SD, %CV, and MAGE were independent factors associated with severe ICA siphon stenosis. In conclusion, glucose fluctuation is significantly associated with severe ICA siphon stenosis in T2DM patients. Thus, glucose fluctuation can be a target of preventive therapies for intracranial artery stenosis and ischemic stroke.


Assuntos
Glicemia/metabolismo , Artéria Carótida Interna/patologia , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Doenças Arteriais Intracranianas/complicações , Doenças Arteriais Intracranianas/diagnóstico , Idoso , Automonitorização da Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Estudos Retrospectivos , Fatores de Risco
4.
Medicine (Baltimore) ; 100(33): e26946, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414956

RESUMO

ABSTRACT: This study aimed to investigate the association between serum uric acid (SUA) level and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2DM).T2DM patients hospitalized in the Department of Hepatology, Yantai Qishan Hospital, between April 2012 and December 2018 were classified into the NAFLD group and the non-NAFLD group. Clinical data, glucose and lipid metabolism biomarkers, and liver and kidney function parameters were retrospectively collected.Five hundred eighty-three T2DM patients met the inclusion and exclusion criteria; 227 patients were included in the non-NAFLD group and 356 patients were included in the NAFLD group. Multiple linear regression analyses showed that SUA was positively correlated with body mass index (P = .003), triglycerides (P = .009), aspartate aminotransferase (P = .036), and alanine aminotransferase (P = .038) and negatively correlated with estimated glomerular filtration rate (P < .001) in T2DM patients. Multivariate regression analyses demonstrated that after adjusting for confounding factors, the SUA tertile was still significantly associated with NAFLD occurrence in T2DM patients (P for trend = .008). With reference to SUA tertile I, the odds ratios for NAFLD in the SUA tertile II and tertile III groups were 1.729 (95% confidence interval [CI]: 1.086-2.753) and 2.315 (95% CI: 1.272-4.213), respectively.The level of SUA in T2DM patients was associated with the occurrence of NAFLD. Elevated SUA was associated with a significantly increased prevalence of NAFLD. The SUA level was an independent risk factor for NAFLD occurrence in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Ácido Úrico/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Taxa de Filtração Glomerular , Humanos , Metabolismo dos Lipídeos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Fatores de Risco
5.
Nutrients ; 13(8)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34445047

RESUMO

Sargassum fusiforme alginate (SF-Alg) possess many pharmacological activities, including hypoglycemic and hypolipidemic. However, the hypoglycemic mechanisms of SF-Alg remain unclear due to its low bioavailability. In this study, we evaluated the therapeutic effect of SF-Alg on high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes (T2D) mice. SF-Alg intervention was found to significantly reduce fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC), while increasing high-density lipoprotein cholesterol (HDL-c) and improving glucose tolerance. In addition, administrating SF-Alg to diabetic mice moderately attenuated pathological changes in adipose, hepatic, and heart tissues as well as skeletal muscle, and diminished oxidative stress. To probe the underlying mechanisms, we further analyzed the gut microbiota using 16S rRNA amplicon sequencing, as well as metabolites by non-targeted metabolomics. Here, SF-Alg significantly increased some benign bacteria (Lactobacillus, Bacteroides, Akkermansia Alloprevotella, Weissella and Enterorhabdus), and significantly decreased harmful bacteria (Turicibacter and Helicobacter). Meanwhile, SF-Alg dramatically decreased branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in the colon of T2D mice, suggesting a positive benefit of SF-Alg as an adjvant agent for T2D.


Assuntos
Alginatos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Sargassum/química , Animais , Glicemia/efeitos dos fármacos , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Camundongos , Estreptozocina , Triglicerídeos/sangue
6.
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
7.
Medicine (Baltimore) ; 100(33): e26879, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414940

RESUMO

ABSTRACT: The current study aimed to investigate circulating glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in Chinese type 2 diabetes mellitus (T2DM) patients, especially those with microalbuminuria. We recruited 67 patients with T2DM and 63 control subjects. We determined circulating GRP78 and CHOP concentrations by ELISA, collected anthropometric data, and measured biochemical parameters in a clinical laboratory. Compared with control groups, patients with T2DM showed decreased circulating levels of GRP78 (0.21 [0.16-0.24] vs 0.16 [0.16-0.19] ng/mL, P < .01) and CHOP ([0.29 ±â€Š0.02] vs [0.27 ±â€Š0.03]ng/mL, P < .01). Reduction in circulating GRP78 and CHOP levels was more pronounced in patients with more severe categories of albuminuria. Amounts of circulating GRP78 correlated directly with serum fasting c-peptide, cystatin-c (Cys-c), creatinine (Cr), blood urea nitrogen (BUN), and uric acid, and inversely with glomerular filtration rates. Circulating CHOP level was positively correlated with age, Cr, BUN, Cys-c, and urinary microalbumin/creatinine (UmALB/Cr). Circulating GRP78 was predicted independently by Cr, BUN, serum uric acid, estimated glomerular filtration rate, and Cys-c, while CHOP depended on age, Cr, BUN, estimated glomerular filtration rate, UmALB/Cr, and Cys-c. After controlling for confounding factors, circulating GRP78 and CHOP expression were significantly associated with diabetic kidney disease (binary logistic regression, P < .01). Patients with T2DM showed increased circulating GRP78 and CHOP concentrations. Receiver operating characteristic areas under the curve for predicting diabetic kidney disease based on GRP78 and CHOP were 0.686 (95% CI: 0.558-0.813) and 0.670 (0.524-0.816), respectively.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Estresse do Retículo Endoplasmático , Proteínas de Choque Térmico/sangue , Fator de Transcrição CHOP/sangue , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Nutrients ; 13(7)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34371798

RESUMO

An overview of vitamins D3 and E suggests micronutrient deficiency contributes to type 2 diabetes mellitus (T2DM). A case-control study was conducted to determine the status of plasma vitamins D3 and E isomers amongst diabetic Malaysians. Two groups were recruited for participation, one comprising fifty diabetic subjects (DM) and one comprising fifty non-diabetic (non-DM) subjects, in order to assess their plasma vitamin D3, calcium and vitamin E status. Glycaemic status (haemoglobin A1c, HbA1c; fasting blood glucose, FBG; C-Peptide) and lipid profiles (total cholesterol, TC; triglycerides, TG; low-density lipoprotein-cholesterol, LDL-C; high-density lipoprotein-cholesterol, HDL-C) were assessed, followed by anthropometric measurements. The Mann-Whitney U-test, Kruskal-Wallis and Spearman's correlation coefficient were used to elucidate the association between levels of plasma vitamins D3 and E and T2DM. The vitamin D3 deficiency group (<20 ng/mL) showed a significant correlation (p < 0.05) with glycaemic status (HbA1c and FBG) and lipid profiles (HDL-C, LDL and TC). Spearman's correlation demonstrated that vitamin D3 status is strongly correlated with HDL levels (p < 0.05). Similarly, plasma total vitamin E levels >4.9 µg/mL revealed significantly different FBG, HbA1c, C-Peptide, LDL, HDL and TC levels across both groups. Moreover, family history, smoking, waist circumference and HbA1c levels demonstrated a significant association (p < 0.05) with levels of vitamins D and E but not FBG and lipid profiles. This could be because the pre-diabetic status among the non-DM group influenced the outcomes of this study.


Assuntos
Colecalciferol/sangue , Diabetes Mellitus Tipo 2/sangue , Estado Nutricional , Vitamina E/sangue , Adulto , Idoso , Glicemia/análise , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobina A Glicada/análise , Humanos , Lipídeos/sangue , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia
9.
Nutrients ; 13(7)2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34371816

RESUMO

(1) Background: Type-2-diabetes-mellitus (DM) is one the most important cardiovascular-risk-factors. Among many molecules regulating vascular tone, nitric oxide appears to be the most pivotal. Although micro- and macrovascular-abnormalities are extensively studied, the alterations in the nitric-oxide-metabolic-pathway require further investigations. Additionally, the role of erythrocytes in the vascular tone regulation has not been extensively explored. The aim of this study was to evaluate the endothelial-function and the nitric-oxide-metabolic-pathway in erythrocytes and plasma of diabetic individuals. (2) Methods: A total of 80 subjects were enrolled in this cross-sectional study, including 35 patients with DM and 45 healthy individuals. The endothelial-function was evaluated in response to different stimuli. (3) Results: In the DM group, decreased Arginine and citrulline concentrations in the plasma compartment with reduced Arginine/ADMA and ADMA/DMA-ratios were observed. Preserved nitric-oxide-metabolism in erythrocytes with reduced citrulline level and significantly higher NO-bioavailability were noted. Significant endothelial dysfunction in DM individuals was proved in response to the heat-stimulus. (4) Conclusions: DM patients at an early stage of disease show significant differences in the nitric-oxide-metabolic-pathway, which are more pronounced in the plasma compartment. Erythrocytes constitute a buffer with a higher nitric-oxide-bioavailability, less affected by the DM-related deviations. Patients at an early-stage of DM reveal endothelial-dysfunction, which could be diagnosed earlier using the laser-Doppler-flowmetry.


Assuntos
Arginina/análogos & derivados , Arginina/sangue , Diabetes Mellitus Tipo 2/sangue , Endotélio Vascular/metabolismo , Eritrócitos/metabolismo , Óxido Nítrico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Citrulina/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade
10.
Nutrients ; 13(7)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34371883

RESUMO

The aim of the study was to evaluate the overall biohumoral and metabolic effects of a 12-week add-on therapy consisting of a new nutraceutical formulation (BHC) based on berberine, hesperidin, and chromium picolinate in type 2 diabetes mellitus (T2D) patients with suboptimal glycemic compensation receiving metformin. After 12 weeks, participants in the group receiving metformin plus BHC, compared to the group receiving metformin only, saw a significant improvement in their glucose profile, in terms of both glycated hemoglobin (HbA1c) and fasting blood glucose (FBG). Their FBG dropped from 145 ± 20 mg/dL to 128 ± 23 mg/dL (p < 0.01), a decrease of 11.7% compared with the baseline. This decrease differed significantly from the situation in the control arm (p < 0.05). HbA1c decreased by 7.5% from the baseline, from 53.5 ± 4.3 mmol/mol to 49.5 ± 5.1 mmol/mol (p < 0.01), in the group given BHC, while no difference was seen in the control group. Advanced glycation end products (AGEs) and malondialdehyde (MDA) were found to be significantly reduced (p < 0.01) only in the BHC group, from 9.34 ± 7.61 µg/mL to 6.75 ± 6.13 µg/mL, and from 1.7 ± 0.15 µmol/L to 1.4 ± 0.25 µmol/L, respectively. In patients with T2D taking metformin with suboptimal glycemic compensation, adding BHC for 3 months significantly improved glucose control in terms of FBG and HbA1c, and had a positive effect on the lipid peroxidation profile, as indicated by a decrease in AGEs and MDA.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Controle Glicêmico/métodos , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Idoso , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Nutrients ; 13(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371867

RESUMO

BACKGROUND: There is a growing interest in the considerable benefits of dietary supplementations, such as folic acid, on the glycemic profile. We aimed to investigate the effects of folic acid supplementation on glycemic control markers in adults. METHODS: Randomized controlled trials examining the effects of folic acid supplementation on glycemic control markers published up to March 2021 were detected by searching online databases, including Scopus, PubMed, Embase, and ISI web of science, using a combination of related keywords. Mean change and standard deviation (SD) of the outcome measures were used to estimate the mean difference between the intervention and control groups at follow-up. Meta-regression and non-linear dose-response analysis were conducted to evaluate the association between pooled effect size and folic acid dosage (mg/day) and duration of the intervention (week). From 1814 detected studies, twenty-four studies reported fasting blood glucose (FBG), fasting insulin, hemoglobin A1C (HbA1C), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) as an outcome measure. RESULTS: Results revealed significant reductions in FBG (weighted mean difference (WMD): -2.17 mg/dL, 95% CI: -3.69, -0.65, p = 0.005), fasting insulin (WMD: -1.63 pmol/L, 95% CI: -2.53, -0.73, p < 0.001), and HOMA-IR (WMD: -0.40, 95% CI: -0.70, -0.09, p = 0.011) following folic acid supplementation. No significant effect was detected for HbA1C (WMD: -0.27%, 95% CI: -0.73, 0.18, p = 0.246). The dose-response analysis showed that folic acid supplementation significantly changed HOMA-IR (r = -1.30, p-nonlinearity = 0.045) in non-linear fashion. However, meta-regression analysis did not indicate a linear relationship between dose, duration, and absolute changes in FBG, HOMA-IR, and fasting insulin concentrations. CONCLUSIONS: Folic acid supplementation significantly reduces some markers of glycemic control in adults. These reductions were small, which may limit clinical applications for adults with type II diabetes. Further research is necessary to confirm our findings.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/terapia , Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Controle Glicêmico/métodos , Adulto , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Jejum/sangue , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Resultado do Tratamento , Adulto Jovem
12.
Front Immunol ; 12: 720363, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447386

RESUMO

Severe coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan dysfunction. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators than a mild disease, and tracking these markers may allow early identification or even prediction of disease progression. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. There are numerous causes of an elevated CRP, including acute and chronic responses, and these can be infectious or non-infectious in etiology. CRP are normally lacking in viral infections, while adaptive immunity appears to be essential for COVID-19 virus clearance, and the macrophage activation syndrome may explain the high serum CRP contents and contribute to the disease progression. Nevertheless, for the assessment of host inflammatory status and identification of viral infection in other pathologies, such as bacterial sepsis, the acute-phase proteins, including CRP and procalcitonin, can provide more important information for guiding clinical diagnosis and antibiotic therapy. This review is aimed to highlight the current and most recent studies with regard to the clinical significance of CRP in severe COVID-19 and other viral associated illnesses, including update advances on the implication of CRP and its form specifically on the pathogenesis of these diseases. The progressive understanding in these areas may be translated into promising measures to prevent severe outcomes and mitigate appropriate treatment modalities in critical COVID-19 and other viral infections.


Assuntos
Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Humanos , Inflamação/sangue , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/sangue , Influenza Humana/complicações , Acidente Vascular Cerebral/sangue , Viroses
13.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360895

RESUMO

BACKGROUND: Type 2 diabetes mellitus is one of the leading causes of morbidity and mortality worldwide and is derived from an accumulation of genetic and epigenetic changes. In this study, we aimed to construct Insilco, a competing endogenous RNA (ceRNA) network linked to the pathogenesis of insulin resistance followed by its experimental validation in patients', matched control and cell line samples, as well as to evaluate the efficacy of CRISPR/Cas9 as a potential therapeutic strategy to modulate the expression of this deregulated network. By applying bioinformatics tools through a two-step process, we identified and verified a ceRNA network panel of mRNAs, miRNAs and lncRNA related to insulin resistance, Then validated the expression in clinical samples (123 patients and 106 controls) and some of matched cell line samples using real time PCR. Next, two guide RNAs were designed to target the sequence flanking LncRNA/miRNAs interaction by CRISPER/Cas9 in cell culture. Gene editing tool efficacy was assessed by measuring the network downstream proteins GLUT4 and mTOR via immunofluorescence. RESULTS: LncRNA-RP11-773H22.4, together with RET, IGF1R and mTOR mRNAs, showed significant upregulation in T2DM compared with matched controls, while miRNA (i.e., miR-3163 and miR-1) and mRNA (i.e., GLUT4 and AKT2) expression displayed marked downregulation in diabetic samples. CRISPR/Cas9 successfully knocked out LncRNA-RP11-773H22.4, as evidenced by the reversal of the gene expression of the identified network at RNA and protein levels to the normal expression pattern after gene editing. CONCLUSIONS: The present study provides the significance of this ceRNA based network and its related target genes panel both in the pathogenesis of insulin resistance and as a therapeutic target for gene editing in T2DM.


Assuntos
Sistemas CRISPR-Cas , Biologia Computacional/métodos , Diabetes Mellitus Tipo 2/genética , Edição de Genes/métodos , Expressão Gênica , Resistência à Insulina/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Linhagem Celular , Diabetes Mellitus Tipo 2/sangue , Feminino , Redes Reguladoras de Genes , Hospitais Universitários , Humanos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade
14.
Molecules ; 26(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34443451

RESUMO

Diabetes mellitus is characterized by tissue oxidative damage and impaired microcirculation, as well as worsened erythrocyte properties. Measurements of erythrocyte deformability together with determination of nitric oxide (NO) production and osmotic resistance were used for the characterization of erythrocyte functionality in lean (control) and obese Zucker diabetic fatty (ZDF) rats of two age categories. Obese ZDF rats correspond to prediabetic (younger) and diabetic (older) animals. As antioxidants were suggested to protect erythrocytes, we also investigated the potential effect of quercetin (20 mg/kg/day for 6 weeks). Erythrocyte deformability was determined by the filtration method and NO production using DAF-2DA fluorescence. For erythrocyte osmotic resistance, we used hemolytic assay. Erythrocyte deformability and NO production deteriorated during aging-both were lower in older ZDF rats than in younger ones. Three-way ANOVA indicates improved erythrocyte deformability after quercetin treatment in older obese ZDF rats only, as it was not modified or deteriorated in both (lean and obese) younger and older lean animals. NO production by erythrocytes increased post treatment in all experimental groups. Our study indicates the potential benefit of quercetin treatment on erythrocyte properties in condition of diabetes mellitus. In addition, our results suggest potential age-dependency of quercetin effects in diabetes that deserve additional research.


Assuntos
Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Eritrócitos/metabolismo , Quercetina/uso terapêutico , Animais , Antioxidantes , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Deformação Eritrocítica/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Óxido Nítrico/metabolismo , Osmose , Estresse Oxidativo , Quercetina/farmacologia , Ratos Zucker
15.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361791

RESUMO

As a key enzyme regulating postprandial blood glucose, α-Glucosidase is considered to be an effective target for the treatment of diabetes mellitus. In this study, a simple, rapid, and effective method for enzyme inhibitors screening assay was established based on α-glucosidase catalyzes reactions in a personal glucose meter (PGM). α-glucosidase catalyzes the hydrolysis of maltose to produce glucose, which triggers the reduction of ferricyanide (K3[Fe(CN)6]) to ferrocyanide (K4[Fe(CN)6]) and generates the PGM detectable signals. When the α-glucosidase inhibitor (such as acarbose) is added, the yield of glucose and the readout of PGM decreased accordingly. This method can achieve the direct determination of α-glucosidase activity by the PGM as simple as the blood glucose tests. Under the optimal experimental conditions, the developed method was applied to evaluate the inhibitory activity of thirty-four small-molecule compounds and eighteen medicinal plants extracts on α-glucosidase. The results exhibit that lithospermic acid (52.5 ± 3.0%) and protocatechualdehyde (36.8 ± 2.8%) have higher inhibitory activity than that of positive control acarbose (31.5 ± 2.5%) at the same final concentration of 5.0 mM. Besides, the lemon extract has a good inhibitory effect on α-glucosidase with a percentage of inhibition of 43.3 ± 3.5%. Finally, the binding sites and modes of four active small-molecule compounds to α-glucosidase were investigated by molecular docking analysis. These results indicate that the PGM method is feasible to screening inhibitors from natural products with simple and rapid operations.


Assuntos
Benzaldeídos/farmacologia , Benzofuranos/farmacologia , Glicemia/análise , Catecóis/farmacologia , Depsídeos/farmacologia , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores de Glicosídeo Hidrolases/farmacologia , Monitorização Ambulatorial/métodos , alfa-Glucosidases/sangue , Acarbose/química , Acarbose/farmacologia , Benzaldeídos/química , Benzaldeídos/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Sítios de Ligação , Técnicas Biossensoriais/instrumentação , Catecóis/química , Catecóis/isolamento & purificação , Depsídeos/química , Depsídeos/isolamento & purificação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hidrólise , Cinética , Maltose/metabolismo , Simulação de Acoplamento Molecular , Monitorização Ambulatorial/instrumentação , Extratos Vegetais/química , Plantas Medicinais , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Termodinâmica , Dispositivos Eletrônicos Vestíveis , alfa-Glucosidases/química
16.
Nutrients ; 13(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34371917

RESUMO

Diabetes mellitus is a chronic condition characterized by increased blood glucose levels from dysfunctional carbohydrate metabolism. Dietary intervention can help to prevent and manage the disease. Food hydrocolloids have been shown to have favorable properties in relation to glycaemic regulation. However, the use of food hydrocolloids of bacterial origin to modulate glucose responses is much less explored than other types of hydrocolloids. We, therefore, carried out the first review examining the impact of intake of food hydrocolloids of bacterial origin (as a direct supplement or incorporated into foods) on glycemic response in humans. Fourteen studies met the inclusion criteria. They used either xanthan gum, pullulan, or dextran as interventions. There was a wide variation in the amount of hydrocolloid supplementation provided and methods of preparation. Postprandial blood glucose responses were reduced in half of the studies, particularly at higher intake levels and longer chain hydrocolloids. When xanthan gum was added to the cooking process of muffins and rice, a significant reduction in postprandial blood glucose was observed. The use of these hydrocolloids is potentially effective though more research is needed in this area.


Assuntos
Bactérias/química , Glicemia/efeitos dos fármacos , Dextranos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucanos/uso terapêutico , Controle Glicêmico , Hipoglicemiantes/uso terapêutico , Polissacarídeos Bacterianos/uso terapêutico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Coloides , Dextranos/efeitos adversos , Dextranos/isolamento & purificação , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Glucanos/efeitos adversos , Glucanos/isolamento & purificação , Controle Glicêmico/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Polissacarídeos Bacterianos/efeitos adversos , Polissacarídeos Bacterianos/isolamento & purificação , Resultado do Tratamento , Adulto Jovem
17.
Medicine (Baltimore) ; 100(30): e26729, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397709

RESUMO

ABSTRACT: Glycemic variability (GV) confers a significantly higher risk of diabetic-related complications, especially cardiovascular. Despite extensive research in this area, data on end-stage kidney disease (ESKD) patients on chronic hemodialysis are scarce. This study aims to determine the magnitude of GV among ESKD (diabetic vs nondiabetic) patients and its associated factors on hemodialysis days (HDD) and non-hemodialysis days (NHDD) where postulation of a higher GV observed among diabetic on HDD.We recruited 150 patients on hemodialysis, 93 patients with type 2 diabetic (DM-ESKD), and 57 with nondiabetic (NDM-ESKD). The GV indices (standard deviation [SD] and percentage coefficient variant [%CV]) were obtained from 11-point and 7-point self-monitoring blood glucose (fasting to post-meal) (SMBG) profiles on HDD and NHDD. The GV indices and its associated factors of both DM-ESKD and NDM-ESKD were analyzed to compare HDD vs NHDD.Mean blood glucose on HDD was 9.33 [SD 2.7, %CV 30.6%] mmol/L in DM-ESKD compared with 6.07 [SD 0.85, %CV 21.3%] mmol/L in NDM-ESKD (P = <.01). The DM-ESKD group experienced significantly above target GV indices compared to NDM-ESKD on both HDD and NHDD, particularly in the subgroup with HbA1c 8-10% (P = <.01). Presence of diabetes, older age, hyperlipidemia, HbA1c, ferritin levels, and albumin were identified as factors associated with GV.DM-ESKD patients have above-target GV indices, especially on HDD, therefore increasing their risk of developing future complications. We identified high HbA1c, older age group, presence of hyperlipidemia, ferritin levels, and albumin as factors associated with GV indices that may be used as surrogate markers for GV. Since these groups of patients are vulnerable to CVD mortality, urgent attention is needed to rectify it.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Falência Renal Crônica/sangue , Diálise Renal , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Pessoa de Meia-Idade
18.
Endocrinol Metab (Seoul) ; 36(4): 904-908, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34311543

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/mortalidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Estudos Observacionais como Assunto/métodos , COVID-19/sangue , Diabetes Mellitus Tipo 2/sangue , Dipeptidil Peptidase 4/sangue , Inibidores da Dipeptidil Peptidase IV/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Mortalidade/tendências
19.
Int Heart J ; 62(4): 843-849, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34276009

RESUMO

The DAPA-HF trial demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduced worsening heart failure (HF) events in chronic HF patients with or without type 2 diabetic mellitus (T2DM). However, it remains unclear whether the effectiveness of SGLT2i is also observed in patients with decompensated HF irrespective of HbA1c level. Eighty-one T2DM patients hospitalized due to decompensated HF were enrolled and divided into 2 groups according to their HbA1c levels (group H, HbA1c 6.9-13.0%, n = 41; group L, HbA1c < 6.9%, n = 40). After the initial management of HF, one of the SGLT2i (canagliflozin 100 mg/day or dapagliflozin 5 mg/day or empagliflozin 10 mg/day) was non-randomly administered, and clinical parameters associating with HF and T2DM were followed for 7 days. No symptomatic hypoglycemia was observed in any patient. In both groups, urine glucose excretion was increased significantly after the administration of SGLT2i. However, its amount was greater in group H than group L. Urine volume was increased significantly at day 1 in both groups. Urine volume returned to the baseline after one week in group L. In contrast, the increase in urine volume persisted at least for one week in group H. Of note, a decrease in B-type natriuretic peptide levels after the initiation of SGLT2i was observed in both groups similarly despite differences in urine output and excretion of urine glucose. In conclusion, SGLT2i can improve decompensated HF in patients with T2DM irrespective of the HbA1c level.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/urina , Humanos , Masculino , Estudos Prospectivos
20.
Nutrients ; 13(7)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206641

RESUMO

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of type 2 diabetes. However, the efficacy of OP on the advanced stage of type 2 diabetes has not been investigated, and the relationship between OP and intestinal flora has not been studied. Therefore, in this study, to explore the relieving effects of OP intake on the advanced stage of type 2 diabetes and the regulatory effects of OP on intestinal microbes, diabetic db/db mice (17-week-old) were treated with OP at the dose of 200 mg/kg for 15 weeks. We found that OP has a significant effect in decreasing fasting blood glucose levels, improving glucose tolerance, lowering the homeostasis model assessment-insulin resistance index, restoring histopathological features of tissues, and promoting hepatic protein kinase B activation in db/db mice. Notably, OP modulates gut microbiota at phylum level, increases the relative abundance of Verrucomicrobia and Deferribacteres, and decreases the relative abundance of Bacteroidetes. OP treatment increases the relative abundance of Akkermansia, as well as decreases the relative abundance of Prevotella, Odoribacter, Ruminococcus, and Parabacteroides at genus level. In conclusion, OP may ameliorate the advanced stage of type 2 diabetes through modulating the composition and function of gut microbiota. Our findings provide a promising therapeutic approach for the treatment of advanced stage type 2 diabetes.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Glucosídeos Iridoides/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Jejum/sangue , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos
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