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1.
J Diabetes Investig ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33460512

RESUMO

AIMS/INTRODUCTION: Diabetic cardiovascular autonomic neuropathy (DCAN) seriously threatens the prognosis and quality of life of patients with type 2 diabetes mellitus, associated with increased mortality. The present study aimed to investigate the relevant risk factors of DCAN. MATERIALS AND METHODS: The present study enrolled a total of 109 patients with type 2 diabetes mellitus. DCAN was defined as a score of at least 2 points in Ewing tests. The updated homeostasis model assessment of insulin resistance (HOMA2-IR) based on fasting C-peptide was calculated to reflect insulin resistance. Logistic regression analysis, interaction and stratified analyses were used to investigate the relationship between HOMA2-IR or other indicators and DCAN. Receiver operating characteristic analysis was carried out to estimate the discriminative value of the variables independently associated with DCAN and to determine the optimal cut-off point of these models to screen DCAN. RESULTS: The HOMA2-IR levels were significantly higher in patients with DCAN, and tended to be worsened with the progression of the DCAN. Logistic regression analysis showed an independent association between HOMA2-IR (odds ratio 39.30, 95% confidence interval 7.17-215.47) and DCAN. HOMA2-IR (area under the curve 0.878, 95% confidence interval 0.810-0.946; cut-off value 1.735) individually predicted DCAN significantly higher than the other independent risk factors individually used, whereas models combining HOMA2-IR and other risk factors did not significantly boost the diagnostic power. CONCLUSIONS: Insulin resistance is independently associated with DCAN. HOMA2-IR presents to be a highly accurate and parsimonious indicator for DCAN screening. Patients with HOMA2-IR >1.735 are at a high risk of DCAN; thus, priority diagnostic tests should be carried out for these patients for timely integrated intervention.

2.
Adipocyte ; 9(1): 384-400, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32684073

RESUMO

We explored potential biomarkers and molecular mechanisms regarding multiple benefits after bariatric surgery. Differentially expressed genes (DEGs) for subcutaneous adipose tissue (AT) after bariatric surgery were identified by analyzing two expression profiles from the GEO. Subsequently, enrichment analysis, GSEA, PPI network, and gene-microRNAs and gene-TFs networks were interrogated to identify hub genes and associated pathways. Co-expressed DEGs included one that was up-regulated and 22 that were down-regulated genes. The enrichment analyses indicated that down-regulated DEGs were significantly involved in inflammatory responses. GSEA provided comprehensive evidence that most genes enriched in pro-inflammation pathways, while gene-sets after surgery enriched in metabolism. We identified nine hub genes in the PPI network, most of which were validated as highly expressed and hypomethylated in obesity by Attie Lab Diabetes and DiseaseMeth databases, respectively. DGIdb was also applied to predict potential therapeutic agents that might reverse abnormally high hub gene expression. Bariatric surgery induces a significant shift from an obese pro-inflammatory state to an anti-inflammatory state, with improvement in adipocyte metabolic function - representing key mechanisms whereby AT function improves after bariatric surgery. Our study deepens a mechanistic understanding of the benefits of bariatric surgery and provides potential biomarkers or treatment targets for further research.

3.
Diabetes Metab Res Rev ; 36(6): e3334, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32390336

RESUMO

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) is increasing among youth worldwide, translating to an increased risk ofearly-onset cardiovascular disease (CVD). Mounting studies have shown that metformin may reduce maximal carotidintima-media thickness (cIMT), improve insulin resistance and metabolic control in subjects with T1DM, and thus, may extend cardioprotective benefits. This systematic review and meta-analysis was performed to assess the efficacy and safety of metformin added to insulin therapy on reducing CVD risks and improving metabolism in T1DM. METHODS: PubMed, EMBASE, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) that compared metformin and insulin combination (duration ≥3 months) to insulin treatment alone in T1DM. Data were expressed as weighted/standardized mean differences (MDs/SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, along with 95% confidence intervals (CIs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to evaluate the overall certainty of the evidence. RESULTS: Nineteen RCTs (n = 1540) met the eligibility criteria. Metformin treatment significantly reduced carotid artery intima-media thickness (MD -0.06 mm [95% CI -0.88, -0.28], P < .001). Though no significant difference was found in insulin sensitivity (SMD 2.21 [95% CI -1.88, 6.29], P = .29), the total daily insulin dosage (SMD -0.81 [95% CI -1.25, -0.36], P < .001) along with traditional CVD risk factors showed improvement by better glycaemic control, partial lipid profiles, diastolic blood pressure, and limited weight gain, with neutral effect on diabetic ketoacidosis, lactic acidosis, and hypoglycaemia. However, metformin therapy increased the incidence of gastrointestinal adverse events. CONCLUSIONS: Metformin with insulin has the potential to retard the progression of atherosclerosis and provides better metabolic control in patients with T1DM, and thus, providing a potential therapeutic strategy for patients with T1DM on reducing CVD risks.

4.
Nutrients ; 11(10)2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623223

RESUMO

The beneficial effects of the Mediterranean diet (MD) adherence in reducing cardiovascular disease (CVD) risk and improving CVD-related physiological indices have been well-documented. However, the exact MD adherence duration needed for these effects to occur is under-researched. The aim of the present, two-arm, two-site study clinical trial was to assess the effects of long- vs. short-term MD adherence on the skin microvascular circulation, and quality of life. Two groups were recruited, one being long-term MD adherers (>5 years; from Greece; control group), and one of the non-adherers (from the UK), with the latter participating in a four-week MD intervention (intervention group). Our main outcome was skin microvascular function assessed by cutaneous vascular conductance (CVC). Secondary outcomes included quality of life, dietary intake, blood pressure and lipidemic profile. At the end of the intervention, both groups had high MD adherence. For the intervention group, significantly improved post-intervention CVC values were noted concerning the initial peak phase (2.0 ± 0.6 vs. 2.8 ± 0.8; p < 0.05). CVC values of the control group, were however higher at the plateau phase in comparison to the intervention group (intervention end; 3.8 ± 0.8 vs. 3.1 ± 1.2; p < 0.05). As per QoL, the physical domain was improved post-intervention (13.7 ± 1.2 vs. 15.9 ± 1.2; p < 0.05). No differences were observed in the lipidemic profile between groups, or between the baseline and final intervention phases. The findings indicate that although short-term MD adherence is effective in improving certain microvascular physiological properties and QoL domains, there is room for additional improvement, observed in long-term adherers. Our findings are important in the design of future, MD-based, lifestyle interventions, with the advisable durations differing between target groups.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Saudável , Dieta Mediterrânea , Microcirculação , Microvasos/fisiologia , Qualidade de Vida , Pele/irrigação sanguínea , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Ingestão de Energia , Inglaterra/epidemiologia , Feminino , Grécia/epidemiologia , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Cooperação do Paciente , Recomendações Nutricionais , Fluxo Sanguíneo Regional , Comportamento de Redução do Risco , Fatores de Tempo , Adulto Jovem
5.
Oxid Med Cell Longev ; 2019: 1896041, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30733849

RESUMO

Diabetic neuropathy (DN) is a common and severe complication of diabetes mellitus. There is still a lack of an effective treatment to DN because of its complex pathogenesis. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of thioredoxin, has been shown to be associated with diabetic retinopathy and nephropathy. Herein, we aim to investigate the role of TXNIP in prediabetic neuropathy and therapeutic potential of verapamil which has been shown to inhibit TXNIP expression. The effects of mediating TXNIP on prediabetic neuropathy and its exact mechanism were performed using high-fat diet- (HFD-) induced diabetic mice and palmitate-treated neurons. Our results showed that TXNIP upregulation is associated with prediabetic neuropathy in HFD-fed mice. TXNIP knockdown improved DN in HFD-induced prediabetic mice. Mechanistically, increased TXNIP in dorsal root ganglion is transferred into the cytoplasm and shuttled to the mitochondria. In cytoplasm, TXNIP binding to TRX1 results in the increased oxidative stress and inflammation. In mitochondria, TXNIP binding to TRX2 induced mitochondria dysfunction and apoptosis. TXNIP isolated from TRX2 then shuttles to the cytoplasm and binds to NLRP3, resulting in further increased TXNIP-NLRP3 complex, which induced the release of IL-1ß and the development of inflammation. Thus, apoptosis and inflammation of dorsal root ganglion neuron eventually cause neural dysfunction. In addition, we also showed that verapamil, a known inhibitor of calcium channels, improved prediabetic neuropathy in the HFD-fed mice by inhibiting the upregulation of TXNIP. Our finding suggests that TXNIP might be a potential target for the treatment of neuropathy in prediabetic patients with dyslipidemia.


Assuntos
Antiarrítmicos/uso terapêutico , Proteínas de Transporte/antagonistas & inibidores , Diabetes Mellitus Experimental/complicações , Estado Pré-Diabético/complicações , Tiorredoxinas/antagonistas & inibidores , Verapamil/uso terapêutico , Animais , Antiarrítmicos/farmacologia , Apoptose , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Feminino , Humanos , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Estado Pré-Diabético/patologia , Verapamil/farmacologia
6.
Nutrients ; 10(12)2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30513972

RESUMO

The Mediterranean diet has been shown to improve cardiovascular health. Vegan diets have demonstrated similar benefits, albeit in fewer studies. In a comparative pilot study, we compared the effects of a short-term Mediterranean Diet (MD) and Vegan Diet (VD) on microvascular function and cholesterol levels in a healthy population. Twenty-four young (aged 18 to 35 years) healthy volunteers followed a four-week intervention (MD = 12; VD = 12) ad libitum. Pre and post-intervention anthropometrics, microvascular function (assessed via LDF and expressed as raw CVC and %CVC MAX), dietary-analysis data (Calories, Protein, Carbohydrates, Total Fat, Saturated Fat, Fibre), Mean Arterial Pressure (MAP), Blood Pressure, Total Cholesterol (TC), High Density Lipoprotein (HDL-C) and TC:HDL-C were compared. MD participants reduced Total Fat intake (p = 0.05). Saturated Fat decreased (MD: p = < 0.001; VD: p = 0.004) and Fibre increased (MD: p = 0.02; VD: p = < 0.001) in both groups. Dietary changes reflected improvements in plateau raw CVC in the MD group (p = 0.005), and a reduction in TC (p = 0.045) and weight loss (p = 0.047) in the VD group. The MD led to improvements in microvascular function; the VD led to reduced TC and weight loss. Although both diets might offer CVD risk-reduction benefits, evidence for the MD appeared to be stronger due to changes in vasodilatory ability and NO bioavailability.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Colesterol/sangue , Dieta Mediterrânea , Dieta Vegana , Adulto , Pressão Sanguínea , Fibras na Dieta , Ingestão de Energia , Feminino , Humanos , Masculino , Projetos Piloto , Fatores de Tempo , Adulto Jovem
7.
Diabetes Ther ; 9(6): 2335-2346, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30302722

RESUMO

INTRODUCTION: Early detection of diabetic peripheral neuropathy (DPN) is critical in patients with type 2 diabetes mellitus (T2DM) due to the lack of targeted therapy for DPN. We have investigated the relationship between different stages of diabetic nephropathy and DPN in an attempt to elucidate whether albuminuria can be used as an early warning signal of DPN progression. METHODS: A total of 217 T2DM patients who met the inclusion criteria were recruited from the Department of Endocrinology, Nanfang Hospital between January 2016 and June 2016. These patients were placed in groups based on urinary albumin excretion rate (UAER) and estimated glomerular filtration rate. Nerve conduction studies, the Semmes-Weinstein monofilament test (SWMT) and the vibration perception threshold (VPT) test were conducted. Multiple linear regression analysis, multivariate logistic regression and receiver-operating characteristic (ROC) analysis were performed to investigate the relationship between different stages of diabetic nephropathy and DPN in these patients. RESULTS: Significant differences were observed in the conduction velocity (CV) and amplitude of sensory/motor nerve potential among the T2DM patients at different stages of diabetic nephropathy (all p < 0.05). The UAER and duration of diabetes were found to be independent factors associated with the mean CV and amplitude of sensory/motor nerve potential (all p < 0.05). A disease duration of > 10 years (p = 0.025) and a higher total cholesterol value (p = 0.024) were found to be significantly associated with abnormal SWMT results. A UAER of > 300 mg/24 h (p = 0.007) and a diastolic blood pressure of > 100 mmHg (p = 0.042) were associated with a higher risk for abnormal VPT. A UAER of > 300 mg/24 h (p < 0.001) and a disease duration of > 10 years (p = 0.02) were observed to be significantly correlated with DPN. The ROC analysis showed that the optimal cutoff values of UAER and duration as indicators of DPN were 90.5 mg/24 h and 9.5 years, respectively (both p < 0.001). CONCLUSIONS: The results suggest that diabetic nephropathy is closely associated with the development of DPN in T2DM patients and that UAER and disease duration can be used as warning indicators of DPN progression. CHINESE CLINICAL TRIALS REGISTER NUMBER: ChiCTR-ROC-16007701.

8.
Nutrition ; 55-56: 185-191, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30086488

RESUMO

OBJECTIVE: The aim of this study was to determine whether short-term adherence to the Mediterranean diet (MD) was associated with improved physiological function. METHODS: This was a single-center, cohort pilot study with 24 healthy, sedentary younger (18-35 y of age) and older (55-75 y of age) adults. Participants were advised to follow the MD for 4 wk. Baseline and post-intervention measurements were taken of weight, height, waist and hip circumference, blood pressure, and heart rate, as well as microvascular physiological assessments using laser Doppler flowmetry (LDF) at rest, as well as transcutaneous oxygen pressure (TcpO2) during a sub-maximal exercise assessment. RESULTS: We identified statistically-significant improvements in axon-mediated microvascular vasodilation (2.24 ± 0.56 to 3.14 ± 0.84; P = 0.03) and endothelial-mediated nitric oxide synthesis (2.59 ± 0.67 to 3.32 ± 0.87; P = 0.022) in the younger group. Despite the intervention not including an exercise element, the rate of perceived exertion was reduced in both groups (P < 0.001), after following the MD for 1 mo. CONCLUSIONS: Improvements in physiological function were observed after a short-term dietary intervention based on the MD in a younger population. These were not statistically matched in an older group. Our findings suggest that different durations should be applied when designing dietary interventions in different age groups, with expectations in physiological improvement differing.


Assuntos
Fatores Etários , Dieta Mediterrânea , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/fisiologia , Comportamento Sedentário , Adolescente , Adulto , Idoso , Pressão Sanguínea , Tamanho Corporal , Estudos de Coortes , Feminino , Voluntários Saudáveis , Frequência Cardíaca , Humanos , Fluxometria por Laser-Doppler , Masculino , Microvasos/fisiologia , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Tempo , Vasodilatação , Adulto Jovem
10.
Exp Ther Med ; 9(4): 1401-1406, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25780442

RESUMO

The ability of metformin, an antidiabetic drug with wide applications, to inhibit tumor cell growth has recently been discovered. The PI3K/Akt signaling pathway has been found to play an important role in the survival, proliferation and apoptosis of tumor cells. The aim of the present study was to explore the effect of metformin on the proliferation of A431 human squamous cell carcinoma cells and the underlying molecular mechanisms. A431 cells in the logarithmic growth phase were treated with 0, 15, 30, 45 and 60 mM metformin for 12, 24 and 36 h, respectively. Cell morphology with 45 mM metformin treatment for 24 h was observed under a microscope. The proliferation of A431 cells was detected by the Cell Counting kit-8 colorimetric method. The mRNA expression levels of PI3K and Akt were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression levels of PI3K, Akt and phosphorylated (p)-Akt were detected by western blot analysis. Metformin treatment caused morphological change in A431 cells and inhibited their proliferation in a significant time- and dose-dependent manner. RT-PCR results showed that the mRNA expression of PI3K was inhibited by metformin in a time- and dose-dependent manner (P<0.05). However, there was no significant change in the mRNA expression of Akt following metformin treatment (P>0.05). Western blotting results showed that the protein expression levels of PI3K and p-Akt were inhibited by metformin in a time- and dose-dependent manner (P<0.05). In conclusion, metformin significantly inhibited the proliferation of A431 cells in the current study, which may be strongly associated with the inhibition of the PI3K/Akt signaling pathway.

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