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BACKGROUND/AIMS: Elevated systemic inflammation, common in obesity, increases cardiovascular disease risk. Obesity is linked to a pro-inflammatory gut microbiota that releases uremic toxins like p-cresylsulfate (PCS) and indoxyl sulfate (IS), which are implicated in coronary atherosclerosis, insulin resistance, and chronic kidney disease. This study examines the relationship between total PCS and IS levels and central obesity in patients with stable coronary artery disease (CAD). METHODS: A cross-sectional study was conducted on 373 consecutive patients with stable CAD from a single center. Serum levels of total PCS and IS were measured using an Ultra Performance LC System. Central obesity was evaluated using a body shape index (ABSI) and conicity index (CI). Six obesity-related proteins were also analyzed. Structural equation modeling (SEM) assessed direct and indirect effects of total PCS, IS, and the six obesity-related proteins on central obesity. RESULTS: Significant positive correlations were found between total PCS and IS with waist-to-hip ratio (WHR) (r = 0.174, p = 0.005 for total PCS; r = 0.144, p = 0.021 for IS), CI (r = 0.273, p < 0.0001 for total PCS; r = 0.260, p < 0.0001 for IS), and ABSI (r = 0.297, p < 0.0001 for total PCS; r = 0.285, p < 0.0001 for IS) in male patients, but not in female patients. Multivariate analysis showed higher odds ratios (ORs) for elevated CI (OR = 3.18, 95% CI: 1.54-6.75, p = 0.002) and ABSI (OR = 3.28, 95% CI: 1.54-7.24, p = 0.002) in patients with high PCS levels, and elevated CI (OR = 2.30, 95% CI: 1.15-4.66, p = 0.018) and ABSI (OR = 2.22, 95% CI: 1.07-4.72, p = 0.033) in those with high IS levels, compared to those with low toxin levels. SEM analysis indicated that total PCS and IS directly impacted central obesity indices and indirectly influenced central adiposity measures like WHR through high sensitivity C-reactive protein (hs-CRP) (ß = 0.252, p < 0.001). CONCLUSIONS: Circulating total PCS and IS contribute to central obesity in male patients with stable CAD, partially mediated by hs-CRP.
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Background: Transcription factor 21 (TCF21, epicardin, capsuling, pod-1) is expressed in the epicardium and is involved in the regulation of cell fate and differentiation via epithelial-mesenchymal transformation during development of the heart. In addition, TCF21 can suppress the differentiation of epicardial cells into vascular smooth muscle cells and promote cardiac fibroblast development. This study aimed to explore whether TCF21 gene (12190287G/C) variants affect coronary artery disease risk. Methods: We enrolled 381 patients who had stable angina, 138 with ST elevation myocardial infarction (STEMI), and 276 healthy subjects. Genotyping of rs12190287 of the TCF21 gene was performed. Results: Higher frequencies of the CC genotype were found in the patients with stable angina/STEMI than in the healthy controls. After adjusting for diabetes mellitus, hypertension, age, sex, smoking, body mass index and hyperlipidemia, the patients with the CC genotype of the TCF21 gene were associated with 2.49- and 9.19-fold increased risks of stable angina and STEMI, respectively, compared to the patients with the GG genotype. Furthermore, TCF21 CC genotypes showed positive correlations with both stable angina and STEMI, whereas TCF21 GG genotypes exhibited a negative correlation with STEMI. Moreover, the stable angina and STEMI patients with the CC genotype had significantly elevated high-sensitivity C-reactive protein levels than those with the GG genotype. In addition, significant associations were found between type 2 diabetes mellitus, hypertension, and hyperlipidemia with TCF21 gene polymorphisms (p for trend < 0.05). Conclusion: TCF21 gene polymorphisms may increase susceptibility to stable angina and STEMI.
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Angina Estável , Diabetes Mellitus Tipo 2 , Hiperlipidemias , Hipertensão , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Angina Estável/genética , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , China , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genéticaRESUMO
BACKGROUND: Sleep disturbances are more prevalent in diabetic patients than in the general population and may consequently be comorbid with hyperglycaemia. OBJECTIVE: The two study aims were to (1) verify the factors associated with sleep disturbances and glycaemic control and (2) further understand the mediation effects of coping and social support in the relationship among stress, sleep disturbances, and glycaemic control. METHODS: A cross-sectional study design was used. Data were collected at two metabolic clinics in southern Taiwan. The study recruited 210 patients with type II diabetes mellitus who were aged 20 years or above. Demographic information and data on stress, coping, social support, sleep disturbances, and glycaemic control were collected. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, and PSQI scores >5 were considered to indicate sleep disturbances. Structural equation modelling (SEM) approaches were employed to analyse the path association for sleep disturbances in diabetic patients. RESULTS: The mean age of the 210 participants was 61.43 (standard deviation, SD 11.41) years old, and 71.9 % reported sleep disturbances. The final path model had acceptable model fit indices. Stress perception was divided into stress perceived positively and negatively. Stress perceived positively was associated with coping (ß = 0.46, p < .01) and social support (ß = 0.31, p < .01), whereas stress perceived negatively was significantly associated with sleep disturbances (ß = 0.40, p < .001). CONCLUSIONS: The study shows that sleep quality is essential to glycaemic control, and stress perceived negatively might play a critical role to sleep quality.
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Diabetes Mellitus Tipo 2 , Transtornos do Sono-Vigília , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Estudos Transversais , Controle Glicêmico , Análise de Classes Latentes , Adaptação Psicológica , SonoRESUMO
BACKGROUND: Fibroblast growth factor 21 (FGF21) is produced by cardiac cells, may acts in an autocrine manner, and was suggested to has a cardioprotective role in atherosclerosis. Wide QRS complex and heart rate-corrected QT interval (QTc interval) prolongation are associated to dangerous ventricular arrhythmias and cardiovascular disease mortality. Yet, the role of FGF21 in cardiac arrhythmia has never been studied. The aim of the study was to investigate the relationship between plasma FGF21 and the QRS duration and QTc interval in patients with stable angina. METHODS: Three hundred twenty-one consecutive stable angina patients were investigated. Plasma FGF21 was measured through ELISA, and each subject underwent 12-lead electrocardiography. RESULTS: FGF21 plasma levels were positively associated with the QRS duration (ß = 0.190, P = 0.001) and QTc interval (ß = 0.277, P < 0.0001). With increasing FGF21 tertiles, the patients had higher frequencies of wide QRS complex and prolonged QTc interval. After adjusting for patients' anthropometric parameters, the corresponding odd ratios (ORs) for wide QRS complex of the medium and high of FGF21 versus the low of FGF21 were 1.39 (95% CI 0.51-3.90) and 4.41 (95% CI 1.84-11.59), respectively, and p for trend was 0.001. Furthermore, multiple logistic regression analysis also showed the corresponding odd ratios (ORs) for prolonged QTc interval of the medium and high of FGF21 versus the low of FGF21 were 1.02 (95% CI 0.53-1.78) and 1.93 (95% CI 1.04-3.60) respectively with the p for trend of 0.037. In addition, age- and sex-adjusted FGF21 levels were positively associated with fasting glucose, HbA1c, creatinine, and adiponectin, but negatively associated with albumin, and the estimated glomerular filtration rate. CONCLUSIONS: This study indicates that plasma FGF21 is associated with wide QRS complex and prolonged corrected QT interval in stable angina patients, further study is required to investigate the role of plasma FGF21 for the underlying pathogenesis.
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Angina Estável , Fatores de Crescimento de Fibroblastos , Síndrome do QT Longo , Humanos , Adiponectina , Albuminas , Arritmias Cardíacas , Creatinina , Eletrocardiografia , Eletrólitos , Fatores de Crescimento de Fibroblastos/metabolismo , Glucose , Hemoglobinas GlicadasRESUMO
Background: Fatty acid-binding protein 3 (FABP3) located in renal mesangial and distal tubular cells, and had been shown to be a sensitive marker of renal injury, potentially be a mediator in pathogenesis of chronic kidney disease (CKD). Our previous study revealed that plasma FABP1 and FABP2 were independently associated with CKD, however, little is known about the relationship between plasma FABP3 level and CKD. The aim of this study was therefore to evaluate the plasma levels of FABP3 at different stages of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 334 subjects with T2DM who enrolled in a disease management program were included in this study and stratified according to eGFR. Plasma FABP3 concentrations were measured by an enzyme-linked immunosorbent assay. Results: FABP3 levels increased in parallel with the eGFR level. Increasing concentrations of FABP3 were independently and significantly associated with eGFR stage G2-G4. Age- and sex-adjusted FABP3 levels were positively associated with uric acid, urinary albumin-to-creatinine ratio, FABP1, FABP2, and fatty liver index, but negatively associated with eGFR and hemoglobin. Conclusion: Our results indicate that circulating FABP3 in patients with T2DM is associated with eGFR, which suggests that increased plasma FABP3 may be involved in the pathogenesis of CKD.
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Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/diagnóstico , Proteína 3 Ligante de Ácido Graxo/sangue , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/diagnóstico , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background: Obesity and cognitive function decline are independent risk factors for chronic kidney disease (CKD). However, few studies have examined the combined effects of obesity status and cognitive function on change in CKD risk. We aimed to evaluate the association between obesity status, cognitive function and CKD risk change in patients with type 2 diabetes mellitus (T2DM). Methods: Data on 3399 T2DM patients were extracted from a diabetes disease management program between 2006 and 2018. Univariate and multivariate analyses were used to assess the association between obesity, cognitive decline, and CKD risk change. Three indexes, including the relative excess risk of interaction (RERI), attributable proportion of interaction (API), and synergy index (SI), were used to analyze interactions. CKD risk was classified according to the KDIGO 2012 CKD definition. Results: In multivariate analysis, the hazard ratio (HR, 95%Cis) for CKD risk progression was 1.34 (1.12-1.61) times higher in the moderate and severely obese patients compared with the normal weight patients, and 1.34 (1.06-1.67) times higher in the patients with a Mini-Mental State Examination (MMSE) score ≤18 compared to those with an MMSE score ≥24. There was a synergistic interaction between moderate and severe obesity and MMSE score ≤18 on CKD risk progression (SI=4.461; 95% CI: 1.998-9.962), and the proportion of CKD risk progression caused by this interaction was 52.7% (API=0.527; 95% CI: 0.295-0.759). However, normal weight and MMSE score ≥24 were not beneficial on CKD risk improvement in the patients with a moderate risk and very high-risk stage of CKD. Conclusion: There may be a synergistic interaction between obesity and cognitive function decline, and the synergistic interaction may increase the risk of CKD progression.
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Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Cognição , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Progressão da Doença , Taxa de Filtração Glomerular , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Growth differentiation factor 1 (GDF1) is a member of the transforming growth factor-ß (TGF-ß) superfamily and a protective mediator against the development of post-infarction cardiac remodeling by negatively regulating MEK-ERK1/2 and Smad signaling pathways in the heart. The TGF-ß/SMAD pathway has been shown to play a key role in the development of hepatic fibrosis. In addition, fatty liver disease has been associated with reduced MEK/ERK1/2 signaling. However, no previous study has investigated the association between GDF1 and liver fibrosis. Therefore, the aim of this study was to investigate the association between plasma GDF1 and liver fibrosis in patients with stable angina. METHODS: We included 327 consecutive patients with stable angina. ELISA was used to measure circulating levels of GDF1, and the fibrosis-4 index was used to assess liver fibrosis. RESULTS: The advanced liver fibrosis group had lower median plasma GDF1 levels than those with minimal liver fibrosis. There was a significant negative association between GDF1 plasma level and fibrosis-4 index (r = -0.135, p = 0.019). A lower concentration of GDF1 was significantly and independently associated with an increased risk of liver fibrosis when concentration was analyzed as a continuous variable and by tertile. In addition, fibrosis-4 index, aspartate aminotransferase (AST)-to-platelet ratio index, and AST/alanine aminotransferase ratio were significantly associated with GDF1 concentration. CONCLUSIONS: Our results indicated an association between low plasma GDF1 and liver fibrosis in the enrolled patients. Further investigations into the role of plasma GDF1 in the pathogenesis of liver fibrosis are warranted.
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Angina Estável , Fator 1 de Diferenciação de Crescimento , Cirrose Hepática , Humanos , Fator 1 de Diferenciação de Crescimento/sangue , Fígado/metabolismo , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Background: Higher concentrations of plasma fatty acid-binding protein 3 (FABP3) play a role in the development of cardiovascular events, cerebrovascular deaths, and acute heart failure. However, little is known about the relationship between plasma FABP3 level and prolonged QT interval and reduced ejection fraction (EF). This study aimed to investigate the relationship between plasma FABP3 level and prolonged corrected QT (QTc) interval and reduced EF in patients with stable angina. Inflammatory cytokine and adipocytokine levels were also measured to investigate their associations with plasma FABP3. Methods: We evaluated 249 consecutive patients with stable angina. Circulating levels of FABP3 were measured by ELISA. In addition, 12-lead ECG and echocardiography recordings were obtained from each patient. Results: Multiple regression analysis showed that high-density lipoprotein cholesterol, high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, visfatin, adiponectin, FABP4, heart rate, QTc interval, left atrial diameter, left ventricular mass index, end-systolic volume, end-systolic volume index, fractional shortening, and EF were independently associated with FABP3 (all p<0.05). Patients with an abnormal QTc interval had a higher median plasma FABP3 level than those with a borderline and normal QTc interval. With increasing FABP3 tertiles, the patients had higher frequencies of abnormal QTc interval, left ventricular systolic dysfunction, and all-cause mortality, incrementally lower EF, higher WBC count, and higher levels of hs-CRP, visfatin, adiponectin, and FABP4. Conclusion: This study indicates that plasma FABP3 may act as a surrogate parameter of prolonged QTc interval and reduced EF in patients with stable angina, partially through the effects of inflammation or cardiomyocyte injury. Further studies are required to elucidate whether plasma FABP3 plays a role in the pathogenesis of QTc prolongation and reduced EF.
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Angina Estável/complicações , Proteína 3 Ligante de Ácido Graxo/sangue , Síndrome do QT Longo/diagnóstico , Disfunção Ventricular Esquerda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Angina Estável/sangue , Angina Estável/fisiopatologia , Angina Estável/cirurgia , Biomarcadores/sangue , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Humanos , Síndrome do QT Longo/sangue , Síndrome do QT Longo/etiologia , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Prospectivos , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
Background: Neutrophil gelatinaseassociated lipocalin (NGAL), also known as lipocalin 2, siderocalin, 24p3 or uterocalin, plays a key role in inflammation and in different types of cancer. In this study, we investigated whether plasma NGAL levels were altered in patients with breast cancer. The relationship between plasma NGAL levels and pretreatment hematologic profile was also explored. Methods: Plasma NGAL concentrations were measured using ELISA in breast cancer patients and control subjects. A total of 75 patients with breast cancer and 65 age- and body mass index-matched control subjects were studied. All of the study subjects were female. Results: Plasma NGAL level was found to be elevated in the patients with breast cancer compared to the control subjects (94.3 ng/mL (interquartile range 39.3-207.6) vs. 55.0 ng/mL (interquartile range 25.8-124.7), p = 0.007). Multiple logistic regression analysis revealed that NGAL was independently associated with breast cancer, even after adjusting for known biomarkers. Furthermore, NGAL level was elevated in the breast cancer patients who were negative progesterone receptor status, had a histologic grade ≥ 2, clinical stage III, and pathologic stage T2+T3+T4. In addition, NGAL level was significantly correlated with white blood cell (WBC) count, monocyte count, neutrophil count, and platelet count (all p < 0.01). Moreover, WBC count, neutrophil count, monocyte count, lymphocyte count, platelet count, and NGAL level gradually increased as the stage progressed. Conclusions: Increased plasma NGAL levels were associated with breast cancer independently of risk factors, and were correlated with inflammatory biomarkers. These results suggest that NGAL may act through inflammatory reactions to play an important role in the pathogenesis of breast cancer.
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Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Lipocalina-2/sangue , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/imunologia , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/imunologia , Lipocalina-2/metabolismo , Pessoa de Meia-Idade , Transdução de Sinais/imunologiaRESUMO
Background: Chronic kidney disease (CKD) is a major risk factor for coronary artery disease and it is often associated with hepatic steatosis. Hepassocin (also known as hepatocyte-derived fibrinogen related protein or fibrinogen-like 1) is a novel hepatokine that causes hepatic steatosis and induces insulin resistance. However, the role of hepassocin in renal function status remains unclear. Our objective was to investigate the association of plasma hepassocin level with fatty liver and renal function status in patients with stable angina. Methods: Plasma hepassocin levels were determined by enzyme-linked immunosorbent assays in 395 consecutive patients with stable angina. Renal function was defined as an estimated glomerular filtration rate (eGFR). Fatty liver was defined by ultrasonography and fibrosis-4 (FIB-4) index. Results: With increasing hepassocin tertiles, patients had higher prevalence of fatty live, an increased waist-to-hip ratio, and neutrophil count, monocyte count, and FIB-4 index, higher levels of uric acid, blood urine nitrogen and higher sensitivity C-reactive protein. They also had incrementally lower eGFR, serum hemoglobin and albumin levels. In multiple linear stepwise regression analysis, only eGFR was significantly independent negatively associated with plasma hepassocin levels. Conclusion: Our results indicate that circulating hepassocin in patients with stable angina is associated with fatty liver and renal function, which suggests that increased plasma hepassocin may be involved in the pathogenesis of fatty liver and CKD.
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Angina Estável/etiologia , Fibrinogênio/análise , Hepatopatia Gordurosa não Alcoólica/sangue , Insuficiência Renal Crônica/sangue , Idoso , Idoso de 80 Anos ou mais , Angina Estável/sangue , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores de RiscoRESUMO
Background: Diabetes mellitus is the leading cause of diabetic nephropathy and a major public health issue worldwide. Approximately 20-30% of patients with type 2 diabetes mellitus (T2DM) have renal impairment. Fatty acid-binding protein 1 (FABP1) is expressed in renal proximal tubule cells and released into urine in response to hypoxia caused by decreased peritubular capillary blood flow, and FABP2 is responsible for the transport of free fatty acids in the intestinal endothelium cells. There is increasing evidence that FABP1 and FABP 2 play a role in the development and progression of chronic kidney disease. The aim of this study was to investigate the relation of circulating FABP1 and FABP2 levels to nephropathy in patients with T2DM. Methods: For this study, 268 subjects with T2DM who were enrolled in a disease management program were stratified according to urinary microalbumin and serum creatinine measurements. The plasma FABP1 and FABP2 concentrations were examined by enzyme-linked immunosorbent assay. Demographic and potential metabolic confounding factors were analyzed with logistic regression to calculate the effects of FABP1 and FABP2 levels on diabetic nephropathy. Results: The FABP1 and FABP2 levels increased in parallel with the advancement of diabetic nephropathy. Increasing concentrations of FABP1 and FABP2 were independently and significantly associated with diabetic nephropathy. Multiple logistic regression analysis revealed FABP1 and FABP2 as an independent association factor for diabetic nephropathy, even after full adjustment of known biomarkers. Furthermore, receiver operating characteristic curve analysis showed that a FABP1 level of >33.8 ng/mL and a FABP2 level of >2.8 ng/mL were associated with diabetic nephropathy. Conclusion: Our results suggest that FABP1 and FABP2 may be novel biomarkers of diabetic nephropathy.
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Albuminúria/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Proteínas de Ligação a Ácido Graxo/sangue , Idoso , Albuminúria/sangue , Albuminúria/etiologia , Albuminúria/urina , Biomarcadores/sangue , Creatinina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/urina , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de DoençaRESUMO
Background: Fatty acid-binding protein 1 (FABP1) (also known as liver-type fatty acid-binding protein or LFABP) is a protein that is mainly expressed in the liver, and is associated with hepatocyte injury in acute transplant rejection. Reduced levels of FABP1 in mice livers have been shown to be effective against nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the association between plasma FABP1 levels and NAFLD in patients with type 2 diabetes mellitus (T2DM). Methods: We enrolled 267 T2DM patients. Clinical and biochemical parameters were measured. The severity of NAFLD was assessed by ultrasound. FABP1 levels were determined using by enzyme-linked immunosorbent assays. Results: FABP1 levels were higher in patients with overt NAFLD, defined as more than a moderate degree of fatty liver compared to those without NAFLD. Age- and sex-adjusted analysis of FABP1 showed positive associations with body mass index (BMI), waist circumference, homeostasis model assessment estimate of ß-cell function, creatinine, and fatty liver index, but showed negative associations with albumin and estimated glomerular filtration rate (eGFR). The odds ratio (OR) for the risk of overt NAFLD with increasing levels of sex-specific FABP1 was significantly increased (OR 2.63 [95% CI 1.30-5.73] vs. 4.94 [2.25-11.48]). The OR in the second and third tertiles of FABP1 remained significant after adjustments for BMI, triglycerides, high-density lipoprotein cholesterol, HbA1C, homeostasis model assessment estimate of insulin resistance, white blood cell count, hepatic enzymes, and eGFR. Conclusion: Our results indicate that FABP1 may play a role in the pathogenesis of NAFLD in patients with T2DM.
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Diabetes Mellitus Tipo 2/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Idoso , Índice de Massa Corporal , Creatinina/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Circunferência da Cintura/fisiologiaRESUMO
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have become the best choice of second-line oral antidiabetic drugs for patients with heart or chronic kidney disease. However, it is not clear how safe this treatment is for elderly patients, especially Asians, who are known to be more insulin deficient than Caucasian individuals with a similar insulin resistance. Here, we report a case concerning an elderly patient with type 2 diabetes mellitus without insulin dependence, whose antidiabetic medication had recently been changed to include an SGLT-2 inhibitor. The patient presented with an atypical hyperosmolar hyperglycemic state and diabetic ketoacidosis but recovered after insulin pump treatment and fluid supplementation. The patient was discharged with a prescription of a mixed-type insulin injection instead of oral antidiabetic medications for diabetes control. Our case demonstrates that if SGLT-2 inhibitors are administered to elderly Asian patients, their benefits and adverse effects should be carefully monitored.
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Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Coma Hiperglicêmico Hiperosmolar não Cetótico , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/tratamento farmacológico , Glucose , Humanos , Hipoglicemiantes/efeitos adversos , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
Low-circulating levels of adiponectin (ADPN) are associated with obesity, diabetes mellitus, and coronary artery disease. On the contrary, some studies have demonstrated a link between relatively high levels of plasma ADPN and heart failure, atrial fibrillation, and adverse outcome. However, little is known about the relationship between ADPN level and prolonged QT interval. The aim of this study was to investigate the association between plasma ADPN levels and prolonged QT interval in patients with stable angina.In this retrospective study, because the diverse disease severity and condition of the study population may have affected the results, we chose individuals with stable angina. Plasma ADPN concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient.We enrolled 479 stable-angina patients. Patients with an abnormal corrected QT (QTc) interval had higher median plasma ADPN levels than those with normal QTc intervals. Age- and sex-adjusted ADPN levels were positively associated with heart rate, QTc interval, left ventricular mass index, and creatinine but negatively associated with left ventricular ejection fraction, waist circumference, current smoking, total cholesterol, triglycerides, low-density lipoprotein cholesterol, albumin, and estimated glomerular filtration rate. A multiple logistic regression analysis revealed ADPN as an independent association factor for abnormal QTc interval. Increasing concentrations of sex-specific ADPN were independently and significantly associated with abnormal QTc interval, even after full adjustment of known biomarkers.Our results indicate that ADPN may play a role in the pathogenesis of abnormal QTc interval in patients with stable angina.
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Adiponectina/sangue , Angina Estável/fisiopatologia , Biomarcadores/sangue , Síndrome do QT Longo/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Angina Estável/metabolismo , Eletrocardiografia , Feminino , Humanos , Modelos Logísticos , Síndrome do QT Longo/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
The proliferation and migration of vascular smooth muscle cells (VSMCs) are essential in the pathogenesis of various vascular diseases, such as atherosclerosis and restenosis. Among the mediators of VSMC during atherosclerosis development, platelet-derived growth factor (PDGF)-BB is a potent mitogen for VSMCs and greatly contributes to the intimal accumulation of VSMCs. Glossogyne tenuifolia (GT, Xiang-Ru) is a traditional antipyretic and hepatoprotective herb from Penghu Island, Taiwan. This study evaluated the inhibitory effect of GT ethanol extract (GTE) and GT water extract (GTW) on proliferative and migratory activities in PDGF-BB-induced VSMCs. The experimental results demonstrated that GTE significantly inhibited the PDGF-BB-stimulated VSMC proliferation and migration, as shown by MTT, wound healing, and Boyden chamber assays. GTE was found to have a much more potent inhibitory activity than GTW. Based on the Western blot analysis, GTE significantly blocked the PDGF-BB-induced phosphorylation of NF-κB and mitogen-activated protein kinase (MAPK) pathways, including extracellular signal-regulated kinase (ERK), p38, and JNK, in VSMCs. In addition, GTE retarded the PDGF-BB-mediated migration through the suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression in VSMCs. Three main ingredients of GT-chlorogenic acid, luteolin-7-glucoside, and luteolin-all showed significant anti-proliferative effects on PDGF-BB-induced VSMCs. As a whole, our findings indicated that GTE has the potential to be a therapeutic agent to prevent or treat restenosis or atherosclerosis.
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Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Aorta , Becaplermina/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Proteínas Quinases Ativadas por Mitógeno , NF-kappa B , Extratos Vegetais/isolamento & purificação , Ratos , Transdução de Sinais , TaiwanRESUMO
Antrodia cinnamomea (AC) has been shown to have anti-inflammatory, anti-tumor, and immunomodulation activities. It is estimated that hundreds of metric tons of AC extraction waste (ACEW) are produced per year in Taiwan. This study aims to assess the feasibility of applying ACEW as feed supplement in the aquaculture industry. ACEW significantly inhibited the growth of microorganisms in the water tank, by around 39.4% reduction on the fifth day with feed supplemented of 10% ACEW. The feed conversion efficiency of zebrafish with 10% ACEW supplementation for 30 days was 1.22-fold compared to that of the control. ACEW dramatically improved the tolerances of zebrafish under the heat and cold stresses. When at water temperature extremes of 38 °C or 11 °C, compared to the 100% mortality rate in the control group, the 10% ACEW diet group still had 91.7% and 83.3% survival rates, respectively. In a caudal fin amputation test, the fin recovery of zebrafish was increased from 68.4% to 93% with 10% ACEW diet after 3-week regeneration. ACEW effectively down-regulated the gene expression of TNF-α, IL-1ß, IL-6, and IL-10, and up-regulated the gene expression of IL-4/13A. Additionally, the supplement of ACEW in the feed can maintain and prevent the fish's body weight from dropping too much under enteritis. Taken together, ACEW has beneficial potential in aquaculture.
Assuntos
Aquicultura , Resíduos Industriais , Polyporales/química , Regeneração/efeitos dos fármacos , Amputação Cirúrgica , Ração Animal , Animais , Anti-Infecciosos/química , Anti-Inflamatórios/química , Peso Corporal/efeitos dos fármacos , Temperatura Baixa , Suplementos Nutricionais , Feminino , Temperatura Alta , Concentração de Íons de Hidrogênio , Inflamação/tratamento farmacológico , Masculino , Polissacarídeos/química , Triterpenos/química , Água/análise , Peixe-Zebra/fisiologiaRESUMO
BACKGROUND: Fatty acid-binding protein 4 (FABP4) (also known as adipocyte FABP or adipocyte P2) is expressed in adipocytes, macrophages, and capillary endothelial cells. Previous studies have shown associations among plasma FABP4, insulin resistance, metabolic syndrome, diabetes mellitus, greater coronary plaque burden, coronary artery disease, heart failure, and mortality. However, little is known about the relationship between FABP4 level and prolonged QT interval. The aim of this study was to investigate whether plasma FABP4 level is associated with a prolonged QT interval by analyzing 12-lead electrocardiograms (ECGs) in patients with stable angina and chronic kidney disease (CKD). METHODS: This study included 397 consecutive patients with stable angina and CKD who were enrolled in a disease management program. Plasma FABP4 concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient. We assessed the relationships between FABP4 levels (both as a continuous variable and stratified by tertile) at admission and corrected QT (QTc) prolongation. RESULTS: Patients with an abnormal QTc interval had higher median plasma FABP4 levels than those with borderline and normal QTc intervals (15.9 ng/mL vs. 10.2 ng/mL vs. 8.5 ng/mL, respectively, P < 0.0001). Statistically significant associations were observed between plasma FABP4 levels and QTc interval (ß = 0.267, P < 0.0001). Using multivariate and trend analyses, a higher concentration of plasma FABP4 level was independently associated with QTc prolongation in patients with stable angina and CKD. CONCLUSION: In this study, plasma FABP4 levels were significantly higher in the patients with an abnormal QTc interval and were correlated with QTc prolongation. Further studies are required to elucidate whether plasma FABP4 plays a role in the pathogenesis of QTc prolongation.
Assuntos
Angina Estável/sangue , Arritmias Cardíacas/sangue , Proteínas de Ligação a Ácido Graxo/sangue , Frequência Cardíaca , Insuficiência Renal Crônica/sangue , Potenciais de Ação , Idoso , Idoso de 80 Anos ou mais , Angina Estável/complicações , Angina Estável/diagnóstico , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Biomarcadores/sangue , Estudos Transversais , Eletrocardiografia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Regulação para CimaRESUMO
BACKGROUND: Increasing evidence suggests an association between lifestyle and white blood cell (WBC) count; however, no study has examined the effects of lifestyle associations on hematological parameters. The aim of this study was to examine the association between lifestyle factors and hematological parameters in a large population-based sample of Chinese male steelworkers. METHODS: This study included 3189 male workers at a steel plant who responded to a cross-sectional questionnaire on basic attributes, lifestyle, and sleep. All workers in the plant underwent periodic health checkups. Hematological parameters were also examined at the checkup. RESULTS: Stepwise linear regression analyses showed that smoking, poor sleep, shift work, and obesity were all significant factors associated with WBC count. Obesity was independently associated with RBC count. Furthermore, smoking and obesity were associated with hemoglobin, and smoking, poor sleep, and obesity were independently associated with hematocrit. Moreover, smoking was the main factor associated with MCV and MCH. When the subjects were divided into quartiles according to WBC count, RBC count, hemoglobin, hematocrit, MCV, MCH, and increased WBC count were associated with smoking, poor sleep, shift work, and obesity. Increased hemoglobin was associated with smoking and obesity. Furthermore, an increased RBC count was associated with obesity, and increased hematocrit was associated with smoking, poor sleep, and obesity. Similarly, increased MCV and MCH were also associated with smoking. CONCLUSION: This study indicates that lifestyle factors may exert an important effect on hematological parameters (eg, WBC count, RBC count, hemoglobin, hematocrit, MCV, and MCH).
Assuntos
Povo Asiático , Testes Hematológicos , Estilo de Vida , Aço , Adulto , Fatores Etários , Hemoglobinas/metabolismo , Humanos , Contagem de Leucócitos , Modelos Lineares , Masculino , Obesidade/epidemiologia , Prevalência , Jornada de Trabalho em Turnos , Sono , Fumar/epidemiologiaRESUMO
Secreted frizzled-related protein-5 (Sfrp5) known as secreted antagonist binds to Wnt protein. It has been shown to be downregulated by histone acetylation and promoter methylation, and to function as a tumor suppressor gene by inducing apoptosis in renal cell cancer cells. However, its relationship with chronic kidney disease (CKD) has not been well studied. Our objective was to investigate the effect of plasma Sfrp5 levels in subjects with and without CKD. Plasma Sfrp5 levels were determined by enzyme-linked immunosorbent assays in 196 consecutive patients with acute ST-segment elevation myocardial infarction (STEMI). CKD was defined as an estimated glomerular filtration rate (eGFR) <60â¯ml/min per 1.73â¯m2. For the purpose of this study, stage 1 or 2 CKD patients (eGFRâ¯≥â¯60â¯ml/min per 1.73â¯m2) were classified as not having CKD. With increasing Sfrp5 tertiles, the patients had higher frequencies of hypertension, stage 4 or 5 CKD, and waist-to-hip ratio, incrementally lower eGFRs and serum hemoglobin levels, and higher levels of blood urine nitrogen (BUN), creatinine, and adiponectin. Multivariate logistic regression analysis showed that an increased plasma Sfrp5 level was independently associated with CKD for all subjects (adjusted odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02-1.14; pâ¯=â¯0.011). Sfrp5 was also significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin. When the patients were stratified by age, plasma Sfrp5 level was independently related to CKD for patients >65â¯years old (adjusted OR, 1.10; 95% CI, 1.00-1.20; pâ¯=â¯0.045), however, the association was not significant for those <65â¯years old. In addition, Sfrp5 was significantly positively related to BUN, creatinine, and adiponectin, and significantly negatively related to eGFR and hemoglobin in patients >65â¯years old. Our results suggest that Sfrp5 may play a role in the pathogenesis of CKD in acute STEMI patients who are older than 65â¯years.
Assuntos
Proteínas do Olho/sangue , Proteínas de Membrana/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Adiponectina/metabolismo , Idoso , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Feminino , Taxa de Filtração Glomerular/fisiologia , Hemoglobinas/metabolismo , Humanos , Hipertensão/sangue , Hipertensão/metabolismo , Masculino , Razão de Chances , Estudos ProspectivosRESUMO
BACKGROUND: Lower concentrations of serum albumin appear to be associated with an increased risk of all-cause and cardiovascular mortality, coronary heart disease, heart failure and stroke. However, little is known about the relationship between serum albumin level and prolonged QT interval. AIM: To investigate whether lower serum albumin is associated with prolonged QT interval by recording 12-lead electrocardiography in patients with coronary artery disease and chronic kidney disease. METHODS: This study included 1383 consecutive patients with coronary artery disease and chronic kidney disease (841 with acute coronary syndrome and 542 with elective percutaneous coronary intervention patients) who were enrolled in a disease management programme. Twelve-lead electrocardiography was recorded in each subject. We assessed the relationship between albumin levels (both as a continuous variable and stratified by tertile) at admission and corrected QT (QTc) prolongation. RESULTS: Patients with abnormal QTc interval had lower serum albumin levels than those with normal and borderline QTc intervals. Statistically significant negative associations were observed between serum albumin levels and QTc interval (ß = -0.211, P < 0.0001). Using multivariate and trend analyses, a lower concentration of serum albumin was independently associated with QTc prolongation in both the patients with acute coronary syndrome and elective percutaneous coronary intervention patients. CONCLUSION: Concentrations of serum albumin were significantly lower in the patients with an abnormal QTc interval and were associated with QTc prolongation. Further studies are needed to clarify whether lower serum albumin plays a role in the pathogenesis of QTc prolongation.