RESUMO
In Taiwan, colorectal cancer (CRC) is the second most common cancer and the cancer with the third highest mortality rate. This may be because of the difficulty of detecting the disease in the early stages, as well as the fact that colonoscopy, a typical method used in screening for CRC, causes discomfort to the recipient and is prone to technical interference. For the earlier detection of CRC, finding an easier screening method with a simpler collection procedure is essential. Thus, in the present study, plasma samples from patients with CRC were analyzed to determine the extent of methylation in SHISA3 DNA. Studies have suggested that SHISA3, a newly identified tumor suppressor, can regulate tumor growth, and that the inactivation of its DNA can be traced to epigenomic alterations in CRC. Another study reported the presence of hypermethylated SHISA3 DNA in CRC biopsy specimens. In the present study, the plasma of 30 patients with CRC and nine healthy controls was collected and analyzed for the concentration of cell-free DNA through bisulfite sequencing. The methylation rates were determined. Our results have shown that an increasing amount of cell-free DNA in the group of CRC patient's plasma compared to the healthy group. Moreover, patients with later stages of CRC had higher concentrations of cell-free DNA. Notably, the methylation rate of SHISA3 was higher in the plasma of the CRC group than in that of the healthy group. The results indicated that the presence of tumor cells does not reduce the degree of SHISA3 DNA in the peripheral blood of patients with CRC. In other words, the hypermethylation of SHISA3, which inactivates the gene, is a potential cause of tumorigenesis. Furthermore, the methylation rate of SHISA3 DNA was higher in the plasma of patients with stage II CRC than in that of those with stage I CRC. In conclusion, the combination of conventional testing and screening for SHISA3 hypermethylation in plasma could improve the rate at which CRC is detected.
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Biomarcadores Tumorais , Neoplasias Colorretais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , DNA/genética , Metilação de DNA , Humanos , Proteínas de Membrana/genética , TaiwanRESUMO
BACKGROUND: Metabolic syndrome's (MetS) role in predicting cardiovascular diseases and diabetes has been confirmed in many large cohort studies. Nontraditionally, hematogram components are significantly related to MetS in many different age groups. However, little is known about its role among the elderly. METHODS: We enrolled 18,907 subjects over the age of 65 years who underwent regular health examinations. They were divided into three groups according to age: young old (YO: ≥ 65 and < 74 years old), old old (OO: ≥ 75 and < 84 years old), and oldest old (ODO: ≥ 85 years old). The MetS components were determined, and correlations between MetS and hematogram components were evaluated using Pearson and multivariate linear regression analyses. The hematogram components were the independent variables evaluated separately against the dependent variable (MetS components). RESULTS: While SBP and HDL-C increased, most other MetS and hematogram parameters decreased in men with age. Fewer significant differences were noted among the women. In the YO and OO groups for both genders, the subjects with MetS had higher WBC and Hb. None of the hematogram components were different for subjects with or without MetS in the ODO group. Multiple regression results show that most of the relationships between hematogram and MetS components disappeared in the ODO groups. The WBC levels were mainly correlated with WC and TG. At the same time, Hb was associated with BP, FPG, and LDL-C. Compared to WBC and Hb, PLT was least related to MetS, except in the cases of LDL-C and TG. Among the MetS components, BMI, LDL-C, and TG were consistently related to all the hematogram components in YO and OO men. However, only TG had the same consistency among YO and OO women. CONCLUSIONS: This study's three major findings are as follows: WBC and Hb are associated with MetS, even among the YO and OO groups, regardless of gender; among the three hematogram components, Hb had the strongest and PLT had the weakest correlation with MetS; and TG is not the only component with relatively higher r values, and it is related to all hematogram components.
Assuntos
Envelhecimento/fisiologia , Contagem de Células Sanguíneas/métodos , Hemoglobinas/análise , Síndrome Metabólica/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Fatores de Risco , Fatores Sexuais , Estatística como Assunto , Taiwan/epidemiologiaRESUMO
OBJECTIVE: To compare four different blood pressure (BP) measurements-systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)-in predicting future metabolic syndrome (MetS) among the normotensive elderly population, and to estimate the optimal cutoff value of the best single measurement for clinical practice. METHODS: A total of 2782 non-medicated participants aged ≥ 60 years were enrolled in a standard health examination program in Taiwan from January 2004 to December 2013. Two thirds of the participants were randomly designated as the training group (n=1855) and the other one third as the validation group (n=927). The mean follow-up time was 3.60 years for both the training and validation groups. MAP and PP were calculated from SBP and DBP. RESULTS: SBP, DBP, and MAP were associated with future MetS, whereas PP was not. MAP had the largest hazard ratio in Cox regression (men 1.342 [95% CI 1.158-1.555] and women 1.348 [95% CI 1.185-1.534] in the training group; men 1.640 [95% CI 1.317-2.041] and women 1.485 [95% CI 1.230-1.794] in the validation group) and the largest area under the receiver operating characteristic curve (men 0.598 ± 0.021 and women 0.602 ± 0.021 in the training group). Multivariable Cox regression further indicated that a higher MAP level was independently associated with the future occurrence of MetS. Participants with MAP above the cutoff value (84.0mm Hg for men, 83.3mm Hg for women) had a higher cumulative incidence of MetS than did their counterparts after four years' follow-up in both the training and validation groups. The results derived from the training data could be replicated in the validation data, indicating that the results were generalizable across distinct samples. CONCLUSIONS: MAP is more accurate than SBP, DBP, and PP in predicting future MetS among the normotensive geriatric population. Calculation of MAP is recommended when dealing with normotensive patients aged ≥ 60 years in clinical practice.
Assuntos
Pressão Sanguínea/fisiologia , Síndrome Metabólica/diagnóstico , Idoso , Determinação da Pressão Arterial/métodos , Estudos de Coortes , Feminino , Humanos , Hipertensão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROCRESUMO
Metastasis plays an important role in mortality of cancer patients. Migration and invasion are the major characteristics of tumor metastasis. The induction of matrix metalloproteinases (MMPs) such as MMP-2 and -9 are particularly important for the invasiveness of various cancer cells. Bufalin, a class of toxic steroids, was purified from the skin glands of Bufo gargarizans or Bufo melanostictus; it is known to inhibit proliferation of human cancer cells. In this study, we investigated the antiinvasive mechanisms of bufalin in the human hepatocellular cancer cell line SK-Hep1. Bufalin significantly reduced serum-induced cell invasion and migration. Furthermore, bufalin markedly inhibited MMP-2 and -9 activity, mRNA expression and protein levels in SK-Hep1 cells. Bufalin attenuated phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT which was associated with reduced levels of nuclear factor kappa B (NF-κB). Bufalin also suppressed protein levels of FAK and Rho A, VEGF, MEKK3, MKK7, and uPA and it diminished NF-κB translocation. Based on these observations, we propose that bufalin is acts as an antiinvasive agent by inhibiting MMP-2 and -9 and involving PI3K/AKT and NF-κB pathways. Bufalin is a potential therapeutic agent that may have efficacy in preventing the invasion and metastasis of malignant liver tumors.
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Antineoplásicos/farmacologia , Bufanolídeos/farmacologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/antagonistas & inibidores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: The white blood cell (WBC) count was one of the first inflammatory markers associated with metabolic syndrome (MetS). Recently, two longitudinal studies have demonstrated a cause and effect relationship between MetS and WBC counts among middle-aged adults. However, no study has used WBC cutoff values to predict MetS in the elderly. METHODS: Subjects who underwent routine health checkups, and were above 60 years of age, were enrolled. All subjects were followed-up until they developed MetS or until 4 years from the date of entry, whichever came earlier. Of the 4539 subjects eligible for enrollment, 3428 subjects comprised the study group and 1111 subjects comprised the validation group. RESULTS: WBC counts were significantly different between subjects with and without MetS in both genders. Using the ROC curve, WBC cutoff values of 5.7 × 10(3)/µl in males and 5.0 × 10(3)/µl in females were associated with the increased risk of developing MetS (all p values <0.001). Using these WBC cutoff values, the hazard ratio (HR) for females was significant in both the study group and validation group. However, the HR for males failed significance in the validation group. Kaplan-Meier plots and κ coefficients confirmed that the WBC cutoff value could predict development of MetS in women but not in men. CONCLUSIONS: The association between WBC count and MetS was gender specific. A WBC cutoff value greater than 5.0 10(3)/µl may predict the development of MetS in elderly women.
Assuntos
Contagem de Leucócitos , Síndrome Metabólica/diagnóstico , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Fatores de Risco , Fatores SexuaisRESUMO
Osteosarcoma is the most common malignant primary bone tumor in children and young adults and lung metastasis is the main cause of death in those patients. Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to exhibit cytotoxic effects, including antiproliferative and anticarcinogenic activities, in several cancers. In the present study, we determined if deguelin would inhibit migration and invasion in U-2 OS human osteosarcoma cells. Deguelin significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells which was associated with a reduction of activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). Furthermore, results from western blotting indicated that deguelin decreased the cell proliferation and cell growth-associated protein levels, such as SOS1, PKC, Ras, PI3K, p-AKT(Ser473), IRE-1α, MEKK3, iNOS, COX2, p-ERK1/2, p-JNK1/2, p-p38; the cell motility and focal adhesion-associated protein levels, such as Rho A, FAK, ROCK-1; the invasion-associated protein levels, such as TIMP1, uPA, MMP-2. MMP-9, MMP-13, MMP-1 and VEGF in U-2 OS cells. Confocal microscopy revealed that deguelin reduced NF-κB p65, Rho A and ROCK-1 protein levels in cytosol. MMP-7, MMP-9 and Rho A mRNA levels were suppressed by deguelin. These in vitro results provide evidence that deguelin may have potential as a novel anti-cancer agent for the treatment of osteosarcoma and provides the rationale for in vivo studies in animal models.
Assuntos
Neoplasias Ósseas/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Osteossarcoma/metabolismo , Rotenona/análogos & derivados , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Invasividade Neoplásica , Osteossarcoma/patologia , Rotenona/farmacologiaRESUMO
The major contributors to the pathogenesis of type 2 diabetes are impaired insulin action and insulin secretion, including second phase insulin secretion (2nd ISEC). This study aimed to compare surrogates derived from the mixed meal tolerance test (MTT) with 2nd ISEC derived from modified low-dose graded glucose infusion (M-LDGGI) in patients with type 2 diabetes. We were subsequently able to decide which surrogate would be performed easily and accurately. Twenty type 2 diabetes patients were enrolled. They received both MTT and M-LDGGI. The standardized MTT meals were provided at 8:00 A.M. and 12:00 P.M. The M-LDGGI was a simplified version of the Polonsky method; only two 80-min stages of glucose infusion (2 and 6 mg/kg/min) were given. The slopes of the insulin to glucose curve during the test were regarded as the 2nd ISEC. First, we used the area under the insulin curve (AUC(IN)) during MTT to quantify the 2nd ISEC. The best correlated AUC(IN) was from 60-240 min. Second, the slopes between any two time points of the plasma insulin to glucose level (SLOPE(I/G)) were also assessed. The time period best correlated with 2nd ISEC was from 0-120 min (SLOPE0â120). Finally, the insulin-to-glucose ratio (IGr) of each time point was used to estimate the 2nd ISEC, and the best correlation was observed at 180 min. In conclusion, estimating 2nd ISEC surrogates derived from MTT proved to be possible. The most accurate surrogate is the SLOPE0â120, while IG(r180) is another less precise but more convenient method.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Técnicas de Diagnóstico Endócrino , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Adulto , Algoritmos , Biomarcadores/sangue , Glicemia/análise , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Insulina/sangue , Secreção de Insulina , Cinética , Masculino , Refeições , Pessoa de Meia-Idade , Período Pós-Prandial , Reprodutibilidade dos Testes , Taiwan , Simplificação do TrabalhoRESUMO
INTRODUCTION: Red blood cell (RBC) storage solution is used for suspending and preserving RBCs for later use in in vitro immunohematology testing. Proper RBC preservation is crucial for obtaining accurate results in RBC phenotyping and pretransfusion antibody screening tests. Haemolysis or RBC antigen degradation during storage can result in inaccurate RBC phenotyping, thereby decreasing the sensitivity of pretransfusion antibody screening and identification assays. The conventional RBC storage solutions usually contain adenosine, adenine, and antibiotics. We designed an RBC storage solution and determined whether it could preserve RBC integrity for 70 days. MATERIALS AND METHODS: The new storage solution has a different formula from that of the conventional solution-in particular, it is strengthened with polyethylene glycol (PEG). The extent of haemolysis and hemagglutination reactivity of the RBC antigen systems, Rh, Duffy, Kidd, Lewis, MNS, P1, and the rare antigen Mia (which has a low prevalence antigen in most parts of the world but a higher prevalence in Taiwan), in the new RBC storage solution was compared with that of the conventionally preserved RBC storage solution. RESULTS: The RBCs preserved in the new solution for 70 days retained a similar haemolysis grade as those preserved in the control solution for 28 days. Although both solutions largely preserved RBC antigenicity, the decline in RBC hemagglutination scores in new solution often occurred later than that in the control solution in most antigen phenotyping assays, especially labile antigens such as D, P1, and M. CONCLUSION: The new solution reduces haemolysis more effectively and preserves antigenicity throughout the 70-day storage period. Moreover, Mia antigen is more stable in the experimental group.
Assuntos
Preservação de Sangue , Hemólise , Humanos , Preservação de Sangue/métodos , Eritrócitos/metabolismo , Adenina/metabolismo , TaiwanRESUMO
OBJECTIVES: To evaluate the association between AGEs and atherosclerotic lipid profiles among aging diabetic patients in Taiwan. DESIGN AND METHODS: After age and gender matching, we selected 207 diabetic subjects and 174 diabetic subjects with proteinuria. Lipid profiles, including total cholesterol (TC), triglycerides (TG), high density cholesterol-lipoprotein (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were measured using standard methods. AGEs were measured with the immunoassay method. RESULTS: In general, males were heavier; however, females had higher AGEs, fasting glucose (GLU), TC, HDL-C and LDL-C levels than males, and had higher TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C ratios compared to males. AGEs were more strongly correlated with TG levels and TCL/LDL-C, LDL-C/HDL-C and TG/HDL-C ratios when compared to glucose or hemoglobin A1c. Subjects had higher AGEs levels (⧠2.0 AU) with more adverse lipid profiles. CONCLUSION: AGEs seem to be a good biomarker to evaluate the association between diabetes and atherosclerotic disorders in aging diabetes.
Assuntos
Aterosclerose/sangue , Diabetes Mellitus Tipo 2/sangue , Produtos Finais de Glicação Avançada/sangue , Lipídeos/sangue , Idoso , Aterosclerose/etiologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Estatísticas não ParamétricasRESUMO
It has been established that prediabetes can causes significant comorbidities, particularly in the elderly. The deterioration of glucose metabolism are generally considered to be results of the impairment of the 4 factors: first, second insulin secretion (FPIS, SPIS, respectively), glucose effectiveness (GE), and insulin resistance. In this study, we enrolled older women to investigate their relationships with prediabetes.Five thousand four hundred eighty-two nonobese, nondiabetic women were included. They were divided into normal glucose tolerance and prediabetes groups. Receiver operating characteristic curve was performed to investigate the effects on whether to have prediabetes for each factors. Two models were built: Model 1: FPISâ+âSPIS, and Model 2: model 1â+âGE. The area under the receiver operating characteristic (aROC) curve was used to determine the predictive power of these models.The aROC curve of GE was significantly higher than the diagonal line followed by SPIS and FPIS accordingly. The aROC curve of Model 1 (0.611) was not different from GE. However, Model 2 improved significantly up to 0.663. Based on this model, an equation was built (-0.003â×âGEâ-â212.6â×âSPISâ-â17.9â×âinsulin resistanceâ+â4.8). If the calculated value is equal or higher than 0 (≥0), then the subject has higher chance to have prediabetes (sensitivityâ=â0.607, specificityâ=â0.635).Among the 4 factors, GE is the most important contributor for prediabetes in older women. By building a model composed of FPIS, SPIS, and GE, the aROC curve increased significantly. The equation built from this model could predict prediabetes precisely.
Assuntos
Povo Asiático/etnologia , Glucose/metabolismo , Resistência à Insulina/fisiologia , Secreção de Insulina/fisiologia , Estado Pré-Diabético/epidemiologia , Idoso , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Pessoa de Meia-Idade , Estado Pré-Diabético/fisiopatologia , Prevalência , Sensibilidade e Especificidade , Taiwan/epidemiologiaRESUMO
Background: This study evaluated the relative influence of insulin resistance (IR), first-phase insulin secretion (FPIS), second-phase insulin secretion (SPIS), and glucose effectiveness (GE) in determining the difference between fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) (ΔPG), in a Chinese population with type 2 diabetes (T2D) mellitus. Methods: In total, we enrolled 1213 participants with T2D (479 women). IR, FPIS, SPIS, and GE were estimated by using equations we built previously. ΔPG was defined as FPG - PPG. Results: The relative contribution of the four diabetogenic factors (DFs) was analyzed by multiple linear regression, and GE was the greatest contributor in the ΔPG value (ß = 0.171, P < 0.001), whereas IR had the least influence on ΔPG (ß = -0.040, P = 0.439). DFs were analyzed by using binary logistic regression to ascertain if ΔPG ≥0 (high fasting plasma glucose, HFG). Three models were built: Model 0: SPIS, Model 1: SPIS + FPIS, and Model 2: Model 1 + GE. Model 2 had the most accurate predictive power; the equation for Model 2 is P = 1/(1 - e-x), where x = -11.88 + 312.89 × (GE) -1.22 × log(SPIS) +1.63 × log(FPIS). In this equation, P refers to the risk of HFG. Conclusions: For Chinese patients, GE had the most profound effect in determining ΔPG, followed by FPIS, SPIS, and IR. The model suggested that participants with high FPIS, SPIS, and GE would have a high incidence of HFG.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Jejum/sangue , Período Pós-Prandial/fisiologia , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Progressão da Doença , Feminino , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina/fisiologia , Secreção de Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , TaiwanRESUMO
Background: Both hepatitis B (HB) and nonalcoholic fatty liver disease (NAFLD) are related to metabolic syndrome (MetS); however, this relationship remains controversial. In this study, we determined the effects of NAFLD and HB infection on the risk of MetS among elderly individuals. Methods: In total, 24,500 individuals aged >65 years were enrolled; they were classified into four groups: normal individuals (N), patients with only HB infection without abnormal echogenicity (HB-alone), patients with only abnormal echogenicity or fatty liver alone (FL-alone), and patients with both HB infection and abnormal echogenicity (HB-FL). Results: After adjustment for age, compared with group N, men and women with NAFLD (FL-alone and HB-FL) had a significantly higher risk of MetS, whereas no significant difference was observed in the incidence of MetS between groups HB-alone and N. However, group HB-FL had a lower risk of MetS than did group FL-alone. HB infection (HB-alone and HB-FL) was associated with a lower risk of high triglycerides (TGs) and fasting plasma glucose (FPG) than HB infection absence (groups N and FL-alone) in men and women. Lower risk of TG derangement was observed in group HB-alone than in group N. In addition, both men and women in group HB-FL had a lower risk of TG and FPG abnormalities than in group FL-alone, whereas a decrease in incidence of high waist circumference and blood pressure was observed only in men. Conclusion: HB infection protects against MetS development, only in patients with HB infection and NAFLD, but not in normal individuals. Additional studies are warranted to clarify the pathogenesis.
Assuntos
Hepatite B/epidemiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Idoso , Glicemia/metabolismo , Estudos de Casos e Controles , Feminino , Hepatite B/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Taiwan/epidemiologia , Triglicerídeos/sangueRESUMO
Adropin is a 76 amino acid peptide hormone with a molecular weight of 4999.9Da that may be associated with energy homeostasis, insulin resistance and lipid metabolism in mice and human. There is only a few studies that examine plasma adropin levels and body composition in children. This study is to evaluate the relationship between plasma adropin levels, body composition and lipid variables amongst young adolescents in Taiwan. We examined 492 adolescents (269 females and 223 males) ranging from 12 to 15 years old, with a mean age of 13.6 years. Body composition was measured using impedance method by Tanita-BC418. Plasma lipid variables were measured using standard methods and plasma adropin levels were measured using the ELISA method. There was no significant difference in plasma adropin levels between males and females (3.52 vs. 3.58ng/ml). Plasma adropin levels were negatively correlated with fat free mass (r=-0.12, p<0.01). More interestingly, children with higher plasma adropin levels had lower waist-to-hip ratios (WHR) and lower body fat percentage by mass. Furthermore, there is no difference in lipid profiles in high vs. low adropin subjects. Plasma adropin levels are not consistency associated with body composition and no association with lipid variables amongst Taiwanese adolescents. The role of adropin in the development of obesity is still not clear, and further studies are need especially for children.
Assuntos
Composição Corporal/fisiologia , Metabolismo Energético/fisiologia , Lipídeos/sangue , Peptídeos/sangue , Adolescente , Biomarcadores/sangue , Proteínas Sanguíneas , Índice de Massa Corporal , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Inquéritos Epidemiológicos , Humanos , Resistência à Insulina/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Obesidade Infantil/sangue , Obesidade Infantil/epidemiologia , Taiwan/epidemiologiaRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0189115.].
RESUMO
AIM: The present study evaluated the relative influence of body mass index (BMI) on insulin resistance (IR), first-phase insulin secretion (FPIS), second-phase insulin secretion (SPIS), and glucose effectiveness (GE) at a fixed fasting plasma glucose level in an older ethnic Chinese population. METHODS: In total, 265 individuals aged 60 years with a fasting plasma glucose level of 5.56 mmol/L were enrolled. Participants had BMIs of 20.0-34.2 kg/m2. IR, FPIS, SPIS, and GE were estimated using our previously developed equations. Pearson correlation analysis was conducted to assess the correlations between the four diabetogenesis factors and BMI. A general linear model was used to determine the differences in the percentage of change among the four factor slopes against BMI. RESULTS: Significant correlations were observed between BMI and FPIS, SPIS, IR, and GE in both women and men, which were higher than those reported previously. In men, BMI had the most profound effect on SPIS, followed by IR, FPIS, and GE, whereas in women, the order was slightly different: IR, followed by FPIS, SPIS, and GE. Significant differences were observed among all these slopes, except for the slopes between FPIS and SPIS in women (p = 0.856) and IR and FPIS in men (p = 0.258). CONCLUSIONS: The contribution of obesity to all diabetes factors, except GE, was higher than that reported previously. BMI had the most profound effect on insulin secretion in men and on IR in women in this 60-year-old cohort, suggesting that lifestyle modifications for obesity reduction in women remain the most important method for improving glucose metabolism and preventing future type 2 diabetes mellitus.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Obesidade/complicações , Glicemia/metabolismo , Índice de Massa Corporal , China , Diabetes Mellitus Tipo 2/sangue , Etnicidade , Jejum/sangue , Jejum/metabolismo , Feminino , Glucose , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangueRESUMO
Hypertension and prehypertension can increase the risk of developing cardiovascular disease (CVD) and diabetes. However, whether the harmful effects of high blood pressure (BP) are also seen with high normotension remains unknown. This 10-year longitudinal follow-up study aimed to investigate the relationships among normal-range BP, metabolic syndrome (MetS), and CVD.A total of 9133 nonmedicated normotensive participants, 4634 males and 4499 females, aged 60 years or older were enrolled in a standard health examination program at 2 academic hospitals and a health screening center in Taiwan. The study subjects were divided into 3 groups according to their BP. The systolic BP (SBP) ranges of groups 1, 2, and 3 were 91 to 100, 101 to 110, and 111 to 119âmmHg, whereas the diastolic BP (DBP) ranges of groups 1, 2, and 3 were 51 to 60, 61 to 70, and 71 to 79âmmHg, respectively.In the SBP3 group, both sexes had a higher odds ratio (OR) for having MetS or abnormal MetS components, except for triglycerides. Females in the DBP3 group had a higher OR for having MetS at baseline. After the follow-up period, the SBP3 group had a significantly higher hazard ratio (HR) for developing MetS. Males in the DBP3 group and females in the DBP2 and DBP3 groups had a significantly higher HR for developing MetS. Neither the SBP3 group nor the DBP3 group had a higher HR for developing nonfatal CVD. In the Kaplan-Meier analysis, SBP and DBP in both sexes showed statistical significance as predictors of MetS, but not of nonfatal CVD.High normotensive elderly individuals have an elevated risk of developing MetS at baseline and within 10 years of follow-up, but they are not at increased risk of CVD. Preventive interventions, such as life-style modification, should be offered early even to the apparently healthy elderly.
Assuntos
Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Síndrome Metabólica/epidemiologia , Centros Médicos Acadêmicos , Idoso , Instituições de Assistência Ambulatorial , Antropometria , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Estudos Longitudinais , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , TaiwanRESUMO
BACKGROUND: Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) production play major roles in progression of diabetic nephropathy. Anti-RAGE effect of peroxisome proliferator-activated receptor-delta (PPARδ) agonists was shown in previous studies. PPARδ agonists also stimulate glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells. METHODS: In this study, the individual and synergic anti-inflammatory effects of GLP-1 receptor (exendin-4) and PPARδ (L-165,041) agonists in AGE-treated rat mesangial cells (RMC) were investigated. RESULTS: The results showed both exendin-4 and L-165,041 significantly attenuated AGE-induced IL-6 and TNF-α production, RAGE expression, and cell death in RMC. Similar anti-inflammatory potency was seen between 0.3 nM exendin-4 and 1 µM L-165,041. Synergic effect of exendin-4 and L-165,041 was shown in inhibiting cytokines production, but not in inhibiting RAGE expression or cell death. CONCLUSIONS: These results suggest that both GLP-1 receptor and PPARδ agonists have anti-inflammatory effect on AGE-treated rat mesangial cells.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Células Mesangiais/efeitos dos fármacos , Peptídeos/farmacologia , Fenoxiacetatos/farmacologia , Peçonhas/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Exenatida , Produtos Finais de Glicação Avançada , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-6/metabolismo , Células Mesangiais/metabolismo , PPAR delta/agonistas , Ratos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: To investigate the risk factors associated with cardiovascular diseases and its relation to BMI, body fat mass and plasma leptin level among adolescents in Taitung, Taiwan. METHODS: A cross-sectional Taitung Children Heart Study for 500 young adolescents between ages 13 and 15 was conducted. Gender-specific regression models were used to determine the associations between BMI, percentage of body fat mass, plasma leptin level and seven CVDs risk factors (systolic and diastolic blood pressure, mean arterial pressure, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol) before and after adjusting for weight status and age. RESULTS: After adjusting for weight status and age, BMI was positively associated with systolic BP, triglycerides, LDL-cholesterol levels but negatively associated with HDL-cholesterol level in boys while positively associated with systolic and diastolic BP, mean arterial pressure, and LDL-cholesterol level in girls. The percentage of body fat mass was positively associated with triglycerides, total cholesterol, and LDL-cholesterol in boys while positively associated with systolic BP, total cholesterol, and LDL-cholesterol in girls. Plasma leptin was positively associated with triglycerides, total cholesterol and LDL-cholesterol in boys but no statistically significant associations with CVDs risk factors in girls. A strong relationship between the percentage of body fat mass and plasma leptin appeared among all participants (r=0.59, p<0.01). CONCLUSIONS: BMI, body fat mass and plasma leptin level may be used to identify certain CVDs risk factors among Taitung adolescents. Future researches could consider measuring body fat mass in the relationship of CVDs risk factors instead of plasma leptin among young adolescents.
Assuntos
Tecido Adiposo/metabolismo , Composição Corporal , Índice de Massa Corporal , Doenças Cardiovasculares/etiologia , Colesterol/sangue , Leptina/sangue , Triglicerídeos/sangue , Adolescente , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Fatores Sexuais , TaiwanRESUMO
The concept of using single criterion of normal blood pressure with systolic blood pressure (SBP)â<â140 mmHg and diastolic blood pressure (DBP)â<â90 mmHg for all ages is still disputable. The aim of the study is to identify the cutoff value of normotension in different age and sex groups.Totally, 127,922 (63,724 men and 64,198 women) were enrolled for the analysis. Finally, four fifths of them were randomly selected as the study group and the other one fifths as the validation group. Due the tight relationship with comorbidities from cardiovascular disease (CVD), metabolic syndrome (MetS) was used as a surrogate to replace the actual cardiovascular outcomes in the younger subjects.For SBP, MetS predicted by our equation had a sensitivity of 55% and specificity of 67% in males and 65%, 83% in females, respectively. At the same time, they are 61%, 73% in males and 73%, 86% in females for DBP, respectively. These sensitivity, specificity, odds ratio, and area under the receiver operating characteristic curve from our equations are all better than those derived from the criteria of 140/90 or 130/85 mmHg in both genders.By using the presence of MetS as the surrogate of CVD, the regression equations between SBP, DBP, and age were built in both genders. These new criteria are proved to have better sensitivity and specificity for MetS than either 140/90 or 130/85 mmHg. These simple equations should be used in clinical settings for early prevention of CVD.