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ABSTRACT Active aging is based on four pillars: health, safety, participation, and lifelong learning. These pillars help individuals improve their quality of life throughout the aging process. Objective: To analyze the effectiveness of the Active Aging Program; identify the sociodemographic profile of the participants; identify prevalent diseases in the initial evaluation; and assess the results of the program after one year of follow-up. Methods: This is a quantitative, cross-sectional, exploratory, desk research, and descriptive study. Data from 545 employees of University of São Paulo participating in the Active Aging Program of the University Teaching Hospital of the University of São Paulo (HU-USP) between 2015 and 2018 were analyzed using the Minitab Program. For data analysis, Pearson's chi-square test was used to determine the association between Groups A and B. For continuous measures, the paired t-test was used to verify differences in means, adopting a 95% confidence interval and significance level of 0.05. Results: Statistically significant correlations were found when crossing sex with smoking; sex with triglycerides; age with risk factors for cardiovascular diseases, being the age group 40-59 statistically more significant; physical activity with risk factors for cardiovascular diseases; and body mass index at program entry with the one-year result. Conclusion: The study expanded knowledge about risk factors for cardiovascular diseases and provided important information for the continuity of the program.
RESUMO O envelhecimento ativo se apoia em quatro pilares: saúde, segurança, participação e aprendizagem ao longo da vida. Esses pilares auxiliam os indivíduos na qualidade de vida ao longo do processo de envelhecimento. Objetivo: Analisar a efetividade do Programa Envelhecimento Ativo; identificar o perfil sociodemográfico dos participantes; identificar patologias predominantes na avaliação inicial; e verificar os resultados do programa após um ano de acompanhamento. Métodos: Trata-se de pesquisa quantitativa, de caráter transversal, exploratória, documentária e descritiva. Foram analisados os dados de 545 funcionários da Universidade de São Paulo que participaram do Programa do Envelhecimento Ativo do Hospital Universitário da Universidade de São Paulo (HU-USP) no período de 2015 a 2018. Os dados foram analisados pelo Programa Minitab. Na análise de dados, usou-se o Qui-quadrado para testar a associação entre os grupos. Já para medida contínua, utilizou-se o Teste T Pareado, para verificar se as médias eram diferentes. Nas análises, foi usado um período de confiabilidade de 95% e nível de relevância de 0,05. Resultados: Foram encontradas correlações estatisticamente expressivas no cruzamento de sexo com tabagismo; sexo com triglicérides; idade com fatores de risco para doenças cardiovasculares sendo que a faixa etária de 40-59 foi estatisticamente mais significativa; atividade física com prevalência de fatores de riscos para doenças cardiovasculares; e índice de massa corpórea inicial com o resultado após um ano. Conclusão: A pesquisa ampliou o conhecimento a respeito dos fatores de risco para doenças cardiovasculares e forneceu informações importantes para a continuidade do programa.
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Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 AËC, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity.
Subject(s)
Polymorphism, Genetic , Diabetes Mellitus , Nutrigenomics , Insulin Receptor Substrate Proteins , Obesity , Carbohydrates , Pilot Projects , Eating , Melanocortins , Fatty AcidsABSTRACT
Polymorphisms in genes of leptin-melanocortin and insulin pathways have been associated with obesity and type 2 diabetes. We hypothesized that polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory markers and food intake composition in Brazilian subjects. This exploratory pilot study included 358 adult subjects. Clinical, anthropometric, and laboratory data were obtained through interview and access to medical records. The variants IRS1 rs2943634 AËC, IRS2 rs1865434 C>T, MC3R rs3746619 C>A, and MC4R rs17782313 T>C were analyzed by real-time polymerase chain reaction. Food intake composition was assessed in a group of subjects with obesity (n = 84) before and after a short-term nutritional counseling program (9 weeks). MC4R rs17782313 was associated with increased risk of obesity (P = .034). Multivariate linear regression analysis adjusted by covariates indicated associations of IRS2 rs1865434 with reduced low-density lipoprotein cholesterol and resistin, MC3R rs3746619 with high glycated hemoglobin, and IRS1 rs2943634 and MC4R rs17782313 with increased high-sensitivity C-reactive protein (P < .05). Energy intake and carbohydrate and total fat intakes were reduced after the diet-oriented program (P < .05). Multivariate linear regression analysis showed associations of IRS2 rs1865434 with high basal fiber intake, IRS1 rs2943634 with low postprogram carbohydrate intake, and MC4R rs17782313 with low postprogram total fat and saturated fatty acid intakes (P < .05). Although significant associations did not survive correction for multiple comparisons using the Benjamini-Hochberg method in this exploratory study, polymorphisms in IRS1, IRS2, MC3R, and MC4R influence metabolic and inflammatory status in Brazilian adults. IRS1 and MC4R variants may influence carbohydrate, total fat, and saturated fatty acid intakes in response to a diet-oriented program in subjects with obesity.
Subject(s)
Diabetes Mellitus, Type 2 , Adult , Humans , Pilot Projects , Diabetes Mellitus, Type 2/genetics , Polymorphism, Single Nucleotide , Brazil , Obesity/genetics , Obesity/metabolism , Eating , Carbohydrates , Fatty Acids , Receptor, Melanocortin, Type 4/genetics , Receptor, Melanocortin, Type 4/metabolism , Insulin Receptor Substrate Proteins/genetics , Insulin Receptor Substrate Proteins/metabolism , Receptor, Melanocortin, Type 3/genetics , Receptor, Melanocortin, Type 3/metabolismABSTRACT
This study explored circulating miRNAs and target genes associated with metabolic syndrome (MetS) and cardiometabolic risk in obese patients. Small-RNA sequencing was used to assess the peripheral blood miRNome of 12 obese subjects (6 MetS and 6 non-MetS). Differentially expressed miRNAs and target genes were further analyzed by qPCR in a larger sample of obese patients (48 MetS and 32 non-MetS). miRNA:mRNA interactions were studied using in silico tools. miRNome analysis identified 10 downregulated miRNAs in MetS compared to non-Met patients (p < 0.05). In silico studies revealed three miRNAs (miR-155, miR-181a, and let-7a) and their predictive targets (CCAAT/enhancer-binding protein beta-CEBPB, KRAS proto-oncogene, GTPase-KRAS and suppressor of cytokine signaling 1-SOCS1) with a potential role in the insulin receptor signaling pathway. miR-155 expression was reduced and CEBPB mRNA levels were increased in MetS patients (p < 0.05), and these effects were correlated with the number of MetS diagnostic criteria (p < 0.05). Increased HOMA-IR (>7.6) was associated with low miR-155 levels, high CEBPB expression, and serum hsCRP (p < 0.05). miR-155 was negatively correlated with CEBPB, HOMA-IR, and plasma fibrinogen, and positively correlated with serum adiponectin (p < 0.05). Downregulation of circulating miR-155 is associated with insulin resistance, poor glycemic control, and increased MetS-related cardiometabolic risk, and these effects are potentially mediated by interaction with CEBPB.
Subject(s)
Cardiovascular Diseases/blood , Metabolic Syndrome/blood , MicroRNAs/metabolism , Obesity/complications , Signal Transduction , Adiponectin/blood , Adult , Biomarkers/blood , CCAAT-Enhancer-Binding Protein-beta/blood , CCAAT-Enhancer-Binding Protein-beta/metabolism , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Computer Simulation , Female , Fibrinogen/analysis , Humans , Male , Metabolic Syndrome/epidemiology , Metabolic Syndrome/etiology , Metabolic Syndrome/metabolism , MicroRNAs/blood , Middle Aged , Obesity/metabolism , Proto-Oncogene Mas , Receptor, Insulin/metabolism , Risk Factors , Sequence Analysis, RNAABSTRACT
Introduction: The effects of ageing on bone can be mitigated with different types of physical training, such as power training. However, stimuli that combine increasing external and internal loads concomitantly may improve bone quality. The goal of this study was to assess the efficacy of a combined power and plyometric training on lumbar spine and distal tibia microstructure and function. Methods: 38 sedentary elderly women between 60 and 70 years were randomly allocated in experimental (N = 21) and control group (N = 17). The effects of the 20-week protocol on lumbar spine microstructure and tibia microstructure and function were assessed by trabecular bone score (TBS), high resolution peripheral quantitative computed tomography (HR-pQCT) and microfinite element analysis. Results: when compared to the effects found in the control group, the experimental group showed significant improvements in lumbar spine TBS (Hedges' g = 0.77); and in distal tibia trabecular thickness (g = 0.82) and trabecular bone mineral density (g=0.63). Conclusion: our findings underscore the effectiveness of the proposed intervention, suggesting it as a new strategy to slow down and even reverse the structural and functional losses in the skeletal system due to ageing.
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RATIONALE, AIMS AND OBJECTIVES: This study aimed to evaluate the effect of a pharmacist-physician collaborative care model on clinical outcomes in patients with uncontrolled type 2 diabetes and determine characteristics that influence this effect. METHODS: A randomized controlled trial was conducted in a secondary care clinic for 80 patients with type 2 diabetes, aged 40-79 years and glycosylated haemoglobin (A1C) level ≥ 7.0%. The intervention group received individual, face-to-face pharmaceutical consultations and remote telephone support after a routine visit. The main measures were clinical outcomes (A1C, blood pressure, LDL cholesterol) and process indicators (medication adherence, medication regimen complexity, use of medicines). Multiple regression models were used to determine the variables that could explain the reduction and individualized control of A1C. RESULTS: From the initial sample of 80 patients, 73 completed this study. Compared with usual care, patients in the intervention group showed greater reduction in A1C (-0.79 vs. -0.16; P = 0.010); and an increase in the percentage of patients achieving the individualized goal of A1C (25.0% vs. 5.4%; P = 0.020). In addition, there was an increase in the percentage of adherent patients and in the average scores of medication adherence. Participation in the intervention group, higher baseline A1C levels and greater change in medication adherence were all significant predictors of improvement in A1C levels. CONCLUSIONS: The results suggest that the collaborative care model proposed is feasible and more effective than the usual care in the reduction and individualized control of A1C levels in patients with uncontrolled type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2 , Intersectoral Collaboration , Patient Care Team/organization & administration , Pharmacists , Physicians , Adult , Aged , Brazil/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Female , Glycated Hemoglobin/analysis , Humans , Male , Medication Adherence , Middle Aged , Models, Organizational , Monitoring, Physiologic/methods , Monitoring, Physiologic/statistics & numerical dataABSTRACT
AIM: The influence of short-term add-on ezetimibe to simvastatin treatment on expression of adipokines and inflammatory markers was investigated in diabetic and nondiabetic patients with hypercholesterolemia. METHOD: Hypercholesterolemic nondiabetic (HC, n = 37) and diabetic (DM, n = 47) patients were treated with simvastatin (SV, 10 or 20 mg/d/8-wk) and then SV plus ezetimibe (SV + EZ, 10 mg each/d/4 wk). Serum lipids, glycemic profile, and inflammatory markers (hsCRP, adiponectin, resistin, VCAM-1, and ICAM-1) were evaluated before and after the add-on ezetimibe therapy. mRNA expression of ADIPOR1, ADIPOR2, RETN, VCAM1, and ICAM1 was measured by real-time PCR in peripheral blood mononuclear cells (PBMC). RESULTS: Serum concentrations of LDL and HDL cholesterol, and adiponectin were higher in HC than DM patients (P < .05). The add-on ezetimibe therapy reduced total and LDL cholesterol, apoB and adiponectin serum levels in HC and DM groups, and resistin in HC subjects (P < .05). DM patients showed higher expression of ADIPOR1, ADIPOR2, RETN, and VCAM1 in PBMC than subjects in HC group, before and after add-on ezetimibe therapy (P < .05). PBMC RETN mRNA expression was reduced by add-on ezetimibe therapy in HC individuals (P < .05), but not in DM subjects. CONCLUSION: Short-term add-on ezetimibe to simvastatin treatment suppressing effects on hypercholesterolemia and adiponectinemia is independent of the diabetes status. Resistin serum levels and leukocyte mRNA expression are influenced by add-on ezetimibe to statin treatment.
Subject(s)
Adipokines/biosynthesis , Anticholesteremic Agents/therapeutic use , Biomarkers/metabolism , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Dyslipidemias/drug therapy , Dyslipidemias/metabolism , Ezetimibe/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation/metabolism , Adult , Aged , Blood Glucose/metabolism , Cytokines/blood , Female , Humans , Lipids/blood , Male , Middle Aged , Monocytes/metabolism , RNA, Messenger/biosynthesis , Simvastatin/therapeutic useABSTRACT
Exercise has been overlooked as a potential therapy in chronic kidney disease (CKD), mainly because of a lack of understanding on its safety aspects. Notably, there are no data on renal function after exercise in CKD considering its stages. We investigated the acute effects of a 30-min moderate-intensity aerobic exercise bout on glomerular filtration rate (GFR) and albuminuria in 22 nondialysis CKD patients divided into: CKD stages 1 and 2 (CKD1-2) and CKD stages 3 and 4 (CKD3-4). Eleven body mass index-, age-, and sex-matched healthy individuals served as control (CON). Blood and urine samples were collected before, immediately after, and up to 90 min postexercise for creatinine and albumin assessments. GFR was determined by creatinine clearance (GFRCr-Cl). All CKD patients had significantly lower peak oxygen uptake than CON. CKD1-2 and CKD3-4 had increasingly higher serum creatinine than CON (9.6 ± 2.6, 25.6 ± 1.01, and 7.5 ± 1.4 mg/l, respectively); however, no within-group changes in serum or urinary creatinine were observed across time. GFRCr-Cl was decreased in CKD1-2 and CKD3-4 compared with CON (91 ± 17 ml·min-1·1.73 m-2; 34 ± 15 ml·min-1·1.73 m-2; 122 ± 20 ml·min-1·1.73 m-2, respectively). Most importantly, exercise did not affect GFRCr-Cl in none of the groups across time. Albuminuria was significantly higher in CKD3-4 (297 ± 284 µg/min) than in CON (5.4 ± 1.4 µg/min), but no within-group changes were observed after exercise. In conclusion, a single 30-min moderate-intensity aerobic exercise bout does not impair renal function in nondialysis CKD patients, regardless of disease stage, supporting the notion that exercise training can be safe in this disease.
Subject(s)
Kidney/physiopathology , Renal Insufficiency, Chronic/physiopathology , Adult , Exercise , Exercise Test , Female , Humans , Kidney Function Tests , Male , Middle AgedABSTRACT
Background The Screening Tool of Older Persons' Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) criteria is used to identify instances of potentially inappropriate prescribing in a patient's medication regimen. Objective To determine the prevalence and predictors of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) among elderly patients at hospital discharge. Setting A university hospital medical clinic in Brazil. Method Discharge prescriptions were examined using the STOPP/START criteria. Subjects were inpatients aged ≥60 years receiving at least one medication prior to hospitalization and with a history of cardiovascular disease. The prevalence of PIMs and PPOs was determined and a multivariable binary regression analysis was performed to identify independent predictors associated with PIMs or PPOs. Main outcome measure Prevalence of PIMs and PPOs. Results Of the 230 subjects, 13.9% were prescribed at least one PIM. The most frequently prescribed PIMs were glibenclamide or chlorpropamide prescribed for type 2 diabetes mellitus (31.0%), and aspirin at doses >150 mg/day (14.3%). Ninety patients had at least one PPO (39.1%). The most prevalent PPOs were statins (29.8%) and antiplatelet therapy (13.7%) for diabetes mellitus when coexisting major cardiovascular risk factors were present. No predictors for PIMs were found. In contrast, diabetes was a risk factor while dyslipidaemia was a protective factor for PPOs. Conclusion PIMs and PPOs commonly occur with elderly people at hospital discharge. Diabetes and dyslipidaemia were significantly associated with PPOs. Our findings show the need for interventions to reduce potentially inappropriate prescribing, such as a pharmacist medication review process at hospital discharge.
Subject(s)
Inappropriate Prescribing/statistics & numerical data , Potentially Inappropriate Medication List/statistics & numerical data , Aged , Aged, 80 and over , Brazil/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Patient Discharge , Prevalence , Risk FactorsABSTRACT
ABSTRACT Statins are the most prescribed lowering-cholesterol drugs. They are well tolerated, however, some patients present muscular adverse symptoms. Clinical and laboratory data from 120 dyslipidemic patients prescribed with statins were obtained from January to December/2013 at a University Hospital in Sao Paulo city, Brazil, to study factors associated with statin-related adverse muscular events (AME). Pharmacotherapy and statin-related AME data (serum CK elevation and any degree of myopathy, myalgia, myositis or rhabdomyolysis) of the dyslipidemic patients were recorded. The study was approved by local Ethics Committees. Simvastatin (70%) and atorvastatin (25%) were the most prescribed statins. AME related to statin treatment were found in 17% of the patients. Mean age and use of simvastatin were lower in AME group than non-AME group (p<0.05). Simvastatin users were less likely to develop AME than atorvastatin users (OR=0.21; 95%CI=0.07-0.57; p<0.01). The use of P-glycoprotein (ABCB1) efflux pump inhibitors was associated with high risk for AME (OR=5.26; 95%CI=1.55-17.79; p<0.01). Serum liver enzymes were increased up to three-fold in 2.5% of the statin-treated patients. The results are suggestive that the type of statin prescribed and the concomitant use of ABCB1 inhibitors increase the susceptibility to adverse muscular events during statin therapy in dyslipidemic outpatients
Subject(s)
Humans , Male , Female , Middle Aged , Outpatients/statistics & numerical data , Hydroxymethylglutaryl-CoA Reductase Inhibitors/analysis , Dyslipidemias/complications , Muscular Diseases , Data Interpretation, Statistical , Risk Factors , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effectsABSTRACT
AIM: The influence of short-term add-on ezetimibe to simvastatin treatment on expression of adipokines and inflammatory markers was investigated in diabetic and nondiabetic patients with hypercholesterolemia. METHOD: Hypercholesterolemic nondiabetic (HC, n = 37) and diabetic (DM, n = 47) patients were treated with simvastatin (SV, 10 or 20 mg/d/8-wk) and then SV plus ezetimibe (SV + EZ, 10 mg each/d/4 wk). Serum lipids, glycemic profile, and inflammatory markers (hsCRP, adiponectin, resistin, VCAM-1, and ICAM-1) were evaluated before and after the add-on ezetimibe therapy. mRNA expression of ADIPOR1, ADIPOR2, RETN, VCAM1, and ICAM1 was measured by real-time PCR in peripheral blood mononuclear cells (PBMC). RESULTS: Serum concentrations of LDL and HDL cholesterol, and adiponectin were higher in HC than DM patients (P < .05). The add-on ezetimibe therapy reduced total and LDL cholesterol, apoB and adiponectin serum levels in HC and DM groups, and resistin in HC subjects (P < .05). DM patients showed higher expression of ADIPOR1, ADIPOR2, RETN, and VCAM1 in PBMC than subjects in HC group, before and after add-on ezetimibe therapy (P < .05). PBMC RETN mRNA expression was reduced by add-on ezetimibe therapy in HC individuals (P < .05), but not in DM subjects...
Subject(s)
Adipokines , Diabetes Mellitus , Dyslipidemias , Ezetimibe , Hydroxymethylglutaryl-CoA Reductase InhibitorsABSTRACT
ABSTRACT Management of pharmacotherapy in elderly with metabolic diseases is challenging and potentially inappropriate medications (PIMs) are risk factors for drug interactions and adverse events. The exposure to PIMs in elderly outpatients with metabolic diseases and its relationship with polypharmacy and other variables was investigated. PIMs prescribed to 207 elderly patients (aged 60 to 96 years) with metabolic diseases who attended a University Hospital of Sao Paulo city, Brazil, from April/2010 to January/2011, were evaluated. PIMs were detected using both 2003 Beers and 2008 STOPP criteria. The association between PIMs and age, gender and polypharmacy was also examined. 2008 STOPP criteria detected more PIMs (44.4 %) than 2003 Beers criteria (16.0%, p<0.001). Beers detected mainly PIMs antihypertensive (clonidine, 20.0%; doxazosin, 10.0%) and antidepressant (fluoxetine, 15.0%; amitriptyline, 10.0%) PIMs. Medicines used for cardiovascular (aspirin, 53.7%) and endocrine system (glibenclamide, 21.3%) were PIMs more frequently detected by 2008 STOPP. Unlike age and gender, polypharmacy increased the risk of PIMs by both 2003 Beers (OR: 4.0, CI95%: 1.2-13.8, p<0.031) and 2008 STOPP (OR: 6.8, CI95%: 3.0-15.3, p<0.001). Beers and STOPP criteria are important tools to evaluate the exposure to PIMs, which is strongly associated with polypharmacy in elderly outpatients with metabolic diseases.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Aged , Risk Factors , Ambulatory Care Facilities , Metabolic Diseases/drug therapy , Polypharmacy , Drug Therapy/instrumentation , Potentially Inappropriate Medication List/ethicsABSTRACT
BACKGROUND: Polymorphisms in genes encoding adiponectin (ADIPOQ) and interleukin-6 (IL6) have been associated with adiposity and obese-related phenotypes. This study investigated the relationship of ADIPOQ and IL6 gene polymorphisms with pro-inflammatory and cardiometabolic markers in obese patients. METHODS: Anthropometric and body composition parameters were measured in 249 Brazilian subjects (30 to 68 yr). Metabolic and inflammatory markers and adipokines were analyzed in blood samples. ADIPOQ rs2241766 (45 T > G) and IL6 rs1800795 (-174G > C) polymorphisms were analyzed by real-time PCR and PCR-RFLP, respectively. RESULTS: Type 2 diabetes, hypertension, dyslipidemia and increased values of waist circumference, body fat, leptin, fibrinogen, IL-1ß, hsCRP and TNFα were related to obesity (p < 0.05). Multiple linear regression analysis showed a positive correlation between BMI and waist circumference, body fat, leptin, fibrinogen, PAI-1, IL-1ß, hsCRP and TNFα values (p < 0.001) but not with adiponectin. Obese group had altered metabolic status, resistance to leptin and insulin, and atherogenic and pro-inflammatory profiles. ADIPOQ and IL6 variants were not directely related to obesity, leptin resistance or alterations in cardiometabolic markers. Individuals carrying ADIPOQ 45G allele (TG + GG genotype) had higher IL-6, IL-1ß and TNFα levels than TT genotype carriers (p < 0.05). IL6 -174GG genotype was associated with increased IL-1ß levels (p = 0.033). CONCLUSION: Obesity is associated with leptin resistance, cardiometabolic alterations and a pro-inflammatory status. Our results are suggestive that ADIPOQ and IL6 polymorphisms contribute to cardiometabolic risk in obese individuals.
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INTRODUCTION: Cholesterol-lowering therapy has been related with several pleiotropic effects including anti-inflammatory action in vascular endothelium; however, their influence on monocyte adhesion molecules is poorly described. AIMS: To investigate the effect of inhibitors of synthesis (statins) and absorption (ezetimibe) of cholesterol on expression of adhesion molecules L-selectin, PSGL-1, VLA-4, LFA-1, and Mac-1 in mononuclear cells in vivo and in vitro using THP-1 cells. METHODS: The influence of simvastatin (10 mg/day), ezetimibe (10 mg/day), and their combination (10 mg each/day) on mRNA expression of adhesion molecules was analyzed in peripheral blood mononuclear cells (PBMC) from hypercholesterolemics. The effects of atorvastatin, simvastatin, and ezetimibe on mRNA and protein expression of adhesion molecules were also evaluated in THP-1 cells. RESULTS: Simvastatin/ezetimibe combination, but not the monotherapies, reduced the mRNA expression of the PSGL-1, LFA-1, and Mac-1 genes in PBMC from hypercholesterolemics. Total and LDL cholesterol in serum correlated with PSGL-1 mRNA expression, whereas HDL cholesterol negatively correlated with mRNA levels of L-selectin and VLA-4 genes (P < 0.05). Plasma hsCRP was also correlated with mRNA levels of VLA-4, LFA-1, and Mac-1 (P < 0.05). Atorvastatin and simvastatin at 10 µM reduced mRNA and protein expression of L-selectin, PSGL-1, and VLA-4 in THP-1 cells (P < 0.05). CONCLUSION: Cholesterol-lowering therapy modulates gene expression of adhesion molecules in PBMC from hypercholesterolemics and THP-1 cells. Simvastatin/ezetimibe combination gives more benefits by reducing to a larger extent the expression of adhesion molecules in mononuclear cells.
Subject(s)
Cell Adhesion Molecules/metabolism , Ezetimibe, Simvastatin Drug Combination/therapeutic use , Ezetimibe/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/drug therapy , Leukocytes, Mononuclear/drug effects , Simvastatin/therapeutic use , Aged , Atorvastatin/pharmacology , Biomarkers/blood , Cell Adhesion Molecules/genetics , Cell Line , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Dose-Response Relationship, Drug , Female , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/diagnosis , Hypercholesterolemia/genetics , Leukocytes, Mononuclear/metabolism , Male , Middle Aged , RNA, Messenger/metabolism , Treatment OutcomeABSTRACT
Background: Polymorphisms in genes encoding adiponectin (ADIPOQ) and interleukin-6 (IL6) have been associated with adiposity and obese-related phenotypes. This study investigated the relationship of ADIPOQ and IL6 gene polymorphisms with pro-inflammatory and cardiometabolic markers in obese patients. Methods: Anthropometric and body composition parameters were measured in 249 Brazilian subjects (30 to 68 yr). Metabolic and inflammatory markers and adipokines were analyzed in blood samples. ADIPOQ rs2241766 (45 T > G)and IL6 rs1800795 (−174G > C) polymorphisms were analyzed by real-time PCR and PCR-RFLP, respectively. Results: Type 2 diabetes, hypertension, dyslipidemia and increased values of waist circumference, body fat, leptin, fibrinogen, IL-1β, hsCRP and TNFα were related to obesity (p < 0.05). Multiple linear regression analysis showed apositive correlation between BMI and waist circumference, body fat, leptin, fibrinogen, PAI-1, IL-1β, hsCRP and TNFαvalues (p < 0.001) but not with adiponectin. Obese group had altered metabolic status, resistance to leptin andinsulin, and atherogenic and pro-inflammatory profiles. ADIPOQ and IL6 variants were not directely related toobesity, leptin resistance or alterations in cardiometabolic markers. Individuals carrying ADIPOQ 45G allele (TG + GGgenotype) had higher IL-6, IL-1β and TNFα levels than TT genotype carriers (p < 0.05). IL6 -174GG genotype wasassociated with increased IL-1β levels (p = 0.033).Conclusion: Obesity is associated with leptin resistance, cardiometabolic alterations and a pro-inflammatory status.Our results are suggestive that ADIPOQ and IL6 polymorphisms contribute to cardiometabolic risk in obese individuals.
Subject(s)
Adiponectin , Inflammation , Obesity , Polymorphism, GeneticABSTRACT
BACKGROUND: Regular exercise is an effective intervention to decrease blood pressure (BP) in hypertension, but no data are available concerning the effects of heated water-based exercise (HEx). This study examines the effects of HEx on BP in resistant hypertensive patients. METHODS: This is a parallel, randomized controlled trial. 125 nonconsecutive sedentary patients with resistant hypertension from a hypertension outpatient clinic in a university hospital were screened; 32 patients fulfilled the study requirements. The training was performed for 60-minute sessions in a heated pool (32°C), three times a week for 12 weeks. The HEx protocol consisted of callisthenic exercises and walking inside the pool. The control group was asked to maintain habitual activities. The main outcome measure was change in mean 24-hour ambulatory BP (ABPM). RESULTS: 32 patients (HEx n=16; control n=16) were randomized; none were lost to follow-up. Office BPs decreased significantly after heated water exercise (36/12 mmHg). HEx decreased 24-hour systolic (from 137±23 to 120±12 mmHg, p=0.001) and diastolic BPs (from 81±13 to 72±10 mmHg, p=0.009); daytime systolic (from 141±24 to 120±13 mmHg, p<0.0001) and diastolic BPs (from 84±14 to 73±11 mmHg, p=0.003); and nighttime systolic (from 129±22 to 114±12 mmHg, p=0.006) and diastolic BPs (from 74±11 to 66±10 mmHg, p<0.0001). The control group after 12 weeks significantly increased in 24-hour systolic and diastolic BPs, and daytime and nighttime diastolic BPs. CONCLUSION: HEx reduced office BPs and 24-hour ABPM levels in resistant hypertensive patients. These effects suggest that HEx may be a potential new therapeutic approach in these patients.
Subject(s)
Exercise Therapy/methods , Hot Temperature/therapeutic use , Hypertension/therapy , Water , Adult , Aged , Blood Pressure/physiology , Blood Pressure Monitoring, Ambulatory , Female , Humans , Hypertension/physiopathology , Male , Middle Aged , Treatment OutcomeABSTRACT
OBJECTIVE: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. SUBJECTS AND METHODS: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. RESULTS: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). CONCLUSIONS: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.
OBJETIVO: O estudo teve por objetivo investigar a influência de polimorfismos nos genes da leptina (LEP) e do receptor de leptina (LEPR) na adiposidade e em marcadores metabólicos, como leptina, glicose e lipídeos, em uma amostra de nossa população. SUJEITOS E MÉTODOS: Um grupo de 326 indivíduos com idade de 30 a 80 anos, 87 homens e 239 mulheres, 148 obesos e 178 não obesos, e de etnia branca foi selecionado aleatoriamente em dois hospitais clínicos da cidade de São Paulo, Brasil. Medidas antropométricas, índice de massa corporal (IMC) e gordura corporal foram avaliados. Amostras de sangue foram obtidas para extração de DNA e determinações de leptina, receptor de leptina solúvel, glicose e lipídeos. Os polimorfismos LEP -2548G>A e LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) e Lys656Asn (c.1968G>C) foram detectados por PCR-RFLP. RESULTADOS: Leptina e lipídeos séricos aumentados e LEPR Arg223Arg (genótipo GG) foram associados com maior risco de obesidade (p < 0,05), enquanto foi encontrado risco reduzido de obesidade, em portadores de LEPR Arg109Arg (genótipo GG) (OR: 0,38, 95%CI: 0,19-0,77, p = 0,007). A análise de regressão linear múltipla mostrou relação entre o alelo LEPR 223Arg e circunferência abdominal e leptinemia aumentadas (p < 0,05), enquanto o alelo LEPR 109Arg foi associado com aumento de colesterol total e triglicerídeos (p < 0,05). Os portadores do haplotipo 3 do LEPR (AGG: 109Lys/233Arg/656Lys) tiveram maior risco aumentado para obesidade (OR: 2.56, 95% CI: 1.19-5.49, p = 0,017). Além disso, esse haplótipo foi associado com IMC, circunferência abdominal e leptinemia aumentados (p < 0,05). CONCLUSÕES: Polimorfismos de LEPR são associados com obesidade, hiperleptinemia e perfil lipídico aterogênico sugerindo seu papel potencial para a resistência à leptina e risco cardiovascular.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adiposity/genetics , Leptin/genetics , Obesity/genetics , Polymorphism, Restriction Fragment Length/genetics , Receptors, Leptin/genetics , Analysis of Variance , Brazil , Biomarkers/blood , Blood Glucose/metabolism , Chi-Square Distribution , Gene Frequency , Glucose/metabolism , Leptin/blood , Obesity/blood , Polymerase Chain Reaction , Risk Factors , Receptors, Leptin/blood , Waist Circumference/geneticsABSTRACT
OBJECTIVE: The aim of the study was to investigate whether adiposity and metabolic markers, such as leptin, glucose, and lipids, are influenced by leptin (LEP) and leptin receptor (LEPR) gene polymorphisms in a sample of our population. SUBJECTS AND METHODS: A group of 326 individuals of Caucasian-European descent, aged 30 to 80 years, 87 men and 239 women, 148 obese and 178 non-obese, was randomly selected at two clinical hospitals in the city of Sao Paulo, Brazil. All individuals declared their ethnic group as white during the initial interview. Anthropometric measurements, body mass index (BMI), and fat mass were evaluated. Blood samples were drawn for DNA extraction and measurements of leptin, soluble leptin receptor, glucose, and lipids. LEP -2548G>A and LEPR Lys109Arg (c.326A>G), Gln233Arg (c.668A>G) and Lys656Asn (c.1968G>C) polymorphisms were detected by PCR-RFLP. RESULTS: Increased leptin and serum lipids, and LEPR Arg223Arg (GG genotype) were associated with higher risk for obesity (p < 0.05), while reduced risk was found in LEPR Arg109Arg (GG genotype) carriers (OR: 0.38, 95%CI: 0.19-0.77, p = 0.007). Multiple linear regression analysis showed a relationship between LEPR 223Arg, increased waist circumference, and leptinemia (p < 0.05), while LEPR 109Arg was associated with high total cholesterol and triglycerides (p < 0.05). LEPR haplotype 3 (AGG: 109Lys/233Arg/656Lys) carriers have increased risk for obesity (OR: 2.56, 95% CI: 1.19-5.49, p = 0.017). Moreover, this haplotype was associated with increased BMI, waist circumference, and leptinemia (p < 0.05). CONCLUSIONS: LEPR polymorphisms are associated with obesity, hyperleptinemia, and atherogenic lipid profile, suggesting their potential role for leptin resistance and cardiovascular risk. Moreover, LEPR haplotype 3 confers susceptibility to adiposity and hyperleptinemia in our population.
Subject(s)
Adiposity/genetics , Leptin/genetics , Obesity/genetics , Polymorphism, Restriction Fragment Length/genetics , Receptors, Leptin/genetics , Adult , Aged , Aged, 80 and over , Analysis of Variance , Biomarkers/blood , Blood Glucose/metabolism , Brazil , Chi-Square Distribution , Female , Gene Frequency , Glucose/metabolism , Humans , Leptin/blood , Male , Middle Aged , Obesity/blood , Polymerase Chain Reaction , Receptors, Leptin/blood , Risk Factors , Waist Circumference/geneticsABSTRACT
BACKGROUND: Highly active antiretroviral therapy for AIDS is known to increase cardiovascular risk, but the effects of potent antiretroviral agents according to gender are unknown. OBJECTIVE: The present study evaluated the impact of HIV infection treatment on aortic stiffness according to gender. METHODS: From university-affiliated hospitals, we recruited 28 AIDS patients undergoing highly active antiretroviral treatment (HAART), 28 treatment-naïve HIV-infected patients, 44 patients with type 2 diabetes, and 30 controls. Aortic stiffness was determined by measuring pulse wave velocity (PWV) using a validated and non-invasive automatic device. RESULTS: The crude mean PWV values and 95% confidence intervals (95% CI) for HAART, diabetics, and controls were 9.77 m/s (95% CI 9.17-10.36), , 9.00 m/s (95% CI 8.37-9.63), 9.90 m/s (95% CI 9.32-10.49), and 9.28 m/s (95% CI 8.61-9.95), respectively, for men (P-value for trend = 0.14), and 9.61 m/s (95% CI 8.56-10.66), 8.45 m/s (95% CI 7.51-9.39), 9.83 (95% CI 9.21-10.44), and 7.79 m/s (95% CI 6.99-8.58), respectively, for women (P-value for trend <0.001). Post-hoc analysis revealed a significant difference between the mean PWV values in the HAART group and controls in women (P-value <0.01). After adjusting for other potential covariates, including systolic blood pressure and diabetes, these results did not change. The findings indicate that the impact of HAART treatment on aortic stiffness was amplified in women with hypertension, dyslipidemia, and metabolic syndrome. CONCLUSION: Potent anti-retroviral agents used in the treatment of HIV infection increases aortic stiffness, mainly among women with higher cardiovascular risk.
Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , HIV Infections/drug therapy , Vascular Stiffness/drug effects , Adult , Age Factors , Cardiovascular Diseases/etiology , Chi-Square Distribution , Cross-Sectional Studies , Female , HIV Infections/complications , Humans , Male , Middle Aged , Organ Size/drug effects , Pulse Wave Analysis , Risk Factors , Sex FactorsABSTRACT
FUNDAMENTO: Sabe-se que a terapia antirretroviral altamente potente para Aids reconhecida aumenta o risco cardiovascular, mas os efeitos dos agentes antirretrovirais de acordo com o gênero ainda são desconhecidos. OBJETIVO: O presente estudo avaliou o impacto do tratamento para o vírus da imunodeficiência humana (HIV) na rigidez aórtica de acordo com o gênero. MÉTODOS: Foram recrutados 28 pacientes com Aids submetidos à terapia antirretroviral altamente potente (HAART), 28 pacientes infectados pelo HIV virgens de tratamento, 44 pacientes com diabetes tipo 2, e 30 controles. A rigidez aórtica foi determinada pela medição da Velocidade da Onda de Pulso (VOP), utilizando um equipamento automático validado e não invasivo. RESULTADOS: Os resultados médios brutos da VOP (e intervalo de confiança de 95%) para participantes nos grupos terapia antirretroviral potente, HIV virgem de tratamento, diabéticos, e controles foram 9,77 m/s (9,17-10,36), 9,00 m/s (8,37-9,63), 9,90 m/s (9,32-10,49) e 9,28 m/s (8,61-9,95), respectivamente, para os homens (p de tendência = 0,14) e 9,61 m/s (8,56-10,66), 8,45 m/s (7,51-9,39), 9,83 (9,21-10,44) e 7,79 m/s (6,99-8,58), respectivamente, para as mulheres (p valor de tendência < 0,001). Análises post-hoc revelaram uma diferença significativa entre os valores médios de VOP no grupo com HAART e controles em mulheres (p < 0,01). Ajustes para as demais covariáveis potenciais, incluindo pressão arterial sistólica e diabetes, não alteraram esses resultados. Os achados indicam que o impacto do tratamento com HAART na rigidez aórtica foi amplificado nas mulheres com hipertensão, dislipidemia e síndrome metabólica. CONCLUSÃO: Agentes antirretrovirais potentes utilizados no tratamento da infecção pelo HIV aumentam a rigidez da aorta, especialmente em mulheres com maior risco cardiovascular.
BACKGROUND: Highly active antiretroviral therapy for AIDS is known to increase cardiovascular risk, but the effects of potent antiretroviral agents according to gender are unknown. OBJECTIVE: The present study evaluated the impact of HIV infection treatment on aortic stiffness according to gender. METHODS: From university-affiliated hospitals, we recruited 28 AIDS patients undergoing highly active antiretroviral treatment (HAART), 28 treatment-naïve HIV-infected patients, 44 patients with type 2 diabetes, and 30 controls. Aortic stiffness was determined by measuring pulse wave velocity (PWV) using a validated and non-invasive automatic device. RESULTS: The crude mean PWV values and 95% confidence intervals (95% CI) for HAART, diabetics, and controls were 9.77 m/s (95% CI 9.17-10.36), , 9.00 m/s (95% CI 8.37-9.63), 9.90 m/s (95% CI 9.32-10.49), and 9.28 m/s (95% CI 8.61-9.95), respectively, for men (P-value for trend = 0.14), and 9.61 m/s (95% CI 8.56-10.66), 8.45 m/s (95% CI 7.51-9.39), 9.83 (95% CI 9.21-10.44), and 7.79 m/s (95% CI 6.99-8.58), respectively, for women (P-value for trend <0.001). Post-hoc analysis revealed a significant difference between the mean PWV values in the HAART group and controls in women (P-value <0.01). After adjusting for other potential covariates, including systolic blood pressure and diabetes, these results did not change. The findings indicate that the impact of HAART treatment on aortic stiffness was amplified in women with hypertension, dyslipidemia, and metabolic syndrome. CONCLUSION: Potent anti-retroviral agents used in the treatment of HIV infection increases aortic stiffness, mainly among women with higher cardiovascular risk.