Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.463
Filtrar
1.
Lancet ; 393(10186): 2155-2167, 2019 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-31226053

RESUMO

Aspirin is one of the most frequently used drugs worldwide and is generally considered effective for the secondary prevention of cardiovascular disease. By contrast, the role of aspirin in primary prevention of cardiovascular disease is controversial. Early trials evaluating aspirin for primary prevention, done before the turn of the millennium, suggested reductions in myocardial infarction and stroke (although not mortality), and an increased risk of bleeding. In an effort to balance the risks and benefits of aspirin, international guidelines on primary prevention of cardiovascular disease have typically recommended aspirin only when a substantial 10-year risk of cardiovascular events exists. However, in 2018, three large randomised clinical trials of aspirin for the primary prevention of cardiovascular disease showed little or no benefit and have even suggested net harm. In this narrative Review, we reappraise the role of aspirin in primary prevention of cardiovascular disease, contextualising data from historical and contemporary trials.


Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Inibidores de Ciclo-Oxigenase/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/farmacologia , Ensaios Clínicos como Assunto , Inibidores de Ciclo-Oxigenase/farmacologia , Angiopatias Diabéticas/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/farmacologia , Prevenção Primária , Fatores Sexuais
2.
Biomed Pharmacother ; 112: 108722, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30970521

RESUMO

Microvascular and macrovascular complications are major causes of disability and death in diabetic patients. High levels of blood glucose sabotage the integrity of blood vessels and induce endothelial dysfunction. Fenofibrate is an agonist of peroxisome proliferator-activated receptor α and can reduce the incidence of cardiovascular events in diabetic patients. This study tested the hypothesis that fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice and relieve high glucose-induced endothelial dysfunction via activating endothelial nitric oxide synthase (eNOS) and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. A streptozotocin (STZ)-induced diabetic model was established by intraperitoneal injection of STZ (dissolved in sodium citrate buffer) at a dose of 60 mg/kg for 5 consecutive days. Mice were administered fenofibrate (100 mg/kg/d, i.g.) for 14 days. The endothelial function of extracted mouse aortae was examined by evaluating acetylcholine induced endothelium-dependent relaxation combined with phenylephrine-induced vasoconstriction and sodium nitroprusside-induced endothelium-independent relaxation. Superoxide onion (O2-) was determined using dihydroethidium staining of aortae. Functions of mouse aortic endothelial cells (MAECs) were assessed, and expression levels of eNOS and AMPK were determined by Western blotting. Fenofibrate ameliorated the impaired endothelium-dependent relaxation in diabetic mice and decreased the level of intracellular O2- in diabetic mouse aortae. In-vitro, fenofibrate treatment improved the impaired function of MAECs, increased nitric oxide production, and decreased the O2- level, as well as activated eNOS and AMPK phosphorylation in cultured MAECs by high glucose. Fenofibrate could ameliorate endothelium-dependent vasodilation in diabetic mice and relieve high glucose-induced endothelial dysfunction, which was possibly related to the activation of eNOS and AMPK phosphorylation.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , Fenofibrato/uso terapêutico , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Endotélio Vascular/fisiopatologia , Fenofibrato/farmacologia , Glucose/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , PPAR alfa/agonistas , Estreptozocina
3.
Wien Klin Wochenschr ; 131(Suppl 1): 139-140, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-30980156

RESUMO

Acute thrombotic complications as a key feature of accelerated atherothrombotic disease typically precipitate cardiovascular events and therefore strongly contribute to cardiovascular morbidity and mortality in diabetic patients. Inhibition of platelet aggregation can reduce the risk for acute atherothrombosis. The present article represents the recommendations of the Austrian Diabetes Association for the use of antiplatelet drugs in diabetic patients according to current scientific evidence.


Assuntos
Angiopatias Diabéticas/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Trombose , Áustria , Plaquetas , Angiopatias Diabéticas/prevenção & controle , Humanos , Agregação Plaquetária , Guias de Prática Clínica como Assunto , Trombose/tratamento farmacológico , Trombose/prevenção & controle
4.
Food Chem Toxicol ; 129: 97-107, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31022479

RESUMO

Vascular diabetic complications are the leading cause of mortality and morbidity for diabetes. The present study was designed to investigate the protective effect of herb pair Salvia miltiorrhiza Bunge-Radix Puerariae (DG) on diabetic vascular injury induced by streptozotocin. The protective effect of DG was determined by oral administration of DG (50 and 200 mg/kg) in rats and on high glucose (HG)-induced endothelial injury. DG showed no effect on body weight, fasting blood glucose (FBG) but decreased the serum levels of insulin, nitric oxide (NO), hydrogen peroxide (H2O2), malondialdehyde (MDA), soluble intercellular cell adhesion molecule-1 (s-ICAM-1) and vascular cell adhesion molecule-1 (s-VCAM-1), and increased superoxide dismutase (SOD) and catalase (CAT) levels. The pathological alterations of aorta was improved by DG. Furthermore, the increased expression of ICAM-1,VCAM-1, NOX2, and NOX4 in aorta were inhibited by DG. HG-induced endothelial ROS formation, ICAM-1,VCAM-1, NOX4 expression and monocyte-endothelial adhesion were dramatically suppressed by DG as well. In addition, both GKT137831, a NOX4 inhibitor, and PDTC, a NF-κB inhibitor, could significantly inhibited HG-induced ICAM-1, VCAM-1 expression and monocyte-endothelial adhesion. These results suggested that DG improved diabetic vascular injury possibly by reducing oxidative stress, which provides scientific evidence for the application of DG for diabetic vascular therapy.


Assuntos
Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Angiopatias Diabéticas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pueraria/química , Salvia miltiorrhiza/química , Animais , Angiopatias Diabéticas/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , NADPH Oxidase 4/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Estreptozocina , Molécula 1 de Adesão de Célula Vascular/metabolismo , Água/química
5.
Cardiovasc Diabetol ; 18(1): 26, 2019 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-30851727

RESUMO

AIMS: The prevalence of asymptomatic coronary artery disease (CAD) in type 2 diabetes (T2D) is unclear. We investigated the extent and prevalence of asymptomatic CAD in T2D patients by utilizing invasive coronary angiography (ICA) and intravascular ultrasound (IVUS), and whether CAD progression, evaluated by ICA, could be modulated with a multi-intervention to reduce cardiovascular (CV) risk. METHODS: Fifty-six T2D patients with ≥ 1 additional CV risk factor participated in a 2 year randomized controlled study comparing hospital-based multi-intervention (multi, n = 30) versus standard care (stand, n = 26), with a pre-planned follow-up at year seven. They underwent ICA at baseline and both ICA and IVUS at year seven. ICA was described by conventional CAD severity and extent scores. IVUS was described by maximal intimal thickness (MIT), percent and total atheroma volume and compared with individuals without T2D and CAD (heart transplant donors who had IVUS performed 7-11 weeks post-transplant, n = 147). RESULTS: Despite CV risk reduction in multi after 2 years intervention, there was no between-group difference in the progression of CAD at year seven. Overall, the prevalence of CAD defined by MIT ≥ 0.5 mm in the T2DM subjects was 84%, and as compared to the non-T2DM controls there was a significantly higher atheroma burden (mean MIT, PAV and TAV in the T2D population were 0.75 ± 0.27 mm, 33.8 ± 9.8% and 277.0 ± 137.3 mm3 as compared to 0.41 ± 0.19 mm, 17.8 ± 7.3% and 134.9 ± 100.6 mm3 in the reference population). CONCLUSION: We demonstrated that a 2 year multi-intervention, despite improvement in CV risk factors, did not influence angiographic progression of CAD. Further, IVUS revealed that the prevalence of asymptomatic CAD in T2D patients is high, suggesting a need for a broader residual CV risk management using alternative approaches. Trial registration Clinical trials.gov id: NCT00133718 ( https://clinicaltrials.gov/ct2/show/NCT00133718 ).


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/prevenção & controle , Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/prevenção & controle , Ultrassonografia de Intervenção , Idoso , Doenças Assintomáticas , Terapia Combinada , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
Saudi Med J ; 40(3): 271-276, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30834423

RESUMO

OBJECTIVES: To determine the association between emergency department (ED) visits, glycemic control and the quality of preventive diabetes care among diabetic patients in a Saudi community. Methods: This study was an observational, cross-sectional study that collected data through interview-based surveys between February and April 2017. Data were collected from 530 diabetic patients in the diabetes clinics at King Saud Medical City, the tertiary center of Riyadh, Kingdom of Saudi Arabia.  Results: This study found statistically significant relationships (p less than 0.05) between ED visits and patient age, the glycated hemoglobin (HbA1c) and education level. Emergency department visits increased by 43% for each unit of increase in HbA1c (odds ratio [OR]=1.43, 95% confidence interval (CI)=1.26-1.62). Graduating from high school decreased the odds of visiting the ED by 43% (OR=0.57, 95% CI=0.34-0.94). Most of the participants were not followed for possible microvascular complications; the majority did not visit nephrology (96.2%), ophthalmology (78.3%) and neurology (97.9%) clinics within the 12 months prior to the interviews. Conclusion: Emergency department visits can indicate poor glycemic control in diabetic patients. Additionally, the current practices of preventive diabetes care in Saudi Arabia are not sufficient, according to the diabetic standards of care recommended by the American Diabetes Association.


Assuntos
Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hemoglobina A Glicada/metabolismo , Qualidade da Assistência à Saúde , Adulto , Fatores Etários , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/prevenção & controle , Escolaridade , Feminino , Humanos , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Cooperação do Paciente , Arábia Saudita , Inquéritos e Questionários
7.
Cardiovasc Diabetol ; 18(1): 16, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30732594

RESUMO

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is the first class of anti-diabetes treatment that reduces mortality and risk for hospitalization due to heart failure. In clinical studies it has been shown that SGLT2i's promote a general shift to fasting state metabolism characterized by reduced body weight and blood glucose, increase in glucagon/insulin ratio and modest increase in blood ketone levels. Therefore, we investigated the connection between metabolic changes and cardiovascular function in the ob/ob-/- mice; a rodent model of early diabetes with specific focus on coronary microvascular function. Due to leptin deficiency these mice develop metabolic syndrome/diabetes and hepatic steatosis. They also develop cardiac contractile and microvascular dysfunction and are thus a promising model for translational studies of cardiometabolic diseases. We investigated whether this mouse model responded in a human-like manner to empagliflozin treatment in terms of metabolic parameters and tested the hypothesis that it could exert direct effects on coronary microvascular function and contractile performance. METHODS: Lean, ob/ob-/- untreated and ob/ob-/- treated with SGLT2i were followed for 10 weeks. Coronary flow velocity reserve (CFVR) and fractional area change (FAC) were monitored with non-invasive Doppler ultrasound imaging. Food intake, urinary glucose excursion and glucose control via HbA1c measurements were followed throughout the study. Liver steatosis was assessed by histology and metabolic parameters determined at the end of the study. RESULTS: Sodium-glucose cotransporter 2 inhibitors treatment of ob/ob-/- animals resulted in a switch to a more catabolic state as observed in clinical studies: blood cholesterol and HbA1c were decreased whereas glucagon/insulin ratio and ketone levels were increased. SGLT2i treatment reduced liver triglyceride, steatosis and alanine aminotransferase, an indicator for liver dysfunction. L-Arginine/ADMA ratio, a marker for endothelial function was increased. SGLT2i treatment improved both cardiac contractile function and coronary microvascular function as indicated by improvement of FAC and CFVR, respectively. CONCLUSIONS: Sodium-glucose cotransporter 2 inhibitors treatment of ob/ob-/- mice mimics major clinical findings regarding metabolism and cardiovascular improvements and is thus a useful translational model. We demonstrate that SGLT2 inhibition improves coronary microvascular function and contractile performance, two measures with strong predictive values in humans for CV outcome, alongside with the known metabolic changes in a preclinical model for prediabetes and heart failure.


Assuntos
Compostos Benzidrílicos/farmacologia , Doença da Artéria Coronariana/prevenção & controle , Circulação Coronária/efeitos dos fármacos , Angiopatias Diabéticas/prevenção & controle , Cardiomiopatias Diabéticas/prevenção & controle , Glucosídeos/farmacologia , Microcirculação/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Obesidade/complicações , Estado Pré-Diabético/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Biomarcadores/sangue , Biomarcadores/urina , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Estado Pré-Diabético/complicações , Estado Pré-Diabético/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo
8.
Vasc Health Risk Manag ; 14: 225-232, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271161

RESUMO

Background: The aim was to evaluate the significance of arteriosclerosis obliterans-related biomarkers in patients with type 2 diabetes mellitus (T2DM), and to compare the effects of sarpogrelate, eicosapentaenoic acid (EPA) and pitavastatin on these markers. Patients and methods: Seventy-two arteriosclerosis obliterans patients with T2DM were classified into two groups, pitavastatin with either sarpogrelate (PS) or EPA (PE). We observed no differences in all biomarkers between the PS and PE groups before treatments. Results: The levels of body mass index, hemoglobin A1c, soluble E-selectin, soluble vascular cell adhesion molecule 1, plasminogen activator inhibitor-1 and platelet-derived microparticle in the PE group decreased significantly after treatment. The ankle branchial pressure index and adiponectin levels significantly increased in the PE group after treatment compared with the PS group. Conclusion: These results suggest that combination therapy using pitavastatin and EPA possesses an antiatherosclerotic effect and may be beneficial for prevention of vascular complications in patients with T2DM.


Assuntos
Arteriosclerose Obliterante/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Ácido Eicosapentaenoico/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Quinolinas/uso terapêutico , Succinatos/uso terapêutico , Adiponectina/sangue , Idoso , Idoso de 80 Anos ou mais , Índice Tornozelo-Braço , Arteriosclerose Obliterante/sangue , Arteriosclerose Obliterante/diagnóstico , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/diagnóstico , Quimioterapia Combinada , Ácido Eicosapentaenoico/efeitos adversos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Japão , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Inibidores da Agregação de Plaquetas/efeitos adversos , Quinolinas/efeitos adversos , Fatores de Risco , Succinatos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
9.
Diabetes ; 67(9): 1729-1741, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30135134

RESUMO

Microvascular and metabolic physiology are tightly linked. This Perspective reviews evidence that 1) the relationship between hyperglycemia and microvascular dysfunction (MVD) is bidirectional and constitutes a vicious cycle; 2) MVD in diabetes affects many, if not all, organs, which may play a role in diabetes-associated comorbidities such as depression and cognitive impairment; and 3) MVD precedes, and contributes to, hyperglycemia in type 2 diabetes (T2D) through impairment of insulin-mediated glucose disposal and, possibly, insulin secretion. Obesity and adverse early-life exposures are important drivers of MVD. MVD can be improved through weight loss (in obesity) and through exercise. Pharmacological interventions to improve MVD are an active area of investigation.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/fisiopatologia , Hiperglicemia/fisiopatologia , Microvasos/fisiopatologia , Estado Pré-Diabético/complicações , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/metabolismo , Animais , Terapia Combinada , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/complicações , Angiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/prevenção & controle , Retinopatia Diabética/complicações , Retinopatia Diabética/etiologia , Retinopatia Diabética/prevenção & controle , Estilo de Vida Saudável , Humanos , Hiperglicemia/complicações , Hiperglicemia/prevenção & controle , Resistência à Insulina , Obesidade/complicações , Obesidade/metabolismo , Obesidade/fisiopatologia , Obesidade/terapia , Estado Pré-Diabético/sangue , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/terapia
10.
Life Sci ; 209: 111-121, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30081006

RESUMO

AIMS: Astragaloside IV (As-IV) is the major active ingredient of Astragalus membranaceus and has diverse pharmacological activities, including anti-inflammatory and antioxidant effects. However, the beneficial effect of As-IV on protecting vascular endothelial dysfunction is not completely understood. The aim of this study was to investigate the protective effect and mechanism of As-IV on vascular endothelial dysfunction. MATERIALS AND METHODS: A diabetes model was established by intraperitoneal injection of streptozotocin (STZ). Endothelial function in isolated aortic rings was examined; serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested by ELISA. The expression of nuclear Factor-κB p65 (NF-κB p65) in aortic tissue was detected by immunohistochemistry. Plasma nitric oxide (NO) was measured by the nitrate reductase method. The expressions of endothelial nitric oxide synthase (eNOS), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and toll-like receptor 4 (TLR4) in aortic tissue were determined by western blot. KEY FINDINGS: The results showed that As-IV significantly improved aortic endothelial function; increased eNOS expression and NO production; and decreased the content of IL-6 and TNF-α and the expressions of VCAM-1, ICAM-1, TLR4, and nuclear NF-κB p65 in vitro and in vivo. In addition, the above mentioned effects of As-IV on human umbilical vein endothelial cells (HUVECs) were similar to TAK-242 (TLR4 inhibitor) and Bay 11-7082 (NF-κB p65 inhibitor). Furthermore, L-NAME (NO synthesis inhibitor) partially abolished the effect of As-IV. SIGNIFICANCE: As-IV could improve vascular endothelial dysfunction induced by hyperglycemia, and the protective effect of As-IV may be via the TLR4/NF-κB signaling pathway.


Assuntos
Diabetes Mellitus Experimental/complicações , Angiopatias Diabéticas/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Saponinas/farmacologia , Receptor 4 Toll-Like/antagonistas & inibidores , Triterpenos/farmacologia , Animais , Citocinas/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
11.
Nutrients ; 10(7)2018 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-30029482

RESUMO

Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis. Supplementation with l-citrulline has shown promise as a blood pressure lowering intervention (both resting and stress-induced) in adults with pre-/hypertension, with pre-clinical (animal) evidence for atherogenic-endothelial protection. Preliminary evidence is also available for l-citrulline-induced benefits to muscle and metabolic health (via vascular and non-vascular pathways) in susceptible/older populations. In this review, we examine the impact of supplementing this important urea cycle intermediate on cardiovascular and metabolic health outcomes and identify future directions for investigating its therapeutic impact on cardiometabolic health.


Assuntos
Anti-Hipertensivos/uso terapêutico , Citrulina/uso terapêutico , Angiopatias Diabéticas/prevenção & controle , Suplementos Nutricionais , Medicina Baseada em Evidências , Hipertensão/prevenção & controle , Modelos Biológicos , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/metabolismo , Antioxidantes/efeitos adversos , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Citrulina/efeitos adversos , Citrulina/metabolismo , Angiopatias Diabéticas/imunologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Suplementos Nutricionais/efeitos adversos , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão/imunologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Síndrome Metabólica/imunologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Síndrome Metabólica/terapia , Sarcopenia/imunologia , Sarcopenia/metabolismo , Sarcopenia/fisiopatologia , Sarcopenia/prevenção & controle , Rigidez Vascular , Vasodilatadores/efeitos adversos , Vasodilatadores/metabolismo , Vasodilatadores/uso terapêutico
12.
Diabetes ; 67(8): 1616-1626, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29941448

RESUMO

Previously, we had shown that a vasopeptidase inhibitor drug containing ACE and neprilysin inhibitors was an effective treatment for diabetic vascular and neural complications. However, side effects prevented further development. This led to the development of sacubitril/valsartan, a drug containing angiotensin II receptor blocker and neprilysin inhibitor that we hypothesized would be an effective treatment for diabetic peripheral neuropathy. Using early and late intervention protocols (4 and 12 weeks posthyperglycemia, respectively), type 2 diabetic rats were treated with valsartan or sacubitril/valsartan for 12 weeks followed by an extensive evaluation of vascular and neural end points. The results demonstrated efficacy of sacubitril/valsartan in improving vascular and neural function was superior to valsartan alone. In the early intervention protocol, sacubitril/valsartan treatment was found to slow progression of these deficits and, with late intervention treatment, was found to stimulate restoration of vascular reactivity, motor and sensory nerve conduction velocities, and sensitivity/regeneration of sensory nerves of the skin and cornea in a rat model of type 2 diabetes. These preclinical studies suggest that sacubitril/valsartan may be an effective treatment for diabetic peripheral neuropathy, but additional studies will be needed to investigate these effects further.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/prevenção & controle , Neuropatias Diabéticas/prevenção & controle , Tetrazóis/uso terapêutico , Valsartana/uso terapêutico , Animais , Fármacos Cardiovasculares/uso terapêutico , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/fisiopatologia , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Progressão da Doença , Combinação de Medicamentos , Masculino , Neprilisina/antagonistas & inibidores , Neprilisina/metabolismo , Condução Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Inibidores de Proteases/uso terapêutico , Ratos Sprague-Dawley , Resistência Vascular/efeitos dos fármacos
13.
Diabetes Care ; 41(8): 1783-1791, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29903847

RESUMO

OBJECTIVE: In the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) cardiovascular (CV) outcomes trial (NCT01179048), liraglutide significantly reduced the risk of CV events (by 13%) and hypoglycemia versus placebo. This post hoc analysis examines the associations between hypoglycemia and CV outcomes and death. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes and high risk for CV disease (n = 9,340) were randomized 1:1 to liraglutide or placebo, both in addition to standard treatment, and followed for 3.5-5 years. The primary end point was time to first major adverse cardiovascular event (MACE) (1,302 first events recorded), and secondary end points included incidence of hypoglycemia. We used Cox regression to analyze time to first MACE, CV death, non-CV death, or all-cause death with hypoglycemia as a factor or time-dependent covariate. RESULTS: A total of 267 patients experienced severe hypoglycemia (liraglutide n = 114, placebo n = 153; rate ratio 0.69; 95% CI 0.51, 0.93). These patients had longer diabetes duration, higher incidence of heart failure and kidney disease, and used insulin more frequently at baseline than those without severe hypoglycemia. In combined analysis (liraglutide and placebo), patients with severe hypoglycemia were more likely to experience MACE, CV death, and all-cause death, with higher risk shortly after hypoglycemia. The impact of liraglutide on risk of MACE was similar in patients with and without severe hypoglycemia (P-interaction = 0.90). CONCLUSIONS: Patients experiencing severe hypoglycemia were at greater risk of CV events and death, particularly shortly after the hypoglycemic episode. While causality remains unclear, reducing hypoglycemia remains an important goal in diabetes management.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Liraglutida/uso terapêutico , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Feminino , Humanos , Hipoglicemia/epidemiologia , Incidência , Nefropatias/complicações , Nefropatias/epidemiologia , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento
14.
Vascul Pharmacol ; 109: 27-35, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29857059

RESUMO

Endothelial injury from high glucose (HG) plays a dominant role in atherosclerosis, diabetes-induced vasculopathy, and vascular remodeling. Notoginsenoside Fc (Fc), a novel saponin isolated from P. notoginseng, has been shown to exhibit properties that counteract platelet aggregation. However, the potential roles and molecular mechanisms of Fc in preventing cardiovascular injury have yet to be explored. In this study, we present novel data that show the ability of Fc to prevent early atherosclerosis of diabetic Sprague-Dawley (SD) rats in vivo and to attenuate endothelial cell injury in vitro. Our results indicate that Fc protects rat aortic endothelial cells (RAOECs) from HG-induced injury by inhibiting apoptosis and promoting proliferation as well as by reducing endothelial cell production of pro-inflammatory cytokines: TNF-α, IL-1ß, IL-6, ICAM-1. Furthermore, the downregulation of peroxisome proliferator-activated receptor-γ (PPAR-γ) in HG-challenged endothelial cells was prevented by Fc. Inhibition of PPAR-γ abrogated the effects of Fc on HG-induced pro-inflammatory cytokine production in RAOECs. These results indicate that Fc has a preventative effect on HG-induced endothelial cell injury partly through a PPARγ-mediated pathway, suggesting that Fc might provide a potential new therapeutic option for the treatment of diabetic vascular complications.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Células Endoteliais/efeitos dos fármacos , Ginsenosídeos/farmacologia , PPAR gama/agonistas , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Citoproteção , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/patologia , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Mediadores da Inflamação/metabolismo , PPAR gama/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Regulação para Cima
15.
Clin Investig Arterioscler ; 30(3): 137-153, 2018 May - Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29754804

RESUMO

This document is an update to the clinical practice recommendations for the management of cardiovascular risk factors in diabetes mellitus. The consensus is made by members of the Cardiovascular Risk Group of the Spanish Diabetes Society. We have proposed and updated interventions on lifestyle, pharmacological treatment indicated to achieve therapeutic objectives according to the levels of HbA1c, degree of obesity, hypertension, hyperlipidemia, heart failure, platelet antiagregation, renal insufficiency, and diabetes in the elderly, as well as new biomarkers of interest in the evaluation of cardiovascular risk in individuals with diabetes mellitus. The work is an update of the interventions and therapeutic objectives in addition, it is noted the need for the inclusion of specialists in Endocrinology, Metabolism and Nutrition in Cardiac Rehabilitation Units for the control and monitoring of this population.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Angiopatias Diabéticas/prevenção & controle , Cardiomiopatias Diabéticas/prevenção & controle , Idoso , Biomarcadores/metabolismo , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/terapia , Humanos , Estilo de Vida , Fatores de Risco , Espanha
16.
Endocr Pract ; 24(3): 265-272, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29547051

RESUMO

OBJECTIVE: Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN. METHODS: This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases. RESULTS: Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 ± 12.3 and 66.8 ± 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 ± 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk. CONCLUSION: THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding. ABBREVIATIONS: CV = cardiovascular DMN = diabetic nephropathy eGFR = estimated glomerular filtration rate fT4 = free thyroxine HbA1c = glycosylated hemoglobin HR = hazard ratio hs-CRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol SCH = subclinical hypothyroidism T2DM = type 2 diabetes THRT = thyroid hormone replacement therapy TSH = thyroid-stimulating hormone.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Terapia de Reposição Hormonal , Hipotireoidismo/tratamento farmacológico , Tiroxina/uso terapêutico , Idoso , Doenças Assintomáticas , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/epidemiologia , Feminino , Seguimentos , Humanos , Hipotireoidismo/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
17.
BMJ Open ; 8(3): e020762, 2018 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-29530914

RESUMO

INTRODUCTION: Northern Mexico has among the highest rates of cardiovascular disease (CVD) and diabetes in the world. This research addresses core gaps in implementation science to develop, test and scale-up CVD risk-reduction interventions in diabetics through a national primary care health system. METHODS AND ANALYSIS: The Meta Salud Diabetes (MSD) research project is a parallel two-arm cluster-randomised clinical behavioural trial based in 22 (n=22) health centres in Sonora, Mexico. MSD aims to evaluate the effectiveness of the MSD intervention for the secondary prevention of CVD risk factors among a diabetic population (n=320) compared with the study control of usual care. The MSD intervention consists of 2-hour class sessions delivered over a 13-week period providing educational information to encourage sustainable behavioural change to prevent disease complications including the adoption of physical activity. MSD is delivered within the context of Mexico's national primary care health centre system by health professionals, including nurses, physicians and community health workers via existing social support groups for individuals diagnosed with chronic disease. Mixed models are used to estimate the effect of MSD by comparing cardiovascular risk, as measured by the Framingham Risk Score, between the trial arms. Secondary outcomes include hypertension, behavioural risk factors and psychosocial factors. ETHICS AND DISSEMINATION: This work is supported by the National Institutes of Health, National Heart Lung and Blood Institute (1R01HL125996-01) and approved by the University of Arizona Research Institutional Review Board (Protocol 1508040144) and the Research Bioethics Committee at the University of Sonora. The first Internal Review Board approval date was 31 August 2015 with five subsequent approved amendments. This article refers to protocol V.0.2, dated 30 January 2017. Results will be disseminated via peer-reviewed publication and presentation at international conferences and will be shared through meetings with health systems officials. TRIAL REGISTRATION NUMBER: NCT0280469; Pre-results.


Assuntos
Diabetes Mellitus/fisiopatologia , Angiopatias Diabéticas/prevenção & controle , Prevenção Primária , Adulto , Análise por Conglomerados , Diabetes Mellitus/epidemiologia , Angiopatias Diabéticas/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Humanos , Masculino , México , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Fatores de Risco
19.
Diab Vasc Dis Res ; 15(4): 277-285, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29466879

RESUMO

BACKGROUND: Short-lasting hyperglycaemia occurs frequently in prediabetes and poorly controlled diabetes mellitus leading to vascular damage. Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to play a protective role in vascular complications of diabetes; moreover, antioxidant effects of PACAP were also described. Therefore, we hypothesized that PACAP exerts protective effects in short-term hyperglycaemia-induced vascular dysfunctions. METHODS: After short-term hyperglycaemia, acetylcholine-induced and sodium nitroprusside-induced vascular relaxation of mouse carotid arteries were tested with a myograph with or without the presence of PACAP or superoxide dismutase. Potential direct antioxidant superoxide-scavenging action of pituitary adenylate cyclase-activating peptide was tested with pyrogallol autoxidation assay; furthermore, the effect of pituitary adenylate cyclase-activating peptide or superoxide dismutase was investigated on hyperglycaemia-associated vascular markers. RESULTS: PACAP administration resulted in reduced endothelial dysfunction after a 1-h hyperglycaemic episode. PACAP was able to restore acetylcholine-induced relaxation of the vessels and improved sodium nitroprusside-induced relaxation. This effect was comparable to the protective effect of superoxide dismutase, but PACAP was unable to directly scavenge superoxide produced by autoxidation of pyrogallol. Endothelial dysfunction was associated with elevated levels of fibroblast growth factor basic, matrix metalloproteinase 9 and nephroblastoma overexpressed gene proteins. Their release was reduced by PACAP administration. CONCLUSION: These results suggest a strong protective role of PACAP in the vascular complications of diabetes.


Assuntos
Artéria Carótida Primitiva/efeitos dos fármacos , Angiopatias Diabéticas/prevenção & controle , Hiperglicemia/tratamento farmacológico , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/fisiopatologia , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Relação Dose-Resposta a Droga , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Depuradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica , Hiperglicemia/genética , Hiperglicemia/metabolismo , Hiperglicemia/fisiopatologia , Técnicas In Vitro , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Miografia , Proteína Sobre-Expressa em Nefroblastoma/genética , Proteína Sobre-Expressa em Nefroblastoma/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fatores de Tempo , Vasodilatadores/farmacologia
20.
Diabetes ; 67(5): 946-959, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29483182

RESUMO

Cardiovascular disease caused by atherosclerosis is the leading cause of mortality associated with type 2 diabetes and metabolic syndrome. Insulin therapy is often needed to improve glycemic control, but it does not clearly prevent atherosclerosis. Upon binding to the insulin receptor (IR), insulin activates distinct arms of downstream signaling. The IR-Akt arm is associated with blood glucose lowering and beneficial effects, whereas the IR-Erk arm might exert less desirable effects. We investigated whether selective activation of the IR-Akt arm, leaving the IR-Erk arm largely inactive, would result in protection from atherosclerosis in a mouse model of metabolic syndrome. The insulin mimetic peptide S597 lowered blood glucose and activated Akt in insulin target tissues, mimicking insulin's effects, but only weakly activated Erk and even prevented insulin-induced Erk activation. Strikingly, S597 retarded atherosclerotic lesion progression through a process associated with protection from leukocytosis, thereby reducing lesional accumulation of inflammatory Ly6Chi monocytes. S597-mediated protection from leukocytosis was accompanied by reduced numbers of the earliest bone marrow hematopoietic stem cells and reduced IR-Erk activity in hematopoietic stem cells. This study provides a conceptually novel treatment strategy for advanced atherosclerosis associated with metabolic syndrome and type 2 diabetes.


Assuntos
Aterosclerose/prevenção & controle , Glicemia/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Receptor de Insulina/efeitos dos fármacos , Animais , Aterosclerose/etiologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/prevenção & controle , Modelos Animais de Doenças , Masculino , Síndrome Metabólica/complicações , Camundongos , Camundongos Knockout , Monócitos , Placa Aterosclerótica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor de Insulina/agonistas , Receptor de Insulina/metabolismo , Receptores de LDL/genética , Transdução de Sinais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA