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1.
PLoS One ; 15(6): e0234319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542057

RESUMO

AIMS: Robust evidence supports intensive glucose control in those with recently diagnosed type 1 diabetes to reduce the risk of developing micro- and macrovascular complications. Data to support longitudinal glycaemic targets is lacking. We aimed to explore if longer duration of diabetes and greater age might reduce the impact of glycaemia on the risk of vascular complications. RESEARCH AND DESIGN METHODS: Data for adults age 20 years or more, was extracted from a clinical database of people with type 1 diabetes cared for at a London teaching hospital. The presence or absence of micro- and macro-vascular complications was recorded. Multivariable logistic regression analysis was performed using HbA1c as independent variable, diabetes duration and age as continuous variable and obesity, hypertension, hypercholesterolaemia, low HDL cholesterol and hypertriglyceridaemia as categorical variables. RESULTS: Data from 495 patients was used. HbA1c above 60 mmol/mol (7.6%) was associated with increased microvascular complications in patients aged 20-44 years, independent of age and duration of diabetes. In older people with T1DM duration of diabetes was the major risk factor. CONCLUSIONS: Our study suggests that increased age and greater duration of diabetes reduce the impact of glycaemia on the risk of vascular complications. Intensive blood glucose management in patients aged ≥45 years may have limited benefits in terms of reducing the risk of complications although this does not dismiss the benefits of good glycaemic control in older people with T1DM.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Angiopatias Diabéticas/sangue , Hemoglobina A Glicada/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/prevenção & controle , Feminino , Carga Glicêmica , Humanos , Hipoglicemiantes , Insulina/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Fatores de Risco , Adulto Jovem
2.
Life Sci ; 255: 117779, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32417374

RESUMO

OBJECTIVE: Kidney is the most common location of microangiopathy in diabetic patients, and we designed this study to investigate the effects of hirudin on renal microangiopathy in STZ-induced diabetes rats and in vitro. METHODS: We established a diabetes model by intraperitoneal injection of STZ and administered hirudin daily by subcutaneous injection. HE staining was used to assess kidney pathological changes. Western blot and immunochemistry was used to detect the protein expression. Glomerular endothelial cells (GEC) in normal rats were assessed by cell scratch test for migration ability and tubule formation experiment for angiogenesis ability. RESULTS: Compared with DN rats without any treatment, the serum creatinine, serum Cys C, 24-hour urine protein of DN rats with hirudin treatment were significantly decrease, the kidney/body weight and glomerular area of DN rats with hirudin treatment were all significantly decrease, and also significant improvement in renal pathology revealed by HE staining in DN rats after treating with hirudin. Moreover, we also found that hirudin coun not only significantly increase the prothrombin time and aivated partial thromboplastin time in DN rats, but also significantly decrease the expression of VEGF and TM-1 protein in kidney tissues of DN rats. In vitro, we found that high glucose could promote the migration and angiogensis of GEC, and significantly increased the expression of VEGF and Ang protein, but significantly decreased the expression of THBS1 and Arg1 protein. More importantly was that hirudin could inhibit the migration and angiogensis of GEC, and reversed HG-induced the expression of VEGF, Ang, THBS1 and Arg1 protein in GEC. In addition, we also found that hirudin could not only decrease HG-enhanced the activity of RhoA in GEC, but also decrease HG-enhanced the expression of p-MYPT1/MYPT1, p-p38/p38 protein in GEC. CONCLUSION: Hirudin reduces nephropathy microangiopathy in STZ-induced diabetes, and might be related to hirudin inhibiting glomerular endothelial cell migration and angiogenesis through Rho-kinase and subsequent p38MAPK/NF-kB signaling pathway.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/prevenção & controle , Hirudinas/farmacologia , Neovascularização Patológica/prevenção & controle , Animais , Movimento Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Glucose/metabolismo , Glomérulos Renais/metabolismo , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Quinases Associadas a rho/metabolismo
3.
Intern Med ; 59(5): 601-609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115517

RESUMO

Objective To examine the add-on effects, compared to the existing antidiabetes treatment, of the sodium-glucose cotransporter 2 inhibitor ipragliflozin on glycemic control and the risk factors of cardiovascular disease (CVD) and chronic kidney disease (CKD) in patients with inadequately controlled type 2 diabetes. Methods This 12-week, randomized, open-label, active-controlled trial included 30 patients with type 2 diabetes who were randomized 1:1 to ipragliflozin and control groups (n=15 each). The ipragliflozin group received 50 mg of ipragliflozin once daily in addition to conventional therapy. The primary outcome was the change in hemoglobin A1c (HbA1c) from the baseline. Secondary outcomes were changes from the baseline in indices of glycemic control, uric acid (UA), renal function, and arterial stiffness. Results The patients' diminished estimated glomerular filtration rate (eGFR) was alleviated in the ipragliflozin group compared to the control group [difference between groups (Δ) =4.6 (95% confidence interval (CI): 1.5-7.7) mL/min/1.73 m2, p=0.006] prior to significant improvements in HbA1c and other parameters, including anthropometric indices and arterial stiffness. Furthermore, ipragliflozin add-on therapy resulted in a greater reduction in serum UA levels than control therapy [Δ=-52.3 (95% CI: -85.5-19.1) µmol/L, p=0.003]. The changes in the eGFR with ipragliflozin treatment were associated with ipragliflozin-mediated changes in the UA, even after adjusting for the age, sex, baseline HbA1c, baseline UA, and baseline eGFR (standardized regression coefficient=-0.535, p=0.010). Conclusion Ipragliflozin add-on therapy was associated with beneficial renal effects in parallel with reducing serum UA levels.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Glucosídeos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Insuficiência Renal Crônica/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Tiofenos/administração & dosagem , Adulto , Idoso , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/fisiopatologia , Angiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/prevenção & controle , Esquema de Medicação , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Resultado do Tratamento , Ácido Úrico/metabolismo , Adulto Jovem
4.
Curr Opin Endocrinol Diabetes Obes ; 27(2): 115-123, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32073426

RESUMO

PURPOSE OF REVIEW: To summarize recent advancements in our understanding of the impact of dyslipidemia on microvascular complications in type 2 diabetes (T2D), with an emphasis on peripheral neuropathy and nephropathy. RECENT FINDINGS: Mounting evidence suggests that rigorous glycemic control only mitigates certain microvascular complications in T2D patients. Particularly, well regulated blood glucose levels only marginally improve peripheral neuropathy in the T2D setting. Dyslipidemia, an abnormal lipid profile, is emerging as a key factor in peripheral neuropathy. Furthermore, although glycemic control may prevent or slow nephropathy, recent developments demonstrate that dyslipidemia can also affect kidney outcomes in normoglycemic patients. Transcriptomic, epigenomic, and lipidomic investigations, as well as integrative approaches, are shedding light on potential pathomechanisms. These molecular studies are identifying possible targets for therapeutic intervention. Complementing molecular research, lifestyle interventions are on-going to assess whether dietary choices and/or exercise, weight-loss, or surgical interventions, such as bariatric surgery, can ameliorate peripheral neuropathy and nephropathy in T2D patients. SUMMARY: Dyslipidemia is an emerging mechanism in microvascular complications in T2D. Elucidating the molecular pathomechanisms may pinpoint potential lipid-centric treatments. Interventional studies of dietary changes, exercise, or weight-loss surgery may also positively impact these highly prevalent and morbid complications.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Dislipidemias/complicações , Cirurgia Bariátrica , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/prevenção & controle , Dietoterapia/métodos , Dislipidemias/sangue , Dislipidemias/terapia , Terapia por Exercício/métodos , Humanos , Fatores de Risco , Perda de Peso/fisiologia
5.
Nitric Oxide ; 96: 54-63, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972252

RESUMO

The metabolic disorders in diabetes, which are usually accompanied by oxidative stress and impaired nitric oxide (NO) bioavailability, increase the risk of detrimental cardiovascular complications. Herein, we investigated the therapeutic potential of dietary nitrate, which is found in high content in green leafy vegetables, on vascular oxidative stress and endothelial dysfunction in diabetic mice induced by high-fat diet and streptozotocin injection. Dietary nitrate in drinking water fuelled a nitrate-nitrite-NO pathway, which inhibited vascular oxidative stress, endothelial dysfunction and many features of metabolic syndrome in diabetic mice. These beneficial effects of nitrate on diabetic mice were abolished by PTIO (NO scavenger) treatment and significantly prevented by febuxostat (xanthine oxidoreductase inhibitor), demonstrating the central importance of NO in bioactivation of nitrate. The favorable effects of nitrate were not further influenced by apocynin (NADPH oxidase inhibitor), suggesting NADPH oxidase as a possible target. In high glucose-incubated vascular endothelial cells, NO donor attenuated oxidative stress and endothelial dysfunction via the inhibition of NADPH oxidase, where a heme oxygenase-1 (HO-1)-dependent mechanism was demonstrated for the antioxidant abilities of NO. Altogether, boosting this nitrate-nitrite-NO signaling pathway resulted in the decreases of NADPH oxidase-derived oxidative stress, endothelial dysfunction and metabolic disorders in diabetic vasculature. These findings may have novel implications for the preventive strategy against diabetes-induced vascular dysfunction and associated complications.


Assuntos
Diabetes Mellitus Experimental/complicações , Angiopatias Diabéticas/prevenção & controle , Endotélio Vascular/efeitos dos fármacos , NADPH Oxidases/antagonistas & inibidores , Nitratos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Angiopatias Diabéticas/etiologia , Heme Oxigenase-1/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Síndrome Metabólica/prevenção & controle , Camundongos , Nitratos/administração & dosagem , Óxido Nítrico/metabolismo
6.
Rev Med Interne ; 41(2): 143-144, 2020 Feb.
Artigo em Francês | MEDLINE | ID: mdl-31928796
9.
J Recept Signal Transduct Res ; 39(4): 341-349, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31680596

RESUMO

Context: Sirtuin-3 (Sirt3), a NAD-dependent deacetylase, has been reported to be involved in many biological processes.Objective: The present study aimed to investigate the effect and mechanism of Sirt3 on diabetic mice and human umbilical vein endothelial cells (HUVECs) under high glucose (HG) condition.Materials and methods: HUVECs were cultured under HG and inflammation pathway was determined via qPCR, western blots, and immunofluorescence.Results: Sirt3 expression was reduced in the progression of diabetic nephropathy. Overexpression of Sirt3 sustains renal function and retard the development of diabetic nephropathy. Mechanistically, Sirt3 overexpression attenuated hyperglycemia-mediated endothelial cells apoptosis in kidney. Besides, Sirt3 overexpression repressed oxidative injury and blocked caspase-9-related apoptosis pathway. Moreover, we found that Sirt3 overexpression was associated with AMPK activation and the latter elevates PGC1α-related mitochondrial protective system, especially mitochondrial autophagy. Loss of opa1 and/or inhibition of AMPK could depress mitochondrial autophagy and exacerbates mitochondrial function, finally contributing to the death of human renal mesangial cells.Conclusions: Our results demonstrated the beneficial effects of Sirt3 in the progression of diabetic nephropathy. Increased Sirt3-activated AMPK pathway, augments PGC1α-related mitochondrial protective system, sustained redox balance and closed caspase-9-involved apoptosis pathway in the setting of diabetic nephropathy.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Angiopatias Diabéticas/prevenção & controle , Hiperglicemia/complicações , Inflamação/prevenção & controle , Mitocôndrias/metabolismo , Sirtuína 3/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Apoptose , Sobrevivência Celular , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Homeostase , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Transgênicos , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Sirtuína 3/genética
10.
Vasc Health Risk Manag ; 15: 419-427, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632046

RESUMO

Introduction: The increasing blood glucose level due to insulin resistance which occurs in diabetes mellitus (DM) may cause vascular damage. This study aims to prove the effect of the polysaccharide peptide (PsP) Ganoderma lucidum on improving vascular damage through an increase of circulating endothelial cells and circulating endothelial cells (CEC) ratio, decreased H2O2, triglyceride (TG), total cholesterol (TC) and insulin resistance in type 2 DM. Methods: Our study is a true experimental study with randomized posttest control group design that used 35 Wistar rats divided into five groups: normal, control (+) and three groups of different variant PsP doses 50, 150 and 300 mg/kg BW (n=7). Results: By using one-way ANOVA and post-hoc Duncan test, the results show a significant increase of endothelial progenitor cell (EPC) concentration (p=0.000) and ratio EPC:CEC (0.000) by dose-dependent fashion and also reduced CEC concentration (p=0.001), H2O2 (p=0.03), TG (p=0.001), TC (p=0.01) and insulin resistance (p=0.003). Conclusion: In this study, PsP induced endothelial repairing process and reduced the risk factor with 300 mg/kg BW as optimum dose. However, further research on EPC and CEC detection markers is important. Further research on PsP and clinical trial for commercial uses is also needed.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Células Endoteliais/efeitos dos fármacos , Proteoglicanas/farmacologia , Reishi , Remodelação Vascular/efeitos dos fármacos , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/induzido quimicamente , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/induzido quimicamente , Angiopatias Diabéticas/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Peróxido de Hidrogênio/sangue , Resistência à Insulina , Lipídeos/sangue , Proteoglicanas/isolamento & purificação , Ratos Wistar , Reishi/química , Estreptozocina
11.
Glob Heart ; 14(4): 355-365, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31523014

RESUMO

BACKGROUND: Eighty percent of premature mortality from cardiovascular disease occurs in low- and middle-income countries. Hypertension, diabetes, and smoking are the top risk factors causing this disease burden. OBJECTIVES: The study aimed to test the hypothesis that utilizing community health workers (CHWs) to manage hypertension, diabetes and smoking in an integrated manner would lead to improved control of these conditions. METHODS: This was a 2-year cluster (n = 12) randomized controlled trial of 3,556 adults (35 to 70 years of age) in a single town in India, who were screened at home for hypertension, diabetes, and smoking. Of these adults, 1,242 (35%) had at least 1 risk factor (hypertension = 650, diabetes = 317, smoking = 500) and were enrolled in the study. The intervention group had behavioral change communication through regular home visits from community health workers. The control group received usual care in the community. The primary outcomes were changes in systolic blood pressure, fasting blood glucose, and average number of cigarettes/bidis smoked daily among individuals with respective risk factors. RESULTS: The mean ± SD change in systolic blood pressure at 2 years was -12.2 ± 19.5 mm Hg in the intervention group as compared with -6.4 ± 26.1 mm Hg in the control group, resulting in an adjusted difference of -8.9 mm Hg (95% confidence interval [CI]: -3.5 to -14.4 mm Hg; p = 0.001). The change in fasting blood glucose was -43.0 ± 83.5 mg/dl in the intervention group and -16.3 ± 77.2 mg/dl in the control group, leading to an adjusted difference of -21.3 mg/dl (95% CI: 18.4 to -61 mg/dl; p = 0.29). The change in mean number of cigarettes/bidis smoked was nonsignificant at +0.2 cigarettes/bidis (95% CI: 5.6 to -5.2 cigarettes/bidis; p = 0.93). CONCLUSIONS: A population-based strategy of integrated risk factor management through community health workers led to improved systolic blood pressure in hypertension, an inconclusive effect on fasting blood glucose in diabetes, and no demonstrable effect on smoking. (Study of a Community-Based Approach to Control Cardiovascular Risk Factors in India [SEHAT]; NCT02115711).


Assuntos
Doenças Cardiovasculares/prevenção & controle , Agentes Comunitários de Saúde/estatística & dados numéricos , Adulto , Idoso , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/fisiopatologia , Análise por Conglomerados , Serviços de Saúde Comunitária/organização & administração , Angiopatias Diabéticas/fisiopatologia , Angiopatias Diabéticas/prevenção & controle , Utilização de Instalações e Serviços , Feminino , Promoção da Saúde/métodos , Humanos , Hipertensão/fisiopatologia , Hipertensão/prevenção & controle , Índia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Prevenção do Hábito de Fumar
13.
Diab Vasc Dis Res ; 16(6): 523-529, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31267765

RESUMO

The impact of the local inhibition of soluble epoxide hydrolase, which metabolizes vasodilator and anti-inflammatory epoxyeicosanoids, on diabetic skin microvascular dysfunction was assessed. In diabetic db/db mice, basal skin blood flow assessed using laser Doppler imaging was similar to that of control mice, but thermal hyperemia was markedly reduced. At 2 h after the topical administration of an aqueous gel containing the soluble epoxide hydrolase inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB: 400 mg/L), the peak concentration of t-AUCB was detected in the skin of diabetic mice, which quickly decreased thereafter. In parallel, 2 h after application of t-AUCB treatment, thermal hyperemia was increased compared to the control gel. Quantification of t-AUCB in plasma of treated animals showed no or low systemic diffusion. Furthermore, haematoxylin and eosin histological staining of skin biopsies showed that skin integrity was preserved in t-AUCB-treated mice. Finally, for pig ear skin, a surrogate for human skin, using Franz diffusion cells, we observed a continuous diffusion of t-AUCB from 2 h after application to beyond 24 h. A single topical administration of a soluble epoxide hydrolase inhibitor improves microcirculatory function in the skin of db/db mice and might represent a new therapeutic approach for preventing the development of skin complications in diabetic patients.


Assuntos
Benzoatos/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Inibidores Enzimáticos/administração & dosagem , Epóxido Hidrolases/antagonistas & inibidores , Microcirculação/efeitos dos fármacos , Ureia/análogos & derivados , Administração Cutânea , Animais , Velocidade do Fluxo Sanguíneo , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/enzimologia , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Epóxido Hidrolases/metabolismo , Géis , Masculino , Camundongos Endogâmicos C57BL , Fluxo Sanguíneo Regional , Transdução de Sinais , Sus scrofa , Ureia/administração & dosagem
14.
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
15.
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
16.
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
17.
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
19.
J Endocrinol Invest ; 42(10): 1165-1169, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30955180

RESUMO

PURPOSE: We did a meta-analysis with meta-regression to evaluate the relationship between hemoglobin A1c (A1C) reduction and the primary CV outcome of cardiovascular outcome trials (CVOTs). METHODS: We used a random effects meta-analysis of the 12 CVOTs to quantify the effect of A1C reduction on major cardiovascular events (MACE) risk by stratifying the difference in achieved A1C (drug vs placebo) in three strata: A1c < 0.3%, A1c ≥ 0.3% and < 0.5%, and A1c ≥ 0.5%. RESULTS: We found a relation between the reduction in achieved A1C and the hazard ratio reduction for MACE (P = 0.002), explaining almost all (94.1%) the between-study variances: lowering A1C by 0.5% conferred a significant HRR of 20% (95% CI 4-33%) for MACE. CONCLUSIONS: Blood glucose reduction may play a more important role than previously thought in reducing the risk of MACE during treatment with the newer glucose-lowering drugs, including peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto/métodos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/prevenção & controle , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Projetos de Pesquisa , Resultado do Tratamento
20.
Pediatr Diabetes ; 20(5): 494-509, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30932298

RESUMO

OBJECTIVE: A systematic review and meta-analysis was conducted to investigate if glycemic control measured by glycated hemoglobin (HbA1c) levels near diagnosis are predictive of future glycemic outcomes and vascular complications in childhood onset type 1 diabetes (T1D). METHODS: Evidence was gathered using electronic databases (MEDLINE, EMBASE, Web of Science, CINAHL, Scopus, and Cochrane Library up to February 2017) and snowballing techniques. Studies investigating the association between the exposure "early glycemic control" and main outcome: "tracking of early control" and secondary outcome: risk of future complications; in children and young people aged 0 to 19 years at baseline; were systematically double-reviewed, quality assessed, and outcome data extracted for synthesis and meta-analysis. FINDINGS: Five studies (N = 4227 participants) were eligible. HbA1c levels were sub-optimal throughout the study period but tended to stabilize in a "track" by 6 months after T1D diagnosis. The group with low HbA1c <53 mmol/mol (<7%) at baseline had lower long-term HbA1c levels than the higher HbA1c group. The estimated standardized mean difference between the sub groups showed a reduction of HbA1c levels on average by 1.6% (range -0.95% to -2.28%) from baseline. Only one study investigated the association between early glycemic control and development of vascular complications in childhood onset T1D. INTERPRETATIONS: Glycemic control after the first few months of childhood onset T1D, remains stable but sub-optimal for a decade. The low and high HbA1c levels at baseline seem to "track" in their respective tracks during the 10-year follow-up, however, the initial difference between groups narrows over time. PROSPERO: CRD42015024546 http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015024546.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/uso terapêutico , Adolescente , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Humanos
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