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1.
Diab Vasc Dis Res ; 17(1): 1479164120903044, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32037878

RESUMO

Diabetes is a proinflammatory and prothrombotic condition that increases the risk of vascular complications. The aim of this study was to develop a diabetic microvascular flow model that allows to study the complex interactions between endothelial cells, blood cells and plasma proteins and their effects on clot formation. Primary human cardiac microvascular endothelial cells from donors without diabetes or donors with diabetes (type 1 or type 2) were grown in a microfluidic chip, perfused with non-diabetic or diabetic whole blood, and clot formation was assessed by measuring fibrin deposition in real time by confocal microscopy. Clot formation in non-diabetic whole blood was significantly increased in the presence of endothelial cells from donors with type 2 diabetes compared with cells from donors without diabetes. There was no significant difference in clot formation between non-diabetic and diabetic whole blood. We present for the first time a diabetic microvascular flow model as a new tool to study clot formation as a result of the complex interactions between endothelial cells, blood cells and plasma proteins in a diabetes setting. We show that endothelial cells affect clot formation in whole blood, attributing an important role to the endothelium in the development of atherothrombotic complications.


Assuntos
Coagulação Sanguínea , Vasos Coronários/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/etiologia , Células Endoteliais/metabolismo , Fibrina/metabolismo , Microcirculação , Trombose/etiologia , Adulto , Estudos de Casos e Controles , Células Cultivadas , Vasos Coronários/fisiopatologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fluxo Sanguíneo Regional , Trombose/sangue , Trombose/fisiopatologia , Fatores de Tempo
2.
Presse Med ; 48(11 Pt 1): 1249-1256, 2019 Nov.
Artigo em Francês | MEDLINE | ID: mdl-31727491

RESUMO

Cardiovascular diseases are become the primary cause of death in women. The cardiovascular risk of the woman has unknown specificities and remains underestimated. At equal age, women have more cardio vascular risk factors than men. All these specificities must be taken into account for an optimized evaluation of cardiovascular risk and for improvement of CV management in women. Some traditional risk factors are more deleterious in women such as hypertension, tobacco, diabetes or psycho-social stress and they are less well controlled compared to men. Women are also exposed to hormonal risk factors (contraception, pregnancy and menopause) or to emergent risk situations (migraine with aura, endometriosis, polycystic ovary syndrome, auto-immune diseases…). Conversely, lifestyle measures (regular physical activity, no smoking, healthy diet, stress management) are extremely effective in primary and secondary prevention in women. Predicting the risk of cardiovascular events in women is difficult because the classic risk scores (SCORE, Framingham…) do not take into account hormonal CV specificities and underestimate the women CV risk. Until then, only the specific women AHA stratification of CVR allowed for appropriate care for them. Recently, at the initiative of the French Society of hypertension, a consensus of experts proposed a stratification of CVR adapted to French women, to help practitioners in their care, especially for the two hormonal periods as contraception and menopause.


Assuntos
Doenças Cardiovasculares/etiologia , Cardiologia , Doenças Cardiovasculares/prevenção & controle , Anticoncepção/efeitos adversos , Angiopatias Diabéticas/etiologia , Endometriose/complicações , Feminino , França , Ginecologia , Humanos , Hipertensão/complicações , Menopausa , Equipe de Assistência ao Paciente , Síndrome do Ovário Policístico/complicações , Gravidez , Prevenção Primária , Medição de Risco , Fatores de Risco , Prevenção Secundária , Fatores Sexuais , Fumar/efeitos adversos , Sociedades Médicas , Estresse Psicológico/complicações
3.
Int J Mol Sci ; 20(18)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31533227

RESUMO

Cardiovascular complications are a major leading cause of mortality in patients suffering from type 2 diabetes mellitus (T2DM). Vascular endothelial dysfunction is a core pathophysiological event in the early stage of T2DM and eventually leads to cardiovascular disease. Vaccarin (VAC), an active flavonoid glycoside extracted from vaccariae semen, exhibits extensive biological activities including vascular endothelial cell protection effects. However, little is known about whether VAC is involved in endothelial dysfunction regulation under high glucose (HG) or hyperglycemia conditions. Here, in an in vivo study, we found that VAC attenuated increased blood glucose, increased glucose and insulin tolerance, relieved the disorder of lipid metabolism and oxidative stress, and improved endothelium-dependent vasorelaxation in STZ/HFD-induced T2DM mice. Furthermore, in cultured human microvascular endothelial cell-1 (HMEC-1) cells, we showed that pretreatment with VAC dose-dependently increased nitric oxide (NO) generation and the phosphorylation of eNOS under HG conditions. Mechanistically, VAC-treated HMEC-1 cells exhibited higher AMPK phosphorylation, which was attenuated by HG stimulation. Moreover, HG-triggered miRNA-34a upregulation was inhibited by VAC pretreatment, which is in accordance with pretreatment with AMPK inhibitor compound C (CC). In addition, both reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) and VAC abolished HG-evoked dephosphorylation of AMPK and eNOS, increased miRNA-34a expression, and decreased NO production. These results suggest that VAC impedes HG-induced endothelial dysfunction via inhibition of the ROS/AMPK/miRNA-34a/eNOS signaling cascade.


Assuntos
Angiopatias Diabéticas/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Glicosídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/patologia , Modelos Animais de Doenças , Glicosídeos/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , MicroRNAs , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Substâncias Protetoras/química , Espécies Reativas de Oxigênio/metabolismo
4.
Acta Diabetol ; 56(12): 1315-1321, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31493030

RESUMO

AIM: To assess the association between alcohol consumption and/or cigarette smoking with other unhealthy behaviors and clinical cardiovascular risk factors in youth with type 1 diabetes. METHODS: Two hundred and twenty-eight youth with type 1 diabetes (age 13-19 years) were consecutively enrolled in three Regional Pediatric Diabetes Centers in Italy. Demographic, anthropometric, lifestyle (adherence to the Mediterranean diet pattern and sports participation) and laboratory parameters were compared among youth reporting isolated or combined alcohol consumption and/or cigarette smoking. RESULTS: Ten percent of the youth reported alcohol consumption, 10% cigarette smoking and 6% both alcohol and cigarette use; 74% did not report alcohol or cigarette use. Compared to non-drinker non-smoker youth, smokers showed significantly higher percentages of each of the behavioral and clinical cardiovascular risk factors. Drinkers showed a significantly higher proportion of abdominal adiposity, dyslipidemia and poor adherence to the Mediterranean diet. Alcohol consumption was independently associated with both dyslipidemia and high glycosylated hemoglobin. CONCLUSIONS: Our findings emphasize the need to increase the awareness of youth with T1D about the negative impact of alcohol drinking on cardiovascular risk, since the effects of alcohol might be underestimated with respect to the well-known detrimental effects of smoking. Clustering of unhealthy lifestyle should be discouraged in type 1 diabetes youth in order to promote cardiovascular protection.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Doenças Cardiovasculares/epidemiologia , Fumar Cigarros/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Angiopatias Diabéticas/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Doenças Cardiovasculares/etiologia , Fumar Cigarros/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Feminino , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Itália/epidemiologia , Estilo de Vida , Masculino , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Adulto Jovem
6.
Diab Vasc Dis Res ; 16(6): 539-548, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31364402

RESUMO

Besides being a metabolic disease, diabetes is considered a vascular disease as many of the complications relate to vascular pathologies. The aim of this study was to investigate how vascular tone and reactivity and vascular cell metabolism were affected in type 2 diabetes mellitus and whether ß-hydroxybutyrate could have a positive effect as alternative energy substrate. Isolated mesenteric arteries of db/db and control mice were incubated in media containing [U-13C]glucose or [U-13C]ß-hydroxybutyrate, and tissue extracts were analysed by mass spectrometry. Functional characterization was performed by wire myography to assess vasodilation and vasocontraction. Hypermetabolism of glucose and ß-hydroxybutyrate was observed for mesenteric arteries of db/db mice; however, hypermetabolism was significant only with ß-hydroxybutyrate as energy substrate. The functional characterization showed impaired endothelial-dependent vasodilation in mesenteric arteries of the db/db mice, whereas the contractility was unaffected. This study provides evidence that the endothelial cells are impaired, whereas the vascular smooth muscle cells are more robust and seemed less affected in the db/db mouse. Furthermore, the results indicate that hypermetabolism of energy substrates may be due to adaptive changes in the mesenteric arteries.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Endotélio Vascular/metabolismo , Metabolismo Energético , Glucose/metabolismo , Artérias Mesentéricas/metabolismo , Vasodilatação , Ácido 3-Hidroxibutírico/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Endotélio Vascular/fisiopatologia , Artérias Mesentéricas/fisiopatologia
7.
Diabetes Metab Syndr ; 13(5): 2869-2872, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31425950

RESUMO

Type 2 diabetes mellitus (T2DM) is a major health problem for morbidity and mortality world-wide due to diabetic vascular complication. Following T2DM, dyslipidemia is known well for the main reason of vascular complication leading to atherosclerosis and impaired life expectancy in diabetes. Thus, a new prediction marker in T2DM could help prevent the progression disease despite of metabolic control. Signal peptide-CUB-EGF like containing protein 2 (SCUBE2), has been detected in vascular endothelium and was affected by cytokines. Recently, SCUBE2 was reported to increase in atherosclerotic human coronary artery, involving vascular smooth muscle cells (VSMCs) and macrophages. The aims of this study were to examine the expression level of SCUBE2 in T2DM patients with dyslipidemia and its correlation with endothelial dysfunction marker, endothelin-1 (ET-1) in this group. This study design was cross sectional control study, recruited 28 patients diagnosed as T2DM who were found with dyslipidemia and 15 healthy control subjects. Our results showed that T2DM patients showed higher LDL cholesterol, triglycerides, and ET-1 expression level compared to healthy subjects. Further, we found that SCUBE2 had strong correlation with ET-1 in these dyslipidemic T2DM patients. In conclusion, our study confirmed first that SCUBE2 was upregulated in T2DM with dyslipidemia. Moreover, Pearson correlation analysis of ET-1 and SCUBE2 in this group showed high correlation r = 0.797, P < 0.001, suggesting that SCUBE2 may plausible target in vascular function changes in dyslipidemic T2DM. Improving our exploration of these findings may lead to uncover SCUBE2 involvement in diabetic vascular complication in T2DM.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/metabolismo , Dislipidemias/metabolismo , Endotelina-1/metabolismo , Adulto , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/etiologia , Dislipidemias/complicações , Dislipidemias/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
8.
Diabetes Metab Syndr ; 13(5): 2873-2877, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31425951

RESUMO

AIM: Diabetic patients predispose to vascular diseases such as nephropathy, and retinopathy. Poor adherence to medical treatment and dietary recommendations in uncontrolled diabetes leads to vascular damages. Vitamin D has been extensively studied and found to be protective against diabetes mellitus. YKL-40 and Monocyte chemoattractant protein-1 (MCP-1) are considered to exert crucial role in diabetes and its complications. Therefore, this study was designed to investigate effects of vitamin D supplementation on serum levels of YKL-40 and MCP-1 involved in the development of diabetic complications. METHODS: For 12 weeks, 48 type 2 diabetic patients enrolled in the trial and randomly were divided into two groups (n = 24 per group), receiving one of the following: 100 µg (4000 IU) vitamin D or placebo. Before and after intervention, serumYKL-40, MCP-1, insulin, IL-6, TNF-α, 25- (OH) vitamin D and HbA1c were measured. RESULTS: Our results revealed that serum levels of 25 (OH) vitamin D significantly increased in vitamin D group (p < 0.001). Vitamin D supplementation also significantly reduced serum YKL-40 levels (-22.7 vs. -2.4 ng/ml; (p-value = 0.003)). There was a significant decline in MCP-1 concentration in intervention group at the end of the study (-45.7 vs. -0.9 pg/ml; (p = 0.001)). Furthermore, there was a significant decrease in IL-6, fasting insulin and HOMA-IR in intervention group after 3 months supplementation. CONCLUSIONS: Daily vitamin D supplementation effectively reduced circulatory YKL-40 and MCP-1 levels in patients with type-2 diabetes and vitamin D deficiency. Vitamin D might contribute in reducing diabetic complications via modulating YKL-40 and MCP-1 signaling pathways.


Assuntos
Biomarcadores/sangue , Quimiocina CCL2/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/sangue , Deficiência de Vitamina D/tratamento farmacológico , Vitamina D/administração & dosagem , Adulto , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/etiologia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia , Vitaminas/administração & dosagem
9.
Diabetes Metab Syndr ; 13(5): 2939-2946, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31425960

RESUMO

OBJECTIVES: To identify the prevalence of micro- and macro-vascular complications and their associated factors for type 2 diabetes mellitus in Bangladesh. METHODS: This retrospective and cross-sectional study was conducted in six diabetes hospitals, covered urban and rural population. From April to September in 2017, a total of 1253 type 2 diabetes patients aged ≥18 years were recruited. Participants answered a pre-tested electronic questionnaire, and their medical records were reviewed for documented diabetes complications. RESULTS: Mean age was 55.1 (±12.6) years. Among macrovascular complications, the prevalence of coronary artery disease was found to be 30.5%, 10.1% for stroke and 12.0% for diabetic foot. Among microvascular complications, nephropathy was prevalent among 34.2%, retinopathy among 25.1% and neuropathy among 5.8% of patients. Risk factors found to be associated with one or more of the complications were female gender, higher age, lower education level, an urban area of residence, higher household income, smoking, physical inactivity, hypertension, poor glycaemic control, poor adherence to treatment, longer duration of diabetes, and insulin use. CONCLUSION: Diabetes complications are highly prevalent among type 2 diabetes population in Bangladesh. Prevention strategies should focus on increasing physical activity, weight loss, smoking cessation, and more strict control of hypertension and glycaemic level.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Bangladesh/epidemiologia , Biomarcadores/análise , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Angiopatias Diabéticas/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco
10.
Diab Vasc Dis Res ; 16(4): 378-384, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31271311

RESUMO

BACKGROUND: Epicardial fat is recognized as active endocrine organ and as emerging risk factor for cardio-metabolic diseases. The aim of this study was to explore the relationship between epicardial fat and carotid intima-media thickness in type 2 diabetes patients. METHODS: Epicardial fat thickness was measured in 76 type 2 diabetes patients without clinical atherosclerotic cardiovascular disease and 30 age- and sex-matched controls. In addition to laboratory tests, all patients underwent transthoracic echocardiography for epicardial fat thickness and ultrasonographic examination of carotid intima-media thickness. RESULTS: Patients with diabetes had higher epicardial fat thickness and carotid intima-media thickness than those of the controls (6.23 ± 1.27 mm vs 4.6 ± 1.03 mm, p < 0.001 and 0.77 ± 0.150 mm vs 0.58 ± 0.08 mm, p < 0.001, respectively). Epicardial fat thickness was correlated significantly with age, duration of type 2 diabetes, body mass index, waist circumference, HbA1c, carotid intima-media thickness, Homeostasis Model Assessment Index for insulin resistance and lipid profile in the type 2 diabetic patients. Stepwise regression analysis showed that carotid intima-media thickness, duration of diabetes, triglyceride and body mass index were the independent predictors of epicardial fat thickness, with carotid intima-media thickness the most important predictor (ß = 3.078, t = 4.058, p < 0.001). Receiver operating characteristic curve analysis was done and cut-off high-risk epicardial fat thickness value of 6.1 mm was determined with a sensitivity and specificity of 71.4% and 72%, respectively. CONCLUSION: Patients with type 2 diabetes have higher carotid intima-media thickness and epicardial fat thickness. Epicardial fat thickness was found to be a strong predictor of subclinical atherosclerosis.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Doença da Artéria Coronariana/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/diagnóstico por imagem , Ecocardiografia , Pericárdio/diagnóstico por imagem , Adulto , Doenças Assintomáticas , Doenças das Artérias Carótidas/etiologia , Estudos de Casos e Controles , Doença da Artéria Coronariana/etiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/etiologia , Egito , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco
11.
Folia Med (Plovdiv) ; 61(2): 231-239, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301656

RESUMO

BACKGROUND AND AIMS: An important factor in the development of vascular wall lesions is the degradation of the major protein of connective tissue - type IV collagen. Type IV collagen peptides (CIVDP) derived from this degradation are present in the circulation and are a stimulus for production of anti-collagen type IV antibodies (ACIVAbs) IgM, IgG and IgA. The aim of this study was to find a possible association between ACIVAbs, lipid indices and the development of microvascular complications. MATERIALS AND METHODS: Sera of 93 patients (mean age 61.4±11.3 yrs, diabetes duration 9.88±3.12 yrs; hypertension duration 9.28±4.98) with type 2 diabetes mellitus (T2DM) and arterial hypertension (AH) were investigated. ACIVAbs was determined using ELISA and then compared to serum ACIVAbs in 42 age- and sex-matched controls. Diabetics were divided into two groups according to presence (group 1, n=67) or absence (group 2, n=26) of microangiopathy. Lipid profile and lipid indices (log TG/HDL, LDL/HDL, TC/HDL and TG/HDL) were examined too. RESULTS: Patients with T2DM and AH showed statistically significant higher levels of serum ACIVAbs IgG than healthy controls [0.298 (0.237÷0.381) vs 0.210 (0.149÷0.262), KW=14.01, p<0.0001]. Group 1 had statistically significant higher levels of ACIVAbs IgG than patients without microangiopathy [0.323 (0.243÷0.391) vs 0.241 (0.207÷0.291), KW=7.66, p=0.006] and healthy controls [0.210 (0.149÷0.262), KW=17.52, p<0.0001). ACIVAbs IgG showed correlation with duration of diabetes (r=0.49, p=0.01), retinopathy (r=-0.20, p=0.04) and BMI (r=-0.24, p=0.05), HbA1c (r=0.21, p=0.04), SBP (r=0.16, p=0.05). ACIVAbs IgG correlated with log TG/HDL (r=0.21, p=0.01), LDL/HDL (r=0.19, p=0.02) TC/HDL (r=0.16, p=0.05) and with TG/HDL (r=0.15, p=0.05). CONCLUSION: Our study shows relationship between elevation of ACIVAbs IgG, high lipid indices and development of microvascular complications in patients with type 2 diabetes mellitus and arterial hypertension.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Neuropatias Diabéticas/metabolismo , Retinopatia Diabética/metabolismo , Hipertensão/metabolismo , Idoso , Autoanticorpos/imunologia , Estudos de Casos e Controles , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Colágeno Tipo IV/imunologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/imunologia , Angiopatias Diabéticas/metabolismo , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/imunologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/imunologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Triglicerídeos/metabolismo
12.
Artigo em Inglês | MEDLINE | ID: mdl-31343130

RESUMO

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterised by a destruction of pancreatic  cells, which leads to absolute insulin deficiency. Persistently high glycaemia causes vascular damage throughout the body. Microvascular complications com-prise the following: nephropathy, retinopathy, and neuropathy. Macrovascular complications include coronary heart disease (CHD), which may result in myocardial infarction, cerebrovascular disease (leading to strokes), and peripheral vascular disease. The pathogene-sis of vascular complications is multifactorial and is probably the combination of direct glucose-mediated endothelial damage, oxidative stress, production of sorbitol, and advanced glycation end-products. Precise understanding of these mechanisms could help clinicians to identify diabetic complications earlier and subsequently implement indispensable therapy on time. It is vital to determine biomarkers of microvascular and macrovascular complications in children affected with T1DM. Advanced glycation end-products and their receptors, adhesive molecules, pro- and anti-inflammatory cytokines, enzymes such as N-acetyl-ß-D-glucosaminidase, and growth factors are the subject of ongoing studies. Numerous biomarkers of diabetic microangiopathy are already known and may constitute therapeutic targets in the future. Unfortunately, despite substantial progress in the understanding of the processes by which microvascular and macrovascu-lar complications develop, much effort still needs to be devoted to the matter, and further investigations are required.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Inflamação , Biomarcadores , Doença das Coronárias/etiologia , Angiopatias Diabéticas/complicações , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Retinopatia Diabética/etiologia , Humanos , Acidente Vascular Cerebral/etiologia
13.
Diabetes Metab Syndr ; 13(2): 1299-1302, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336481

RESUMO

Diabetes mellitus (DM) is a chronic debilitating illness, and atherosclerotic changes are inevitable and usually neglected during the follow-up of diabetic patients. Toll-like receptor 2 (TLR2) is under trial in many studies to hold responsibility for atherosclerosis process progression as they suggest a malfunction of these receptors expressed on monocytes in diabetic patients. This study aimed to assess the association between the TLR2 and type 2 diabetes mellitus (T2DM) in Egyptian diabetic patients and to investigate its relationship with some diabetic complications. METHODS: This study included a 60 diabetic patients group 1 (diabetic complicated), group 2 (diabetic non-complicated) and 30 age-matched normal healthy blood donors. RESULTS: Toll-like receptors (TLRs) expression was significantly associated with T2DM. In this study, the mean fluorescent intensity (MFI) of TLR2 was 596.9 ±â€¯84.78 in group 1, 326.23 ±â€¯62.98 in group 2 while in group 3 it was 208.47 ±â€¯156.73. There was a significant correlation between MFI of TLR2 and random blood sugar (RBS) and glycated haemoglobin (HbA1c) (p < 0.05). CONCLUSION: TLR2 was overexpressed in diabetic patients with microvascular complications compared to diabetic non-complicated patients and normal healthy controls.


Assuntos
Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/diagnóstico , Monócitos/metabolismo , Receptor 2 Toll-Like/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
14.
Diabetes Metab Syndr ; 13(2): 1615-1622, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336530

RESUMO

OBJECTIVE: The aim was to estimate the burden of macro- and micro-vascular complications on hospitalisation and healthcare cost among people with type 2 diabetes mellitus in Bangladesh. METHODS: A cross-sectional study was carried out in 2017. A total of 1253 patients were recruited from six hospitals. Information related to cost and complications of type 2 diabetes were collected. Multiple logistic and non-parametric regression analyses were performed to evaluate the effect of complications on hospitalisation and average annual cost. RESULTS: Overall, 63.4% of the participants had complications of which 14.8% and 20.7% had macro- and micro-vascular complications respectively and 27.9% had both. Use of insulin, presence of both hypertension and dyslipidaemia, coronary artery diseases, stroke, nephropathy, and retinopathy were significantly associated with hospitalisation. Further, use of oral hypoglycaemic agent with a combination of insulin, presence of coronary artery diseases, stroke, nephropathy, and retinopathy increased the average annual cost. CONCLUSION: The prevalence of macro- and micro-vascular complications were very high in Bangladesh and majority of them are key drivers for hospitalisation and increased healthcare cost. An improvement of primary prevention strategy for complications is urgently needed which in turn will reduce the long-term healthcare cost for type 2 diabetes in Bangladesh.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/etiologia , Bangladesh/epidemiologia , Estudos Transversais , Angiopatias Diabéticas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco
15.
Mol Med Rep ; 20(2): 931-938, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173254

RESUMO

Vascular remodeling induced by long­term hyperglycaemia is the main pathological process in diabetic vascular complications. Thus, vascular remodeling may be a potential therapeutic target in diabetes mellitus (DM) with macrovascular disease. The present study aimed to investigate the effect of RING finger protein 10 (RNF10) on vascular remodeling under conditions of chronic hyperglycaemia stimulation. We found that overexpression of RNF10 clearly decreased intimal thickness and attenuated vascular remodeling in DM. TUNEL staining showed that apoptosis was clearly inhibited, an effect that may be mediated by decreases in Bcl­2 protein expression. Quantitative analysis demonstrated that overexpression of RNF10 could suppress inflammation by reducing the levels of TNF­α, and MCP­1 mRNA and NF­κB protein. Meanwhile, overexpression of RNF10 prevented vascular smooth muscle cell (VSMC) hyperproliferation through the downregulation of cyclin D1 and CDK4 proteins. Notably, short hairpin RNF10 (shRNF10) greatly aggravated the pathological responses of diabetic vascular remodeling. These outcomes revealed that the differential expression of RNF10 had a completely opposite effect on vascular damage under hyperglycaemia, further displaying the core function of RNF10 in regulating vascular remodeling induced by diabetes. Consequently, RNF10 could be a novel target for the treatment of diabetic vascular complications.


Assuntos
Proteínas de Transporte/genética , Diabetes Mellitus Experimental/genética , Angiopatias Diabéticas/genética , Hiperglicemia/genética , Miócitos de Músculo Liso/metabolismo , Proteínas do Tecido Nervoso/genética , Animais , Apoptose/genética , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/patologia , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Resistência à Insulina/genética , Masculino , Miócitos de Músculo Liso/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Cardiovasc Diabetol ; 18(1): 74, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31167666

RESUMO

BACKGROUND: Type-2 diabetes mellitus is one of the major risk factors of atherosclerosis, particularly in peripheral artery disease (PAD). Several studies have documented a correlation between omentin-1 serum levels, atherosclerosis, and cardiovascular diseases. However, a clear link between circulating omentin-1 and PAD in diabetic patients has yet to be established. The aim of this study was to investigate the potential role of omentin-1 in PAD in type-2 diabetic patients. METHODS: In this cross-sectional study, we analyzed omentin-1 serum levels by ELISA in 600 type-2 diabetic patients with (n = 300) and without (n = 300) PAD at Fontaine's stage II, III, or IV. RESULTS: We found that omentin-1 serum levels were significantly lower in diabetic patients with PAD than in diabetic controls (29.46 vs 49.24 ng/mL, P < 0.001) and that the levels gradually decreased in proportion to disease severity (P < 0.05). The association between omentin-1 levels and PAD remained significant after adjusting for major risk factors in a multivariate analysis. CONCLUSIONS: Our results suggest that omentin-1 is reduced in type 2 diabetic patients with PAD and that omentin-1 levels are related to disease severity.


Assuntos
Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Lectinas/sangue , Doença Arterial Periférica/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/etiologia , Regulação para Baixo , Feminino , Proteínas Ligadas por GPI/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/etiologia , Índice de Gravidade de Doença
17.
Diab Vasc Dis Res ; 16(6): 513-522, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31144511

RESUMO

The aim of this study was to assess the blood vessel density and maturity in the skin of adults with type 1 diabetes in relation to the presence of late neurovascular complications. We included 148 patients (87 men) with a median (interquartile range) age of 41 (31-49) and median diabetes duration of 21 (17-30) years. Microvessel (CD133, CD34, CD31 and von Willebrand factor) markers were evaluated by indirect immunohistochemistry assay in material from a skin biopsy. Diabetic retinopathy was diagnosed using direct ophthalmoscopy, and diabetic kidney disease was estimated in people with increased albuminuria and a 10-year duration of diabetes or evidence of diabetic retinopathy . Diabetic peripheral neuropathy diagnosis was based on Toronto definition, cardiac autonomic neuropathy on validated ProSciCard III program. Microvessel density, assessed by CD34 and CD133, was significantly higher in patients with cardiac autonomic neuropathy [160 (125-175) vs 121 (100-154)/1 mm2, p = 0.001 and 92 (83-104) vs 79 (63-92)/1 mm2, p = 0.007, respectively] and CD34 in patients with diabetic peripheral neuropathy [135 (106-168) vs 121 (95-145)/1 mm2, p = 0.018], as compared with subjects without complications. In multivariate logistic regression, density of CD34 and CD133 positive vessels was associated with presence of cardiac autonomic neuropathy [odds ratio 1.016 (95% confidence interval: 1.002-1.029), p = 0.019 and odds ratio 1.037 (95% confidence interval: 1.008-1.067), p = 0.011, respectively]. It was independent from age, sex, diabetes duration, smoking status, body mass index and HbA1c value. Density of CD34 positive vessels was also associated with diabetic peripheral neuropathy, independently from sex and diabetes duration [odds ratio 1.009 (95% confidence interval: 1.001-1.020), p = 0.037]. Skin microvessel density is increased in adults with clinical evidence of neurovascular complications of type 1 diabetes. This is associated with predominance of the vessels of low maturity.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/etiologia , Neuropatias Diabéticas/etiologia , Microvasos/patologia , Neovascularização Patológica , Pele/irrigação sanguínea , Adulto , Diabetes Mellitus Tipo 1/patologia , Angiopatias Diabéticas/patologia , Neuropatias Diabéticas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Adulto Jovem
18.
Nutr Metab Cardiovasc Dis ; 29(8): 815-821, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31133497

RESUMO

BACKGROUND AND AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is rapidly gaining attention as a potential risk of developing atherosclerosis due to its crucial role in the regulation of low-density lipoprotein cholesterol (LDL-C) metabolism. The present study investigated the relationship between serum PCSK9 levels and early atherosclerosis as assessed by carotid intimal-medial thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) in newly diagnosed type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: A total of 100 newly diagnosed T2DM were enrolled and further divided into the thickened CIMT group (n = 41) and the non-thickened CIMT group (n = 59) according to the results of color Doppler ultrasonography. Serum PCSK9 levels, CIMT, ba-PWV, and metabolic parameters were measured. Patients in the thickened CIMT group had higher serum PCSK9 levels than patients in the non-thickened CIMT group (all P < 0.05). CIMT and ba-PWV were both positively correlated to serum PCSK9 levels, while serum PCSK9 levels were positively correlated to white blood cell count, neutrophil, lymphocyte, and high-sensitivity C-reactive protein (P < 0.05). Multiple linear regression indicated that serum PCSK9 level was an independent predictor of CIMT (ß = 0.637, P < 0.001) and ba-PWV (ß = 0.600, P < 0.001). Binary logistic regression analysis showed that serum PCSK9 levels were independent risk factors of thickened CIMT [OR = 1.120, 95%CI (1.041-1.204), P = 0.002]. CONCLUSION: Serum PCSK9 levels are significantly correlated with CIMT and ba-PWV, independent of CAD risk factors. Therefore, serum PCSK9 level may have the potential to serve as a prescriptive biomarker for early arteriosclerosis in newly diagnosed T2DM.


Assuntos
Doenças das Artérias Carótidas/sangue , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Doença Arterial Periférica/sangue , Pró-Proteína Convertase 9/sangue , Idoso , Índice Tornozelo-Braço , Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/enzimologia , Doenças das Artérias Carótidas/etiologia , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/enzimologia , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/enzimologia , Angiopatias Diabéticas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/enzimologia , Doença Arterial Periférica/etiologia , Valor Preditivo dos Testes , Fatores de Risco , Ultrassonografia Doppler em Cores , Regulação para Cima
19.
Cardiovasc Diabetol ; 18(1): 61, 2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077210

RESUMO

BACKGROUND: The relationship between dyslipidemia, inflammation and CV organ damage in type 2 diabetes mellitus (T2DM) is complex. Insulin resistance and inflammatory cytokines interleukins (ILs) increase plasma triglycerides (TG). ILs also up-regulate expression of matrix-metalloproteinases (MMPs) that, together with TG, decrease high density lipoprotein cholesterol (HDL) levels. High TG, low HDL, increased ILs and MMPs trigger structural and functional changes in different parts of cardiovascular (CV) system. To understand better the role of lipids and inflammation in CV organ damage, the present study investigated the inter-relationships between lipids, ILs and MMPs, as well as the associations of lipids, ILs and MMPs with various CV measures, both in diabetic and non-diabetic population (nonT2DM). METHODS: In T2DM patients (N = 191) and nonT2DM subjects (N = 94) were assessed carotid intima-media thickness (cIMT) and inter-adventitial diameter (IADiam), carotid wave speed (ccaWS), carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, LV systolic (s') and early diastolic (e') longitudinal velocities of mitral annulus, together with glycemic control, lipid profile, IL-6, IL-18 and MMP-12. RESULTS: T2DM patients, as compared to nonT2DM subjects, had significantly higher plasma levels of IL-6, IL-18, MMP-12 and lower HDL (P < 0.05-0.0001). They had also higher cIMT, IADiam, ccaWS, cfPWV and LV mass, and lower e' velocity (P < 0.005-0.0001). Both in T2DM patients and nonT2DM subjects, MMP-12 increased with IL-6 (r = 0.43 and 0.39; P < 0.0001) and IL-18 (r = 0.32 and 0.42; P < 0.0001), and HDL decreased with MMP-12 (r = - 0.29 and - 0.42; P < 0.0001). In both populations, MMP-12 was directly associated with IADiam, ccaWS, cfPWV and LV mass (r = 0.42, 0.32, 0.26 and 0.29; P < 0.0001 in T2DM patients, and r = 0.39, 0.28, 0.32 and 0.27; P < 0.01-0.0001 in nonT2DM subjects). In multivariate analysis, MMP-12 remained independently related to IADiam, ccaWS, cfPWV and LV mass in T2DM patients, and to IADiam only in nonT2DM subjects. CONCLUSIONS: This cross-sectional study demonstrated a direct association between ILs and MMP-12, as well as an inverse association between MMP-12 and HDL, both in T2DM patients and in nonT2DM subjects. In T2DM patients, who had higher levels of ILs and MMP-12, the latter was independently related to several structural and functional markers of preclinical CV organ damage.


Assuntos
Doenças das Artérias Carótidas/etiologia , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/etiologia , Dislipidemias/complicações , Mediadores da Inflamação/sangue , Inflamação/complicações , Lipídeos/sangue , Idoso , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/fisiopatologia , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Interleucinas/sangue , Masculino , Metaloproteinases da Matriz/sangue , Pessoa de Meia-Idade , Fatores de Risco , Remodelação Vascular , Remodelação Ventricular
20.
Biochimie ; 162: 1-7, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30922869

RESUMO

OBJECTIVES: The potential implication of micro-RNAs (miRs) in the negative association between diabetes and abdominal aortic aneurysm (AAA) has so far never been addressed. The aim of this study was to compare miR expression between diabetic and non-diabetic patients with AAA. METHODS: Ten diabetic patients were prospectively included and compared to 10 age- and sex-matched non-diabetic patients with infrarenal AAA. A profiling analysis of 752 human miRs was performed from peripheral blood mononuclear cells (PBMCs) using miRCURY LNA Universal RT microRNA PCR (Exiqon- Qiagen®). miR that showed significant differential expression (P < 0.05) were selected and further analyzed in the entire cohort in sera, plasma and aneurysmal aortic tissues. RESULTS: Four miRs were significantly differentially expressed in PBMCs of diabetic patients compared to non-diabetics: 3 were upregulated (miR-144-3p, 20a-5p and 188-3p) and 1 downregulated (miR-548k). miR-144-3p and miR-548k were also increased in aneurysmal tissue and miR-20a-5p was increased in serum. The expression of miR-20a-5p in PBMCs was correlated with fructosamine concentration (r = 0.62, p = 0.006). CONCLUSIONS: Even if further studies are required to determine their direct role in AAA, these miRs could represent interesting new targets.


Assuntos
Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/metabolismo , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/etiologia , MicroRNAs/metabolismo , Idoso , Aneurisma da Aorta Abdominal/sangue , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade
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