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[PMID]: 27771154 [Au] Autor: Barbieri M; Marfella R; Esposito A; Rizzo MR; Angellotti E; Mauro C; Siniscalchi M; Chirico F; Caiazzo P; Furbatto F; Bellis A; D'Onofrio N; Vitiello M; Ferraraccio F; Paolisso G; Balestrieri ML [Ad] Endereço: Department of Medical, Surgical, Neurological, Aging and Metabolic Sciences, Second University of Naples, Piazza Miraglia 2, 80138, Naples, Italy. Electronic address: michelangela.barbieri@unina2.it. [Ti] Título: Incretin treatment and atherosclerotic plaque stability: Role of adiponectin/APPL1 signaling pathway. [So] Source: J Diabetes Complications;31(2):295-303, 2017 Feb. [Is] ISSN: 1873-460X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: AIMS: Glucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated. METHODS: The effect of incretin therapy in the regulation of adiponectin/APPL1 signaling was evaluated both on carotid plaques of asymptomatic diabetic (n=71) and non-diabetic patients (n=52), and through in vitro experiments on endothelial cell (EC). RESULTS: Atherosclerotic plaques of T2DM patients showed lower adiponectin and APPL1 levels compared with non-diabetic patients, along with higher oxidative stress, tumor necrosis factor-α (TNF-α), vimentin, and matrix metalloproteinase-9 (MMP-9) levels. Among T2DM subjects, current incretin-users presented higher APPL1 and adiponectin content compared with never incretin-users. Similarly, in vitro observations on endothelial cells co-treated with high-glucose (25mM) and GLP-1 (100nM) showed a greater APPL1 protein expression compared with high-glucose treatment alone. CONCLUSIONS: Our findings suggest a potential role of adiponectin/APPL1 signaling in mediating the effect of incretin in the prevention of atherosclerosis progression or plaque vulnerability in T2DM. [Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/agonistas Adiponectina/metabolismo Diabetes Mellitus Tipo 2/tratamento farmacológico Angiopatias Diabéticas/prevenção & controle Incretinas/uso terapêutico Placa Aterosclerótica/prevenção & controle Transdução de Sinais/efeitos dos fármacos [Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo Idoso Anti-Inflamatórios não Esteroides/farmacologia Anti-Inflamatórios não Esteroides/uso terapêutico Antioxidantes/farmacologia Antioxidantes/uso terapêutico Estenose das Carótidas/complicações Estenose das Carótidas/epidemiologia Estenose das Carótidas/prevenção & controle Estenose das Carótidas/cirurgia Células Cultivadas Diabetes Mellitus Tipo 2/complicações Diabetes Mellitus Tipo 2/metabolismo Diabetes Mellitus Tipo 2/patologia Angiopatias Diabéticas/epidemiologia Angiopatias Diabéticas/patologia Angiopatias Diabéticas/cirurgia Endarterectomia das Carótidas Endotélio Vascular/efeitos dos fármacos Endotélio Vascular/imunologia Endotélio Vascular/metabolismo Endotélio Vascular/patologia Feminino Peptídeo 1 Semelhante ao Glucagon/metabolismo Seres Humanos Incretinas/farmacologia Itália/epidemiologia Masculino Estresse Oxidativo/efeitos dos fármacos Placa Aterosclerótica/complicações Placa Aterosclerótica/epidemiologia Placa Aterosclerótica/patologia Fatores de Risco Prevenção Secundária [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE [Nm] Nome de substância: 0 (ADIPOQ protein, human); 0 (APPL1 protein, human); 0 (Adaptor Proteins, Signal Transducing); 0 (Adiponectin); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antioxidants); 0 (Incretins); 89750-14-1 (Glucagon-Like Peptide 1) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180226 [Lr] Data última revisão: 180226 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161025 [St] Status: MEDLINE

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[PMID]: 27770590 [Au] Autor: Cho YH; Craig ME; Januszewski AS; Benitez-Aguirre P; Hing S; Jenkins AJ; Donaghue KC [Ad] Endereço: Institute of Endocrinology and Diabetes, Children's Hospital at Westmead, Westmead, Australia. [Ti] Título: Higher skin autofluorescence in young people with Type 1 diabetes and microvascular complications. [So] Source: Diabet Med;34(4):543-550, 2017 Apr. [Is] ISSN: 1464-5491 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: AIM: To test the hypothesis that non-invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long-term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes. METHODS: Forearm skin autofluorescence (arbitrary units) was measured in a cross-sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8.7 ± 3.5 years, HbA 72 ± 16 mmol/mol (8.7 ± 1.5%)]. Retinopathy, assessed using seven-field stereoscopic fundal photography, was defined as ≥1 microaneurysm or haemorrhage. Cardiac autonomic function was measured by standard deviation of consecutive RR intervals on a 10-min continuous electrocardiogram recording, as a measure of heart rate variability. RESULTS: Skin autofluorescence was significantly associated with age (R = 0.15; P < 0.001). Age- and gender-adjusted skin autofluorescence was associated with concurrent HbA (R = 0.32; P < 0.001) and HbA over the previous 2.5-10 years (R = 0.34-0.43; P < 0.002). Age- and gender-adjusted mean skin autofluorescence was higher in adolescents with retinopathy vs those without retinopathy [mean 1.38 (95% CI 1.29, 1.48) vs 1.22 (95% CI 1.17, 1.26) arbitrary units; P = 0.002]. In multivariable analysis, retinopathy was significantly associated with skin autofluorescence, adjusted for duration (R = 0.19; P = 0.03). Cardiac autonomic dysfunction was also independently associated with skin autofluorescence (R = 0.11; P = 0.006). CONCLUSIONS: Higher skin autofluorescence is associated with retinopathy and cardiac autonomic dysfunction in adolescents with Type 1 diabetes. The relationship between skin autofluorescence and previous glycaemia may provide insight into metabolic memory. Longitudinal studies will determine the utility of skin autofluorescence as a non-invasive screening tool to predict future microvascular complications. [Mh] Termos MeSH primário: Diabetes Mellitus Tipo 1/fisiopatologia Angiopatias Diabéticas/diagnóstico por imagem Retinopatia Diabética/diagnóstico por imagem Microaneurisma/diagnóstico por imagem Hemorragia Retiniana/diagnóstico por imagem Pele/diagnóstico por imagem [Mh] Termos MeSH secundário: Adolescente Doenças do Sistema Nervoso Autônomo/etiologia Doenças do Sistema Nervoso Autônomo/fisiopatologia Diabetes Mellitus Tipo 1/complicações Diabetes Mellitus Tipo 1/metabolismo Angiopatias Diabéticas/etiologia Angiopatias Diabéticas/fisiopatologia Retinopatia Diabética/etiologia Retinopatia Diabética/fisiopatologia Eletrocardiografia Feminino Fundo de Olho Hemoglobina A Glicada/metabolismo Frequência Cardíaca Seres Humanos Masculino Microaneurisma/etiologia Microaneurisma/fisiopatologia Análise Multivariada Imagem Óptica Hemorragia Retiniana/etiologia Hemorragia Retiniana/fisiopatologia Pele/irrigação sanguínea [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Glycated Hemoglobin A); 0 (hemoglobin A1c protein, human) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180213 [Lr] Data última revisão: 180213 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161023 [St] Status: MEDLINE [do] DOI: 10.1111/dme.13280

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[PMID]: 28467200 [Au] Autor: Santesson P; Lins PE; Kalani M; Adamson U; Lelic I; von Wendt G; Fagrell B; Jörneskog G [Ad] Endereço: 1 Microcirculatory Laboratory, Division of Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden. [Ti] Título: Skin microvascular function in patients with type 1 diabetes: An observational study from the onset of diabetes. [So] Source: Diab Vasc Dis Res;14(3):191-199, 2017 May. [Is] ISSN: 1752-8984 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: BACKGROUND: The development of disturbances in skin microcirculation in type 1 diabetes is not well characterised. We assessed skin microcirculation longitudinally from the onset of diabetes up to 29 years of duration to investigate when such disturbances start. MATERIAL AND METHODS: Seventeen adult patients with type 1 diabetes participated. Skin microvascular function in digit IV of the left hand was investigated by laser Doppler fluxmetry (LDF, arbitrary units [AU]). LDF was carried out at rest and following one-min arterial occlusion. Time to peak LDF (s) and percentage increase of LDF (post-occlusive reactive hyperaemia, PRH%) were determined. Retinopathy was assessed from fundus photographs or ophthalmoscopic recordings. RESULTS: Skin microvascular function remained normal during the first five years. Compared with baseline and a non-diabetic reference group, time to peak LDF was prolonged after 7-9 years of diabetes ( p < 0.01). PRH% was lower than in the reference group after 7-9 years ( p < 0.01), and lower than baseline after 24-29 years of diabetes ( p < 0.05). All but one patient developed retinopathy and the first signs were found after 10 years of diabetes. CONCLUSIONS: Functional disturbances in total skin microcirculation were observed after seven years in patients with type 1 diabetes and preceded diabetic complications such as retinopathy. [Mh] Termos MeSH primário: Diabetes Mellitus Tipo 1/complicações Angiopatias Diabéticas/etiologia Microcirculação Microvasos/fisiopatologia Pele/irrigação sanguínea [Mh] Termos MeSH secundário: Adulto Velocidade do Fluxo Sanguíneo Estudos de Casos e Controles Diabetes Mellitus Tipo 1/diagnóstico Diabetes Mellitus Tipo 1/fisiopatologia Angiopatias Diabéticas/diagnóstico Angiopatias Diabéticas/fisiopatologia Neuropatias Diabéticas/diagnóstico Neuropatias Diabéticas/etiologia Retinopatia Diabética/diagnóstico Retinopatia Diabética/etiologia Progressão da Doença Feminino Seres Humanos Fluxometria por Laser-Doppler Estudos Longitudinais Masculino Meia-Idade Oftalmoscopia Estudos Prospectivos Fluxo Sanguíneo Regional Fatores de Risco Temperatura Cutânea Fatores de Tempo Adulto Jovem [Pt] Tipo de publicação: JOURNAL ARTICLE; OBSERVATIONAL STUDY [Em] Mês de entrada: 1712 [Cu] Atualização por classe: 171219 [Lr] Data última revisão: 171219 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170504 [St] Status: MEDLINE [do] DOI: 10.1177/1479164117694463

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[PMID]: 28467198 [Au] Autor: Ng HH; Yildiz GS; Ku JM; Miller AA; Woodman OL; Hart JL [Ad] Endereço: 1 School of BioSciences, University of Melbourne, Parkville, VIC, Australia. [Ti] Título: Chronic NaHS treatment decreases oxidative stress and improves endothelial function in diabetic mice. [So] Source: Diab Vasc Dis Res;14(3):246-253, 2017 May. [Is] ISSN: 1752-8984 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Hydrogen sulphide (H S) is endogenously produced in vascular tissue and has anti-oxidant and vasoprotective properties. This study investigates whether chronic treatment using the fast H S donor NaHS could elicit a vasoprotective effect in diabetes. Diabetes was induced in male C57BL6/J mice with streptozotocin (60 mg/kg daily, ip for 2 weeks) and confirmed by elevated blood glucose and glycated haemoglobin levels. Diabetic mice were then treated with NaHS (100 µmol/kg/day) for 4 weeks, and aortae collected for functional and biochemical analyses. In the diabetic group, both endothelium-dependent vasorelaxation and basal nitric oxide (NO ) bioactivity were significantly reduced ( p < 0.05), and maximal vasorelaxation to the NO donor sodium nitroprusside was impaired ( p < 0.05) in aorta compared to control mice. Vascular superoxide generation via nicotine adenine dinucleotide phosphate (NADPH) oxidase ( p < 0.05) was elevated in aorta from diabetic mice which was associated with increased expression of NOX2 ( p < 0.05). NaHS treatment of diabetic mice restored endothelial function and exogenous NO efficacy back to control levels. NaHS treatment also reduced the diabetes-induced increase in NADPH oxidase activity, but did not affect NOX2 protein expression. These data show that chronic NaHS treatment reverses diabetes-induced vascular dysfunction by restoring NO efficacy and reducing superoxide production in the mouse aorta. [Mh] Termos MeSH primário: Antioxidantes/administração & dosagem Diabetes Mellitus Experimental/tratamento farmacológico Angiopatias Diabéticas/prevenção & controle Endotélio Vascular/efeitos dos fármacos Estresse Oxidativo/efeitos dos fármacos Sulfetos/administração & dosagem [Mh] Termos MeSH secundário: Animais Glicemia/metabolismo Diabetes Mellitus Experimental/sangue Diabetes Mellitus Experimental/complicações Angiopatias Diabéticas/etiologia Angiopatias Diabéticas/metabolismo Angiopatias Diabéticas/fisiopatologia Relação Dose-Resposta a Droga Esquema de Medicação Endotélio Vascular/metabolismo Endotélio Vascular/fisiopatologia Hemoglobina A Glicada/metabolismo Masculino Camundongos Endogâmicos C57BL Músculo Liso Vascular/efeitos dos fármacos Músculo Liso Vascular/metabolismo Músculo Liso Vascular/fisiopatologia NADPH Oxidase 2/metabolismo Óxido Nítrico/metabolismo Doadores de Óxido Nítrico/farmacologia Óxido Nítrico Sintase Tipo III/metabolismo Superóxidos/metabolismo Fatores de Tempo Vasodilatação/efeitos dos fármacos Vasodilatadores/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antioxidants); 0 (Blood Glucose); 0 (Glycated Hemoglobin A); 0 (HbA(1c) protein, mouse); 0 (Nitric Oxide Donors); 0 (Sulfides); 0 (Vasodilator Agents); 11062-77-4 (Superoxides); 31C4KY9ESH (Nitric Oxide); EC 1.14.13.39 (Nitric Oxide Synthase Type III); EC 1.14.13.39 (Nos3 protein, mouse); EC 1.6.3.- (Cybb protein, mouse); EC 1.6.3.- (NADPH Oxidase 2); FWU2KQ177W (sodium bisulfide) [Em] Mês de entrada: 1712 [Cu] Atualização por classe: 171219 [Lr] Data última revisão: 171219 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170504 [St] Status: MEDLINE [do] DOI: 10.1177/1479164117692766

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[PMID]: 28467197 [Au] Autor: Wu HT; Lee KW; Pan WY; Liu AB; Sun CK [Ad] Endereço: 1 Department of Electrical Engineering, National Dong Hwa University, Hualien, Taiwan, R.O.C. [Ti] Título: Difference in bilateral digital volume pulse as a novel non-invasive approach to assessing arteriosclerosis in aged and diabetic subjects: A preliminary study. [So] Source: Diab Vasc Dis Res;14(3):254-257, 2017 May. [Is] ISSN: 1752-8984 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVE: This study aimed at validating photoplethysmography for assessing bilateral blood pressure differences through investigating the correlations of digital volume pulse with arteriosclerosis risk. METHODS: Totally, 111 subjects (70 healthy and 41 diabetic) were recruited. Demographic, blood pressure and anthropometric data were recorded. Blood was collected for determining serum cholesterol, total triglyceride, total cholesterol, high-/low-density lipoprotein cholesterol, fasting blood sugar and glycated haemoglobin concentrations. Arterial stiffness was assessed with electrocardiogram-based pulse wave velocity, crest time and inter-digital volume pulse differences. RESULTS: Receiver operating characteristic curve demonstrated high inter-digital volume pulse difference sensitivity to glycated haemoglobin level over 6.5%. Linear regression analysis demonstrated significant correlation between inter-digital volume pulse difference and electrocardiogram-based pulse wave velocity ( r = 0.692, p < 0.001). Compared with electrocardiogram-based pulse wave velocity, inter-digital volume pulse difference exhibited highly significant correlations with age, glycated haemoglobin level, pulse pressure, total cholesterol/high-density lipoprotein ratio, crest time, high-density lipoprotein and systolic blood pressure (all ps < 0.001). CONCLUSION: In conclusion, the results not only demonstrated successful application of a novel non-invasive waveform contour index, inter-digital volume pulse difference, in differentiating young from aged subjects and patients with good diabetic control from those with poor diabetic control but also validated its use in identifying arteriosclerosis risks. The results, therefore, endorse its domestic application as non-invasive tool for arteriosclerosis risk screening. [Mh] Termos MeSH primário: Aterosclerose/diagnóstico Pressão Sanguínea Angiopatias Diabéticas/diagnóstico Dedos/irrigação sanguínea Fotopletismografia [Mh] Termos MeSH secundário: Adulto Fatores Etários Área Sob a Curva Aterosclerose/sangue Aterosclerose/fisiopatologia Biomarcadores/sangue Glicemia/análise Estudos de Casos e Controles Angiopatias Diabéticas/sangue Angiopatias Diabéticas/fisiopatologia Hemoglobina A Glicada/análise Seres Humanos Modelos Lineares Lipídeos/sangue Projetos Piloto Valor Preditivo dos Testes Dados Preliminares Análise de Onda de Pulso Curva ROC Reprodutibilidade dos Testes Rigidez Vascular Adulto Jovem [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; VALIDATION STUDIES [Nm] Nome de substância: 0 (Biomarkers); 0 (Blood Glucose); 0 (Glycated Hemoglobin A); 0 (Lipids); 0 (hemoglobin A1c protein, human) [Em] Mês de entrada: 1712 [Cu] Atualização por classe: 171219 [Lr] Data última revisão: 171219 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170504 [St] Status: MEDLINE [do] DOI: 10.1177/1479164116688870

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[PMID]: 28749197 [Au] Autor: Yandrapalli S; Jolly G; Horblitt A; Sanaani A; Aronow WS [Ad] Endereço: a Cardiology Division, Department of Medicine , Westchester Medical Center /New York Medical College , Valhalla , NY , USA. [Ti] Título: Cardiovascular benefits and safety of non-insulin medications used in the treatment of type 2 diabetes mellitus. [So] Source: Postgrad Med;129(8):811-821, 2017 Nov. [Is] ISSN: 1941-9260 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Diabetes mellitus is a growing in exponential proportions. If the current growth trend continues, it may result in every third adult in the United States having diabetes mellitus by 2050, and every 10 adult worldwide. Type 2 diabetes mellitus (T2DM) confers a 2- to 3-fold increased risk of cardiovascular (CV) events compared with non-diabetic patients, and CV mortality is responsible for around 80% mortality in this population. Patients with T2DM can have other features of insulin resistance-metabolic syndrome like hypertension, lipid abnormalities, and obesity which are all associated with increased CV disease and stroke risk even in the absence of T2DM. The management of a T2DM calls for employing a holistic risk factor control approach. Metformin is the first line therapy for T2DM and has been shown to have cardiovascular beneficial effects. Intense debate regarding the risk of myocardial infarction with rosiglitazone led to regulatory agencies necessitating cardiovascular outcome trials with upcoming anti-diabetic medications. Glucagon like peptide-1 agonists and sodium glucose co-transporter-2 inhibitors have shown promising CV safety and additional CV benefit in recent clinical trials. These drugs have favorable effects on traditional CV risk factors. The findings from these studies further support that fact that CV risk factor control plays an important role in reducing morbidity and mortality in T2DM patients. This review article will discuss briefly the cardiovascular safety and benefits of the oral medications which are currently being used for T2DM and will then discuss in detail about the newer medications being investigated for the treatment of T2DM. [Mh] Termos MeSH primário: Doenças Cardiovasculares/etiologia Doenças Cardiovasculares/prevenção & controle Diabetes Mellitus Tipo 2/complicações Diabetes Mellitus Tipo 2/tratamento farmacológico Hipoglicemiantes/uso terapêutico [Mh] Termos MeSH secundário: Benzamidas/uso terapêutico Angiopatias Diabéticas/prevenção & controle Inibidores da Dipeptidil Peptidase IV/uso terapêutico Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas Inibidores de Glicosídeo Hidrolases/uso terapêutico Seres Humanos Hipoglicemiantes/administração & dosagem Hipoglicemiantes/efeitos adversos Metformina/uso terapêutico Ensaios Clínicos Controlados Aleatórios como Assunto Fatores de Risco Transportador 2 de Glucose-Sódio/antagonistas & inibidores Compostos de Sulfonilureia/uso terapêutico Tiazolidinedionas/uso terapêutico [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Benzamides); 0 (Dipeptidyl-Peptidase IV Inhibitors); 0 (Glucagon-Like Peptide-1 Receptor); 0 (Glycoside Hydrolase Inhibitors); 0 (Hypoglycemic Agents); 0 (Sodium-Glucose Transporter 2); 0 (Sulfonylurea Compounds); 0 (Thiazolidinediones); 8V6OK1I088 (meglitinide); 9100L32L2N (Metformin) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171128 [Lr] Data última revisão: 171128 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170728 [St] Status: MEDLINE [do] DOI: 10.1080/00325481.2017.1358064

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[PMID]: 28436035 [Au] Autor: D'Amico AG; Maugeri G; Rasà DM; La Cognata V; Saccone S; Federico C; Cavallaro S; D'Agata V [Ad] Endereço: Department of Human Science and Promotion of Quality of Life, San Raffaele Open University of Rome, Italy. [Ti] Título: NAP counteracts hyperglycemia/hypoxia induced retinal pigment epithelial barrier breakdown through modulation of HIFs and VEGF expression. [So] Source: J Cell Physiol;233(2):1120-1128, 2018 Feb. [Is] ISSN: 1097-4652 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Diabetic macular edema (DME) is a common complication leading to a central vision loss in patients with diabetes. In this eye pathology, the hyperglycaemic/hypoxic microenvironment of pigmented epithelium is responsible for outer blood retinal barrier integrity changes. More recently, we have shown that a small peptide derived from the activity-dependent neuroprotective protein (ADNP), known as NAP, counteracts damages occurring during progression of diabetic retinopathy by modulating HIFs/VEGF pathway. Here, we have investigated for the first time the role of this peptide on outer blood retinal barrier (BRB) integrity exposed to hyperglycaemic/hypoxic insult mimicking a model in vitro of DME. To characterize NAP role on disease's pathogenesis, we have analyzed its effect on HIFs/VEGF system in human retinal pigmented epithelial cells, ARPE-19, grown in high glucose and low oxygen tension. The results have shown that NAP prevents outer BRB breakdown by reducing HIF1α/HIF2α, VEGF/VEGFRs, and increasing HIF3α expression, moreover it is able to reduce the percentage of apoptotic cells by modulating the expression of two death related genes, BAX and Bcl2. Further investigations are needed to determine the possible use of NAP in DME treatment. [Mh] Termos MeSH primário: Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo Barreira Hematorretiniana/efeitos dos fármacos Angiopatias Diabéticas/tratamento farmacológico Células Epiteliais/efeitos dos fármacos Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo Edema Macular/tratamento farmacológico Oligopeptídeos/farmacologia Epitélio Pigmentado da Retina/efeitos dos fármacos Fator A de Crescimento do Endotélio Vascular/metabolismo [Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos Barreira Hematorretiniana/metabolismo Barreira Hematorretiniana/patologia Hipóxia Celular Linhagem Celular Citoproteção Angiopatias Diabéticas/metabolismo Angiopatias Diabéticas/patologia Impedância Elétrica Células Epiteliais/metabolismo Células Epiteliais/patologia Glucose/metabolismo Seres Humanos Edema Macular/metabolismo Edema Macular/patologia Proteínas Proto-Oncogênicas c-bcl-2/metabolismo Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo Epitélio Pigmentado da Retina/metabolismo Epitélio Pigmentado da Retina/patologia Transdução de Sinais/efeitos dos fármacos Proteína X Associada a bcl-2/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (BAX protein, human); 0 (BCL2 protein, human); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (HIF1A protein, human); 0 (HIF3A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Oligopeptides); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (VEGFA protein, human); 0 (Vascular Endothelial Growth Factor A); 0 (bcl-2-Associated X Protein); 0 (endothelial PAS domain-containing protein 1); EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor); GF00K3IIWE (davunetide); IY9XDZ35W2 (Glucose) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171128 [Lr] Data última revisão: 171128 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170425 [St] Status: MEDLINE [do] DOI: 10.1002/jcp.25971

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[PMID]: 29059687 [Au] Autor: Conlin PR; Colburn J; Aron D; Pries RM; Tschanz MP; Pogach L [Ad] Endereço: From VA Boston Healthcare System, West Roxbury, Massachusetts; San Antonio Military Medical Center, Fort Sam Houston, Texas; Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio; VHA National Center for Health Promotion and Disease Prevention, Durham, North Carolina; San Diego Internal Medicine [Ti] Título: Synopsis of the 2017 U.S. Department of Veterans Affairs/U.S. Department of Defense Clinical Practice Guideline: Management of Type 2 Diabetes Mellitus. [So] Source: Ann Intern Med;167(9):655-663, 2017 Nov 07. [Is] ISSN: 1539-3704 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Description: In April 2017, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the management of type 2 diabetes mellitus. Methods: The VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included a multidisciplinary panel of practicing clinician stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions in collaboration with the ECRI Institute, which systematically searched and evaluated the literature through June 2016, developed an algorithm, and rated recommendations by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: This synopsis summarizes key features of the guideline in 7 areas: patient-centered care and shared decision making, glycemic biomarkers, hemoglobin A1c target ranges, individualized treatment plans, outpatient pharmacologic treatment, glucose targets for critically ill patients, and treatment of hospitalized patients. [Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/terapia [Mh] Termos MeSH secundário: Biomarcadores/sangue Glicemia/metabolismo Tomada de Decisão Clínica Tomada de Decisões Diabetes Mellitus Tipo 2/sangue Diabetes Mellitus Tipo 2/complicações Angiopatias Diabéticas/prevenção & controle Frutosamina/sangue Hemoglobina A Glicada/metabolismo Seres Humanos Hipoglicemiantes/uso terapêutico Expectativa de Vida Preferência do Paciente Assistência Centrada no Paciente [Pt] Tipo de publicação: JOURNAL ARTICLE; PRACTICE GUIDELINE [Nm] Nome de substância: 0 (Biomarkers); 0 (Blood Glucose); 0 (Glycated Hemoglobin A); 0 (Hypoglycemic Agents); 4429-04-3 (Fructosamine) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 171024 [St] Status: MEDLINE [do] DOI: 10.7326/M17-1362

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[PMID]: 28973526 [Au] Autor: Tinsley LJ; Kupelian V; D'Eon SA; Pober D; Sun JK; King GL; Keenan HA [Ad] Endereço: Section on Vascular Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215. [Ti] Título: Association of Glycemic Control With Reduced Risk for Large-Vessel Disease After More Than 50 Years of Type 1 Diabetes. [So] Source: J Clin Endocrinol Metab;102(10):3704-3711, 2017 Oct 01. [Is] ISSN: 1945-7197 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Context: Previously we demonstrated, in individuals who have had type 1 diabetes (T1D) for 50 or more years (Medalists), that glycemic control was unrelated to diabetic complications, with the exception of cardiovascular disease (CVD), contrary to what has been documented in registry-based studies. Objective: The purpose of this study is to validate these initial findings and identify contributors to mortality on an individual basis in a large cohort. Design: Cross-sectional and longitudinal study. Setting: Joslin Diabetes Center (JDC), Boston, Massachusetts. Patients: 50-year Medalists presenting to JDC for study participation. Interventions: None. Main Outcomes Measures: Microvascular and macrovascular complications of diabetes and mortality. Results: Glycemic control was not significantly associated with small-vessel complications in Medalists but was associated with CVD in the overall cohort, yet with varying effect by tertile of cohort duration. CVD was the largest contributor to mortality, whereas hemoglobin A1c was not an independent predictor of mortality either overall or substantially by diagnosis interval. Additionally, exercise mitigated mortality risk imparted by CVD. Conclusions: Few large populations with long duration of (T1D) have been available to examine the effects of long-term exposure to hyperglycemia. These data indicate that an association of glycemic control, complications, and mortality may change in an older population with T1D. These results suggest that careful control is still warranted in older populations with T1D. [Mh] Termos MeSH primário: Glicemia/metabolismo Doenças Cardiovasculares/epidemiologia Diabetes Mellitus Tipo 1/sangue Diabetes Mellitus Tipo 1/complicações Diabetes Mellitus Tipo 1/epidemiologia Angiopatias Diabéticas/epidemiologia [Mh] Termos MeSH secundário: Idoso Idoso de 80 Anos ou mais Doenças Cardiovasculares/sangue Doenças Cardiovasculares/mortalidade Estudos Transversais Diabetes Mellitus Tipo 1/mortalidade Angiopatias Diabéticas/sangue Angiopatias Diabéticas/mortalidade Progressão da Doença Feminino Hemoglobina A Glicada/metabolismo Seres Humanos Estudos Longitudinais Masculino Meia-Idade Fatores de Risco Análise de Sobrevida Fatores de Tempo [Pt] Tipo de publicação: JOURNAL ARTICLE; VALIDATION STUDIES [Nm] Nome de substância: 0 (Blood Glucose); 0 (Glycated Hemoglobin A) [Em] Mês de entrada: 1710 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 171004 [St] Status: MEDLINE [do] DOI: 10.1210/jc.2017-00589

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[PMID]: 28930839 [Au] Autor: Li Y; Li Q; Liang S; Liang X; Zhou W; He H; Jin R; Wang K; Zhu Z; Yan Z [Ad] Endereço: aCenter for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology bDepartment of Nuclear Medicine, Daping Hospital cSchool of Biomedical Engineering, Third Military Medical University, Chongqing, P.R. China. [Ti] Título: A novel use of hill function and utility of 99mTc-MIBI scintigraphy to detect earlier lower extremity microvascular perfusion in patients with type 2 diabetes. [So] Source: Medicine (Baltimore);96(38):e8038, 2017 Sep. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: We use the Hill function to analyze the dynamics of Tc-99m 2 methoxy-isobutyl-isonitrile (Tc-MIBI) scintigraphy data and to examine the earlier lower extremity microvascular perfusion of diabetic patients without typical clinical symptoms and with the preserved normal ankle-brachial index (ABI).Eighty-eight participants (30 healthy control, 34 diabetic patients, and 24 diabetic patients with peripheral arterial disease [PAD]) were recruited and applied Tc-MIBI scintigraphy. Fourteen diabetic patients with PAD also underwent computed tomography angiography (CTA) examination and were performed endovascular interventions.Diabetic patients with normal ABI already have significantly impaired maximum Tc-MIBI muscle perfusion counts (P < .001) and the peak times of the lower extremity muscle perfusion (P < .05). Tc-MIBI scintigraphy showed great consistent with ABI and CTA in detecting PAD. Tc-MIBI scintigraphy was also found to be effective in evaluating lower extremity circulation after endovascular interventions (P < .05).Hill function-based analysis of Tc-MIBI scintigraphy might be effective method to evaluate earlier lower extremity perfusion changes in diabetic patients. [Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/diagnóstico por imagem Angiopatias Diabéticas/diagnóstico por imagem Extremidade Inferior/irrigação sanguínea Extremidade Inferior/diagnóstico por imagem Doença Arterial Periférica/diagnóstico por imagem Compostos Radiofarmacêuticos Tecnécio Tc 99m Sestamibi [Mh] Termos MeSH secundário: Idoso Índice Tornozelo-Braço Diabetes Mellitus Tipo 2/complicações Feminino Seres Humanos Masculino Microcirculação Meia-Idade [Pt] Tipo de publicação: JOURNAL ARTICLE; OBSERVATIONAL STUDY [Nm] Nome de substância: 0 (Radiopharmaceuticals); 971Z4W1S09 (Technetium Tc 99m Sestamibi) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 171015 [Lr] Data última revisão: 171015 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 170921 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000008038

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