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SARS-Cov2 infection has recently spread to Italy with important consequences on pregnancy management, mother and child health and mother-child contact. Breastfeeding improves the health of mother and child and reduces risk of neonatal infection with other pathogens that are likely to cause serious illness. To date no evidence confirmed COVID-19 vertical transmission from infected pregnant mother to their fetus. However it is well known that an infected mother can transmit the COVID-19 virus through respiratory droplets during breastfeeding or intimate contact. Thus, the mothers with known or suspected COVID-19 should adhere to standard and contact precautions during breastfeeding. Woman Study Group of AMD, after reviewing current knowledge about COVID-19 vertical transmission and the compatibility of breastfeeding in COVID-19 mother, the available recommendations from Health Care Organizations and main experts opinions, issued the following suggestions on breastfeeding during the COVID-19 pandemic, addressed both to mothers with and without diabetes. It should be considered that following suggestions may change in the future when more evidence is acquired regarding SARS-Cov2 infection.
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Aleitamento Materno/efeitos adversos , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/fisiopatologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/fisiopatologia , Betacoronavirus , COVID-19 , China/epidemiologia , Infecções por Coronavirus/complicações , Complicações do Diabetes , Feminino , Humanos , Recém-Nascido , Itália/epidemiologia , Pneumonia Viral/complicações , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/virologia , Gravidez em Diabéticas , SARS-CoV-2RESUMO
BACKGROUND: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. METHODS: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. RESULTS: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. CONCLUSIONS: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors.
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Adiposidade , Glicemia , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Carboidratos da Dieta/administração & dosagem , Comportamento Alimentar , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Criança , Pré-Escolar , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIMS: Hospitalized patients with comorbid diabetes mellitus may have worse outcomes than the others. We conducted a study to assess whether comorbid diabetes affects in-hospital mortality and length of stay. METHODS: For this population-based study, we analyzed the administrative databases of the Regional Health Information System of the Region Friuli Venezia Giulia, where the Hospital of Udine is located. Hospital discharge data were linked at the individual patient level with the regional Diabetes Mellitus Registry to identify diabetic patients. For each 3-digit ICD-9-CM discharge diagnosis code, we assessed the difference in length of stay and in-hospital mortality between diabetic and non-diabetic patients. We conducted both univariate and multivariate analyses, adjusted for age, sex, Charlson's comorbidity score, and urgency of hospitalization, through linear and logistic regression models. RESULTS: After adjusting for potential confounders, diabetes significantly increased the risk of in-hospital death among patients hospitalized for bacterial pneumonia (OR = 1.94) and intestinal obstruction (OR = 4.23) and length of stay among those admitted for several diagnoses, including acute myocardial infarction and acute renal failure. Admission glucose blood level was associated with in-hospital death in patients with pneumonia and intestinal obstruction, and increased length of stay for several conditions. CONCLUSIONS: Patients with diabetes mellitus who are hospitalized for other health problems may have increased risk of in-hospital death and longer hospital stay. For this reason, diabetes should be promptly recognized upon admission and properly managed.
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Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Mortalidade Hospitalar , Tempo de Internação/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Comorbidade , Bases de Dados Factuais , Feminino , Hospitalização/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Itália/epidemiologia , Nefropatias/epidemiologia , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/terapiaRESUMO
BACKGROUND: The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. METHODS: TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50-75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2-3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15-45 mg) or a sulfonylurea (5-15 mg glibenclamide, 2-6 mg glimepiride, or 30-120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. FINDINGS: Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74-1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p<0·0001). Moderate weight gain (less than 2 kg, on average) occurred in both groups. Rates of heart failure, bladder cancer, and fractures were not significantly different between treatment groups. INTERPRETATION: In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas (mostly glimepiride and gliclazide) and pioglitazone as add-on treatments to metformin. Both of these widely available and affordable treatments are suitable options with respect to efficacy and adverse events, although pioglitazone was associated with fewer hypoglycaemia events. FUNDING: Italian Medicines Agency, Diabete Ricerca, and Italian Diabetes Society.
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Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêutico , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/epidemiologia , Quimioterapia Combinada , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pioglitazona , Resultado do TratamentoRESUMO
OBJECTIVES: The preferred countermeasure to avoid exercise-related hypoglycemia was investigated in a group of patients with type 1 diabetes participating in a stressful event, a 24×1-hour relay marathon. The carbohydrates actually consumed were compared to those estimated for each patient by applying a customizable algorithm, Exercise Carbohydrates Requirement Estimating Software (ECRES), based on patient's usual therapy and diet and on the exercise characteristics. METHODS: Glycemia was tested at the start, middle and end of the races. Usual therapies and diets and the adopted countermeasures were recorded in detail. RESULTS: We studied 19 patients who walked/ran 10.4±2.8 km with a heart rate of 167±11 beats per minute. Of the 19 patients, 7 patients reduced the administered insulin (premeal bolus or basal infusion rate). Glycemia fell by the end of the races (p=0.006; median -1.8 mmolâ L-1; interquartile range -0.4 mmolâ L-1 to -5.3 mmolâ L-1), despite 9 patients being hyperglycemic at the start. Of the patients, 14 concluded the race with glycemia on target, and 4 patients were hyperglycemic. Amounts of carbohydrates actually consumed (median 30 g; interquartile range 0 g to 71 g) were not significantly different from those estimated by ECRES (median 38 g; interquartile range 24 g to 68 g), the 2 quantities being significantly related (R=0.64; p=0.003). ECRES estimated lower carbohydrate levels (-13 g) than the amounts actually consumed by the 4 patients who concluded their exercises with hyperglycemia. CONCLUSIONS: Patients preferred to consume extra carbohydrates to avoid the possible exercise-induced hypoglycemia. ECRES would provide satisfactory estimates of the carbohydrate requirements, even for a stressful condition, and almost equal to the quantities consumed following medical advice.
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Diabetes Mellitus Tipo 1/complicações , Carboidratos da Dieta/uso terapêutico , Exercício Físico/fisiologia , Hipoglicemia/prevenção & controle , Adulto , Algoritmos , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Dietoterapia , Feminino , Humanos , Hipoglicemia/dietoterapia , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , SoftwareRESUMO
BACKGROUND: The role of polyphenol intake on cardiovascular risk factors is little explored, particularly in people with diabetes. AIM: To evaluate the association between the intake of total polyphenols and polyphenol classes with the major cardiovascular risk factors in a population with type 2 diabetes. METHODS: Dietary habits were investigated in 2573 males and females participants of the TOSCA.IT study. The European Prospective Investigation on Cancer and Nutrition (EPIC) questionnaire was used to assess dietary habits. In all participants, among others, we assessed anthropometry, plasma lipids, blood pressure, C-reactive protein and HbA1c following a standard protocol. The USDA and Phenol-Explorer databases were used to estimate the polyphenol content of the habitual diet. RESULTS: Average intake of polyphenols was 683.3 ± 5.8 mg/day. Flavonoids and phenolic acids were the predominant classes (47.5% and 47.4%, respectively). After adjusting for potential confounders, people with the highest intake of energy-adjusted polyphenols (upper tertile) had a more favorable cardiovascular risk factors profile as compared to people with the lowest intake (lower tertile) (BMI was 30.7 vs 29.9 kg/m2, HDL-cholesterol was 45.1 vs 46.9 mg/dl, LDL-cholesterol was 103.2 vs 102.1 mg/dl, triglycerides were 153.4 vs 148.0 mg/dl, systolic and diastolic blood pressure were respectively 135.3 vs 134.3 and 80.5 vs 79.6 mm/Hg, HbA1c was 7.70 vs 7.67%, and C-reactive Protein was 1.29 vs 1.25 mg/dl, p < .001 for all). The findings were very similar when the analysis was conducted separately for flavonoids or phenolic acids, the two main classes of polyphenols consumed in this population. CONCLUSIONS: Polyphenol intake is associated with a more favorable cardiovascular risk factors profile, independent of major confounders. These findings support the consumption of foods and beverages rich in different classes of polyphenols particularly in people with diabetes. CLINICAL TRIAL: http://www.clinicaltrials.gov; Study ID number: NCT00700856.
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Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/sangue , Dieta , Polifenóis/administração & dosagem , Idoso , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Relação Dose-Resposta a Droga , Feminino , Flavonoides/administração & dosagem , Flavonoides/sangue , Humanos , Hidroxibenzoatos/administração & dosagem , Hidroxibenzoatos/sangue , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Polifenóis/sangue , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Triglicerídeos/sangueRESUMO
AIMS: The main objective of this study was to estimate the incidence rate and prevalence of pediatric type 1 diabetes mellitus (T1DM; population 0-18 years of age) in the northeastern Italian region Friuli Venezia Giulia and to characterize the subjects affected by the disease. METHODS: This was a retrospective population-based study conducted through the individual-level linkage of several health administrative databases of the Friuli Venezia Giulia region. The incidence rate and prevalence were calculated in the population 0-18 years of age. Using the Mid-p exact method, 95 % confidence intervals for rates were calculated. RESULTS: The incidence rate of pediatric T1DM in the years 2010-2013 was 15.8 new cases/100,000 person-years, peaking in the age class 10-14 years. The rate has increased substantially as compared with the previous regional estimate that dated back to 1993. We observed a seasonal pattern both in the date of birth of the incident cases and in the date of onset of the disease. In the region in 2013, there were 294 prevalent cases (15.1/10,000 inhabitants). Most of them had at least one glycated hemoglobin test in the year. More than 15 % had co-existing autoimmune comorbidities. CONCLUSIONS: The incidence rate of pediatric T1DM in Friuli Venezia Giulia has increased in the last years, and the disease is a relevant public health issue in the region.
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Diabetes Mellitus Tipo 1/epidemiologia , Adolescente , Doenças Autoimunes/epidemiologia , Criança , Pré-Escolar , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Itália/epidemiologia , Masculino , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: The objective of the study was to investigate the relationship between first trimester maternal serum levels of the TTR-RBP4-ROH complex components and the later insurgence of an altered glucose metabolism during pregnancy. METHODS: Retrospective case control study including 96 patients between the 12th and 14th week of gestation, 32 that developed gestational diabetes mellitus (GDM), respectively, 21 non-insulin-treated (dGDM) and 11 insulin-treated (iGDM), 20 large for gestational age fetuses (LGA) without GDM and 44 patients with normal outcome as control. Serum concentrations of RBP4 and TTR were assessed by ELISA; serum concentration of ROH by reverse-phase high performance liquid chromatography (rpHPLC). The molecular heterogeneity of TTR and RBP4 was analyzed after immunoprecipitation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean±SD: TTR 3.96±0.89 µmol/L vs. 4.68±1.21 µmol/L, RBP4 1.13±0.25 µmol/L vs. 1.33±0.38 µmol/L and ROH 1.33±0.17 µmol/L vs. 1.62±0.29 µmol/L, p<0.05). TTR containing Gly10 in place of Cys10 was lower in the iGDM group (p<0.05) compared to controls. In the final logistic regression model ROH significantly predicted the diagnosis of iGDM (OR 0.93, 95% CI 0.87-0.98, p<0.05). CONCLUSIONS: First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.
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Diabetes Gestacional/diagnóstico , Pré-Albumina/análise , Proteínas Plasmáticas de Ligação ao Retinol/análise , Vitamina A/análise , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Diabetes Gestacional/sangue , Feminino , Idade Gestacional , Humanos , Insulina/uso terapêutico , Testes para Triagem do Soro Materno , Gravidez , Primeiro Trimestre da Gravidez/sangue , Estudos Retrospectivos , Vitamina A/sangueRESUMO
BACKGROUND: Diabetes is a significant health problem in Italy as in other western countries. OBJECTIVE: To review available epidemiological data and the legislative framework for diabetes care in Italy. METHODS: Review of Italian Health Ministry's official documents and analysis of epidemiological data published by Italian Scientific Societies. FINDINGS: Diabetes affects more than 5% of the Italian population. The expenditures for the care of people with diabetes are about 10 billion ($US 11 billion) a year and are increasing over time. Italian law regulates the clinical care of people with diabetes and creates a clinical framework involving medical organizations, prevention programs, personnel training, and legal protection. The National Health Program is structured in essential levels of assistance that can be defined differently in the various regions. In 2013, the "National Diabetes Plan," defining priority areas for intervention, was approved and represents the main regulatory tool for the management of diabetes within the Italian National Health Service. In Italy, the status of diabetes care is being monitored using the data from 2 permanent observatories: the ARNO Observatory Diabetes and the Associazione Medici Diabetologi Annals. CONCLUSIONS: A comprehensive approach to diabetes is offered to all citizens, consonant with the constitutionally guaranteed right to health. However, this important effort translates into a relevant financial burden for the National Health Service.
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Diabetes Mellitus/economia , Diabetes Mellitus/terapia , Gastos em Saúde/estatística & dados numéricos , Recursos em Saúde , Programas Nacionais de Saúde/economia , Análise Custo-Benefício , Diabetes Mellitus/epidemiologia , Humanos , Itália , Prevalência , Indicadores de Qualidade em Assistência à Saúde , Resultado do TratamentoRESUMO
In this study, we investigated the effects of microtubule-targeting drugs, which either destabilize (the Vinca alkaloid vincristine) or stabilize (the taxane derivative docetaxel) microtubules, on the cell-cell and cell-matrix adhesive junctions of Caco-2 tumor epithelial cells, using fluorescence imaging and functional assays. We found that, in sub-confluent (but not confluent) cells, vincristine (but not docetaxel) affected cell-cell junction morphology. Furthermore, docetaxel (but not vincristine) attenuated the formation of the peri-junctional actomyosin ring and enhanced the internalization of junctional adhesion molecule-A. However, these effects of vincristine and docetaxel did not translate into appreciable functional changes during the opening and resealing of the cell-cell junctions. We also found that vincristine caused enlargement of focal adhesions (the major cell-matrix junctions) without affecting cell adhesion onto the matrix. Thus, we conclude that the microtubule-targeting drugs interfere to variable degrees with the morphology and/or function of the cell-cell and cell-matrix adhesive junctions. In addition, the results highlight the importance of considering the cellular context and dynamics (e.g. cell confluence and junction opening, respectively), when determining the final effects of microtubule manipulation on cell adhesiveness.
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Junções Célula-Matriz/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Junções Intercelulares/efeitos dos fármacos , Microtúbulos/efeitos dos fármacos , Células CACO-2 , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Citoesqueleto/efeitos dos fármacos , Docetaxel , Células Epiteliais/efeitos dos fármacos , Humanos , Moléculas de Adesão Juncional , Microtúbulos/patologia , Terapia de Alvo Molecular , Taxoides/farmacologia , Moduladores de Tubulina/farmacologia , Vincristina/farmacologiaRESUMO
BACKGROUND: As n-3 Polyunsaturated Fatty Acids exert a beneficial action on the cardiovascular system, it is important to investigate their effects on endothelial cell responses that (like migration) contribute to repairing vascular lesions. METHODS: To this purpose, using functional and morphological in vitro assays, we have examined the effect of n-3 Polyunsaturated Fatty Acids on the migration of endothelial cells. RESULTS: We report here that incubation of endothelial cells with n-3 Polyunsaturated Fatty Acids impaired cell migration into a wound, triggered peripheral distribution of focal adhesions and caused partial disassembly of actin filaments. We also found that eicosapentaenoic acid and docosahexaenoic acid exerted similar effects on the focal adhesions, but that eicosapentaenoic acid was sufficient for inhibiting cell migration. CONCLUSIONS: Given the importance of endothelial cell migration in the repair of vascular injuries, these in vitro findings call for in vivo evaluation of vascular repair in response to different dietary ratios of eicosapentaenoic to docosahexaenoic acid.
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OBJECTIVE: A trial was performed to establish whether our group care model for lifestyle intervention in type 2 diabetes can be exported to other clinics. RESEARCH DESIGN AND METHODS: This study was a 4-year, two-armed, multicenter controlled trial in 13 hospital-based diabetes clinics in Italy (current controlled trials no. ISRCTN19509463). A total of 815 non-insulin-treated patients aged <80 years with > or =1 year known diabetes duration were randomized to either group or individual care. RESULTS: After 4 years, patients in group care had lower A1C, total cholesterol, LDL cholesterol, triglycerides, systolic and diastolic blood pressure, BMI, and serum creatinine and higher HDL cholesterol (P < 0.001, for all) than control subjects receiving individual care, despite similar pharmacological prescriptions. Health behaviors, quality of life, and knowledge of diabetes had become better in group care patients than in control subjects (P < 0.001, for all). CONCLUSIONS: The favorable clinical, cognitive, and psychological outcomes of group care can be reproduced in different clinical settings.
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Diabetes Mellitus Tipo 2/terapia , Estilo de Vida , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Resultado do TratamentoRESUMO
Tight junctions are the most apical organelle of the apical junctional complex and are primarily involved in the regulation of paracellular permeability and membrane polarity. Extensive research in the past two decades has identified not only the individual molecules of the tight junctions but also their mutual interactions, which are the focus of the present review article. While a complete map of the interactions among the tight junction molecules is probably far from being complete, the available evidence already allows outlining the general molecular architecture of the tight junctions. Here, with the aim of gaining deeper mechanistic understanding of tight junction assembly, regulation and function, we have subdivided the known molecular interactions into four major clusters that are centered on cell surface, polarity, cytoskeletal and signaling molecules.
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Proteínas de Membrana/química , Proteínas de Membrana/fisiologia , Junções Íntimas/química , Junções Íntimas/fisiologia , Animais , Moléculas de Adesão Celular/química , Moléculas de Adesão Celular/fisiologia , Ciclo Celular , Polaridade Celular , Citoesqueleto/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Modelos Biológicos , Modelos Moleculares , Estrutura Molecular , Proteínas Monoméricas de Ligação ao GTP/química , Proteínas Monoméricas de Ligação ao GTP/fisiologia , Complexos Multiproteicos , Ocludina , Transdução de Sinais , Fatores de Transcrição/fisiologiaRESUMO
BACKGROUND: Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through oxidative stress; however, the distinct role of these two factors is a matter of debate. METHODS AND RESULTS: Thirty type 2 diabetic patients and 20 normal subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial function were assayed during the tests. Subsequently, diabetics took 40 mg/d simvastatin or placebo for 12 weeks. The 3 tests were performed again at baseline, between 3 to 6 days after the start, and at the end of each study. High-fat load and glucose alone produced a decrease of endothelial function and an increase of nitrotyrosine in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters but reduced the effect on endothelial function and nitrotyrosine observed during each different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations of endothelial function and nitrotyrosine during the tests. CONCLUSIONS: This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, suggesting oxidative stress as common mediator of such effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug.
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Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/fisiopatologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertrigliceridemia/fisiopatologia , Sinvastatina/uso terapêutico , Tirosina/análogos & derivados , Glicemia/análise , Doenças Cardiovasculares/etiologia , Estudos Cross-Over , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Método Duplo-Cego , Esquema de Medicação , Feminino , Teste de Tolerância a Glucose , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hipertrigliceridemia/tratamento farmacológico , Hipertrigliceridemia/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Período Pós-Prandial , Fatores de Risco , Sinvastatina/administração & dosagem , Triglicerídeos/análise , Tirosina/análise , VasodilataçãoRESUMO
OBJECTIVE: Recently, much attention has been paid to the possibility that postprandial hyperglycemia may be a cardiovascular risk factor in diabetes. Oxidative stress has been involved in the pathogenesis of diabetic complications, and increased plasma levels of nitrotyrosine, a product of peroxynitrite action, have been found in the plasma of diabetic subjects. The aim of the present study was to evaluate whether postprandial hyperglycemia is accompanied by nitrotyrosine generation and, if so, to explore a possible direct role of hyperglycemia in such a phenomenon. RESEARCH DESIGN AND METHODS: A total of 23 type 2 diabetic patients and 15 matched normal healthy subjects were recruited for this study. Two different tests were performed in diabetic patients: a standard meal preceded by regular insulin (0.15 units/kg body wt) or insulin aspart (0.15 units/kg body wt) to achieve different levels of postprandial hyperglycemia. The meal test was also performed in healthy control subjects. At 0 min and 1, 2, 4, and 6 h after each meal, blood glucose, triglyceride, and nitrotyrosine levels were measured. RESULTS: Fasting nitrotyrosine was significantly increased in diabetic patients and was further increased during both meal tests in diabetic subjects but not normal subjects. As compared with regular insulin, aspart administration significantly reduced the area under the curve of both glycemia (P < 0.04) and nitrotyrosine (P < 0.03), whereas that of triglycerides was not significantly affected by the treatment. CONCLUSIONS: This study shows a direct correlation between postprandial hyperglycemia and the production of nitrotyrosine, a marker of oxidative stress, in patients with type 2 diabetes.