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1.
PLoS One ; 15(10): e0240588, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064756

RESUMO

INTRODUCTION: Diabetes-related lower extremity amputation has a major psycho-social and economic cost on the patient as well as a direct impact on financial expenditure within health facilities. AIM: This study aimed to determine the incidence and patient-related factors related to diabetes-related amputations amongst patients that were referred to the quaternary hospital between 1 January 2014 and 31 December 2015. METHODS: A retrospective cohort study. Data were retrieved from the medical record for each diabetes patient that was managed at IALCH during the study period. The following variables were collected: sociodemographic parameters (age, gender, and ethnicity) and diabetes-related parameters (type of diabetes) and additional complications. RESULTS: Ninety-nine patients (0, 73%) of all diabetes patients managed were new diabetes-related lower-extremity amputations. There were statistically significant increased odds of female patients (OR: 1, 7) and patients with non-insulin dependent diabetes (OR: 1, 64) to have new diabetes-related amputations. Patients older than 60 years (OR: 1, 31); African patients (OR: 1, 35) patients with cardiovascular complications (OR: 1, 04) and patients with retinopathy (OR: 1, 48) were more likely to have diabetes-related amputations but not statistically significant. CONCLUSIONS: A combination of primary preventive strategies, early detection and appropriate management of patients with diabetes and specific guidelines on the frequency, clinical and laboratory tests required for early diagnosis and referrals with early signs of diabetes-related complicationsat primary care level will assist in reducing the long term adverse outcomes including amputations.


Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Pé Diabético/cirurgia , Sistema Musculoesquelético/cirurgia , Adulto , Idoso , Amputação , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/cirurgia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/cirurgia , Pé Diabético/patologia , Feminino , Hospitais , Humanos , Extremidade Inferior/fisiopatologia , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade , Sistema Musculoesquelético/fisiopatologia , Fatores de Risco , África do Sul
2.
Pan Afr Med J ; 36: 158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32874422

RESUMO

Diabetes mellitus is a non-infectious disease and has affected about 425 million adults globally and nearly 15.9 million of them reside in Africa. Moreover, the prevalence of undiagnosed diabetes mellitus is very high in Africa and approximates to around 62%. Nearly 75% of the total deaths due to diabetes are in individuals lesser than 60 years of age. The multifaceted disease of diabetes mellitus produces chronic complications such as, neuropathy, nephropathy, retinopathy, microangiopathy etc. These patients of diabetes mellitus are more susceptible to infections due to compromised immune system. Hence these patients of diabetes mellitus and undiagnosed diabetes mellitus are at greater risk of contracting COVID-19 infections. The dual impact of pathophysiology of COVID-19 infections in diabetes mellitus may increase morbidity and mortality in these patients. Hence there is need of health awareness in diabetics as well in the high-risk group for diabetes such as persons with hypertension and obesity. The scarcity of health resources, shortage of trained medical personnel and disease burden of infectious and non-infectious diseases has laid a heavy impact on the economy in Africa and this has been further strained due to the COVID-19 pandemic. The practice of preventive measures by the risk group of Undiagnosed Diabetes Mellitus patients will prevent them from getting infected by COVID-19 and at the same time decrease mortality rates and hence the undiscovered group that is the patients of undiagnosed diabetes mellitus needs to be vigilant regarding safe preventive practices.


Assuntos
Infecções por Coronavirus/epidemiologia , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , África/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatologia , Humanos , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Prevalência , Fatores de Risco
3.
Diabetes Res Clin Pract ; 166: 108346, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32710998

RESUMO

AIMS: Diabetes mellitus has been reported to be one of the most prevalent comorbidity in patients with Coronavirus Disease 2019 (COVID-19). We aimed to assess the association of comorbid diabetes with COVID-19 severity or mortality in China. METHODS: We performed a systematic literature search from six electronic databases on diabetes and COVID-19. The outcome of interest was disease severity or mortality. Heterogeneity among the studies was assessed by the Cochran Q test and the I2 statistic. A random effects model was applied to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). RESULTS: Nine studies from different provinces/cities were identified according to the predefined inclusion and exclusion criteria. There were a total of 1070 patients with diabetes, out of the 8807 COVID-19 cases. The majority of the cases were derived from Hubei Province. A low degree of heterogeneity in the risk estimates was observed in the included studies. Meta-analysis showed that there was a significant association of preexisting diabetes with disease severity or death. The pooled RR was 2.96 (95% CI: 2.31-3.79; p < 0.001). Sensitivity analysis demonstrated no significant changes in the pooled estimates. CONCLUSIONS: Comorbid diabetes was associated with an increased risk of disease severity or death in Chinese COVID-19 patients.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/mortalidade , Complicações do Diabetes/mortalidade , Diabetes Mellitus/mortalidade , Pneumonia Viral/mortalidade , China/epidemiologia , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/virologia , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/virologia , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prevalência , Prognóstico , Índice de Gravidade de Doença , Taxa de Sobrevida
4.
Rev Saude Publica ; 54: 54, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-537882

RESUMO

The coronavirus disease 2019 (covid-19) pandemic has caused a public health emergency worldwide. Risk, severity and mortality of the disease have been associated with non-communicable chronic diseases, such as diabetes mellitus. Accumulated evidence has caused great concern in countries with high prevalence of this morbidity, such as Brazil. This text shows the picture of diabetes in Brazil, followed by epidemiological data and explanatory hypothesis for the association between diabetes and covid-19. We emphasized how the burden of these two morbidities in a middle-income country has aggravated this pandemic scenario. The comprehension of this association and biological plausibility may help face this pandemic and future challenges.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Comorbidade , Infecções por Coronavirus/fisiopatologia , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/fisiopatologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença
5.
J Diabetes Investig ; 11(5): 1104-1114, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32558211

RESUMO

Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin-angiotensin-aldosterone system inhibitors with COVID-19. Suggested recommendations for the use of antidiabetic medications for COVID-19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID-19 patients. In addition, we aim to increase clinicians' awareness of the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.


Assuntos
/imunologia , Complicações do Diabetes/imunologia , Diabetes Mellitus/imunologia , Obesidade/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Glicemia/metabolismo , /tratamento farmacológico , /uso terapêutico , Cloroquina/uso terapêutico , Comorbidade , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Cetoacidose Diabética/complicações , Cetoacidose Diabética/terapia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Combinação de Medicamentos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hidroxicloroquina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Resistência à Insulina , Secreção de Insulina , Interferon Tipo I/uso terapêutico , Lopinavir/uso terapêutico , Pulmão/fisiopatologia , Metformina/uso terapêutico , Obesidade/complicações , Obesidade/metabolismo , Obesidade/fisiopatologia , Pâncreas/metabolismo , Ritonavir/uso terapêutico , Índice de Gravidade de Doença , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Tiazolidinedionas/uso terapêutico
8.
Rev Saude Publica ; 54: 54, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32491053

RESUMO

The coronavirus disease 2019 (covid-19) pandemic has caused a public health emergency worldwide. Risk, severity and mortality of the disease have been associated with non-communicable chronic diseases, such as diabetes mellitus. Accumulated evidence has caused great concern in countries with high prevalence of this morbidity, such as Brazil. This text shows the picture of diabetes in Brazil, followed by epidemiological data and explanatory hypothesis for the association between diabetes and covid-19. We emphasized how the burden of these two morbidities in a middle-income country has aggravated this pandemic scenario. The comprehension of this association and biological plausibility may help face this pandemic and future challenges.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Complicações do Diabetes/epidemiologia , Diabetes Mellitus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Comorbidade , Infecções por Coronavirus/fisiopatologia , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus/fisiopatologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença
9.
Stroke ; 51(6): 1865-1867, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32390546

RESUMO

Background and Purpose- This study aimed to develop and validate a nomogram for predicting the risk of stroke recurrence among young adults after ischemic stroke. Methods- Patients aged between 18 and 49 years with first-ever ischemic stroke were selected from the Nanjing Stroke Registry Program. A stepwise Cox proportional hazards regression model was employed to develop the best-fit nomogram. The discrimination and calibration in the training and validation cohorts were used to evaluate the nomogram. All patients were classified into low-, intermediate-, and high-risk groups based on the risk scores generated from the nomogram. Results- A total of 604 patients were enrolled in this study. Hypertension (hazard ratio [HR], 2.038 [95% CI, 1.504-3.942]; P=0.034), diabetes mellitus (HR, 3.224 [95% CI, 1.848-5.624]; P<0.001), smoking status (current smokers versus nonsmokers; HR, 2.491 [95% CI, 1.304-4.759]; P=0.006), and stroke cause (small-vessel occlusion versus large-artery atherosclerosis; HR, 0.325 [95% CI, 0.109-0.976]; P=0.045) were associated with recurrent stroke. Educational years (>12 versus 0-6; HR, 0.070 [95% CI, 0.015-0.319]; P=0.001) were inversely correlated with recurrent stroke. The nomogram was composed of these factors, and successfully stratified patients into low-, intermediate-, and high-risk groups (P<0.001). Conclusions- The nomogram composed of hypertension, diabetes mellitus, smoking status, stroke cause, and education years may predict the risk of stroke recurrence among young adults after ischemic stroke.


Assuntos
Pressão Sanguínea , Nomogramas , Sistema de Registros , Acidente Vascular Cerebral , Adulto , Infarto Cerebral/diagnóstico , Infarto Cerebral/etiologia , Infarto Cerebral/fisiopatologia , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/fisiopatologia , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fumar/efeitos adversos , Fumar/fisiopatologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Adulto Jovem
10.
Stroke ; 51(6): 1682-1689, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32390549

RESUMO

Background and Purpose- Cerebrovascular disease contributes to age-related cognitive decline, but the mechanisms underlying this phenomenon remain incompletely understood. We hypothesized that vascular risk factors would lead to cognitive impairment through the disruption of brain white matter network efficiency. Methods- Participants were 19 346 neurologically healthy individuals from UK Biobank that underwent diffusion MRI and cognitive testing (mean age=62.6). Global efficiency, a measure of network integration, was calculated from white matter networks constructed using deterministic diffusion tractography. First, we determined whether demographics (age, sex, ethnicity, socioeconomic status, and education), vascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, smoking, body mass index), and white matter hyperintensities were related to global efficiency using multivariate linear regression. Next, we used structural equation modeling to model a multiple regression. The dependent variable was a latent cognition variable using all cognitive data, while independent variables were a latent factor including all vascular risk factors (vascular burden), demographic variables, white matter hyperintensities, and global efficiency. Finally, we used mediation analysis to determine whether global efficiency explained the relationship between vascular burden and cognition. Results- Hypertension and diabetes mellitus were consistently associated with reduced global efficiency even after controlling for white matter hyperintensities. Structural equation models revealed that vascular burden was associated with cognition (P=0.023), but not after adding global efficiency to the model (P=0.09), suggesting a mediation effect. Mediation analysis revealed a significant indirect effect of global efficiency on cognition through vascular burden (P<0.001), suggesting a partial mediation effect. Conclusions- Vascular burden is associated with reduced global efficiency and cognitive impairment in the general population. Network efficiency partially mediates the relationship between vascular burden and cognition. This suggests that treating specific risk factors may prevent reductions in brain network efficiency and preserve cognitive functioning in the aging population.


Assuntos
Envelhecimento , Bancos de Espécimes Biológicos , Disfunção Cognitiva , Complicações do Diabetes , Imagem de Tensor de Difusão , Hipertensão , Modelos Neurológicos , Idoso , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Complicações do Diabetes/diagnóstico por imagem , Complicações do Diabetes/fisiopatologia , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Socioeconômicos , Reino Unido/epidemiologia
11.
Stroke ; 51(6): 1640-1646, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32404039

RESUMO

Background and Purpose- Type 2 diabetes mellitus (T2D) is associated with cognitive impairment and an increased risk of dementia, but the association between prediabetes and cognitive impairment is less clear, particularly in a setting of major cerebrovascular events. This article examines the impact of impaired fasting glucose and T2D on cognitive performance in a stroke population. Methods- Seven international observational studies from the STROKOG (Stroke and Cognition) consortium (n=1601; mean age, 66.0 years; 70% Asian, 26% white, and 2.6% African American) were included. Fasting glucose level (FGL) during hospitalization was used to define 3 groups, T2D (FGL ≥7.0 mmol/L), impaired fasting glucose (FGL 6.1-6.9 mmol/L), and normal (FGL <6.1 mmol/L), and a history of diabetes mellitus and the use of a diabetes mellitus medication were also used to support a diagnosis of T2D. Domain and global cognition Z scores were derived from standardized neuropsychological test scores. The cross-sectional association between glucose status and cognitive performance at 3 to 6 months poststroke was examined using linear mixed models, adjusting for age, sex, education, stroke type, ethnicity, and vascular risk factors. Results- Patients with T2D had significantly poorer performance in global cognition (SD, -0.59 [95% CI, -0.82 to -0.36]; P<0.001) and in all domains compared with patients with normal FGL. There was no significant difference between impaired fasting glucose patients and those with normal FGL in global cognition (SD, -0.10 [95% CI, -0.45 to 0.24]; P=0.55) or in any cognitive domain. Conclusions- Diabetes mellitus, but not prediabetes, is associated with poorer cognitive performance in patients 3 to 6 months after stroke.


Assuntos
Glicemia/metabolismo , Cognição , Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Acidente Vascular Cerebral , Idoso , Estudos Transversais , Complicações do Diabetes/sangue , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/fisiopatologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia
12.
Diabetes Metab Syndr ; 14(4): 665-669, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32438330

RESUMO

BACKGROUND & AIM: As on date, no specific treatment is available for devastating COVID-19 (SARS-CoV-2) infection. This pandemic viral infection has affected over 200 countries within a very short time and created a calamitous situation across the globe. As per WHO guidelines, the treatment is mainly symptomatic and supportive. This clinical protocol has not proven sufficient to save the lives of COVID-19 patients suffering from diabetes or having underlying liver diseases; hence there is utmost need to tackle this situation by other means such as Convalescent Plasma (CP) therapy. METHODS: A comprehensive literature survey was carriedout using Elsevier, PubMed, Taylor & Francis, Springer, Nature and Google search engines. RESULTS: The patients suffering from diabetes or liver dysfunction or any other underlying diseases are at greatest risk of SARS-CoV-2 infection. From the study, it is proved that plasma collected from the recovered patients of viral infection has considerable potential to treat the viral disease without the occurrence of adverse effects. CONCLUSION: The CP therapy can be a possible life saving alternative to treat critical COVID-19 patients having diabetes or underlying liver dysfunction. Hence, randomised clinical trials are recommended at the earliest to save the lives of infected individuals of COVID-19.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Complicações do Diabetes/fisiopatologia , Hepatopatias/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Betacoronavirus/imunologia , Protocolos Clínicos , Comorbidade , Complicações do Diabetes/imunologia , Complicações do Diabetes/terapia , Humanos , Imunização Passiva , Hepatopatias/imunologia , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Pandemias , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Biol Res Nurs ; 22(3): 403-411, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32367734

RESUMO

BACKGROUND: Far-infrared radiation (FIR) therapy improves vessel dilation, circulation, vessel endothelial function, and angiogenesis and reduces atherosclerosis. However, evidence of FIR therapy's effects on foot circulation among diabetic patients undergoing hemodialysis is scarce. AIM: To determine whether FIR therapy improves foot circulation in diabetic patients undergoing hemodialysis. DESIGN: Quasi-experimental. METHODS: In June to November 2017, diabetic patients undergoing hemodialysis (N = 58) at a hemodialysis center in northern Taiwan were divided into two groups: the experimental group (n = 31) received FIR therapy to the bilateral dorsalis pedis artery (40 min/session, 3 times/week for 6 months) and the control group (n = 27) received conventional dialysis care. Paired t test, independent samples t test, two-proportion Z test, and repeated-measures analysis of covariance were performed to compare changes from baseline to the end of the 6-month intervention between the groups. RESULTS: Significant positive effects of FIR therapy on temperature, pulse, and blood flow of the dorsalis pedis artery were observed. Sensitivity to pain, tactility, and pressure also improved significantly in the experimental group. The Edinburgh Claudication Questionnaire revealed that the experimental group had reductions in subjective experiences of soreness, tingling, and coldness in the feet. CONCLUSION: The findings of significant improvements to objective and subjective measures of blood flow and neural function in the experimental group indicate that FIR therapy improves blood circulation to the feet. This therapy thus has great potential to be an effective adjuvant treatment for patients with diabetes mellitus undergoing hemodialysis.


Assuntos
Circulação Sanguínea/efeitos da radiação , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/terapia , Traumatismos do Pé/radioterapia , Raios Infravermelhos/uso terapêutico , Diálise Renal/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan , Resultado do Tratamento
14.
Circ Res ; 126(10): 1456-1474, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: covidwho-217630

RESUMO

ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.


Assuntos
Betacoronavirus/fisiologia , Doenças Cardiovasculares , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral , Sistema Renina-Angiotensina/fisiologia , Proteína ADAM17/fisiologia , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Humanos , Terapia de Alvo Molecular , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Receptores Virais/fisiologia , Ligação Viral
15.
Circ Res ; 126(10): 1456-1474, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: covidwho-42135

RESUMO

ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.


Assuntos
Betacoronavirus/fisiologia , Doenças Cardiovasculares , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral , Sistema Renina-Angiotensina/fisiologia , Proteína ADAM17/fisiologia , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Humanos , Terapia de Alvo Molecular , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Receptores Virais/fisiologia , Ligação Viral
16.
Life Sci ; 250: 117598, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243927

RESUMO

AIMS: To investigate if autonomic dysregulation is exacerbated in female rats, subjected to diabetes mellitus (DM), via a paradoxical estrogen (E2)-evoked provocation of neuroinflammation/injury of the hypothalamic paraventricular nucleus (PVN). MAIN METHODS: We measured cardiac autonomic function and conducted subsequent PVN neurochemical studies, in DM rats, and their respective controls, divided as follows: male, sham operated (SO), ovariectomized (OVX), and OVX with E2 supplementation (OVX/E2). KEY FINDINGS: Autonomic dysregulation, expressed as sympathetic dominance (higher low frequency, LF, band), only occurred in DM E2-replete (SO and OVX/E2) rats, and was associated with higher neuronal activity (c-Fos) and higher levels of TNFα and phosphorylated death associated protein kinase-3 (p-DAPK3) in the PVN. These proinflammatory molecules likely contributed to the heightened PVN oxidative stress, injury and apoptosis. The PVN of these E2-replete DM rats also exhibited upregulations of estrogen receptors, ERα and ERß, and proinflammatory adenosine A1 and A2a receptors. SIGNIFICANCE: The E2-dependent autonomic dysregulation likely predisposes DM female rats and women to hypersensitivity to cardiac dysfunction. Further, upregulations of proinflammatory mediators including adenosine A1 and A2 receptors, TNFα and DAPK3, conceivably explain the paradoxical hypersensitivity of DM females to PVN inflammation/injury and the subsequent autonomic dysregulation in the presence of E2.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Diabetes Mellitus Experimental/complicações , Estrogênios/farmacologia , Cardiopatias/fisiopatologia , Hipotálamo/fisiopatologia , Inflamação/patologia , Animais , Apoptose , Proteínas Quinases Associadas com Morte Celular/metabolismo , Complicações do Diabetes/fisiopatologia , Feminino , Coração/efeitos dos fármacos , Frequência Cardíaca , Masculino , Estresse Oxidativo , Núcleo Hipotalâmico Paraventricular/metabolismo , Fosforilação , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptor A1 de Adenosina/metabolismo , Receptor A2A de Adenosina/metabolismo , Fatores Sexuais , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
17.
Circ Res ; 126(10): 1456-1474, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32264791

RESUMO

ACE2 (angiotensin-converting enzyme 2) has a multiplicity of physiological roles that revolve around its trivalent function: a negative regulator of the renin-angiotensin system, facilitator of amino acid transport, and the severe acute respiratory syndrome-coronavirus (SARS-CoV) and SARS-CoV-2 receptor. ACE2 is widely expressed, including, in the lungs, cardiovascular system, gut, kidneys, central nervous system, and adipose tissue. ACE2 has recently been identified as the SARS-CoV-2 receptor, the infective agent responsible for coronavirus disease 2019, providing a critical link between immunity, inflammation, ACE2, and cardiovascular disease. Although sharing a close evolutionary relationship with SARS-CoV, the receptor-binding domain of SARS-CoV-2 differs in several key amino acid residues, allowing for stronger binding affinity with the human ACE2 receptor, which may account for the greater pathogenicity of SARS-CoV-2. The loss of ACE2 function following binding by SARS-CoV-2 is driven by endocytosis and activation of proteolytic cleavage and processing. The ACE2 system is a critical protective pathway against heart failure with reduced and preserved ejection fraction including, myocardial infarction and hypertension, and against lung disease and diabetes mellitus. The control of gut dysbiosis and vascular permeability by ACE2 has emerged as an essential mechanism of pulmonary hypertension and diabetic cardiovascular complications. Recombinant ACE2, gene-delivery of Ace2, Ang 1-7 analogs, and Mas receptor agonists enhance ACE2 action and serve as potential therapies for disease conditions associated with an activated renin-angiotensin system. rhACE2 (recombinant human ACE2) has completed clinical trials and efficiently lowered or increased plasma angiotensin II and angiotensin 1-7 levels, respectively. Our review summarizes the progress over the past 20 years, highlighting the critical role of ACE2 as the novel SARS-CoV-2 receptor and as the negative regulator of the renin-angiotensin system, together with implications for the coronavirus disease 2019 pandemic and associated cardiovascular diseases.


Assuntos
Betacoronavirus/fisiologia , Doenças Cardiovasculares , Infecções por Coronavirus , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral , Sistema Renina-Angiotensina/fisiologia , Proteína ADAM17/fisiologia , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Humanos , Terapia de Alvo Molecular , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Receptores Virais/fisiologia , Ligação Viral
19.
Curr Diab Rep ; 20(5): 15, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198703

RESUMO

PURPOSE OF REVIEW: Due to treatment advancements, individuals with type 1 diabetes (T1D) are living longer, presenting a unique understudied population with advanced complex needs. This article is a review of the aging literature in T1D and identifies existing gaps while serving as a call to the research community. RECENT FINDINGS: Recent studies have identified an association between cognitive impairment and glycemic variability, as well as increased risk and frequency of hypoglycemia in older adults with T1D. However, limited research exists about additional physical and mental health conditions and barrier to successful treatment in this population. Older adults may experience both age- and diabetes-related barriers to diabetes management. Due to the scarcity of aging T1D research, current treatment guidelines for this age group are based on type 2 diabetes research. There is a critical need to further investigate the physical and mental effects of T1D and aging as well as public health policy; insurance challenges; and needs for support and interventions for older adults with T1D.


Assuntos
Envelhecimento , Complicações do Diabetes , Diabetes Mellitus Tipo 1 , Glicemia/análise , Transtornos Cognitivos/etiologia , Complicações do Diabetes/etiologia , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 1/terapia , Humanos , Hipoglicemia/etiologia
20.
Curr Diabetes Rev ; 16(8): 797-806, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32000646

RESUMO

Diabetes mellitus is associated with an increased risk of micro and macrovascular complications. During hyperglycemic conditions, endothelial cells and vascular smooth muscle cells are exquisitely sensitive to high glucose. This high glucose-induced sustained reactive oxygen species production leads to redox imbalance, which is associated with endothelial dysfunction and vascular wall remodeling. Nrf2, a redox-regulated transcription factor plays a key role in the antioxidant response element (ARE)-mediated expression of antioxidant genes. Although accumulating data indicate the molecular mechanisms underpinning the Nrf2 regulated redox balance, understanding the influence of the Nrf2/ARE axis during hyperglycemic condition on vascular cells is paramount. This review focuses on the context-dependent role of Nrf2/ARE signaling on vascular endothelial and smooth muscle cell function during hyperglycemic conditions. This review also highlights improving the Nrf2 system in vascular tissues, which could be a potential therapeutic strategy for vascular dysfunction.


Assuntos
Elementos de Resposta Antioxidante/genética , Diabetes Mellitus Tipo 2/genética , Células Endoteliais/metabolismo , Hiperglicemia/genética , Miócitos de Músculo Liso/metabolismo , Fator 2 Relacionado a NF-E2/genética , Animais , Elementos de Resposta Antioxidante/fisiologia , Antioxidantes/metabolismo , Complicações do Diabetes/genética , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Epigênese Genética , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Humanos , Hiperglicemia/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Fosfotransferases/genética , Fosfotransferases/metabolismo , Espécies Reativas de Oxigênio/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
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