Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.039
Filtrar
1.
Adv Exp Med Biol ; 1307: 129-152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32266607

RESUMO

Diabetes mellitus is constantly increasing worldwide. Vascular complications are the most common in the setting of long-standing disease, claiming the greatest burden in terms of morbidity and mortality. Glucotoxicity is involved in vascular damage through different metabolic pathways, such as production of advanced glycation end-products, activation of protein kinase C, polyol pathway activation and production of reactive oxygen species. Vascular complications can be classified according to the calibre of the vessels involved as microvascular (such as diabetic retinopathy, nephropathy and neuropathy) or macrovascular (such as cerebrovascular, coronary and peripheral artery disease). Previous studies showed that the severity of vascular complications depends on duration and degree of hyperglycaemia and, as consequence, early trials were designed to prove that intensive glucose control could reduce the number of vascular events. Unfortunately, results were not as satisfactory as expected. Trials showed good results in reducing incidence of microvascular complications but coronary heart diseases, strokes and peripheral artery diseases were not affected despite optimal glycemia control. In 2008, after the demonstration that rosiglitazone increases cardiovascular risk, FDA demanded stricter rules for marketing glucose-lowering drugs, marking the beginning of cardiovascular outcome trials, whose function is to demonstrate the cardiovascular safety of anti-diabetic drugs. The introduction of new molecules led to a change in diabetes treatment, as some new glucose-lowering drugs showed not only to be safe but also to ensure cardiovascular benefit to diabetic patients. Empaglifozin, a sodium-glucose cotransporter 2 inhibitor, was the first molecule to show impressing results, followed on by glucagon-like peptide 1 receptor agonists, such as liraglutide. A combination of anti-atherogenic effects and hemodynamic improvements are likely explanations of the observed reduction in cardiovascular events and mortality. These evidences have opened a completely new era in the field of glucose-lowering drugs and of diabetes treatment in particular with respect to vascular complications.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2 , Hiperglicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico
2.
J Stroke Cerebrovasc Dis ; 30(1): 105380, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33166769

RESUMO

BACKGROUND AND PURPOSE: Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated with poor outcome but the effect of glucose level on infarct growth is not well studied. MATERIALS AND METHODS: This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core. RESULTS: We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03). CONCLUSION: In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.


Assuntos
Glicemia/metabolismo , Infarto Encefálico/terapia , Procedimentos Endovasculares , Hiperglicemia/complicações , Reperfusão , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Infarto Encefálico/complicações , Infarto Encefálico/diagnóstico por imagem , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reperfusão/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
3.
Curr Opin Endocrinol Diabetes Obes ; 28(1): 35-42, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33278126

RESUMO

PURPOSE OF REVIEW: Type 2 diabetes (T2DM) is a major comorbidity of coronavirus disease 2019 (COVID-19) but less is known about COVID-19 and type 1 diabetes (T1DM). Thus, our goal was to review the literature on COVID and T1DM. RECENT FINDINGS: We identified 21 reports focusing on COVID-19 infections among patients with preexisting T1DM (n = 7), incident T1DM presentations during the COVID-19 quarantine (n = 6), and outpatient management of T1DM during the COVID-19 quarantine (n = 8). These studies showed that patients with preexisting T1DM and COVID-19 infection often present with hyperglycemia and/or diabetic ketoacidosis (DKA). Although the risk of in-hospital mortality may be increased, hospitalization rates among patients with T1DM mirror that of the general population. The numbers of patients presenting with incident T1DM during COVID-19 quarantine have remained stable, but cases with severe DKA may have increased. COVID-19 quarantine has also impacted outpatient T1DM management and studies examining changes in glycemic control have shown mixed results. SUMMARY: COVID-19 has important implications for patients with type 1 diabetes, but additional studies with larger numbers of patients and longer term follow-up are needed to confirm the early findings highlighted in this review.


Assuntos
/complicações , Diabetes Mellitus Tipo 1/complicações , Comorbidade , Humanos , Hiperglicemia/complicações
4.
Ann Med ; 53(1): 103-116, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33063540

RESUMO

BACKGROUND: Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19. METHODS: This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: <140 mg/dL, 140-180 mg/dL and >180 mg/dL. The primary endpoint was all-cause in-hospital mortality. RESULTS: Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (<140 mg/dL), 33.7% (140-180 mg) and 41.1% (>180 mg/dL), p<.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p<.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31-1.73) (BG 140-180 mg/dL; HR 1.48; 95%CI: 1.29-1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality. CONCLUSIONS: Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes.


Assuntos
Infecções por Coronavirus/mortalidade , Hiperglicemia/complicações , Pneumonia Viral/mortalidade , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Glicemia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Cuidados Críticos/estatística & dados numéricos , Feminino , Humanos , Hiperglicemia/mortalidade , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Respiração Artificial/estatística & dados numéricos , Espanha/epidemiologia
5.
PLoS One ; 15(10): e0240839, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33095794

RESUMO

BACKGROUND: Many people living with diabetes are at risk for poor glycemic control, hyperlipidemia, hypertension, and macro vascular complications. Glycemic control and psychological wellbeing of the patient is mandatory for diabetes management. Addressing these issues in the early stages of the disease are the best interventions for decreasing poor glycemic control and psychological problems. OBJECTIVE: To explore and analyze the literature for evidence of the effect of Motivational Interviewing (MI) intervention has on glycosylated hemoglobin A1C (HgbA1C) and depression in people with Type 2 diabetes mellitus (T2DM). METHODS: A systemic review and meta-analysis of studies published in Cochrane Library, Google scholar, PubMed, & clinical trials.gov between 01/01/2009 and 12/06/2020 was performed. Inclusion criteria included RCT and pre post studies that assessed the effects of Motivational Interviewing on Hgb.A1C and depression in adults with T2DM. Weighted mean differences with 95% confidence intervals were calculated for continuous data. The data were synthesized and analyzed in a narrative form in systematic review and meta-analysis which was conducted using RevMan 5.2.0 & STATA version 11 software. Data were evaluated by weighted mean differences (WMDs) and 95% CIs. RESULT: Of the total identified 121 studies, eight were eligible for inclusion in the review. The pooled results showed that MI resulted in a significant improvement of mean HgbA1C level in the intervention group when compared with the control group (WMD, -0.29; 95% CI, -0.47 to -0.10; p = 0.003, I2 = 48%). Effect of MI intervention on depressive symptoms was identified through subgroup analysis according to intervention session time (30 or 60-80 minutes) and Follow-up period (3 or 24 months) then result showed that there was no significant difference in the reduction of depressive symptoms between the intervention and control groups. The output results were (WMD, -1.58; 95% CI, -5.05 to -0.188; p = 0.37; I2 = 48%), (WMD, -4.30; 95% CI, -9.32 to -0.73; p = 0.09; I2 = 95%), (WMD, -4.45; 95% CI, -10.58 to 1.69; p = 0.16; I2 = 96%) and (WMD, -2.12; 95% CI, -5.54 to 1.30; p = 0.22; I2 = 83%) respectively. CONCLUSION: The pooled result in meta-analysis indicated that motivational interviewing is effective in reducing HgbA1C but not depressive symptoms of patients with type 2 diabetes. Motivational interviewing intervention is important for diabetes management and effective in glycemic control with no effect on the reduction of depressive symptoms among persons with type 2 diabetes mellitus. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42019146368.


Assuntos
Depressão , Diabetes Mellitus Tipo 2/complicações , Hiperglicemia , Entrevista Motivacional , Adulto , Glicemia/análise , Depressão/complicações , Depressão/prevenção & controle , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/complicações , Hiperglicemia/prevenção & controle
6.
Metabolism ; 113: 154403, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33065162

RESUMO

BACKGROUND: Retinol-binding protein 4 (RBP4) is elevated and associated with inflammation in metabolic diseases. Disruption of the retinol cascade and O-GlcNAcylation of the RBP4 receptor (STRA6) are found in diabetic kidneys. OBJECTIVES: We investigated whether the disruption of the retinol cascade induces RBP4 overproduction and if O-linked GlcNAc modification targets RBPR2 and contributes to the disruption of retinol cascades in diabetic livers. METHODS: Western blot or immunohistochemistry for RBPR2, CRBP1, LRAT, RALDH, RARα, RARγ, RXRα, RBP4, GFAT, OGT, OGA and inflammatory markers, as well as ELISA for RBP4, were performed in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. Immunoprecipitation and dual fluorescence staining were used to explore O-GlcNAc-modified RBPR2 and RBP4 binding activity on RBPR2. Transfection of the CRBP1 gene was done to verify whether a disrupted retinol cascade induces RBP4 overproduction. OGT silencing was done to investigate the association of O-GlcNAcylation with the disruption of retinol cascade. RESULTS: Disruption of retinol cascade, RBP4 overproduction, O-GlcNAcylation of RBPR2, decreased RBP4 binding activity on RBPR2 and inflammation were found in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. CRBP1 gene transfection reversed the suppression of the cellular retinol cascade and simultaneously attenuated the RBP4 overproduction and inflammation in high glucose-treated hepatocytes. The silencing of OGT reversed the disruption of the cellular retinol cascade, RBP4 overproduction and inflammation induced by high glucose in hepatocytes. CONCLUSIONS: This study indicates that the disruption of cellular retinol cascade is strongly associated with RBP4 overproduction and inflammation in diabetic livers. RBPR2 is one target for high glucose-mediated O-linked GlcNAc modification, which causes liver retinol dyshomeostasis.


Assuntos
Diabetes Mellitus/metabolismo , Homeostase , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Vitamina A/metabolismo , Tecido Adiposo/metabolismo , Animais , Hepatite Animal/complicações , Hiperglicemia/complicações , Hiperlipidemias/complicações , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Celulares de Ligação ao Retinol/genética , Proteínas Plasmáticas de Ligação ao Retinol/genética , Transdução de Sinais
7.
PLoS One ; 15(9): e0238750, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32886728

RESUMO

PURPOSE: The purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal. METHODS: Six-week-old male C57BL/6 mice were fed a high fat diet (HFD) or a normal diet (ND) for 5-15 weeks. Diet reversal (DiR) mice were fed a HFD for 5 weeks, followed by a ND for 5 or 10 weeks. Corneal sensitivity was determined using aesthesiometry. Corneal cytokine expression was analyzed using a 32-plex Luminex assay. Excised corneas were prepared for immunofluorescence microscopy to evaluate diet-induced changes and wound healing. For wounding studies, mice were fed a HFD or a ND for 10 days prior to receiving a central 2mm corneal abrasion. RESULTS: After 10 days of HFD consumption, corneal sensitivity declined. By 10 weeks, expression of corneal inflammatory mediators increased and nerve density declined. While diet reversal restored nerve density and sensitivity, the corneas remained in a heightened inflammatory state. After 10 days on the HFD, corneal circadian rhythms (limbal neutrophil accumulation, epithelial cell division and Rev-erbα expression) were blunted. Similarly, leukocyte recruitment after wounding was dysregulated and accompanied by delays in wound closure and nerve recovery. CONCLUSION: In the mouse, obesogenic diet consumption results in corneal dysfunction that precedes the onset of sustained hyperglycemia. Diet reversal only partially ameliorated this dysfunction, suggesting a HFD diet may have a lasting negative impact on corneal health that is resistant to dietary therapeutic intervention.


Assuntos
Córnea/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Hiperglicemia/fisiopatologia , Obesidade/induzido quimicamente , Obesidade/complicações , Animais , Composição Corporal/efeitos dos fármacos , Córnea/efeitos dos fármacos , Modelos Animais de Doenças , Homeostase/efeitos dos fármacos , Hiperglicemia/complicações , Leucócitos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo , Cicatrização/efeitos dos fármacos
8.
J Card Surg ; 35(10): 2759-2767, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32939829

RESUMO

OBJECTIVES: Hyperglycemia is associated with an increased risk of adverse cardiovascular outcomes, such as heart failure, coronary heart disease, stroke, and in-hospital mortality. For those receiving cardiac surgery, up to half develop hyperglycemia while 30% have a diagnosis of diabetes, which is defined by chronic hyperglycemia. Due to a prothrombic state and endovascular damage, patients with diabetes have a twofold increased risk of cardiovascular events. METHODS: Electronic literature search was done to identify articles that have discussed antidiabetic medications and how it is impacting the glycemia status as well as cardiovascular outcomes. No limits were placed on timing of the publication or type of the article. Key words and MeSH terms were used to conduct the search and the results are summarized in a narrative manner within each relevant section. RESULTS: Antidiabetic medications play a key role in lowering blood glucose levels to reduce adverse cardiovascular outcomes. However, it is a challenge to assess their cardiovascular safety due to confounding factors, such as age, obesity, smoking, hyperlipidemia, and high blood pressure. Further research in this field is required to understand this correlation closely. CONCLUSION: Optimizing blood glucose level during the perioperative period with correct medication and dose have a significant role in reducing morbidities. Measures should be taken to provide a safe blood glucose level for optimum outcomes.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/cirurgia , Complicações do Diabetes/complicações , Diabetes Mellitus/tratamento farmacológico , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Assistência Perioperatória , Complicações Pós-Operatórias/prevenção & controle , Humanos , Risco , Resultado do Tratamento
9.
In Vivo ; 34(5): 3029-3032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871848

RESUMO

BACKGROUND/AIM: Reports indicate that coronaviridae may inhibit insulin secretion. In this report we aimed to describe the course of glycemia in critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. PATIENTS AND METHODS: We studied 36 SARS-CoV-2 patients (with no history of diabetes) in one intensive care unit (ICU). All the patients were admitted for hypoxemic respiratory failure; all but four required mechanical ventilation. The mean (±SD) age of the patients was 64.7 (9.7) years; 27 were men; the mean (±SD) duration of ICU stay was 12.9 (8.3 days). RESULTS: Twenty of 36 patients presented with hyperglycemia; brief intravenous infusions of short-acting insulin were administered in six patients. As of May 29 2020, 11 patients had died (seven with hyperglycemia). In 17 patients the Hyperglycemia Index [HGI; defined as the area under the curve of (hyper)glycemia level*time (h) divided by the total time in the ICU] was <16.21 mg/dl (0.90 mmol/l), whereas in three patients the HGI was ≥16.21 mg/dl (0.90 mol/l) and <32.25 mg/dl (1.79 mmol/l). CONCLUSION: In our series of ICU patients with SARS-CoV-2 infection, and no history of diabetes, a substantial number of patients had hyperglycemia, to a higher degree than would be expected by the stress of critical illness, lending credence to reports that speculated a tentative association between SARS-CoV-2 and hyperglycemia. This finding is important, since hyperglycemia can lead to further infectious complications.


Assuntos
Infecções por Coronavirus/terapia , Diabetes Mellitus/terapia , Hiperglicemia/terapia , Insulina/metabolismo , Pneumonia Viral/terapia , Betacoronavirus/patogenicidade , Glicemia/metabolismo , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Diabetes Mellitus/genética , Diabetes Mellitus/virologia , Feminino , Hospitalização , Humanos , Hiperglicemia/complicações , Hiperglicemia/virologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Respiração Artificial , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/virologia
10.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 530-535, 2020 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879102

RESUMO

OBJECTIVES: To describe the clinical characteristics and outcomes of severely ill patients with coronavirus disease 2019, and to investigate the relationship between plasma glucose level and the prognosis of severely ill patients with coronavirus disease 2019. METHODS: We enrolled 52 severely ill patients with coronavirus disease 2019. Among them, 12 cases progressed to critical illness. The clinical and biochemical characteristics of severely and critically ill patients were compared. RESULTS: Compared with the severely ill patients, critically ill patients had higher white blood cell and neutrophil counts, as well as higher levels of D-dimer, IL-6 and C-reactive protein (all P<0.05). Before treatment, the fasting plasma glucose (FPG) levels were significantly higher in the critically ill patient's group [(10.23±3.71) mmol/L] compared to those in the severely ill patients [(7.12±3.35) mmol/L, P<0.05]. After adjusting for age, gender, and course of the disease, fasting blood glucose at admission (OR=1.308, 95% CI 1.066 to 1.606, P=0.01) and hyperglycemia at admission (OR=29.198, 95% CI 2.903 to 293.639, P=0.004) were closely related to whether severely ill patients progressed to critical patients with coronavirus disease 2019. In our study, 15 (34.8%) of the severely ill and 10 (83.3%) critically ill patients received the steroid treatment. Compared with the severely ill patients, the FPG levels in critically ill patients were higher (P<0.05). CONCLUSIONS: Fasting hyperglycemia at admission is a significant predictor for the prognosis of severely ill patients with coronavirus disease 2019. Closely monitoring and the optimal management of hyperglycemia may improve the prognosis of patients with coronavirus disease 2019.


Assuntos
Glicemia , Infecções por Coronavirus/sangue , Hiperglicemia/complicações , Pneumonia Viral/sangue , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Estado Terminal , Humanos , Contagem de Leucócitos , Pandemias , Pneumonia Viral/diagnóstico , Prognóstico
11.
Invest Ophthalmol Vis Sci ; 61(10): 49, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32852545

RESUMO

Purpose: Recent evidence suggests that there is a correlation between the micro- and macrovascular complications of diabetes mellitus. The aim of this study is to investigate the molecular mechanisms by which diabetes promotes the development of microvascular disease (diabetic retinopathy [DR]) through characterization of the effects of hyperglycemia in the retina of mouse models of diabetic atherosclerosis. Methods: Hyperglycemia was induced in apolipoprotein E-deficient (ApoE-/-) mice, a model of accelerated atherosclerosis, either through streptozotocin (STZ) injection or introduction of the Ins2Akita mutation (ApoE-/-Ins2+/Akita). Another subset of ApoE-/- mice was supplemented with glucosamine (GlcN). To attenuate atherosclerosis, subsets of mice from each experimental group were treated with the chemical chaperone, 4-phenylbutyric acid (4PBA). Eyes from 15-week-old mice were either trypsin digested and stained with periodic acid-Schiff (PAS) or frozen for cryostat sectioning and immunostained for endoplasmic reticulum (ER) stress markers, including C/EBP homologous protein (CHOP) and 78-kDa glucose-regulated protein (GRP78). PAS-stained retinal flatmounts were analyzed for microvessel density, acellular capillaries, and pericyte ghosts. Results: Features of DR, including pericyte ghosts and reduced microvessel density, were observed in hyperglycemic and GlcN-supplemented mice. Treatment with 4PBA reduced ER stress in the retinal periphery and attenuated DR in the experimental groups. Conclusions: Mouse models of diabetic atherosclerosis show characteristic pathologies of DR that correlate with atherosclerosis. The increased magnitude of these changes and responses to 4PBA in the peripheral retina suggest that future studies should be aimed at assessing regional differences in mechanisms of ER stress-related pathways in these mouse models.


Assuntos
Aterosclerose/etiologia , Angiopatias Diabéticas/patologia , Retinopatia Diabética/etiologia , Estresse do Retículo Endoplasmático , Animais , Apolipoproteínas E/metabolismo , Aterosclerose/patologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Angiopatias Diabéticas/complicações , Retinopatia Diabética/patologia , Modelos Animais de Doenças , Feminino , Imunofluorescência , Hiperglicemia/complicações , Hiperglicemia/patologia , Masculino , Camundongos , Camundongos Knockout , Microvasos/patologia , Vasos Retinianos/patologia
12.
Diabetes Res Clin Pract ; 168: 108381, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853687

RESUMO

AIMS: Coronavirus disease 2019 (COVID-19) has become a recognized worldwide pandemic. Researchers now know that mortality from COVID-19 can be reduced through early prevention measures. This retrospective, multi-centered study of 293 COVID-19 patients without diabetes explores the association between fasting blood glucose (FBG) levels and the risk of COVID-19 disease progression, with the goal of providing clinical evidence for glycemic targets in patients. METHODS: The multivariate stepwise binary logistic regression analysis was used to test the dose-response effects of FBG levels on the risk of severe and critical condition in COVID-19 patients. RESULTS: FBG levels were plotted in quintiles with set at <4.74, 4.74-5.21, 5.21-5.78, 5.78-7.05, and ≧7.05 mmol/L. The constituent ratio of severe or critical cases in each FBG quintile was 20.7%, 1.7%, 13.8%, 27.1%, and 67.2%, respectively (P < 0.0001). When the second quintile was used as the reference, the adjusted odds ratios (AORs) (95%CI) for the risk of severe/critical condition in COVID-19 was 25.33 (2.77, 231.64), 1.00 (Reference), 3.13 (0.33, 29.67), 10.59 (1.23, 91.24), 38.93 (4.36, 347.48) per FBG quintile respectively (P < 0.001). CONCLUSIONS: We provide evidence of J-shaped associations between FBG and risk of severe and critical condition in non-diabetes patients with COVID-19, with nadir at 4.74-5.78 mmol/L.


Assuntos
Glicemia/análise , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Jejum/sangue , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Adulto , Idoso , Betacoronavirus/fisiologia , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Progressão da Doença , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
14.
Diabetes Res Clin Pract ; 168: 108374, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32805345

RESUMO

AIMS: We investigated whether pre-existing diabetes, newly-diagnosed diabetes, and admission hyperglycemia were associated with COVID-19 severity independently from confounders. METHODS: We retrospectively analyzed data on patients with COVID-19 hospitalized between February and April 2020 in an outbreak hospital in North-East Italy. Pre-existing diabetes was defined by self-reported history, electronic medical records, or ongoing medications. Newly-diagnosed diabetes was defined by HbA1c and fasting glucose. The primary outcome was a composite of ICU admission or death. RESULTS: 413 subjects were included, 107 of whom (25.6%) had diabetes, including 21 newly-diagnosed. Patients with diabetes were older and had greater comorbidity burden. The primary outcome occurred in 37.4% of patients with diabetes compared to 20.3% in those without (RR 1.85; 95%C.I. 1.33-2.57; p < 0.001). The association was stronger for newly-diagnosed compared to pre-existing diabetes (RR 3.06 vs 1.55; p = 0.004). Higher glucose level at admission was associated with COVID-19 severity, with a stronger association among patients without as compared to those with pre-existing diabetes (interaction p < 0.001). Admission glucose was correlated with most clinical severity indexes and its association with adverse outcome was mostly mediated by a worse respiratory function. CONCLUSION: Newly-diagnosed diabetes and admission hyperglycemia are powerful predictors of COVID-19 severity due to rapid respiratory deterioration.


Assuntos
Infecções por Coronavirus/diagnóstico , Complicações do Diabetes/diagnóstico , Diabetes Mellitus/diagnóstico , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Admissão do Paciente , Pneumonia Viral/diagnóstico , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/fisiologia , Glicemia/análise , Glicemia/metabolismo , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Complicações do Diabetes/sangue , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/patologia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Feminino , Humanos , Hiperglicemia/epidemiologia , Hiperglicemia/terapia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-32754119

RESUMO

Background: Diabetes correlates with poor prognosis in patients with COVID-19, but very few studies have evaluated whether impaired fasting glucose (IFG) is also a risk factor for the poor outcomes of patients with COVID-19. Here we aimed to examine the associations between IFG and diabetes at admission with risks of complications and mortality among patients with COVID-19. Methods: In this multicenter retrospective cohort study, we enrolled 312 hospitalized patients with COVID-19 from 5 hospitals in Wuhan from Jan 1 to Mar 17, 2020. Clinical information, laboratory findings, complications, treatment regimens, and mortality status were collected. The associations between hyperglycemia and diabetes status at admission with primary composite end-point events (including mechanical ventilation, admission to intensive care unit, or death) were analyzed by Cox proportional hazards regression models. Results: The median age of the patients was 57 years (interquartile range 38-66), and 172 (55%) were women. At the time of hospital admission, 84 (27%) had diabetes (and 36 were new-diagnosed), 62 (20%) had IFG, and 166 (53%) had normal fasting glucose (NFG) levels. Compared to patients with NFG, patients with IFG and diabetes developed more primary composite end-point events (9 [5%], 11 [18%], 26 [31%]), including receiving mechanical ventilation (5 [3%], 6 [10%], 21 [25%]), and death (4 [2%], 9 [15%], 20 [24%]). Multivariable Cox regression analyses showed diabetes was associated increased risks of primary composite end-point events (hazard ratio 3.53; 95% confidence interval 1.48-8.40) and mortality (6.25; 1.91-20.45), and IFG was associated with an increased risk of mortality (4.11; 1.15-14.74), after adjusting for age, sex, hospitals and comorbidities. Conclusion: IFG and diabetes at admission were associated with higher risks of adverse outcomes among patients with COVID-19.


Assuntos
Glicemia/metabolismo , Infecções por Coronavirus/mortalidade , Complicações do Diabetes/mortalidade , Diabetes Mellitus/fisiopatologia , Intolerância à Glucose/complicações , Hiperglicemia/complicações , Pneumonia Viral/mortalidade , Adulto , Idoso , Betacoronavirus/isolamento & purificação , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/virologia , Diabetes Mellitus/virologia , Jejum , Feminino , Seguimentos , Intolerância à Glucose/virologia , Mortalidade Hospitalar , Hospitalização , Humanos , Hiperglicemia/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida
16.
Diabetes Care ; 43(10): 2345-2348, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788285

RESUMO

OBJECTIVE: To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: Hospitalized COVID-19 patients (N = 271) were subdivided based on at-admission glycemic status: 1) glucose levels <7.78 mmol/L (NG) (N = 149 [55.0%]; median glucose 5.99 mmol/L [range 5.38-6.72]), 2) known diabetes mellitus (DM) (N = 56 [20.7%]; 9.18 mmol/L [7.67-12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N = 66 [24.3%]; 8.57 mmol/L [8.18-10.47]). RESULTS: Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27-3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92-3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03-3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46-8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91-5.96, P = 0.079) vs. Q1. CONCLUSIONS: Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Hiperglicemia/complicações , Pneumonia Viral/complicações , Glicemia , Infecções por Coronavirus/diagnóstico , Complicações do Diabetes , Diabetes Mellitus , Feminino , Hospitalização , Humanos , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Prognóstico , Índice de Gravidade de Doença
18.
PLoS One ; 15(8): e0237660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841254

RESUMO

This study evaluated the influence of type 2 diabetes mellitus on bone loss, bone repair and cytokine production in hyperglycemic rats, treated or not with metformin. The animals were distributed as follow: Non-Hyperglycemic (NH), Non Hyperglycemic with Ligature (NH-L), Treated Non Hyperglycemic (TNH), Treated Non Hyperglycemic with Ligature Treated (TNH-L), Hyperglycemic (H), Treated Hyperglycemic (TH), Hyperglycemic with Ligature (H-L), Treated Hyperglycemic with Ligature (TH-L). At 40th day after induction of hyperglycemia, the groups NH-L, TNH-L, H-L, TH-L received a ligature to induce periodontitis. On the 69th, the TNH, TNH-L, TH, TH-L groups received metformin until the end of the study. Bone repair was evaluated at histometric and the expression levels of Sox9, RunX2 and Osterix. Analysis of the ex-vivo expression of TNF-α, IFN-γ, IL-12, IL-4, TGF-ß, IL-10, IL-6 and IL-17 were also evaluated. Metformin partially reverse induced bone loss in NH and H animals. Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis. The expression of SOX9 and RunX2 were also decreased by hyperglycemia and metformin treatment. Increased ex vivo levels of TNF-α, IL-6, IL-4, IL-10 and IL-17 was observed. Hyperglycemia promoted increased IL-10 levels compared to non-hyperglycemic ones. Treatment of NH with metformin was able to mediate increased levels of TNF-α, IL-10 and IL-17, whereas for H an increase of TNF-α and IL-17 was detected in the 24- or 48-hour after stimulation with LPS. Ligature was able to induce increased levels of TNF-α and IL-17 in both NH and H. This study revealed the negative impact of hyperglycemia and/or treatment with metformin in the bone repair via inhibition of transcription factors associated with osteoblastic differentiation.


Assuntos
Perda do Osso Alveolar/prevenção & controle , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Hiperglicemia/complicações , Metformina/administração & dosagem , Periodontite/prevenção & controle , Perda do Osso Alveolar/etiologia , Perda do Osso Alveolar/metabolismo , Processo Alveolar/citologia , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/metabolismo , Processo Alveolar/patologia , Animais , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/genética , Diferenciação Celular/efeitos dos fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Osteoblastos/fisiologia , Periodontite/etiologia , Periodontite/metabolismo , Ratos , Estreptozocina/toxicidade , Fatores de Transcrição/metabolismo
20.
Diabetes Res Clin Pract ; 166: 108299, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32623030

RESUMO

AIMS: To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. METHODS: From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of ≤11 mmol/L (group 1) and >11 mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. RESULTS: Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.2%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of ≥1.5 µg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of ≥10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. CONCLUSIONS: In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11 mmol/L) may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.


Assuntos
Betacoronavirus/isolamento & purificação , Glicemia/metabolismo , Infecções por Coronavirus/mortalidade , Complicações do Diabetes/mortalidade , Diabetes Mellitus/fisiopatologia , Intolerância à Glucose/complicações , Hiperglicemia/complicações , Pneumonia Viral/mortalidade , Idoso , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/virologia , Diabetes Mellitus/virologia , Feminino , Intolerância à Glucose/virologia , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/virologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Alta do Paciente/estatística & dados numéricos , Pneumonia Viral/complicações , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA