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1.
Medicine (Baltimore) ; 100(15): e25488, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847657

RESUMO

BACKGROUND: To assess T-cell exhaustion mediated by programmed cell death 1 (PD-1) pathway in patients living with type 2 diabetes (T2D). METHODS: MEDLINE and ProQuest electronic databases were searched for eligible studies from inception up to February 2020. The risk of bias and the quality of evidence were independently assessed by two reviewers using the modified Newcastle-Ottawa Scale adapted for cross-sectional studies and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool, respectively. The random effects model was used to calculate effect estimates. RESULTS: We identified 5 studies involving 380 participants which met the inclusion criteria. The pooled estimates showed elevated T helper cell exhaustion in patients with T2D in comparison to controls (mean difference [MD]: 2.57% [95% confidence interval [CI]: -3.84, 8.97]; I2 = 100%, P < .00001). Likewise, T2D patients had increased levels of cytotoxic T-cells exhaustion (MD: 3.09% [95% CI: -12.96, 19.14]; I2 = 100%, P < .00001). Although the upregulation of PD-1 on T-cells did not affect glucose metabolism-related profiles, it was associated with inflammation and the development of cardiovascular disease. CONCLUSION: In patients living with T2D, immune dysfunction is at least in part due to T-cell exhaustion mediated by the upregulation of PD-1 expression. Therefore, the use of immune checkpoint inhibitors as a therapeutic strategy may be beneficial in restoring immune function in patients with T2D.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T/imunologia , Regulação para Cima/imunologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Imunidade Celular/imunologia , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/imunologia
2.
Front Endocrinol (Lausanne) ; 12: 596518, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33776910

RESUMO

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04365634. Context: Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear. Objective: We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients. Design and Methods: In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups. Results: Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4+ T cells, CD8+ T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8+ T cells and NK cells than survivors. Conclusion: The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8+ T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.


Assuntos
/imunologia , Diabetes Mellitus Tipo 2/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , /complicações , China/epidemiologia , Citocinas/análise , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/imunologia , Hiperglicemia/mortalidade , Sistema Imunitário/metabolismo , Sistema Imunitário/patologia , Células Matadoras Naturais/patologia , Contagem de Linfócitos , Linfopenia/sangue , Linfopenia/complicações , Linfopenia/imunologia , Linfopenia/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , /fisiologia , Células Th1/patologia , Células Th2/patologia
3.
Sci Rep ; 11(1): 6428, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742062

RESUMO

Hyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS). The objective was to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects. A case-controlled interventional pilot study in OT2D (n = 23) and control subjects (n = 23). OT2D subjects underwent hyperinsulinemic clamp to normalize serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-h of insulin clamp (OT2D subjects only). Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers, CXCL9 and CXCL10, were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGß-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia. In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences could potentially predispose diabetic individuals to increased infection severity complicated by ARDS. Clinical trial reg. no: NCT03102801; registration date April 6, 2017.


Assuntos
/etiologia , Diabetes Mellitus Tipo 2/complicações , Ativação de Macrófagos , Obesidade/complicações , Adulto , Idoso , Biomarcadores/sangue , /imunologia , Citocinas/sangue , Citocinas/imunologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Inflamação/sangue , Inflamação/complicações , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/imunologia , Projetos Piloto , Estudos Prospectivos , Fatores de Risco
4.
Molecules ; 26(3)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535560

RESUMO

Brassicaceae are an outstanding source of bioactive compounds such as ascorbic acid, polyphenols, essential minerals, isothiocyanates and their precursors, glucosinolates (GSL). Recently, GSL gained great attention because of the health promoting properties of their hydrolysis products: isothiocyanates. Among them, sulforaphane (SFN) became the most attractive one owing to its remarkable health-promoting properties. SFN may prevent different types of cancer and has the ability to improve hypertensive states, to prevent type 2 diabetes-induced cardiomyopathy, and to protect against gastric ulcer. SFN may also help in schizophrenia treatment, and recently it was proposed that SFN has potential to help those who struggle with obesity. The mechanism underlying the health-promoting effect of SFN relates to its indirect action at cellular level by inducing antioxidant and Phase II detoxifying enzymes through the activation of transcription nuclear factor (erythroid-derived 2)-like (Nrf2). The effect of SFN on immune response is generating scientific interest, because of its bioavailability, which is much higher than other phytochemicals, and its capacity to induce Nrf2 target genes. Clinical trials suggest that sulforaphane produces favorable results in cases where pharmaceutical products fail. This article provides a revision about the relationship between sulforaphane and immune response in different diseases. Special attention is given to clinical trials related with immune system disorders.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Sistema Imunitário/efeitos dos fármacos , Isotiocianatos/uso terapêutico , Neoplasias/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Esquizofrenia/tratamento farmacológico , Sulfóxidos/uso terapêutico , Animais , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Humanos , Neoplasias/imunologia , Neoplasias/patologia , Esquizofrenia/imunologia , Esquizofrenia/patologia
5.
Int J Mol Sci ; 22(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578952

RESUMO

Macrophages are highly heterogeneous and plastic immune cells with peculiar characteristics dependent on their origin and microenvironment. Following pathogen infection or damage, circulating monocytes can be recruited in different tissues where they differentiate into macrophages. Stimuli present in the surrounding milieu induce the polarisation of macrophages towards a pro-inflammatory or anti-inflammatory profile, mediating inflammatory or homeostatic responses, respectively. However, macrophages can also derive from embryonic hematopoietic precursors and reside in specific tissues, actively participating in the development and the homeostasis in physiological conditions. Pancreatic islet resident macrophages are present from the prenatal stages onwards and show specific surface markers and functions. They localise in close proximity to ß-cells, being exquisite sensors of their secretory ability and viability. Over the years, the crucial role of macrophages in ß-cell differentiation and homeostasis has been highlighted. In addition, macrophages are emerging as central players in the initiation of autoimmune insulitis in type 1 diabetes and in the low-grade chronic inflammation characteristic of obesity and type 2 diabetes pathogenesis. The present work reviews the current knowledge in the field, with a particular focus on the mechanisms of communication between ß-cells and macrophages that have been described so far.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/imunologia , Células Secretoras de Insulina/imunologia , Macrófagos/imunologia , Animais , Proliferação de Células , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Homeostase , Humanos , Inflamação/imunologia , Inflamação/patologia , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/patologia , Macrófagos/citologia , Macrófagos/patologia
6.
Nat Rev Endocrinol ; 17(4): 235-245, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33526907

RESUMO

Intrauterine growth restriction (IUGR) is a common complication of pregnancy and increases the risk of the offspring developing type 2 diabetes mellitus (T2DM) later in life. Alterations in the immune system are implicated in the pathogenesis of IUGR-induced T2DM. The development of the fetal immune system is a delicate balance as it must remain tolerant of maternal antigens whilst also preparing for the post-birth environment. In addition, the fetal immune system is susceptible to an altered intrauterine milieu caused by maternal and placental inflammatory mediators or secondary to nutrient and oxygen deprivation. Pancreatic-resident macrophages populate the pancreas during fetal development, and their phenotype is dynamic through the neonatal period. Furthermore, macrophages in the islets are instrumental in islet development as they influence ß-cell proliferation and islet neogenesis. In addition, cytokines, derived from ß-cells and macrophages, are important to islet homeostasis in the fetus and adult and, when perturbed, can cause islet dysfunction. Several activated immune pathways have been identified in the islets of people who experienced IUGR, with alternations in the levels of IL-1ß and IL-4 as well as changes in TGFß signalling. Leptin levels are also altered. Immunomodulation has shown therapeutic benefit in T2DM and might be particularly useful in IUGR-induced T2DM.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/imunologia , Desenvolvimento Fetal/imunologia , Retardo do Crescimento Fetal/imunologia , Animais , Humanos , Sistema Imunitário/imunologia , Lesões Pré-Natais/imunologia
7.
Int Immunopharmacol ; 93: 107406, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33601246

RESUMO

In patients with COVID-19,type 2 diabetes mellitus (T2DM) can impair the function of nasal-associated lymphoid tissue (NALT) and result in olfactory dysfunction. Exploring the causative alterations of T2DM within the nasal mucosa and NALT could provide insight into the pathogenic mechanisms and bridge the gap between innate immunity and adaptive immunity for virus clearance. Here, we designed a case-control study to compare the olfactory function (OF) among the groups of normal control (NC), COVID-19 mild pneumonia (MP), and MP patients with T2DM (MPT) after a 6-8 months' recovery, in which MPT had a higher risk of hyposmia than MP and NC. No significant difference was found between the MP and NC. This elevated risk of hyposmia indicated that T2DM increased COVID-19 susceptibility in the nasal cavity with unknown causations. Therefore, we used the T2DM animal model (db/db mice) to evaluate how T2DM increased COVID-19 associated susceptibilities in the nasal mucosa and lymphoid tissues. Db/db mice demonstratedupregulated microvasculature ACE2 expression and significant alterations in lymphocytes component of NALT. Specifically, db/db mice NALT had increased immune-suppressive TCRγδ+ CD4-CD8- T and decreased immune-effective CD4+/CD8+ TCRß+ T cells and decreased mucosa-protective CD19+ B cells. These results indicated that T2DM could dampen the first-line defense of nasal immunity, and further mechanic studies of metabolic damage and NALT restoration should be one of the highest importance for COVID-19 healing.


Assuntos
/imunologia , /imunologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/virologia , Adulto , Animais , Linfócitos B/imunologia , /fisiopatologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Imunidade nas Mucosas/imunologia , Tecido Linfoide/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Modelos Animais , Mucosa Nasal/imunologia , Mucosa Olfatória/metabolismo , Fatores de Risco , Serina Endopeptidases/metabolismo , Linfócitos T/imunologia
8.
J Clin Endocrinol Metab ; 106(5): e2025-e2034, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33524125

RESUMO

PURPOSE: Comorbidities making up metabolic syndrome (MetS), such as obesity, type 2 diabetes, and chronic cardiovascular disease can lead to increased risk of coronavirus disease-2019 (COVID-19) with a higher morbidity and mortality. SARS-CoV-2 antibodies are higher in severely or critically ill COVID-19 patients, but studies have not focused on levels in convalescent patients with MetS, which this study aimed to assess. METHODS: This retrospective study focused on adult convalescent outpatients with SARS-CoV-2 positive serology during the COVID-19 pandemic at NewYork Presbyterian/Weill Cornell. Data collected for descriptive and correlative analysis included SARS-COV-2 immunoglobin G (IgG) levels and history of MetS comorbidities from April 17, 2020 to May 20, 2020. Additional data, including SARS-CoV-2 IgG levels, body mass index (BMI), hemoglobin A1c (HbA1c) and lipid levels were collected and analyzed for a second cohort from May 21, 2020 to June 21, 2020. SARS-CoV-2 neutralizing antibodies were measured in a subset of the study cohort. RESULTS: SARS-CoV-2 IgG levels were significantly higher in convalescent individuals with MetS comorbidities. When adjusted for age, sex, race, and time duration from symptom onset to testing, increased SARS-CoV-2 IgG levels remained significantly associated with obesity (P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with HbA1c ≥6.5% compared to those with HbA1c <5.7% (P = 0.0197) and remained significant on multivariable analysis (P = 0.0104). A positive correlation was noted between BMI and antibody levels [95% confidence interval: 0.37 (0.20-0.52) P < 0.0001]. Neutralizing antibody titers were higher in COVID-19 individuals with BMI ≥ 30 (P = 0.0055). CONCLUSION: Postconvalescent SARS-CoV-2 IgG and neutralizing antibodies are elevated in obese patients, and a positive correlation exists between BMI and antibody levels.


Assuntos
Anticorpos Neutralizantes/imunologia , Imunoglobulina G/imunologia , Síndrome Metabólica/imunologia , Adulto , Anticorpos Neutralizantes/sangue , /complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/virologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/virologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/imunologia , Obesidade/virologia , Estudos Retrospectivos
9.
Am J Physiol Renal Physiol ; 320(4): F548-F558, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33586497

RESUMO

Palmitic acid (PA) leads to lipotoxicity in type 2 diabetes and induces oxidative stress in podocytes. Oxidized cellular proteins are degraded by proteasomes. The role of proteasomes in PA- or oxidative stress-induced podocyte injury and pathogenesis of diabetic nephropathy (DN) is unknown. We investigated the effects of PA on expression of 20S and 26S proteasomes, proteasome activator 28 (PA28) regulators, and the immunoproteasome in cultured podocytes and renal cortical tissues of db/db and db/m mice using Western blot analysis. Glomerular areas and glomerular basement membrane (GBM) widths of db/db and db/m mice were examined using morphometry. Short-term incubation of PA or low levels of H2O2 upregulated only the immunoproteasome in cultured podocytes. Long-term exposure of podocytes to PA ultimately downregulated the immunoproteasome as with other proteasomes, whereas oleic acid (OA) or eicosapentaenoic acid (EPA) restored the PA-induced decreased protein levels. In db/db mice, renal cortical immunoproteasome expression with PA28α was significantly decreased compared with db/m mice, and glomerular areas and GBM widths were significantly increased compared with db/m mice. Feeding of an OA-rich olive oil or EPA-rich fish oil protected db/db mice against the reduced renal cortical immunoproteasome expression, glomerular enlargement, and GBM thickening. These results demonstrate that lipotoxicity downregulates the immunoproteasome in podocytes and kidneys in type 2 diabetes and that OA and EPA protected type 2 diabetic mice against decreased renal cortical immunoproteasome expression and the progression of DN. Given this, lipotoxicity-induced podocyte injury with impaired immunoproteasome expression appears to play an important role in the pathogenesis of DN.NEW & NOTEWORTHY In podocytes, PA rapidly induced immunoproteasome expression but ultimately decreased it, while OA and EPA restored the decreased immunoproteasome levels. In the renal cortex of type 2 diabetic mice, immunoproteasome expression was significantly decreased, whereas feeding of OA-rich olive oil or EPA-rich fish oil diets protected them against the reduced immunoproteasome expression and progression of diabetic nephropathy. Thus, lipotoxicity-induced podocyte injury with impaired immunoproteasome expression may be related to the pathogenesis of diabetic nephropathy.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Ácido Eicosapentaenoico/farmacologia , Peróxido de Hidrogênio/farmacologia , Ácido Oleico/farmacologia , Podócitos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/imunologia , Nefropatias Diabéticas/imunologia , Nefropatias Diabéticas/metabolismo , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Rim/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Podócitos/efeitos dos fármacos
10.
J Diabetes Res ; 2021: 9526701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33490288

RESUMO

The induction of inflammation and cytokine storm was proposed to play a critical role in COVID-19. This study is aimed at investigating the relationship between glucose metabolism and the inflammatory state of inpatients with COVID-19. 71 inpatients with COVID-19 were classified into nondiabetes mellitus (NDM) group, impaired fasting glucose (IFG) group, and diabetes mellitus (DM) group. The average hospitalization days were significantly shorter in DM patients when compared with patients in the IFG group and NDM group. CD4+ T cell percentage was higher while CD8+ T cells percentage was lower in the DM group than those in the NDM group. The serum levels of IL-6, IL-2, IL-10, and INF-γ in the DM group were upregulated when compared with those in the NDM group. The serum levels of TNF-α, IL-4, IL-2, IL-10, and INF-γ were significantly higher in the DM group than those in the IFG group. A significant difference was observed in CD4+ T cell, CD4+/CD8+ ratio percentage, IL-6, and IL-10 between the NDM group and DM group with adjusted BMI. In conclusion, COVID-19 patients with elevated glucose levels have promoted cytokine profiles and immune response.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Diabetes Mellitus Tipo 2/imunologia , Mediadores da Inflamação/imunologia , /imunologia , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , /epidemiologia , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo
11.
Clin Interv Aging ; 16: 97-105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33469277

RESUMO

Background: Depression is highly prevalent in patients with diabetes mellitus (DM). Diabetic depression has been shown to be associated with low-grade systemic inflammation. In recent years, the systemic immune-inflammation (SII) index has been developed as an integrated and novel inflammatory indicator. The aims of this study were to investigate the relationship between diabetic depression and SII levels, adjusting for a wide range of potential confounding factors, to examine the potential of SII in predicting diabetic depression. Methods: The present cross-sectional study was conducted among adults with DM in the National Health and Nutrition Examination Survey between 2009 and 2016, the SII level was calculated as the platelet counts × neutrophil counts/lymphocyte counts. Patient Health Questionnaire-9 was used to measure depression in patients with DM. Multivariable logistic regression and propensity score-matched analysis were used to analyze the association between SII levels and depression. Results: A total of 2566 patients with DM were included in the study, of which 370 (13.3%) were diagnosed with depression. Multivariable logistic regression showed that high SII level was an independent risk factor for diabetic depression (OR = 1.347, 95% CI: 1.031-1.760, P = 0.02882) after adjusting for covariates. The relationship between SII and diabetic depression was further verified by propensity score-matched analysis. Conclusion: Our data suggest that SII is a risk factor for depression in patients with DM. The SII may be an easily accessible and cost-effective strategy for identifying depression in patients with DM. More studies are warranted to further analyze the role of SII in depression in diabetic patients.


Assuntos
Depressão/diagnóstico , Depressão/imunologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Inflamação/diagnóstico , Estudos Transversais , Depressão/etiologia , Feminino , Humanos , Inflamação/etiologia , Contagem de Linfócitos , Masculino , Neutrófilos/imunologia , Inquéritos Nutricionais , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Fatores de Risco
12.
Diabetes Metab Syndr ; 15(1): 193-196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33385765

RESUMO

BACKGROUND AND AIMS: Patients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM). METHODS: Records of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis. RESULTS: Thirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA1c at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14-17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019). CONCLUSIONS: COVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM.


Assuntos
Anticorpos Antivirais/sangue , Formação de Anticorpos/fisiologia , /sangue , Diabetes Mellitus Tipo 2/sangue , /metabolismo , Adulto , Idoso , Anticorpos Antivirais/imunologia , /imunologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
13.
J Glob Antimicrob Resist ; 24: 106-107, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33359936

RESUMO

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a positive-sense single-stranded RNA virus. As of today, no specific treatment has been found COVID-19. Intravenous immunoglobulin (IVIG) is a widely used therapy to prevent life-threatening infections in patients with primary and secondary immune deficiencies and autoimmune/inflammatory conditions. IVIG administration could be beneficial in the treatment of patients with severe COVID-19. In this respect, this presentation aimed to report a case of COVID-19 treated with IVIG.


Assuntos
/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Antivirais/uso terapêutico , /imunologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/virologia , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/virologia , Masculino , Pessoa de Meia-Idade , /isolamento & purificação
14.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33370949

RESUMO

Melioidosis is caused by the tropical soil pathogen Burkholderia pseudomallei Infection, usually in the form of pneumonia, disproportionately affects people with a risk factor for immune dysregulation and mortality remains high even with treatment. Climate change and increasing rates of diabetes render the populations of endemic areas increasingly vulnerable to the disease, which is emerging as a serious global health threat. We present here a case of a 68-year-old man from northern Australia with sepsis and osteoarticular melioidosis of the hip, and explore the links between diabetes mellitus and melioidosis, particularly with respect to musculoskeletal infection.


Assuntos
Burkholderia pseudomallei/isolamento & purificação , Diabetes Mellitus Tipo 2/complicações , Melioidose/diagnóstico , Osteoartrite do Quadril/microbiologia , Sepse/microbiologia , Idoso , Antibacterianos/uso terapêutico , Austrália , Burkholderia pseudomallei/imunologia , Diabetes Mellitus Tipo 2/imunologia , Quimioterapia Combinada/métodos , Articulação do Quadril/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Masculino , Melioidose/tratamento farmacológico , Melioidose/imunologia , Melioidose/microbiologia , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Quadril/imunologia , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/imunologia , Resultado do Tratamento
15.
Front Immunol ; 11: 576818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335527

RESUMO

COVID-19 is a disease caused by the coronavirus SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), known as a highly contagious disease, currently affecting more than 200 countries worldwide. The main feature of SARS-CoV-2 that distinguishes it from other viruses is the speed of transmission combined with higher risk of mortality from acute respiratory distress syndrome (ARDS). People with diabetes mellitus (DM), severe obesity, cardiovascular disease, and hypertension are more likely to get infected and are at a higher risk of mortality from COVID-19. Among elderly patients who are at higher risk of death from COVID-19, 26.8% have DM. Although the reasons for this increased risk are yet to be determined, several factors may contribute to type-2 DM patients' increased susceptibility to infections. A possible factor that may play a role in increasing the risk in people affected by diabetes and/or obesity is the impaired innate and adaptive immune response, characterized by a state of chronic and low-grade inflammation that can lead to abrupt systemic metabolic alteration. SARS patients previously diagnosed with diabetes or hyperglycemia had higher mortality and morbidity rates when compared with patients who were under metabolic control. Similarly, obese individuals are at higher risk of developing complications from SARS-CoV-2. In this review, we will explore the current and evolving insights pertinent to the metabolic impact of coronavirus infections with special attention to the main pathways and mechanisms that are linked to the pathophysiology and treatment of diabetes.


Assuntos
Imunidade Adaptativa , Complicações do Diabetes , Imunidade Inata , Obesidade , Fatores Etários , /imunologia , /terapia , Complicações do Diabetes/imunologia , Complicações do Diabetes/mortalidade , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/terapia , Humanos , Obesidade/imunologia , Obesidade/mortalidade , Obesidade/terapia , /imunologia , /terapia
16.
Eur Rev Med Pharmacol Sci ; 24(21): 11409-11420, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33215463

RESUMO

OBJECTIVE: Diabetes is a lifestyle disease and it has become an epidemic worldwide in recent decades. In the ongoing COVID-19 pandemic situation, diabetes has become a serious health concern since large numbers of patients are vulnerable to die from the virus. Thus, diabetic patients affected by COVID-19 cause a major health crisis now. Reports show that large occurrence of diabetes makes it a serious comorbidity in COVID-19 patients. MATERIALS AND METHODS: It is crucial to understand how COVID-19 affects diabetes patients. This paper has reviewed published literature extensively to understand the pattern, importance, care, and medication. RESULTS: This review summarizes the association between COVID-19 and diabetes in terms of susceptibility for pneumonia and other diseases. It also discusses the harshness of COVID-19 with diabetes populations and immunological impacts. It further adds the ACE2 receptor role in diabetes with COVID-19 patients. CONCLUSIONS: Finally, this paper illustrates different types of diabetes management techniques, such as blood glucose management, self-management, mental health management, and therapeutic management. It also summarizes the current knowledge about diabetic patients with COVID-19 to fight this pandemic.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Suscetibilidade a Doenças/imunologia , Pneumonia Viral/imunologia , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/imunologia , Humanos , Hipoglicemiantes/administração & dosagem , Pâncreas/patologia , Pandemias/prevenção & controle , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/metabolismo , Replicação Viral/imunologia
17.
Mediators Inflamm ; 2020: 6914878, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061829

RESUMO

Background: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has threatened every civilian as a global pandemic. The immune system poses the critical interactive chain between the human body and the virus. Here, we make efforts to examine whether comorbidity with type 2 diabetes (T2D) affects the immunological response in COVID-19 patients. Methods: We conducted a retrospective pilot study investigating immunological characteristics of confirmed cases of COVID-19 with or without comorbid T2D. Two subcohorts of sex- and age-matched participants were eligible for data analysis, of which 33 participants were with T2D and the remaining 37 were nondiabetic (NDM). Cellular immunity was assessed by flow cytometric determination of surface markers including CD3, CD4, CD8, CD19, CD16, and CD56 in peripheral blood. Levels of C reactive protein, immunoglobulin (IgG, IgM, IgA, and IgE), and complements (C3, C4) were detected by rate nephelometry immunoassay. And Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were detected by Cytometric Bead Array. Results: Neutrophil counts were found to be significantly higher in the T2D group than in the NDM group and had a significant relevance with clinical severity. Lymphocyte frequencies showed no significant differences in the two groups. However, the proportions and absolute counts of T, Tc, Th, and NK cells decreased in both groups to different degrees. An abnormal increase in neutrophil count and a decrease in lymphocyte subpopulations may represent risk factors of COVID-19 severity. The level of IgG, IgM, IgA, C3, and C4 showed no significant difference between the two groups, while the IgE levels were higher in the T2D group than in the NDM group (p < 0.05). Th1 cytokines including IFN-γ, TNF-α, and IL-6, as well as CRP, appeared significantly higher in the T2D group. Conclusions: The COVID-19 patients comorbid with T2D demonstrated distinguishable immunological parameters, which represented clinical relevancies with the predisposed disease severity in T2D.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 2/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Comorbidade , Proteínas do Sistema Complemento/metabolismo , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Citocinas/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Imunidade Celular , Imunoglobulinas/sangue , Mediadores da Inflamação/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Projetos Piloto , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Células Th1/imunologia , Células Th2/imunologia
18.
J Diabetes Res ; 2020: 3918723, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062712

RESUMO

People with diabetes have higher risks of various infections. Therefore, these diabetic patients might be at increased risk of COVID-19 and have a poorer prognosis. Up until now, little is known about critical role in the pathogenesis. This study aims to investigate the clinical characteristics of COVID-19 patients with diabetes and secondary hyperglycemia, as well as to explore the purported mechanisms. 80 confirmed COVID-19 subjects were classified into the euglycemia group, secondary hyperglycemia group, and diabetes group. Severity of COVID-19 was defined based on the diagnostic and treatment guideline for SARS-CoV-2 issued by Chinese National Health Committee. According to the severity of the disease, patients of the mild type and common type were registered as mild cases (patients with minimal symptoms and negative CT findings), while patients of the severe type and critical type were enrolled as severe cases (patients with positive CT findings and different extent of clinical manifestations). Patients in the diabetes group were older than those in the euglycemia group, and most of them were male. In the diabetes group, the proportion of severe cases was 57.14%, which was significantly higher than those in the other two groups, and 32% of the COVID-19 patients diagnosed as severe cases were with diabetes. The CD4+ cell counts in the diabetes group were lower than those in the other two groups, while the levels of LDH and hs-CRP were higher. Compared with the euglycemia group, the CD3+ cell counts and the CD4+/CD8+ ratio were decreased, whereas the levels of IL-6 were increased in the secondary hyperglycemia group and diabetes group, with the diversities in the diabetes group being especially more significant. The Spearman correlation analysis revealed that the presence of diabetes was positively correlated with age, hs-CRP, LDH, IL-6, CD8+ cells, and severity of COVID-19 and negatively correlated with CD3+ cell counts, CD4+ cell counts, and CD4+/CD8+ ratio. Compared with the other two groups, the diabetes group exhibited more diverse and multifocal features in CT imagings. Diabetes is a risk factor for influence of the progression and prognosis of COVID-19 due to ongoing inflammation and impaired immune response.


Assuntos
Betacoronavirus/patogenicidade , Glicemia/metabolismo , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 2/imunologia , Hiperglicemia/imunologia , Pneumonia Viral/virologia , Adulto , Idoso , Betacoronavirus/imunologia , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Progressão da Doença , Feminino , Interações Hospedeiro-Patógeno , Humanos , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Estudos Retrospectivos , Fatores de Risco
19.
Nat Commun ; 11(1): 5225, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067434

RESUMO

Patients with type 2 diabetes (T2D) have a lower risk of Mycobacterium tuberculosis infection, progression from infection to tuberculosis (TB) disease, TB morality and TB recurrence, when being treated with metformin. However, a detailed mechanistic understanding of these protective effects is lacking. Here, we use mass cytometry to show that metformin treatment expands a population of memory-like antigen-inexperienced CD8+CXCR3+ T cells in naive mice, and in healthy individuals and patients with T2D. Metformin-educated CD8+ T cells have increased (i) mitochondrial mass, oxidative phosphorylation, and fatty acid oxidation; (ii) survival capacity; and (iii) anti-mycobacterial properties. CD8+ T cells from Cxcr3-/- mice do not exhibit this metformin-mediated metabolic programming. In BCG-vaccinated mice and guinea pigs, metformin enhances immunogenicity and protective efficacy against M. tuberculosis challenge. Collectively, these results demonstrate an important function of CD8+ T cells in metformin-derived host metabolic-fitness towards M. tuberculosis infection.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Animais , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Cobaias , Humanos , Masculino , Camundongos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/fisiologia , Tuberculose/etiologia , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/prevenção & controle
20.
Front Immunol ; 11: 573662, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123152

RESUMO

Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities [e.g., obesity and type 2 diabetes (T2D)] are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile, could immunesenescence be a generic contributory factor in the development of severe COVID-19? Here, by focussing on three key aspects of an immune response, namely pathogen recognition, elimination and resolution, we address this question by discussing how immunesenescence may weaken or exacerbate the immune response to SARS-CoV-2. We also highlight how aspects of immunesenescence could render potential COVID-19 treatments less effective in older adults and draw attention to certain therapeutic options, which by reversing or circumventing certain features of immunesenescence may prove to be beneficial for the treatment of groups at high risk of severe COVID-19.


Assuntos
Senescência Celular/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Envelhecimento/imunologia , Betacoronavirus/imunologia , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Masculino , Monócitos/imunologia , Neutrófilos/imunologia , Obesidade/imunologia , Pandemias , Fatores de Risco , Linfócitos T/imunologia
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