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1.
Cardiovasc Diabetol ; 23(1): 174, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762719

RESUMO

BACKGROUND: Growth differentiation factor 15 (GDF15) is a mitokine, the role of which, total or H-specific, in modulating energy metabolism and homeostasis in obesity-related diseases, such as metabolic dysfunction associated steatotic liver disease (MASLD), has not been fully elucidated in adult humans. We aimed to investigate the fasting and stimulated levels of GDF15, total and H-specific, glucose-dependent insulinotropic polypeptide (GIP) and C-peptide, in two physiology interventional studies: one focusing on obesity, and the other on MASLD. METHODS: Study 1 investigated individuals with normal weight or with obesity, undergoing a 3-h mixed meal test (MMT); and study 2, examined adults with MASLD and controls undergoing a 120-min oral glucose tolerance test (OGTT). Exploratory correlations of total and H-specific GDF15 with clinical, hormonal and metabolomic/lipidomic parameters were also performed. RESULTS: In study 1, 15 individuals were included per weight group. Fasting and postprandial total and H-specific GDF15 were similar between groups, whereas GIP was markedly higher in leaner individuals and was upregulated following a MMT. Baseline and postprandial C-peptide were markedly elevated in people with obesity compared with lean subjects. GIP was higher in leaner individuals and was upregulated after a MMT, while C-peptide and its overall AUC after a MMT was markedly elevated in people with obesity compared with lean subjects. In study 2, 27 individuals were evaluated. Fasting total GDF15 was similar, but postprandial total GDF15 levels were significantly higher in MASLD patients compared to controls. GIP and C-peptide remained unaffected. The postprandial course of GDF15 was clustered among those of triglycerides and molecules of the alanine cycle, was robustly elevated under MASLD, and constituted the most notable differentiating molecule between healthy and MASLD status. We also present robust positive correlations of the incremental area under the curve of total and H-specific GDF15 with a plethora of lipid subspecies, which remained significant after adjusting for confounders. CONCLUSION: Serum GDF15 levels do not differ in relation to weight status in hyperlipidemic but otherwise metabolically healthy individuals. In contrast, GDF15 levels are significantly increased in MASLD patients at baseline and they remain significantly higher compared to healthy participants during OGTT, pointing to a role for GDF15 as a mitokine with important roles in the pathophysiology and possibly therapeutics of MASLD. Trial registration ClinicalTrials.gov NCT03986684, NCT04430946.


Assuntos
Biomarcadores , Peptídeo C , Polipeptídeo Inibidor Gástrico , Fator 15 de Diferenciação de Crescimento , Hiperlipidemias , Obesidade , Período Pós-Prandial , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Glicemia/metabolismo , Peptídeo C/sangue , Estudos de Casos e Controles , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico , Polipeptídeo Inibidor Gástrico/sangue , Teste de Tolerância a Glucose , Fator 15 de Diferenciação de Crescimento/sangue , Hiperlipidemias/sangue , Hiperlipidemias/diagnóstico , Obesidade/sangue , Obesidade/diagnóstico , Fatores de Tempo , Regulação para Cima
2.
Nutrients ; 16(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674919

RESUMO

This study investigates the effect of daily consumption of wheat biscuits enriched with plant proteins in postprandial metabolic responses of women with overweight/obesity who follow an energy-restricted diet. Thirty apparently healthy women participated in a 12-week randomized controlled trial and were assigned either to a control (CB) or an intervention (PB) group. Participants consumed daily either a conventional (CB) or an isocaloric wheat biscuit enriched with plant proteins (PB) containing high amounts of amino acids with appetite-regulating properties, i.e., BCAAs and L-arg. At baseline and the end of the intervention, a mixed meal tolerance test was performed. The responses of glucose, insulin, ghrelin, GLP-1, and glicentin were evaluated over 180 min. After 12 weeks, both groups experienced significant decreases in body weight, fat mass, and waist circumference. In the PB group, a trend towards higher weight loss was observed, accompanied by lower carbohydrate, fat, and energy intakes (p < 0.05 compared to baseline and CB group), while decreases in fasting insulin and the HOMA-IR index were also observed (p < 0.05 compared to baseline). In both groups, similar postprandial glucose, ghrelin, and GLP-1 responses were detected, while iAUC for insulin was lower (p < 0.05). Interestingly, the iAUC of glicentin was greater in the PB group (p < 0.05 compared to baseline). Subjective appetite ratings were beneficially affected in both groups (p < 0.05). Consumption of wheat biscuits enriched in plant proteins contributed to greater weight loss, lower energy intake, and insulin resistance and had a positive impact on postprandial glicentin response, a peptide that can potentially predict long-term weight loss and decreased food intake.


Assuntos
Glicemia , Obesidade , Sobrepeso , Período Pós-Prandial , Triticum , Humanos , Feminino , Adulto , Obesidade/dietoterapia , Obesidade/metabolismo , Sobrepeso/dietoterapia , Sobrepeso/metabolismo , Glicemia/metabolismo , Pessoa de Meia-Idade , Insulina/sangue , Proteínas de Plantas/administração & dosagem , Grelina/sangue , Restrição Calórica/métodos , Redução de Peso , Ingestão de Energia , Peptídeo 1 Semelhante ao Glucagon/sangue
3.
Nutrients ; 16(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474855

RESUMO

BACKGROUND: Association studies of vitamin D receptor (VDR) polymorphisms with COVID-19 severity have produced inconsistent results in different populations. Herein we examined VDR gene polymorphisms in a Caucasian Greek cohort of COVID-19 patients. METHODS: This was a case-control study in a tertiary university hospital in Greece including 137 COVID-19 patients with varying disease severities and 72 healthy individuals. In total 209 individuals were genotyped for the FokI (rs10735810), ApaI (rs7975232), TaqI (rs731236) and BsmI (rs1544410) single-nucleotide polymorphisms (SNP) of the VDR gene by polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLPs). Statistical analyses were performed to determine the association between genotype and disease severity, adjusting for various confounding factors. RESULTS: Genotype distribution of the studied VDR SNPs in the control group was in Hardy-Weinberg equilibrium. The TaqI variant was differentially distributed between controls and COVID-19 patients according to the additive model (p = 0.009), and the CC genotype was significantly associated with an increased risk for severe COVID-19 according to the recessive model [OR: 2.52, 95%CI:1.2-5.29, p = 0.01]. Multivariate analysis demonstrated a robust association of COVID-19 severity and TaqI polymorphism in the recessive model even after adjusting for multiple confounders, including age, sex and CRP levels [Adj.OR:3.23, 95%CI:1.17-8.86, p = 0.023]. The distribution of FokI, ApaI and BsmI genotypes was similar between COVID-19 patients and controls. CONCLUSIONS: The CC genotype of TaqI polymorphism is significantly associated with an increased risk for severe COVID-19 independently of age, sex or degree of inflammation.


Assuntos
COVID-19 , Imidoésteres , Receptores de Calcitriol , Humanos , Receptores de Calcitriol/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , Genótipo , Polimorfismo de Nucleotídeo Único
4.
Int J Low Extrem Wounds ; : 15347346241233938, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38414376

RESUMO

Diabetic neuropathy is a common complication of diabetes; yet its pathophysiology is still incompletely understood and until today, there is no specific treatment against it. In the two 2023 large congresses on diabetes (American Diabetes Association, ADA, European Association for the Study of Diabetes, EASD), several high-level studies have been presented. They have attempted to delineate the pathophysiology of DN, the characteristics of affected patients, and future potential treatments. We herein review the presented studies on diabetic neuropathy at these diabetes congresses and discuss the needs for future research on this topic.

5.
Metabolism ; 152: 155773, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38181882

RESUMO

BACKGROUND: Bariatric surgery has long-term beneficial effects on body weight and metabolic status, but there is an apparent lack of comprehensive cardiometabolic, renal, liver, and metabolomic/lipidomic panels, whereas the underlying mechanisms driving the observed postoperative ameliorations are still poorly investigated. We aimed to study the long-term effects of bariatric surgery on metabolic profile, cardiorenal and liver outcomes in association with underlying postoperative gut hormone adaptations. METHODS: 28 individuals who underwent bariatric surgery [17 sleeve gastrectomy (SG), 11 Roux-en-Y gastric bypass (RYGB)] were followed up 3, 6 and 12 and at 10 years following surgery. Participants at 10 years were cross-sectionally compared with an age-, sex- and adiposity-matched group of non-operated individuals (n = 9) and an age-matched pilot group of normal-weight individuals (n = 4). RESULTS: There were durable effects of surgery on body weight and composition, with an increase of lean mass percentage persisting despite some weight regain 10 years postoperatively. The improvements in metabolic and lipoprotein profiles, cardiometabolic risk markers, echocardiographic and cardiorenal outcomes persisted over the ten-year observation period. The robust improvements in insulin resistance, adipokines, activin/follistatin components and postprandial gastrointestinal peptide levels persisted 10 years postoperatively. These effects were largely independent of surgery type, except for a lasting reduction of ghrelin in the SG subgroup, and more pronounced increases in proglucagon products, mainly glicentin and oxyntomodulin, and in the cardiovascular risk marker Trimethylamine-N-oxide (TMAO) within the RYGB subgroup. Despite similar demographic and clinical features, participants 10 years after surgery showed a more favorable metabolic profile compared with the control group, in conjunction with a dramatic increase of postprandial proglucagon product secretion. CONCLUSIONS: We demonstrate that cardiorenal and metabolic benefits of bariatric surgery remain robust and largely unchanged ten years postoperatively and are associated with durable effects on gastrointestinal- muscle- and adipose tissue-secreted hormones. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04170010.


Assuntos
Cirurgia Bariátrica , Doenças Cardiovasculares , Derivação Gástrica , Hormônios Gastrointestinais , Obesidade Mórbida , Humanos , Estudos de Casos e Controles , Proglucagon , Obesidade/cirurgia , Fígado , Doenças Cardiovasculares/prevenção & controle , Gastrectomia , Obesidade Mórbida/cirurgia
6.
Int J Low Extrem Wounds ; : 15347346231212332, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37956650

RESUMO

INTRODUCTION: Wound healing is a dynamic process that begins with inflammation, proliferation, and cell migration of a variety of fibroblast cells. As a result, identifying possible compounds that may improve fibroblast cell wound healing capacity is crucial. Hypericin is a natural quinine that has been reported to possess a wide range of pharmacological profiles, including antioxidant and anti-inflammatory, activities. Herein we examined for the first time the effect of hypericin on normal human dermal fibroblasts (NHDFs) under oxidative stress. METHODS: NHDF were exposed to different concentrations of hypericin (0-20 µg/mL) for 24 h. For the oxidative stress evaluation, H2O2 was used as a stressor factor. Cell viability and proliferation levels were evaluated. Immunohistochemistry and flow cytometry were performed to assess cell apoptosis levels and with confocal microscopy we identified the mitochondrial superoxide production under oxidative stress and after the treatment with hypericin. Scratch assay was performed under oxidative stress to evaluate the efficacy of hypericin in wound closure. To gain an insight into the molecular mechanisms of hypericin bioactivity, we analyzed the relative expression levels of genes involved in oxidative response and in wound healing process. RESULTS: We found that the exposure of NHDF to hypericin under oxidative stress resulted in an increase in cell viability and ATP levels. We found a decrease in apoptosis and mitochondrial superoxide levels after treatment with hypericin. Moreover, treatment with hypericin reduced wound area and promoted wound closure. The levels of selected genes showed that hypericin upregulated the levels of antioxidants genes. Moreover, treatment with hypericin in wound under oxidative stress downregulated the levels of proinflammatory cytokines, and metalloproteinases; and upregulated transcription factors and extracellular matrix genes. CONCLUSION: These findings indicated that hypericin possesses significant in vitro antioxidant activity on NHDF and provide new insights into its potential beneficial role in the management of diabetic ulcers.

7.
J Clin Med ; 12(15)2023 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-37568543

RESUMO

Thanks to technical advances in the field of medical imaging, it is now possible to study key features of renal anatomy and physiology, but so far poorly explored due to the inherent difficulties in studying both the metabolism and vasculature of the human kidney. In this narrative review, we provide an overview of recent research findings on renal perfusion, oxygenation, and substrate uptake. Most studies evaluating renal perfusion with positron emission tomography (PET) have been performed in healthy controls, and specific target populations like obese individuals or patients with renovascular disease and chronic kidney disease (CKD) have rarely been assessed. Functional magnetic resonance (fMRI) has also been used to study renal perfusion in CKD patients, and recent studies have addressed the kidney hemodynamic effects of therapeutic agents such as glucagon-like receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) in an attempt to characterise the mechanisms leading to their nephroprotective effects. The few available studies on renal substrate uptake are discussed. In the near future, these imaging modalities will hopefully become widely available with researchers more acquainted with them, gaining insights into the complex renal pathophysiology in acute and chronic diseases.

8.
Mini Rev Med Chem ; 23(21): 2041-2052, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37165506

RESUMO

BACKGROUND: Protein, lipid, and nucleic acid glycation reactions begin and continue as a result of persistent hyperglycemia in patients with diabetes mellitus. Advanced glycated end products (AGEs) are a complex group of chemical moieties that are formed as a result of the glycation process and play an important role in the pathogenesis of diabetes mellitus. When AGEs interact with their cellular receptor (RAGE), numerous signaling pathways, including nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB), c-Jun N-terminal kinase (JNK), and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), are activated, increasing oxidative stress. OBJECTIVE: The aim of this review was to summarize in vitro and in vivo studies underlining the involvement of AGEs on beta cell dysfunction and death via oxidative stress. METHODS: A literature search of publications published between 1912 and December 2022 was conducted using MEDLINE, EMBASE, and the Cochrane Library, with restrictions on articles written in English. RESULTS: Recent insights have revealed that oxidative stress has a crucial role in the development of beta cell dysfunction and insulin resistance, the major hallmarks of type 2 diabetes mellitus. Studies also revealed that AGEs decrease insulin synthesis and secretion in the pancreatic beta cells and induce cell apoptosis. CONCLUSION: Experimental data have shown that both AGEs and oxidative stress contribute to beta cell dysfunction and development as well as to the progression of diabetic complications. Many anti- AGE therapies are being developed; however, it remains to be seen whether these therapies can help maintain beta cell function and prevent diabetes complications.

9.
J Biochem Mol Toxicol ; 36(8): e23099, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35593412

RESUMO

Τhe natural history of type 2 diabetes mellitus is characterized by a progressive loss of pancreatic beta cell function and insulin resistance. Bisphenol A (BPA) is an endocrine-disrupting chemical that is used widely in industry; people are exposed to BPA and its products daily. Studies have delineated that BPA alters the function of pancreatic beta cells. Herein, we examined the effect of low doses of BPA on pancreatic beta cell viability and apoptosis and we tried to elucidate the mechanisms involved in these processes. Beta-TC-6 (ATCC® CRL-11506™) cells were cultured with a medium containing the following dilutions of BPA: 0.002, 0.02, 0.1, 0.2, 2 µΜ up to 72 h. We examined the viability and adenosine triphosphate (ATP) levels of cells. Then, we measured apoptosis, cell cycle, and insulin levels. We quantified the levels of proteins implicated in the mitochondrial pathway of apoptosis; and finally, we quantified the intracellular reactive oxygen species and mitochondrial superoxide. We found that the exposure of Beta-TC-6 cells to BPA results in a decrease in cell viability, ATP levels, and an increase in insulin levels. We found an increase in apoptosis levels and a decrease in cell cycle levels. In addition, we provide evidence of the levels of apoptotic proteins. Finally, we found an increase in the cellular reactive oxygen species and mitochondrial superoxide production. Exposure to low concentrations of BPA triggers the mitochondrial pathway of apoptosis via the generation of intracellular reactive oxygen species and mitochondrial superoxide on Beta-TC-6 cells in a dose-dependent way.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Insulinas , Trifosfato de Adenosina/metabolismo , Apoptose , Compostos Benzidrílicos/toxicidade , Humanos , Células Secretoras de Insulina/metabolismo , Insulinas/farmacologia , Fenóis , Espécies Reativas de Oxigênio/metabolismo , Superóxidos
10.
Vaccines (Basel) ; 10(3)2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35335014

RESUMO

The mRNA-based BNT162b2 vaccine has demonstrated high efficacy against severe SARS-CoV-2. However, data regarding immune response in people with diabetes mellitus (DM) after vaccination with the BNT162b2 vaccine are limited. In this prospective observational study, we examined humoral immune response in participants with and without DM after vaccination with the BNT162b2 mRNA vaccine. A total of 174 participants (58 with and 116 without diabetes, matched for age) were included. Antibodies were measured 21 days after the first dose, 7−15 days after the second dose, and 70−75 days after the second and before the third dose of the vaccine. Antibodies were measured by an anti-SARS-CoV-2 receptor-binding domain IgG (Abs-RBD-IgG) assay by a chemiluminescent microparticle immune assay; values > 50 AU/mL are considered protective from severe disease. Almost 17% of participants with DM did not develop adequate humoral immune response to the BNT162b2 mRNA vaccine after the first dose; however, it was high and similar after the second dose in both participants with and without DM and remained so almost 2 months after the second dose of the vaccine. Geometric mean values of Abs-RBD-IgG were not significantly different between participants with and without DM during the study. At least two doses of the BNT162b2 vaccine are necessary to ensure adequate and sustainable immune response in people with DM.

11.
Int J Low Extrem Wounds ; 20(4): 291-299, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34142897

RESUMO

Diabetic foot ulcers are one of the most dreadful complications of diabetes mellitus and efforts to accelerate diabetic wound healing are of paramount importance to prevent ulcer infections and subsequent lower-limb amputations. There are several treatment approaches for the management of diabetic foot ulcers and honey seems to be a safe and cost-effective therapeutic approach on top of standard of care. The aim of this review was to summarize the therapeutic properties of honey and the data regarding its possible favorable effects on diabetic wound healing. A literature search of articles from 1986 until April 2021 was performed using MEDLINE, EMBASE, and the Cochrane Library to assess for studies examining the therapeutic wound healing properties of honey, it's in vitro effect, and the efficacy and/or mechanism of action of several types of honey used for the treatment of diabetic animal wounds. Honey has antioxidant, anti-inflammatory, and antibacterial properties and in vitro studies of keratinocytes and fibroblasts, as well as studies in diabetic animal models show that treatment with honey is associated with increased re-epithelialization and collagen production, higher wound contraction, and faster wound healing. The use of honey could be a promising approach for the management of diabetic foot ulcers.


Assuntos
Diabetes Mellitus , Pé Diabético , Mel , Administração Tópica , Amputação Cirúrgica , Animais , Pé Diabético/tratamento farmacológico , Cicatrização
12.
Curr Med Chem ; 28(30): 6110-6122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33719949

RESUMO

BACKGROUND: Cancer cells are characterized by metabolic heterogeneity. Although many research groups make efforts to analyze this heterogeneity, little attention has been paid to cancer cells utilizing otherwise unusable substrates as fuel for tumor development. Of the two stereoisomers of glucose, D-glucose but not L-glucose, the mirror image isomer of D-glucose is abundantly found in nature. D-glucose is the human body's key source of energy through aerobic respiration. However, data from in vitro and in vivo studies examining the ability of cancer cells to take up L-glucose are scarce. OBJECTIVES: The present mini-review aims to present current literature data on the role of L-glucose in cancer diagnosis based on in vitro and in vivo studies. METHODS: The MEDLINE, EMBASE, and the Cochrane Library with restrictions to articles in English language databases were searched to retrieve available data. RESULTS: There are limited data in the literature regarding in vitro and in vivo studies that examined the ability of cancer cells to take up L-glucose. Research work so far has shown that that the binding of a fluorescent detector to an L-glucose molecule produced a fluorescent probe that was specifically taken up by malignant cancer cells, thus providing a unique method for their detection. CONCLUSION: Given that L-glucose is taken up by cancer cells, L-glucose fluorescent probes can be a useful tool for visualization and characterization of cancer cells. More research on the potential biologic effects of L-glucose in cancer is necessary.


Assuntos
Glucose , Neoplasias , Humanos , Neoplasias/diagnóstico
13.
Curr Med Chem ; 28(7): 1328-1346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32452321

RESUMO

BACKGROUND: Oxidative stress is a hallmark of many diseases. A growing body of evidence suggests that hyperglycemia-induced oxidative stress plays an important role in pancreatic ß-cells dysfunction and apoptosis, as well as in the development and progression of diabetic complications. Considering the vulnerability of pancreatic ß-cells to oxidative damage, the induction of endogenous antioxidant enzymes or exogenous antioxidant administration has been proposed to protect pancreatic ß-cells from damage. OBJECTIVES: The present review aims to provide evidence of the effect of oxidative stress and antioxidant therapies on pancreatic ß-cell function, based on in vitro and in vivo studies. METHODS: The MEDLINE and EMBASE databases were searched to retrieve available data. RESULTS: Due to poor endogenous antioxidant mechanisms, pancreatic ß-cells are extremely sensitive to Reactive Oxygen Species (ROS). Many natural extracts have been tested in vitro in pancreatic ß-cell lines in terms of their antioxidant and diabetes mellitus ameliorating effects, and the majority of them have shown a dose-dependent protective role. On the other hand, there is relatively limited evidence regarding the in vitro antioxidant effects of antidiabetic drugs on pancreatic ß -cells. Concerning in vivo studies, several natural extracts have shown beneficial effects in the setting of diabetes by decreasing blood glucose and lipid levels, increasing insulin sensitivity, and by up-regulating intrinsic antioxidant enzyme activity. However, there is limited evidence obtained from in vivo studies regarding antidiabetic drugs. CONCLUSION: Antioxidants hold promise for developing strategies aimed at the prevention or treatment of diabetes mellitus associated with pancreatic ß-cells dysfunction, as supported by in vitro and in vivo studies. However, more in vitro studies are required for drugs.


Assuntos
Diabetes Mellitus Experimental , Células Secretoras de Insulina , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/metabolismo , Furocumarinas , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Estresse Oxidativo
14.
J Diabetes Complications ; 34(10): 107677, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32713708

RESUMO

BACKGROUND: Sclerostin inhibits bone formation and its expression is upregulated in the vasculature during the arterial calcification process as a counterregulatory mechanism preventing further calcification. Lower extremity arterial calcification (LEAC) is common in neuropathic patients with type 2 diabetes (T2DM). Herein, we investigated for associations between plasma sclerostin levels and diabetic neuropathy as well as LEAC in subjects with T2DM. METHODS: A total of 74 individuals with and 76 without T2DMwere recruited. Plasma sclerostin levels were measured by ELISA. Diagnosis of cardiac autonomic neuropathy (CAN) was based on the battery of the four autonomic tests, while of somatosensory peripheral neuropathy (DPN) on neuropathy symptom score and neuropathy disability score. LEAC was assessed with conventional ankle and foot x-rays. RESULTS: Plasma sclerostin levels were higher in participants with LEAC vs. those without LEAC in both diabetes and non-diabetes cohorts (p = 0.035 and p = 0.003, respectively). In the diabetes cohort, patients with CAN, but not with DPN, had higher sclerostin levels when compared with those without CAN (p < 0.001). Multivariate analysis in the diabetes cohort demonstrated that sclerostin levels were associated positively with CAN and LEAC, while in the non-diabetes cohort there was a trend for a positive association with male gender and presence of LEAC. CONCLUSION: Plasma sclerostin levels are increased in individuals with LEAC irrespectively of diabetes status. In addition, plasma sclerostin concentrations are associated independently with LEAC and CAN in people with T2DM.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Doenças do Sistema Nervoso Autônomo/sangue , Diabetes Mellitus Tipo 2/sangue , Neuropatias Diabéticas/sangue , Doença Arterial Periférica/sangue , Calcificação Vascular/sangue , Idoso , Doenças do Sistema Nervoso Autônomo/complicações , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/etiologia , Fatores de Risco , Calcificação Vascular/etiologia
15.
Curr Med Chem ; 27(27): 4542-4548, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32400323

RESUMO

BACKGROUND: In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged from China, causing pneumonia outbreaks first in the Wuhan region and then spread worldwide. Due to a lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find a therapeutic solution. OBJECTIVES: The aim of this study was to summarize in vitro data of current agents used for the management of SARS-CoV-2 all over the world. METHODS: A literature search of articles from January 2000 until April 2020 was performed using MEDLINE, EMBASE and the Cochrane Library to assess in vitro data of current or putative therapies for SARS-CoV-2. RESULTS: Although in vitro studies are scarce, data regarding chloroquine, hydroxychloroquine, remdesivir, nitazoxanide, teicoplanin, ivermectin, lopinavir, homoharringtonine, and emetine seem promising. CONCLUSION: Scientists all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Betacoronavirus , COVID-19 , China , Cloroquina , Reposicionamento de Medicamentos , Emetina , Mepesuccinato de Omacetaxina , Humanos , Hidroxicloroquina , Ivermectina , Lopinavir , Nitrocompostos , Pandemias , SARS-CoV-2 , Teicoplanina , Tiazóis , Tratamento Farmacológico da COVID-19
16.
J Diabetes Complications ; 34(4): 107517, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31928893

RESUMO

AIMS: To examine for differences in circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) in patients with and without diabetic peripheral neuropathy (DPN). METHODS: A total of 105 participants were included: 50 patients with type 2 diabetes (T2DM) and DPN, 30 patients with T2DM without DPN and 25 healthy individuals. CPCs and 6 different EPCs phenotypes were assessed with flow cytometry. We also measured plasma levels of vascular endothelial growth factor (VEGF), stromal cell-derived factor 1 (SDF-1), vascular cell adhesion protein-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM) and tumor necrosis factor a (TNFa). RESULTS: No difference was observed in the number of CPCs among the 3 groups. Patients with DPN had higher numbers of all 6 EPCs phenotypes when compared with patients without DPN and higher number of 5 EPCs phenotypes when compared with healthy individuals. Plasma VEFG, VCAM-1, ICAM-1 and TNFa levels did not differ among the 3 groups. Patients with DPN had lower SDF-1 levels in comparison with healthy individuals. CONCLUSION: Circulating EPCs are increased while SDF-1 levels are decreased in the presence of DPN. Our findings suggest that DPN may be associated with impaired trafficking of EPCs and impaired EPCs homing to the injured endothelium.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Neuropatias Diabéticas/patologia , Células Progenitoras Endoteliais/patologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/complicações , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/sangue , Doenças do Sistema Nervoso Periférico/etiologia , Doenças do Sistema Nervoso Periférico/patologia
17.
Diabetes Metab Syndr ; 13(2): 1159-1164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336459

RESUMO

AIM: To examine management of diabetes mellitus (DM) and patients' attitude towards DM in a random sample of the adult Greek population. METHODS: s: We selected a random sample of adults with self-reported DM (n = 1002) from a population-based nationwide study using the effective random sampling technique. Collection of data was performed through phone interviews. RESULTS: Prevalence of type 1 DM was 3.5% and of type 2 DM 96.5%. Prevalence of type 1 DM declined while of type 2 DM increased with age. No gender or residency differences were found between type 1 and type 2 DM. A total of 72.0% of subjects with type 2 DM were treated with oral antidiabetic drugs (OAD), 11.5% were treated with insulin and 7.1% were treated with both OAD and insulin. Internists specialized in DM were mainly doctors who started insulin treatment. Almost half of insulin naive subjects were skeptical towards insulin initiation and their main concern was the needle punch. CONCLUSIONS: In a random nationwide sample of the adult population in Greece the majority of subjects with self-reported DM had type 2 DM. Most patients with type 2 were treated with OAD. Almost half of insulin naive subjects were skeptical towards insulin initiation.


Assuntos
Atitude Frente a Saúde , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/psicologia , Dieta para Diabéticos , Exercício Físico , Hipoglicemiantes/uso terapêutico , Autocuidado/psicologia , Adulto , Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Gerenciamento Clínico , Feminino , Seguimentos , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Inquéritos e Questionários , Adulto Jovem
18.
Horm Metab Res ; 50(11): 803-810, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30286484

RESUMO

Irisin is a myokine that increases energy expenditure. In this cross-sectional study, we examined for differences in plasma irisin concentrations between subjects with type 1 diabetes mellitus and healthy individuals and searched for associations between plasma irisin levels and clinical and biochemical characteristics as well as self-reported physical activity. A total of 79 subjects with type 1 diabetes [age 38.2±12.5 years, men/women (n): 27/52], were consecutively recruited. Moreover, 53 healthy controls, matched for age and body mass index with those with diabetes were recruited. Plasma irisin was measured with ELISA. Participants were asked about their physical activity during the last week. We also measured trunk and visceral fat. Circulating irisin levels were lower in subjects with diabetes than in controls [median value (interquartile range): 53.0 (35.2, 106.3) vs. 178.1 (42.6, 641.6) ng/ml, respectively, p<0.001]. In the group of diabetes, univariate analysis showed that irisin levels were associated with waist circumference (beta=-0.283, p=0.023), serum triglycerides (beta=-0.282, p=0.031), and trunk fat (beta=-0.324, p=0.012). In multivariate analysis after adjustment for potential confounders, irisin levels were associated independently only with waist circumference (beta=-0.403, p=0.005). Among controls, multivariate analysis demonstrated that irisin levels were associated with pack-years of smoking (beta=-0.563, p=0.012) and fasting triglycerides (beta=-0.338, p=0.041). Circulating irisin levels were lower in subjects with diabetes in comparison with healthy-matched controls. In conclusion, plasma irisin concentrations in subjects with diabetes were associated with waist circumference, while in controls with serum triglycerides and pack-years of smoking.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Fibronectinas/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/fisiopatologia , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Circunferência da Cintura
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