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1.
Curr Diab Rep ; 21(10): 40, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495377

RESUMO

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the leading causes of vision loss worldwide. Although screening and early treatment guidelines for DR have significantly reduced the disease burden, restrictions related to the COVID-19 pandemic have changed real-world practice patterns in the management of DR. This review summarizes evolving guidelines and outcomes of the treatment of DR in the setting of the pandemic. RECENT FINDINGS: Intravitreal injections for DR have decreased significantly globally during the pandemic, ranging from approximately 30 to nearly 100% reduction, compared to corresponding timepoints in 2019. Most studies on functional outcomes show a decrease in visual acuity on delayed follow-up. Changing practice patterns in the management of DR has led to fewer intravitreal injections and overall reduction in visual acuity on follow-up. As COVID variants emerge, it will be necessary to continue evaluating practice guidelines.


Assuntos
COVID-19 , Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Seguimentos , Humanos , Edema Macular/tratamento farmacológico , Pandemias , SARS-CoV-2 , Tomografia de Coerência Óptica , Resultado do Tratamento
2.
BMJ Open ; 11(9): e044394, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489264

RESUMO

INTRODUCTION: Diabetes is common (about 20 million patients in Europe) and patients with diabetes have more surgical interventions than the general population. There are plausible pathophysiological and clinical mechanisms suggesting that patients with diabetes are at an increased risk of postoperative complications. When postoperative complications occur in the general population, they increase major adverse events and subsequently increase 1-year mortality. This is likely to be worse in patients with diabetes. There is variation in practice guidelines in different countries in the perioperative management of patients with diabetes undergoing major surgery and whether this may affect postoperative outcome has not been investigated on a large scale. Neither is it known whether different strata of preoperative glycaemic control affects outcome. METHODS AND ANALYSIS: A prospective, observational, international, multicentre cohort study, recruiting 5000 patients with diabetes undergoing elective or emergency surgery in at least n=50 centres. Inclusion criteria are any patient with diabetes undergoing surgery under any substantive anaesthetic technique. Exclusion criteria are not being a confirmed diabetic patient and patients with diabetes undergoing procedures under monitored sedation or local anaesthetic infiltration only. Follow-up duration is 30 days after surgery. Primary outcome is days at home at 30 days. Secondary outcomes are Comprehensive Complications Index, Quality of Recovery (QoR-15) score on Day 1 postoperatively, 30-day mortality, length of hospital stay and incidence of specific major adverse events (Myocardial Infarction (MI), Myocardial Injury after Non-cardiac Surgery (MINS), Acute Kidney Injury (AKI), Postoperative Pulmonary Complications (PPC), Cerebrovascular Accident (CVA), Pulmonary Embolism (PE), DVT, surgical site infection, postoperative pulmonary infection). Tertiary outcomes include time to resumption of normal diabetes therapy, incidence of diabetic ketoacidosis or hypoglycaemia, incidence and duration of use of intravenous insulin infusion therapy and change in diabetic management at 30 days. ETHICS AND DISSEMINATION: This study will adhere to the principles of the Declaration of Helsinki (amendment 2013) by the World Medical Association and the ICH-Good Clinical Practice (GCP) Guidelines E6(R2). Specific national and local regulatory authority requirements will be followed as applicable. Ethical approval has been granted by the Institutional Review Board of the Mater Misericordiae University Hospital, Dublin, Ireland (Reference: 1/378/2167). As enrolment for this study is ongoing, ethical approval from additional centres is being added continuously. The main results of Management and Outcomes of Perioperative Care among European Diabetic Patients and its substudies will be published in peer-reviewed international medical journals and presented at Euroanaesthesia congress and other international and national meetings. TRIAL REGISTRATION NUMBER: NCT04511312.


Assuntos
Diabetes Mellitus , Motocicletas , Anestesia Local , Estudos de Coortes , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Humanos , Assistência Perioperatória , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos
3.
Acta Biomed ; 92(4): e2021271, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34487063

RESUMO

As the world continues to struggle with the pandemic of COVID-19 (coronavirus disease 2019), several cases of mucormycosis have been reported in these patients with a high mortality rate. We conducted a review of literature and found 19 articles with 20 patients who developed mucormycosis during their COVID-19 infection.14 (70%) were males, and 6(30%) were females. While their mean age was 52.2 ± 17.3, affected men were older than females. Ten (50%) patients also had diabetes. Common clinical findings included ophthalmologic complaints, fever, shortness of breath, and facial pain. Amphotericin B was the most common antifungal used and 40% of cases needed surgical management of the infection. Steroid use was reported in around 12 cases (60%). Unfortunately, the mortality rate was 65% in this group of patients. Several changes in care should be brought for a consistent prevention, early diagnosis, and strong management of mucormycosis in COVID-19 patients.


Assuntos
COVID-19 , Diabetes Mellitus , Mucormicose , Adulto , Idoso , Antifúngicos/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucormicose/diagnóstico , Mucormicose/epidemiologia , Mucormicose/terapia , SARS-CoV-2
4.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445786

RESUMO

Diabetes, and several diseases related to diabetes, including cancer, cardiovascular diseases and neurological disorders, represent one of the major ongoing threats to human life, becoming a true pandemic of the 21st century. Current treatment strategies for diabetes mainly involve promoting ß-cell differentiation, and one of the most widely studied targets for ß-cell regeneration is DYRK1A kinase, a member of the DYRK family. DYRK1A has been characterized as a key regulator of cell growth, differentiation, and signal transduction in various organisms, while further roles and substrates are the subjects of extensive investigation. The targets of interest in this review are implicated in the regulation of ß-cells through DYRK1A inhibition-through driving their transition from highly inefficient and death-prone populations into efficient and sufficient precursors of islet regeneration. Increasing evidence for the role of DYRK1A in diabetes progression and ß-cell proliferation expands the potential for pharmaceutical applications of DYRK1A inhibitors. The variety of new compounds and binding modes, determined by crystal structure and in vitro studies, may lead to new strategies for diabetes treatment. This review provides recent insights into the initial self-activation of DYRK1A by tyrosine autophosphorylation. Moreover, the importance of developing novel DYRK1A inhibitors and their implications for the treatment of diabetes are thoroughly discussed. The evolving understanding of DYRK kinase structure and function and emerging high-throughput screening technologies have been described. As a final point of this work, we intend to promote the term "diabetic kinome" as part of scientific terminology to emphasize the role of the synergistic action of multiple kinases in governing the molecular processes that underlie this particular group of diseases.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Animais , Diabetes Mellitus/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo
5.
Vestn Oftalmol ; 137(4): 136-142, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34410069

RESUMO

Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, its treatment involves specialists of different areas - endocrinologists, diabetes specialists, therapists, cardiologists, surgeons, anesthesiologists etc. For ophthalmologists the objective is to diagnose ocular pathological changes associated with diabetes mellitus, and to prescribe required treatment in a timely manner. Treatment methods used in DR can be divided into three main groups: laser coagulation of the retina, intravitreal injection of medications - inhibitors of the vascular endothelial growth factor (VEGF) and glucocorticoids, as well as surgical treatment. The present literature review addresses the use of anti-VEGF drugs in the therapy of DR, specifically the latest medications, the most important studies on the treatment of DR and diabetic macular edema (DME), as well as post hoc analysis of such studies, the role of these medications in the therapy of refractory DME and proliferative stage DR. The review also addresses the upcoming strategies for therapy, as well as the importance of medications in prevention of DR and DME.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Fotocoagulação a Laser , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Fator A de Crescimento do Endotélio Vascular
6.
BMC Public Health ; 21(1): 1559, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404385

RESUMO

BACKGROUND: Promoting a healthy lifestyle and achieving strict adherence to medical treatment among patients with diabetes are key objectives in public health. Yet health behaviors are often culturally driven, especially in closed religious communities. This study seeks to reveal key cultural-religious factors, attitudes and behaviors characterizing the lifestyle in one such closed community-the ultra-Orthodox Jewish community-by understanding the attitudes of ultra-Orthodox patients with diabetes toward coping with their illness and the factors impacting their adherence to medicinal treatment. METHOD: Qualitative interviews were conducted with 16 ultra-Orthodox patients with diabetes using a semi-structured, in-depth questionnaire. RESULTS: Three main themes emerged: 1) "The disease as a secret": Hiding the disease among patients with diabetes in ultra-Orthodox society; 2) "Distinguishing between sacred and secular occasions": ultra-Orthodox diabetes patients distinguish between treatment adherence on weekdays and treatment adherence on holidays or special occasions; 3) "Ask the rabbi": In cases of dilemmas that involved conflicts between halakhic rulings and doctors' instructions, the rabbi's decision was usually the final one. CONCLUSIONS: The findings of this study may help provide an in-depth understanding of the obstacles and motives of ultra-Orthodox patients in adhering to medicinal treatment of diabetes in particular and to medicinal treatment in general, thus helping family physicians who treat this population provide optimal and appropriate treatment.


Assuntos
Diabetes Mellitus , Judeus , Diabetes Mellitus/tratamento farmacológico , Humanos , Israel , Judaísmo , Adesão à Medicação , Percepção
7.
Front Endocrinol (Lausanne) ; 12: 696087, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367067

RESUMO

Background and Objective: Recently, insulin treatment has been found to be associated with increased mortality and other adverse outcomes in patients with coronavirus disease 2019 (COVID-19) and diabetes, but the results remain unclear and controversial, therefore, we conducted this meta-analysis. Methods: Four databases, namely, PubMed, Web of Science, EMBASE and the Cochrane Library, were used to identify all studies concerning insulin treatment and the adverse effects of COVID-19, including mortality, incidence of severe/critical complications, in-hospital admission and hospitalization time. To assess publication bias, funnel plots, Begg's tests and Egger's tests were used. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to access the effect of insulin therapy on mortality, severe/critical complications and in-hospital admission. The association between insulin treatment and hospitalization time was calculated by the standardized mean difference (SMD) with 95% CIs. Results: Eighteen articles, involving a total of 12277 patients with COVID-19 and diabetes were included. Insulin treatment was significantly associated with an increased risk of mortality (OR=2.10; 95% CI, 1.51-2.93) and incidence of severe/critical COVID-19 complications (OR=2.56; 95% CI, 1.18-5.55). Moreover, insulin therapy may increase in-hospital admission in patients with COVID-19 and diabetes (OR=1.31; 95% CI, 1.06-1.61). However, there was no significant difference in the hospitalization time according to insulin treatment (SMD=0.21 95% CI, -0.02-0.45). Conclusions: Insulin treatment may increase mortality and severe/critical complications in patients with COVID-19 and diabetes, but more large-scale studies are needed to confirm and explore the exact mechanism.


Assuntos
COVID-19/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , COVID-19/complicações , Humanos , Resultado do Tratamento
8.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361774

RESUMO

Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance.


Assuntos
Antioxidantes/farmacologia , Cardiotônicos/farmacologia , Composição de Medicamentos/métodos , Hipertensão/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Polifenóis/farmacologia , Elementos de Resposta Antioxidante , Antioxidantes/química , Antioxidantes/farmacocinética , Arginina/análogos & derivados , Arginina/antagonistas & inibidores , Arginina/metabolismo , Cardiotônicos/química , Cardiotônicos/farmacocinética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Mellitus/fisiopatologia , Portadores de Fármacos , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Dislipidemias/metabolismo , Dislipidemias/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/química , Polifenóis/farmacocinética , Transdução de Sinais
9.
AMIA Annu Symp Proc ; 2021: 495-504, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457165

RESUMO

Improving quality of care in diabetes requires a good understanding of variations in diabetes outcomes and related interventions. However, little is known about the impact of diabetes interventions on outcome measures at the subpopulation-level. In this study, we developed methods that combine causal inference techniques with subset scanning techniques to study the heterogeneous effects of treatments on binary health outcomes. We analyzed a diabetes dataset consisting of 70,000 initial inpatient encounters to investigate the anomalous patterns associated with the impact of 4 anti-diabetic medication classes on 30-day readmission in diabetes. We discovered anomalous subpopulations where the likelihood of readmission was up to 1.8 times higher than that of the overall population suggesting subpopulation-level heterogeneity. Identifying such subpopulations may lead to a better understanding of the heterogeneous effects of treatments and improve targeted intervention planning.


Assuntos
Diabetes Mellitus , Readmissão do Paciente , Diabetes Mellitus/tratamento farmacológico , Hospitais , Humanos , Pacientes Internados
10.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201756

RESUMO

Diabetes mellitus and related disorders significantly contribute to morbidity and mortality worldwide. Despite the advances in the current therapeutic methods, further development of anti-diabetic therapies is necessary. Mitochondrial dysfunction is known to be implicated in diabetes development. Moreover, specific types of mitochondrial diabetes have been discovered, such as MIDD (maternally inherited diabetes and deafness) and DAD (diabetes and Deafness). Hereditary mitochondrial disorders are caused by certain mutations in the mitochondrial DNA (mtDNA), which encodes for a substantial part of mitochondrial proteins and mitochondrial tRNA necessary for mitochondrial protein synthesis. Study of mtDNA mutations is challenging because the pathogenic phenotype associated with such mutations depends on the level of its heteroplasmy (proportion of mtDNA copies carrying the mutation) and can be tissue-specific. Nevertheless, modern sequencing methods have allowed describing and characterizing a number of mtDNA mutations associated with human disorders, and the list is constantly growing. In this review, we provide a list of mtDNA mutations associated with diabetes and related disorders and discuss the mechanisms of their involvement in the pathology development.


Assuntos
Diabetes Mellitus/genética , Genoma Mitocondrial/genética , Inflamação/genética , Mutação , Animais , Doença Crônica , DNA Mitocondrial/genética , Surdez/genética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Camundongos , Doenças Mitocondriais/genética
11.
Molecules ; 26(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207498

RESUMO

Cardiovascular diseases (CVDs) are a global health burden that greatly impact patient quality of life and account for a huge number of deaths worldwide. Despite current therapies, several side effects have been reported that compromise patient adherence; thus, affecting therapeutic benefits. In this context, plant metabolites, namely volatile extracts and compounds, have emerged as promising therapeutic agents. Indeed, these compounds, in addition to having beneficial bioactivities, are generally more amenable and present less side effects, allowing better patient tolerance. The present review is an updated compilation of the studies carried out in the last 20 years on the beneficial potential of essential oils, and their compounds, against major risk factors of CVDs. Overall, these metabolites show beneficial potential through a direct effect on these risk factors, namely hypertension, dyslipidemia and diabetes, or by acting on related targets, or exerting general cellular protection. In general, monoterpenic compounds are the most studied regarding hypotensive and anti-dyslipidemic/antidiabetic properties, whereas phenylpropanoids are very effective at avoiding platelet aggregation. Despite the number of studies performed, clinical trials are sparse and several aspects related to essential oil's features, namely volatility and chemical variability, need to be considered in order to guarantee their efficacy in a clinical setting.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Óleos Voláteis/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Dislipidemias/complicações , Dislipidemias/metabolismo , Dislipidemias/patologia , Humanos , Óleos Voláteis/química , Estresse Oxidativo , Qualidade de Vida , Fatores de Risco
12.
J Med Case Rep ; 15(1): 403, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34311786

RESUMO

BACKGROUND: Intravitreal injections of anti-vascular endothelial growth factor are commonly used to treat macular diseases, including diabetic macular edema. Anti-vascular endothelial growth factor drugs can enter the systemic circulation after intravitreal injections and appear to suppress circulating vascular endothelial growth factor levels. However, whether this can cause any systemic adverse events remains unknown. CASE PRESENTATION: A 70-year-old Japanese man diagnosed with diabetic macular edema in both eyes was treated with anti-vascular endothelial growth factor intravitreal injections. One month after receiving two intravitreal injections of aflibercept 1 week apart for diabetic macular edema in both eyes, he complained of a severe acute headache. The patient was diagnosed with hypertensive cerebral hemorrhage of the occipital lobe based on an elevated blood pressure of 195/108 mmHg and the results of computed tomography and magnetic resonance imaging of his brain. The patient was treated with an intravenous injection of nicardipine hydrochloride to lower his systemic blood pressure. Two days after the stroke, the patient began oral treatment with 80 mg/day telmisartan, which was continued for 3 days, and the telmisartan dose was reduced to 40 mg/day thereafter. His blood pressure promptly dropped to 130/80 mmHg, and his severe headache disappeared. One year after the cerebrovascular stroke, the telmisartan was discontinued because his blood pressure stabilized at a normal level. His plasma vascular endothelial growth factor levels were measured via specific enzyme-linked immunosorbent assay before and after the intravitreal injections of aflibercept. Immediately before the injections, the vascular endothelial growth factor level was 28 pg/ml, but it rapidly fell below the detection limit within 1 week, where it remained for over 2 months. Two days before the cerebral hemorrhage, his plasma vascular endothelial growth factor level was below the detection limit, and 2 months later after the stroke, his plasma vascular endothelial growth factor level recovered to 41 pg/ml. CONCLUSION: This case suggests that hypertension and resultant cerebral hemorrhage can occur in patients with diabetic macular edema when plasma vascular endothelial growth factor levels are systemically decreased below the detection limit for a prolonged time after local injections of anti-vascular endothelial growth factor agents into the vitreous cavity. Therefore, severely reduced plasma vascular endothelial growth factor levels could be a higher risk factor to develop generally infrequent stroke. Ophthalmologists should be aware of possible severe reduction of plasma vascular endothelial growth factor levels and resultant increase in blood pressure after intravitreal injections of an anti-vascular endothelial growth factor drug. If the plasma vascular endothelial growth factor levels could be monitored more easily and quickly during the treatment, it would help to prevent adverse events.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Hemorragia Intracraniana Hipertensiva , Edema Macular , Preparações Farmacêuticas , Idoso , Inibidores da Angiogênese/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Humanos , Hemorragia Intracraniana Hipertensiva/tratamento farmacológico , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Masculino , Ranibizumab , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Acuidade Visual
13.
Int J Mol Sci ; 22(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205264

RESUMO

Patients with type 2 diabetes have an increased risk of fracture compared to the general population. Glucose absorption is accelerated by incretin hormones, which induce insulin secretion from the pancreas. The level of the incretin hormone, glucagon-like peptide-1 (GLP-1), shows an immediate postprandial increase, and the circulating level of intact GLP-1 is reduced rapidly by dipeptidyl peptidase-4 (DPP-4)-mediated inactivation. Therefore, GLP-1 receptor agonists and DPP-4 inhibitors are effective in the treatment of type 2 diabetes. However, these incretin-related diabetic agents have been reported to affect bone metabolism, including bone formation and resorption. These agents enhance the expression of bone markers, and have been applied to improve bone quality and bone density. In addition, they have been reported to suppress chronic inflammation and reduce the levels of inflammatory cytokine expression. Previously, we reported that these incretin-related agents inhibited both the expression of inflammatory cytokines and inflammation-induced bone resorption. This review presents an overview of current knowledge regarding the effects of incretin-related diabetes drugs on osteoblast differentiation and bone formation as well as osteoclast differentiation and bone resorption. The mechanisms by which incretin-related diabetes drugs regulate bone formation and bone resorption are also discussed.


Assuntos
Reabsorção Óssea , Inibidores da Dipeptidil Peptidase IV/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Osteogênese/efeitos dos fármacos , Animais , Diabetes Mellitus/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Humanos
14.
Front Endocrinol (Lausanne) ; 12: 649405, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220705

RESUMO

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness.


Assuntos
COVID-19/tratamento farmacológico , Glucocorticoides/efeitos adversos , Insulina/uso terapêutico , Doenças Metabólicas/induzido quimicamente , Doenças Metabólicas/prevenção & controle , COVID-19/complicações , Cuidados Críticos/métodos , Estado Terminal/terapia , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Complicações do Diabetes/diagnóstico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/mortalidade , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Glucocorticoides/uso terapêutico , Humanos , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hiperglicemia/mortalidade , Doenças Metabólicas/etiologia , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/mortalidade , SARS-CoV-2/fisiologia , Resultado do Tratamento
15.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281162

RESUMO

Diabetes is a worldwide emergency. Its chronic complications impose a heavy burden on patients, health systems, and on society as a whole. Diabetic retinopathy is one of the most common and serious complications of diabetes, and an established risk factor for blindness in adults. Over 15 years of investigation led to the identification of vascular endothelial growth factor (VEGF) as a main pathogenic factor in diabetic retinopathy and to the introduction of highly effective anti-VEGF-based therapies, such as the monoclonal antibody bevacizumab or its fragment ranibizumab, which helped to prevent diabetes-related blindness in millions of patients. Recently, a pathogenic role for uncontrolled increases in the extracellular ATP concentration (eATP) and for overactivation of the purinergic receptor P2X7 (P2X7R) has been suggested. The P2X7R is an eATP-gated plasma membrane channel expressed in multiple tissues and organs, with a pleiotropic function in inflammation, immunity, cancer, and hormone and growth factor release. P2X7R stimulation or overexpression positively regulate the secretion and buildup of VEGF, thus promoting neo-angiogenesis in a wide variety of disease processes. In this review, we explore current evidence that supports the role of P2X7R receptor signaling in the pathogenesis of diabetic retinopathy, as well as the most appealing current therapeutical options for P2X7R targeting.


Assuntos
Retinopatia Diabética/genética , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/metabolismo , Bevacizumab/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Humanos , Inflamação/metabolismo , Ranibizumab/uso terapêutico , Receptores Purinérgicos P2X7/efeitos dos fármacos , Receptores Purinérgicos P2X7/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/fisiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-34209616

RESUMO

The COVID-19 pandemic has impacted the management of non-communicable diseases in health systems around the world. This study aimed to understand the impact of COVID-19 on diabetes medicines dispensed in Australia. Publicly available data from Australia's government subsidised medicines program (Pharmaceutical Benefits Scheme), detailing prescriptions by month dispensed to patients, drug item code and patient category, was obtained from January 2016 to November 2020. This study focused on medicines used in diabetes care (Anatomical Therapeutical Chemical code level 2 = A10). Number of prescriptions dispensed were plotted by month at a total level, by insulins and non-insulins, and by patient category (general, concessional). Total number of prescriptions dispensed between January and November of each year were compared. A peak in prescriptions dispensed in March 2020 was identified, an increase of 35% on March 2019, compared to average growth of 7.2% in previous years. Prescriptions dispensed subsequently fell in April and May 2020 to levels below the corresponding months in 2019. These trends were observed across insulins, non-insulins, general and concessional patient categories. The peak and subsequent dip in demand have resulted in a small unexpected overall increase for the period January to November 2020, compared to declining growth for the same months in prior years. The observed change in consumer behaviour prompted by COVID-19 and the resulting public health measures is important to understand in order to improve management of medicines supply during potential future waves of COVID-19 and other pandemics.


Assuntos
Aparelho Sanitário , COVID-19 , Diabetes Mellitus , Austrália/epidemiologia , Comportamento do Consumidor , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Humanos , Carne , Pandemias , SARS-CoV-2
17.
Molecules ; 26(13)2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34202801

RESUMO

In this research, the selected drugs commonly used in diabetes and its comorbidities (gliclazide, cilazapril, atorvastatin, and acetylsalicylic acid) were studied for their interactions with bovine serum albumin-native and glycated. Two different spectroscopic methods, fluorescence quenching and circular dichroism, were utilized to elucidate the binding interactions of the investigational drugs. The glycation process was induced in BSA by glucose and was confirmed by the presence of advanced glycosylation end products (AGEs). The interaction between albumin and gliclazide, with the presence of another drug, was confirmed by calculation of association constants (0.11-1.07 × 104 M-1). The nature of changes in the secondary structure of a protein depends on the drug used and the degree of glycation. Therefore, these interactions may have an influence on pharmacokinetic parameters.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/química , Soroalbumina Bovina/química , Animais , Bovinos , Humanos , Hipoglicemiantes/uso terapêutico , Ligação Proteica , Estrutura Secundária de Proteína
18.
Int J Mol Sci ; 22(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205123

RESUMO

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRK1A, 1B, 2-4) and cdc2-like kinases (CLK1-4) belong to the CMGC group of serine/threonine kinases. These protein kinases are involved in multiple cellular functions, including intracellular signaling, mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle control, differentiation, homocysteine/methionine/folate regulation, body temperature regulation, endocytosis, neuronal development, synaptic plasticity, etc. Abnormal expression and/or activity of some of these kinases, DYRK1A in particular, is seen in many human nervous system diseases, such as cognitive deficits associated with Down syndrome, Alzheimer's disease and related diseases, tauopathies, dementia, Pick's disease, Parkinson's disease and other neurodegenerative diseases, Phelan-McDermid syndrome, autism, and CDKL5 deficiency disorder. DYRKs and CLKs are also involved in diabetes, abnormal folate/methionine metabolism, osteoarthritis, several solid cancers (glioblastoma, breast, and pancreatic cancers) and leukemias (acute lymphoblastic leukemia, acute megakaryoblastic leukemia), viral infections (influenza, HIV-1, HCMV, HCV, CMV, HPV), as well as infections caused by unicellular parasites (Leishmania, Trypanosoma, Plasmodium). This variety of pathological implications calls for (1) a better understanding of the regulations and substrates of DYRKs and CLKs and (2) the development of potent and selective inhibitors of these kinases and their evaluation as therapeutic drugs. This article briefly reviews the current knowledge about DYRK/CLK kinases and their implications in human disease.


Assuntos
Doença de Alzheimer/genética , Quinases relacionadas a CDC2 e CDC28/genética , Síndrome de Down/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Doença de Alzheimer/tratamento farmacológico , Diferenciação Celular/genética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Síndrome de Down/tratamento farmacológico , Humanos , Fosforilação/genética , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
19.
Oncology ; 99(9): 555-561, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34247166

RESUMO

INTRODUCTION: Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. METHODS: All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, t tests, and χ2 tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. RESULTS: Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01-2.06], p = 0.011, and HR 1.5 [1.08-2.08], p = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61-1.93], p = 0.79, and HR 1.29 [0.69-2.39], p = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. CONCLUSION: Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/complicações , Complicações do Diabetes , Humanos , Hipoglicemiantes/uso terapêutico , Neoplasias Pulmonares/complicações , Metformina/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos
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