Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63.478
Filtrar
1.
Food Chem ; 335: 127645, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32738537

RESUMO

The dried Ganoderma lucidum (GL) has been widely used for its pharmacological properties and bioactive ganoderic acids (GAs). Herein, extraction procedures combining ultra-sonication and heating were optimized using response surface methodology based on four variables (antioxidant activity, anti-diabetic activity, total GAs content, and total polysaccharide content) and principal component analysis. The extraction of freeze-dried GL at temperatures between 64.2 and 70 °C for 1.2 h maximized the antioxidant activity and GA content, whereas the polysaccharide content and anti-diabetic activity were maximized by extraction between 66.8 and 70 °C for more than 2.8 h. Heat-dried GL extracted at 50 °C for 3 h provided the greatest anti-inflammatory activity against HaCaT cells by suppressing the response to inflammation related cytokines at mRNA levels. These results suggest that extraction conditions might be a limiting factor for target-oriented investigations, and optimized extraction methods may improve the potential effect and quality of harvested GL products.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Fracionamento Químico/métodos , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Reishi/química , Triterpenos/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular , Fracionamento Químico/instrumentação , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Triterpenos/química , Triterpenos/farmacologia
2.
Food Chem ; 336: 127676, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32768902

RESUMO

Chicory (Cichorium intybus L.) is a perennial herb from the Cichorium genus, Asteraceae family, and is worldwide cultivated. So far, chicory has been used mainly in animal feed, but also in several cases in the food industry: as salad, for teas and tea blends, for coffee supplementation, and as a source for the inulin production. Nowadays there is an increasing interest in chicory utilization for food production and supplementation. Some compounds present in chicory, such as polyphenols, inulin, oligofructose and sesquiterpene lactones may be considered as potential carriers of food functionality. This review describes nutritional, mineral and bioactive composition of the chicory plant and summarized the main biological activities associated with the presence of bioactive compounds in the different plant parts. Finally, the review explores possibilities of uses of chicory and its implementation in food products, with intention to design new functional foods.


Assuntos
Chicória/química , Ingredientes de Alimentos , Compostos Fitoquímicos/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Valor Nutritivo , Compostos Fitoquímicos/química , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia
3.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4677-4685, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33164432

RESUMO

To evaluate the quality differences of four mainstream species of Berberidis Cortex,~1H-NMR metabolomics was applied to detect its primary and secondary metabolites, and the partial least squares discriminant analysis and analysis of variance were integrated to screen differential metabolites between species. Furthermore, diabetic rat model was established by high fat diet and streptozotocin to assess differences in antidiabetic activities among the four species. Sixteen compounds were simultaneously detected and identified, including alkaloids, organic acids, carbohydrates and amino acids. Interspecific difference markers were revealed as magnoflorine, jateorhi-zine, bufotenidine and saccharose for the first time. Berberis vernae and B. kansuensis presented superior activities on reducing blood glucose level, improving insulin resistance, increasing insulin sensibility and anti-inflammation. B. dictyophylla showed moderate antidiabe-tic effect, while B. diaphana rendered inferior antidiabetic capacity. Based on the contents of four differential markers and the results of antidiabetic activity evaluation, the quality of four Berberidis Cortex species was ranked as B.vernae≈B.kansuensis>B. dictyophylla>B. diaphana. These results provided references for species collation, quality standard establishment and exploitation of Berberidis Cortex. The antidiabetic activities of B. vernae and B. kansuensis as well as their mechanisms of action merit further study in the future.


Assuntos
Berberis , Diabetes Mellitus , Animais , Hipoglicemiantes/farmacologia , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética , Ratos
4.
Kardiologiia ; 60(9): 122-133, 2020 Oct 14.
Artigo em Russo | MEDLINE | ID: mdl-33131483

RESUMO

Cardiovascular diseases remain a leading cause for unfavorable outcomes, including death, in patients with type 2 diabetes mellitus (DM2). In the recent decade, novel drugs, including glucagon-like peptide-1 receptor agonists (GPP-1-RA) and sodium-glucose cotransporter-2 inhibitors, have convincingly demonstrated their ability to reduce risk of cardiovascular complications in patients with DM2. This review discusses one of GPP-1-RA, semaglutide, with a special focus on the evidence-based data on its use, cardioprotective properties, and algorithms of administration consistent with current clinical recommendations.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon , Humanos , Hipoglicemiantes
5.
J Oleo Sci ; 69(11): 1389-1401, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33132278

RESUMO

The oral route is the most prevalent route of drug administration among various routes. Dapagliflozin is an oral hypoglycemic drug used for lowering the blood glucose level. The objective of this work is to developed and optimized dapagliflozin loaded nanostructured lipid carriers (DG-NLCs) for the improvement of oral delivery. DG-NLCs were prepared by a high-pressure homogenization method (hot) and optimized by Box-Behnken design software using lipid, surfactant, and homogenization cycle as an independent variable. DG-NLCs were evaluated for particle size (Y1), entrapment efficiency (Y2), drug release (Y3). The DG-NLCs were further evaluated for morphology, thermal and X-ray diffraction analysis, ex-vivo intestinal permeation, and stability study. Particle size (nm), entrapment efficiency (%) and drug release (%) of all seventeen formulations were found in the range of 113.71-356.22 nm, 60.43-96.54% and 63.44-83.62% respectively. Morphology of optimized formulation exhibited spherical in shape confirmed by transmission electron microscopy. Thermal and X-ray diffraction analysis of NLCs showed the drug was solubilized and lost the crystallinity. DG-NLCs-opt exhibited dual release pattern initial fast and later sustained-release (90.01±2.01% in 24 h) whereas DG-dispersion showed 31.54±1.87% release in 24 h. Korsmeyer-Peppas model was found to be the best fit model (R2=0.999). The DG-NLCs-opt exhibited significant-high (p < 0.05, 1.293 µg/cm2/h) flux than DG-dispersion (0.2683 µg/cm2/h). Apparent permeation coefficient of DG-NLCs-opt was found to be significantly higher (p < 0.05, 4.14×10-5 cm/min) than DG-dispersion (8.61×10-6 cm/min). The formulation showed no significant changes (p < 0.05) on six months of storage study at 25±2°C/60±5%RH. The finding concluded that quality by design (QbD) based lipid nanocarrier for oral delivery could be a promising approach of dapagliflozin for the management of diabetes.


Assuntos
Compostos Benzidrílicos , Portadores de Fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Glucosídeos , Hipoglicemiantes , Absorção Intestinal , Lipídeos , Nanopartículas , Nanoestruturas , Administração Oral , Compostos Benzidrílicos/química , Compostos Benzidrílicos/metabolismo , Formas de Dosagem , Portadores de Fármacos/química , Desenho de Fármacos , Estabilidade de Medicamentos , Glucosídeos/química , Glucosídeos/metabolismo , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Modelos Biológicos , Tamanho da Partícula
7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 49(5): 629-636, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33210492

RESUMO

Endothelial progenitor cells (EPCs) play an important role in diabetic vascular complications. A large number of studies have revealed that some clinical antihyperglycemics can improve the complications of diabetes by regulating the function of EPCs. Metformin can improve EPCs function in diabetic patients by regulating oxidative stress level or downstream signaling pathway of adenosine monophosphate activated protein kinase; Pioglitazone can delay the aging of EPCs by regulating telomerase activity; acarbose, sitagliptin and insulin can promote the proliferation, migration and adhesion of EPCs. In addition to lowering blood glucose, the effects of antihyperglycemics on EPCs may also be one of the mechanisms to improve the complications of diabetes. This article reviews the research progress on the regulation of EPC proliferation and function by antihyperglycemics.


Assuntos
Células Progenitoras Endoteliais , Hipoglicemiantes , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Células Progenitoras Endoteliais/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Transdução de Sinais/efeitos dos fármacos
8.
BMC Med ; 18(1): 359, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33190637

RESUMO

BACKGROUND: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.


Assuntos
Infecções por Coronavirus/mortalidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/normas , Insulina/uso terapêutico , Metformina/uso terapêutico , Pneumonia Viral/mortalidade , Respiração Artificial/estatística & dados numéricos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Estudos de Coortes , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Hipoglicemiantes/uso terapêutico , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Ventilação não Invasiva/estatística & dados numéricos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Estudos Prospectivos , Espanha
9.
Biomolecules ; 10(11)2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33147723

RESUMO

Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.


Assuntos
Antivirais/farmacologia , Triterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Antiprotozoários/química , Antiprotozoários/farmacologia , Antivirais/química , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Plantas/química , Triterpenos/química , Triterpenos/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-33115820

RESUMO

INTRODUCTION: The COVID-19 pandemic forced the Italian government to issue extremely restrictive measures on daily activities since 11 March 2020 ('lockdown'), which may have influenced the metabolic control of type 1 diabetes mellitus (T1D). The aims of the study were to investigate continuous glucose monitoring (CGM) metrics in children and adults with T1D during lockdown and to identify their potentially related factors. RESEARCH DESIGN AND METHODS: We enrolled 130 consecutive patients with T1D (30 children (≤12 years), 24 teenagers (13-17 years), and 76 adults (≥18 years)) using either Dexcom or FreeStyle LibreCGM>70% during the study period, without hybrid closed-loop insulin pump. CGM metrics during the 20 days before and the 20 days after lockdown were calculated. By telephonic contact, we performed validated physical activity and perceived stress questionnaires. RESULTS: In children, significantly lower glucose SD (SDglu) (p=0.029) and time below range (TBR)<54 mg/dL (TBR2) (p=0.029) were detected after lockdown. CGM metrics were comparable in teenagers before and during lockdown. After lockdown, adults improved significantly time in range (TIR) 70-180 mg/dL (p<0.001) and remaining metrics, except percent coefficient of variation and TBR2. In adults, considering the changes in SDglu and TIR occurred before and during lockdown, we identified a group with improved TIR and SDglu who performed more physical activity, one with improved glucose variability who was younger than the other patients, and one with worsened glucose variability who showed higher perceived stress than others. CONCLUSION: In patients with T1D during lockdown, CGM metrics mostly improved in children and adults, whereas it was unchanged in teenagers. In adults, age, physical activity, and perceived stress may be relevant contributing factors.


Assuntos
Glicemia/metabolismo , Controle de Doenças Transmissíveis , Infecções por Coronavirus , Diabetes Mellitus Tipo 1/metabolismo , Pandemias , Pneumonia Viral , Adolescente , Adulto , Betacoronavirus , Automonitorização da Glicemia , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Exercício Físico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Estresse Psicológico/metabolismo
11.
Cochrane Database Syst Rev ; 10: CD004730, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33075159

RESUMO

BACKGROUND: The Cystic Fibrosis Foundation recommends both short-term and long-acting insulin therapy when cystic fibrosis-related diabetes (CFRD) has been diagnosed. Diagnosis is based on: an elevated fasting blood glucose level greater than 6.94 mmol/L (125 mg/dL); or oral glucose tolerance tests greater than 11.11 mmol/L (200 mg/dL) at two hours; or symptomatic diabetes for random glucose levels greater than 11.11 mmol/L (200 mg/dL); or glycated hemoglobin levels of at least 6.5%. This is an update of a previously published review. OBJECTIVES: To establish the effectiveness of insulin and oral agents for managing diabetes in people with cystic fibrosis in relation to blood sugar levels, lung function and weight management. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also handsearched abstracts from pulmonary symposia and the North American Cystic Fibrosis Conferences. Date of most recent register search: 10 September 2020. We searched online trials registries; date of most recent searches: 21 March 2020. SELECTION CRITERIA: Randomized controlled trials comparing all methods of pharmacological diabetes therapy in people with diagnosed CFRD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias in the included studies. Authors also used GRADE to assess the quality of the evidence. MAIN RESULTS: The searches identified 29 trials (45 references). Four included trials provide results: one short-term single-center cross-over trial (seven adults) comparing insulin with oral repaglinide and no medication in adults with CFRD and normal fasting glucose; one long-term multicenter trial (61 adults with CFRD) comparing insulin with oral repaglinide and placebo; one long-term multicenter trial (67 adults) comparing insulin with oral repaglinide; and one 12-week single-center cross-over trial (20 adults) comparing the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin. Two ongoing trials of newly approved incretin mimics have been noted for possible future inclusion. Downgrading of the quality of the evidence was mainly due to risks of bias across all domains, but particularly due to concerns surrounding allocation concealment and selective reporting. There were also some concerns due to imprecision from small sample sizes and low event rates. Finally, there may be some bias due to the amounts of insulin and repaglinide given not being comparable. Data from one trial comparing insulin to placebo (39 participants) did not show any difference between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) or nutritional status (low-quality evidence). Similarly, no differences between groups were seen for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or quality of life (QoL). These results were mirrored in the narrative reports for the second trial in this comparison (seven participants). Data from the one-year trial comparing repaglinide to placebo (38 participants), showed no differences between groups for the primary outcomes of blood glucose levels (very low-quality evidence), lung function (low-quality evidence) and nutritional status (low-quality evidence). Also, no differences were seen between groups for the secondary outcomes of number of hypoglycemic episodes (low-quality evidence), secondary infection complications or QoL. These findings were mirrored in the narrative reports for the second trial (n = 7) in this comparison. Three trials compared insulin to repaglinide (119 participants). Data from one trial (n = 67) showed no difference in blood glucose levels at either 12 months (high-quality evidence) or 24 months; narrative reports from one trial (45 participants) reported no difference between groups, but the second trial (7 participants) reported a beneficial effect of insulin over repaglinide. Two trials (112 participants) found no difference between insulin and repaglinide in lung function or nutritional status (moderate-quality evidence). Two trials (56 participants) reported no difference in the number of hypoglycemic episodes (low-quality evidence). One trial (45 participants) reported no difference between groups in secondary infections and cystic fibrosis QoL. The single trial comparing glargine to neutral protamine Hagedorn insulin did not report directly on the review's primary outcomes, but did report no differences between groups in post-prandial glucose values and weight; neither group reported infectious complications. There was no difference in episodes of hypoglycemia (very low-quality evidence) and while there was no difference reported in QoL, all participants opted to continue treatment with glargine after the trial was completed. Mortality was not reported by any trial in any comparison, but death was not given as a reason for withdrawal in any trial. AUTHORS' CONCLUSIONS: This review has not found any conclusive evidence that any agent has a distinct advantage over another in controlling hyperglycemia or the clinical outcomes associated with CFRD. Given the treatment burden already experienced by people with cystic fibrosis, oral therapy may be a viable treatment option. While some cystic fibrosis centers use oral medications to help control diabetes, the Cystic Fibrosis Foundation (USA) clinical practice guidelines support the use of insulin therapy and this remains the most widely-used treatment method. Randomized controlled trials specifically related to controlling diabetes and its impact on the course of pulmonary disease process in cystic fibrosis continue to be a high priority. Specifically, investigators should evaluate adherence to different therapies and also whether there is benefit in using additional hypoglycemic agents as well as the newly approved incretin mimics. Agents that potentiate insulin action, especially agents with additional anti-inflammatory potential should also be further investigated as adjuvant therapy to insulin.


Assuntos
Fibrose Cística/complicações , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Administração Oral , Viés , Glicemia/análise , Carbamatos/administração & dosagem , Fibrose Cística/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/etiologia , Jejum/sangue , Humanos , Hiperglicemia/tratamento farmacológico , Insulina Glargina/administração & dosagem , Insulina Isófana/administração & dosagem , Piperidinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
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
16.
Expert Opin Pharmacother ; 21(15): 1799-1803, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33108240

RESUMO

INTRODUCTION: The majority of patients with type 1 diabetes mellitus (T1DM) do not achieve glycemic targets. In addition, treatment with insulin is associated with increased risk for hypoglycemia and weight gain. Accordingly, there is an unmet need for new safe and effective glucose-lowering agents in this population. Sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2, has been recently approved for use in patients with T1DM. AREAS COVERED: The authors review the major trials that have evaluated the safety and efficacy of sotagliflozin and provide their expert opinion. EXPERT OPINION: Even though sotagliflozin reduces HbA1 c levels and does not appear to increase the risk for hypoglycemia in most patients, the substantially increased risk for diabetic ketoacidosis limits the use of this agent to a carefully selected subgroup of patients with T1DM. Based on the existing evidence, sotagliflozin should be considered only in patients who have failed to achieve adequate glycemic control despite optimal insulin therapy, are at low risk for diabetic ketoacidosis, have been adequately trained to recognize this complication and are able to be in close contact with their physician.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/metabolismo , Cetoacidose Diabética/induzido quimicamente , Glicosídeos/administração & dosagem , Glicosídeos/efeitos adversos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Risco , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo
17.
Arch Pathol Lab Med ; 144(10): 1204-1208, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002153

RESUMO

CONTEXT.­: Glycemic control requires accurate blood glucose testing. The extent of hematocrit interference is difficult to assess to assure quality patient care. OBJECTIVE.­: To predict the effect of patient hematocrit on the performance of a glucose meter and its corresponding impact on insulin-dosing error. DESIGN.­: Multilevel mixed regression was conducted to assess the extent that patient hematocrit influences Roche Accu-Chek Inform II glucose meters, using the Radiometer ABL 837 as a reference method collected during validation of 35 new meters. Regression coefficients of fixed effects for reference glucose, hematocrit, an interaction term, and random error were applied to 4 months of patient reference method results extracted from the laboratory information system. A hospital inpatient insulin dose algorithm was used to determine the frequency of insulin dose error between reference glucose and meter glucose results. RESULTS.­: Fixed effects regression for method and hematocrit predicted biases to glucose meter results that met the "95% within ±12%" for the US Food and Drug Administration goal, but combinations of fixed and random effects exceeded that target in emergency and hospital inpatient units. Insulin dose errors were predicted from the meter results. Twenty-eight percent of intensive care unit, 20.8% of hospital inpatient, and 17.7% of emergency department results were predicted to trigger a ±1 insulin dose error by fixed and random effects. CONCLUSIONS.­: The current extent of hematocrit interference on glucose meter performance is anticipated to cause insulin error by 1-dose category, which is likely associated with low patient risk.


Assuntos
Glicemia/análise , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Erros Médicos , Algoritmos , Hematócrito , Humanos , Medição de Risco , Estados Unidos
18.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5093-5096, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019132

RESUMO

The daily challenge for people with type 1 diabetes is maintaining glycaemia in the "normal" range after meals, by injecting themselves the correct amount of insulin. Artificial pancreas systems were developed to adjust insulin delivery based on real-time monitoring of glycaemia and meal patient's report. Meal reporting is a heavy burden for patients as it requires carbohydrate estimation several times per day. To improve patient's quality of life and treatment, several methods aim at detecting unannounced meals. While untreated meals lead to hyperglycaemia and in the long-term to comorbidities, treating falsely detected meals can cause hypoglycaemia and coma. In this paper, we propose to customise the meal detection to the patient's hourly meal probability in order to limit false detection of unannounced meals.


Assuntos
Pâncreas Artificial , Humanos , Hipoglicemiantes/efeitos adversos , Insulina , Refeições , Qualidade de Vida
19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5140-5145, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019143

RESUMO

Continuous Glucose Monitoring (CGM) has enabled important opportunities for diabetes management. This study explores the use of CGM data as input for digital decision support tools. We investigate how Recurrent Neural Networks (RNNs) can be used for Short Term Blood Glucose (STBG) prediction and compare the RNNs to conventional time-series forecasting using Autoregressive Integrated Moving Average (ARIMA). A prediction horizon up to 90 min into the future is considered. In this context, we evaluate both population-based and patient-specific RNNs and contrast them to patient-specific ARIMA models and a simple baseline predicting future observations as the last observed. We find that the population-based RNN model is the best performing model across the considered prediction horizons without the need of patient-specific data. This demonstrates the potential of RNNs for STBG prediction in diabetes patients towards detecting/mitigating severe events in the STBG, in particular hypoglycemic events. However, further studies are needed in regards to the robustness and practical use of the investigated STBG prediction models.


Assuntos
Automonitorização da Glicemia , Glicemia , Algoritmos , Humanos , Hipoglicemiantes , Redes Neurais de Computação
20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5502-5505, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019225

RESUMO

Type 1 diabetes (T1D) therapy requires multiple daily insulin injections to compensate the lack of endogenous insulin production due to ß-cells destruction. An empirical standard formula (SF) is commonly used for such a task. Unfortunately, SF does not include information on glucose dynamics, e.g. the glucose rate-of-change (ROC) provided by continuous glucose monitoring (CGM) sensor. Hence, SF can sometimes lead to under/overestimations that can cause critical hypo/hyperglycemic episodes during/after the meal. Recently, to overcome this limitation, we proposed new linear regression models, integrating ROC information and personalized features. Despite the first encouraging results, the nonlinear nature of the problem calls for the application of nonlinear models. In this work, random forest (RF) and gradient boosting tree (GBT), nonlinear machine learning methodologies, were investigated. A dataset of 100 virtual subjects, opportunely divided into training and testing sets, was used. For each individual, a single-meal scenario with different meal conditions (preprandial ROC, BG and meal amounts) was simulated. The assessment was performed both in terms of accuracy in estimating the optimal bolus and glycemic control. Results were compared to the best performing linear model previously developed. The two tree-based models proposed lead to a statistically significant improvement of glycemic control compared to the linear approach, reducing the time spent in hypoglycemia (from 32.49% to 27.57-25.20% for RF and GBT, respectively). These results represent a preliminary step to prove that nonlinear machine learning techniques can improve the estimation of insulin bolus in T1D therapy. Particularly, RF and GBT were shown to outperform the previously linear models proposed.Clinical Relevance- Insulin bolus estimation with nonlinear machine learning techniques reduces the risk of adverse events in T1D therapy.


Assuntos
Diabetes Mellitus Tipo 1 , Insulina , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes , Aprendizado de Máquina , Dinâmica não Linear
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA