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1.
Medicine (Baltimore) ; 99(37): e22031, 2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32925737

RESUMEN

BACKGROUND: Diabetes is a common chronic metabolic disease. COVID-19 is a large-scale infectious disease that broke out in 2019, and 212 countries have now been infected with this infectious disease. Some studies have shown that COVID-19 combined with diabetes is an independent risk factor for death or other adverse outcomes. There is currently no specific and effective drug treatment. More and more people have realized that the low-cost CQ and its derivative HCQ have antiviral and anti-inflammatory capabilities and may play a huge role in the fight against COVID-19. At the same time, HCQ can be used as an oral hypoglycemic agent and has the effect of lowering blood glucose. However, there is no evidence-based medicine to confirm the effectiveness and safety of CQ and HCQ in the treatment of COVID-19 patients with diabetes. Therefore, we will conduct a systematic review and meta-analysis to synthesize the existing clinical evidences. METHODS AND ANALYSIS: Chinese literature comes from CNKI, Wanfang, VIP, CBM databases. English literature mainly searches Cochrane Library, PubMed, Web of Science, EMBASE. We will retrieve each database from December 2019 to August 2020. At the same time, we will look for clinical trial registration and gray literature. This study only included clinical randomized controlled trials. The reviewers independently conduct literature selection, data analysis, quality analysis, and evaluation. The primary outcomes include Sputum virus nucleic acid negative time, lung imaging improvement time, mortality rate, mechanical ventilation rate, ICU hospitalization time, hospitalization time, clinical improvement, symptoms Improvement, fasting blood glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin, fasting insulin, adverse reactions, etc. Finally, we will conducted a meta-analysis through Review Manager Software version 5.3. RESULTS: The results will be published in peer-reviewed journals and presented at a relevant conference. CONCLUSION: This study will explore the effectiveness and safety of CQ and HCQ in the treatment of COVID-19 patients with diabetes. It will provide evidence-based medical evidence for CQ and HCQ in the treatment of diabetes with COVID-19. REGISTRATION NUMBER: INPLASY202070109.


Asunto(s)
Cloroquina/farmacología , Infecciones por Coronavirus , Diabetes Mellitus , Hidroxicloroquina/farmacología , Pandemias , Neumonía Viral , Antiinfecciosos/farmacología , Betacoronavirus , Comorbilidad , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Humanos , Hipoglucemiantes/farmacología , Metaanálisis como Asunto , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
2.
Medicine (Baltimore) ; 99(35): e21939, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32871938

RESUMEN

RATIONALE: Maturity-onset diabetes of the young type 5 (MODY 5) is a form of monogenic diabetes that is often accompanied by pancreatic dysfunction. To date, no cases of MODY 5 treated with glucagon-like peptide-1 receptor agonist (GLP-1RA) have been reported. We present the first case of MODY 5 treated with GLP-1RA. PATIENT CONCERNS: A 17-year-old woman, with a history of being operated for congenital ileal atresia at birth, was admitted to our hospital due to hyperglycemia. She had been clinically diagnosed with type 1 diabetes 1 month prior, and administered 14 units of insulin glargine 300 U/mL per day. DIAGNOSIS: She had hypopotassemia, hypomagnesaemia, pancreatic body, and tail defects, multiple renal cysts, and a family history of diabetes, and urogenital anomaly. Genetic testing revealed heterozygous deletion of hepatocyte nuclear transcription factor-1 beta, leading to the diagnosis of MODY 5. INTERVENTIONS: The patient was treated with multiple daily insulin injections for 9 days (22 units/d) before administration of GLP-1RA, and then liraglutide was initiated. OUTCOMES: Liraglutide treatment (0.6 mg/d) alone maintained the patient's glycated hemoglobin level below 7.0% for at least 12 months after discharge. A higher dose, 0.9 mg/d, of liraglutide was not tolerated by the patient due to nausea. Serum levels of C-peptide immunoreactivity were 1.15 ng/mL and 1.91 ng/mL, respectively, after 6 and 12 months of liraglutide therapy. LESSONS: GLP-1RA might be effective at regulating glucose metabolism by utilizing residual pancreatic endocrine function in patients with MODY 5. Imaging and genetic screening were helpful in the diagnosis of MODY 5.


Asunto(s)
Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Esmalte Dental/anomalías , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Enfermedades Renales Quísticas/tratamiento farmacológico , Liraglutida/uso terapéutico , Adolescente , Enfermedades del Sistema Nervioso Central/diagnóstico por imagen , Esmalte Dental/diagnóstico por imagen , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Femenino , Humanos , Hipoglucemiantes/farmacología , Enfermedades Renales Quísticas/diagnóstico por imagen , Liraglutida/farmacología , Páncreas/diagnóstico por imagen
3.
Int J Nanomedicine ; 15: 4877-4898, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32753869

RESUMEN

Background: Although dynamics and uses of modified nanoparticles (NPs) as orally administered macromolecular drugs have been researched for many years, measures of molecule stability and aspects related to important transport-related mechanisms which have been assessed in vivo remain as relatively under characterized. Thus, our aim was to develop a novel type of oral-based delivery system for insulin and to overcome barriers to studying the stability, transport mechanisms, and efficacy in vivo of the delivery system. Methods: NPs we developed and tested were composed of insulin (INS), dicyandiamide-modified chitosan (DCDA-CS), cell-penetrating octaarginine (r8), and hydrophilic hyaluronic acid (HA) and were physically constructed by electrostatic self-assembly techniques. Results: Compared to free-insulin, levels of HA-DCDA-CS-r8-INS NPs were retained at more desirable measures of biological activity in our study. Further, our assessments of the mechanisms for NPs suggested that there were high measures of cellular uptake that mainly achieved through active transport via lipid rafts and the macropinocytosis pathway. Furthermore, investigations of NPs indicated their involvement in caveolae-mediated transport and in the DCDA-CS-mediated paracellular pathway, which contributed to increasing the efficiency of sequential transportation from the apical to basolateral areas. Accordingly, high efficiency of absorption of NPs in situ for intestinal loop models was realized. Consequently, there was a strong induction of a hypoglycemic effect in diabetic rats of NPs via orally based administrations when compared with measures related to free insulin. Conclusion: Overall, the dynamics underlying and influenced by HA-DCDA-CS-r8-INS may hold great promise for stability of insulin and could help overcome interference by the epithelial barrier, and thus showing a great potential to improve the efficacy of orally related treatments.


Asunto(s)
Quitosano/química , Ácido Hialurónico/química , Insulina/administración & dosificación , Nanopartículas Multifuncionales/química , Nanopartículas/química , Administración Oral , Animales , Transporte Biológico/efectos de los fármacos , Células CACO-2 , Muerte Celular/efectos de los fármacos , Quitosano/síntesis química , Diabetes Mellitus Experimental/tratamiento farmacológico , Impedancia Eléctrica , Endocitosis/efectos de los fármacos , Guanidinas/síntesis química , Guanidinas/química , Humanos , Ácido Hialurónico/síntesis química , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Insulina/uso terapéutico , Absorción Intestinal/efectos de los fármacos , Masculino , Moco/metabolismo , Nanopartículas/ultraestructura , Ratas , Solubilidad , Porcinos
5.
Medicine (Baltimore) ; 99(32): e21568, 2020 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-32769900

RESUMEN

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries, and strongly associated with type 2 diabetes mellitus (T2DM). Several studies have shown that hypoglycemic agents are effective for NAFLD combined with T2DM. However, there is still controversy over which hypoglycemic agent is the best for NAFLD combined with T2DM patients. OBJECTIVE: To systematically evaluate the efficacy and safety of hypoglycemic agents in NAFLD combined with T2DM patients. METHODS: A comprehensive electronic search will be conducted by searching Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Clinical Trials and Chinese Biomedical Medicine. All randomized controlled trials of hypoglycemic agents interventions for NAFLD combined with T2DM will be identified. Two reviewers independently screened and evaluated each included study and extracted the outcome indexes. ADDIS 1.16.8 software will be used for the network meta-analysis and STATA 14 software will be used for drawing network evidence plots and funnel plots. CONCLUSION: This network meta-analysis will provide stronger evidence for the efficacy and safety of hypoglycemic agents in the treatment of NAFLD combined with T2DM, and provide a reference for clinical application. PROTOCOL REGISTRATION NUMBER: INPLASY202070016.


Asunto(s)
Protocolos Clínicos , Hipoglucemiantes/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/farmacología , Metaanálisis como Asunto , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Revisiones Sistemáticas como Asunto
6.
Fundam Clin Pharmacol ; 34(5): 530-547, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32603486

RESUMEN

Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug-drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.


Asunto(s)
Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Medicamentos bajo Prescripción/farmacología , Analgésicos/farmacología , Antiasmáticos/farmacología , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Anticoagulantes/farmacología , Antineoplásicos/farmacología , Antituberculosos/farmacología , Antivirales/farmacología , Betacoronavirus , Fármacos Cardiovasculares/farmacología , Interacciones Farmacológicas , Humanos , Hidroxicloroquina/farmacología , Hipoglucemiantes/farmacología , Hipolipemiantes/farmacología , Interferon beta-1b/farmacología , Pandemias , Medicamentos bajo Prescripción/farmacocinética , Psicotrópicos/farmacología , Receptores de Interleucina/antagonistas & inhibidores , Medición de Riesgo , Hormonas Tiroideas/farmacología
7.
PLoS One ; 15(7): e0235376, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32629460

RESUMEN

AIM: To develop a statistical model to identify determinants of glycemic control. MATERIALS AND METHODS: A database was extracted from patients' records with at least one glycated hemoglobin (HbA1c) analysis and with antidiabetic therapy established and stabilized. A logistic regression model was designed to identify the statistical significance of factors associated with glycemic control. RESULTS: Higher probability of success (HbA1c ≤8% [64 mmol/mol]) was found for those who were older in age, those who were men, and those with higher education levels. Increased values for the following variables were associated with the poorest glycemic control: number of years of T2DM since diagnosis, number of antidiabetic medicines, body mass index, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure and number of diabetes consultations in the last twelve months. The following pharmacotherapeutic treatments were associated with glycemic control (in decreasing order of the results): oral antidiabetic drugs; oral antidiabetic drugs and insulin; insulin. Patients using metformin and a dipeptidyl peptidase-4 inhibitors have a higher probability of success than do patients using metformin and a sulfonylurea, and patients using insulin and metformin have a higher probability of success than do patients using insulin alone. CONCLUSIONS: Sociodemographic, clinical and therapeutic parameters can strongly affect glycemic control. Studies based on real-life patient data provide important information on the development of more effective glycemic control.


Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hemoglobina A Glucada/análisis , Hipoglucemiantes/uso terapéutico , Modelos Biológicos , Factores de Edad , Anciano , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Quimioterapia Combinada/métodos , Femenino , Estudios de Seguimiento , Hemoglobina A Glucada/efectos de los fármacos , Humanos , Hipoglucemiantes/farmacología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores Sexuales , Factores Socioeconómicos , Factores de Tiempo , Resultado del Tratamiento
8.
Food Chem ; 328: 127076, 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-32480257

RESUMEN

The tunillo (Stenocereus stellatus [Pfeiffer] Riccobono) is a relatively little known cactus fruit with a significant pharmacological potential. However, all currently known variants are identified visually mostly on the basis of pulp color. Differences in chemical composition and pharmacological properties also remain largely unknown. Support vector machine classifiers were applied to UV-Visible spectra of liquid samples to obtain the following, color-based categories of tunillo fruits: A1-white, A2-red, A3-purple, and A4-orange. The spectrum of A2-red could be duplicated by combining those from A3-purple and A4-orange, while UPGMA-based hierarchical clustering of psbA-trnH and matK suggested that certain differences in color might actually have a genetic basis. The pigment quantification established A2-red and A3-purple as the most suitable candidates for the extraction of betalains and complex colored matrices, respectively. A2-red also had the highest content of phenols and flavonoids and displayed a noticeable anti-hyperglycemic effect.


Asunto(s)
Cactaceae/química , Frutas/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Color , Sequías , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , México
9.
Metabolism ; 109: 154295, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32553739

RESUMEN

INTRODUCTION: The dipeptidyl peptidase-4 inhibitors (DPP-4is), which belong to the class of incretin-based medications, are recommended as second or third-line therapies in guidelines for the management of type 2 diabetes mellitus. They have a favorable drug tolerability and safety profile compared to other glucose-lowering agents. OBJECTIVE: This review discusses data concerning the use of DPP-4is and their cardiovascular profile, and gives an updated comparison with the other oral glucose-lowering medications with regards to safety and efficacy. Currently available original studies, abstracts, reviews articles, systematic reviews and meta-analyses were included in the review. DISCUSSION: DPP4is are moderately efficient in decreasing the HbA1c by an average of 0.5% as monotherapy, and 1.0% in combination therapy with other drugs. They have a good tolerability and safety profile compared to other glucose-lowering drugs. However, there are possible risks pertaining to acute pancreatitis and pancreatic cancer. CONCLUSION: Cardiovascular outcome trials thus far have proven the cardiovascular safety for ischemic events in patients treated with sitagliptin, saxagliptin, alogliptin, linagliptin and vildagliptin. Data showing increased rate of hospitalisation in the case of saxagliptin did not seem to be a class effect.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Hipoglucemiantes/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Incretinas/uso terapéutico , Neoplasias Pancreáticas/inducido químicamente , Pancreatitis/inducido químicamente , Resultado del Tratamiento
10.
Life Sci ; 257: 118025, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32598933

RESUMEN

BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) co-agonists have emerged as treatment options for reversing diabetes and obesity. Here, we screened the high potency receptor-biased GLP-1R agonists via a newly designed high-throughput GLP-1R extracellular domain (ECD)-based system and demonstrated its in vitro and in vivo therapeutic characters. METHODS: Twelve 9-mer peptides (named XEL1-XEL12) which were screened from a large phage-displayed peptide library were fused to the N-terminus of GIP (3-30) to generate another twelve fusion peptides, termed XEL13-24. Using the six lysine-altered XEL17 as leading sequences, eighteen fatty chain modified fusion peptides were further assessed via in vitro GLP-1R/GIPR-based cell assay. Moreover, the acute and long-acting in vivo effects of selected candidate on diabetic db/db mice and diet-induced obesity (DIO) rats were both carefully evaluated. RESULTS: XEL17 exhibited balanced activation potency on GLP-1R/GIPR in stable cell lines, and further assessment was performed to evaluate the XEL32, a fatty chain modified XEL17 derivative. Preclinical pharmacodynamic results in diabetic db/db mice demonstrated that XEL32 held outstanding insulinotropic and glucose-lowering activities. In addition, protracted antidiabetic effects of XEL32 were also proved by the hypoglycemic test and multiple oral glucose tolerance test. Furthermore, chronic treatment of XEL32 in DIO rats exhibited outstanding beneficial effects on body weight control, fat loss, food intake control, hemoglobin A1C (HbA1C) reduction as well as the glucose tolerance. CONCLUSIONS: XEL32, as a novel GLP-1/GIP dual receptor agonist, may supply efficient glycemic control and weight loss.


Asunto(s)
Receptor del Péptido 1 Similar al Glucagón/metabolismo , Péptidos/farmacología , Receptores de la Hormona Gastrointestinal/metabolismo , Pérdida de Peso/efectos de los fármacos , Animales , Glucemia/metabolismo , China , Diabetes Mellitus/tratamiento farmacológico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Células HEK293 , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Hipoglucemiantes/farmacología , Masculino , Ratones , Obesidad/metabolismo , Ratas , Receptores de la Hormona Gastrointestinal/agonistas , Receptores de la Hormona Gastrointestinal/efectos de los fármacos
12.
PLoS One ; 15(6): e0235221, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32584888

RESUMEN

Ficus krishnae stem bark and leaves are used for diabetes treatment in traditional medicines. Stem bark of F. krishnae was sequentially extracted with hexane, methanol and water, and these extracts were tested for their antihyperglyceamic activity by oral glucose tolerance test (OGTT) in overnight fasted glucose loaded normal rats. Hexane extract showed significant glucose lowering activity in OGTT, and the triterpene alcohols (cycloartenol+24-methylenecycloartanol) (CA+24-MCA) were isolated together from it by activity guided isolation and characterized by NMR and mass spectroscopy. The ratio of the chemical constituents CA and 24-MCA in (CA+24-MCA) was determined as 2.27:1.00 by chemical derivatization and gas chromatographic quantification. (CA+24-MCA) in high fat diet-streptozotocin induced type II diabetic rats showed significant antidiabetes activity at 1 mg/kg and ameliorated derailed blood glucose and other serum biochemical parameters. Cytoprotective activity of (CA+24-MCA) from glucose toxicity was evaluated in cultured RIN-5F cells by MTT assay and fluorescent microscopy. (CA+24-MCA) in in vitro studies showed enhanced cell viability in RIN-5F cells and significant protection of beta cells from glucose toxicity. Both in in vivo and in vitro studies (CA+24-MCA) showed enhancement in insulin release from the beta cells. In short term toxicity studies in mice (CA+24-MCA) did not show any conspicuous toxic symptoms. The combination of the phytosterols (CA+24-MCA) obtained through activity guided isolation of the stem bark of F. krishnae showed significant activity, and therefore is a promising candidate for new generation antidiabetes drug development.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Ficus/química , Hipoglucemiantes/uso terapéutico , Fitosteroles/química , Triterpenos/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Ficus/metabolismo , Prueba de Tolerancia a la Glucosa , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Insulina/metabolismo , Hígado/metabolismo , Masculino , Ratones , Conformación Molecular , Fitosteroles/aislamiento & purificación , Fitosteroles/uso terapéutico , Tallos de la Planta/química , Tallos de la Planta/metabolismo , Ratas , Ratas Wistar , Triterpenos/aislamiento & purificación , Triterpenos/uso terapéutico
14.
Gene ; 754: 144903, 2020 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-32540374

RESUMEN

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among reproductive-age women. The circRNA-miRNA axis functions in various diseases progression have been partially revealed in the past two decades. However, little is known about the role of the circRNA-miRNA axis in PCOS progression. MicroRNA miR-760, which is characterized by tissue-specific, has been studied in several cancers. Firstly, we found that miR-760 expression was decreased in PCOS tissues insulin treated GCs, KGN and SVOG cells. Secondly, The CCK-8 and apoptosis experiment results suggested that downregulated miR-760 promoted cell proliferation ability and suppressed apoptosis activity in KGN and SVOG cells. Then, the bioinformatic analysis result indicated that circPUM1 was a potential sponge to miR-760. By performing AGO2-RIP, RNA pull-down, Luciferase reporter, and qRT-PCR experiments, we demonstrated that circPUM1 acted as a molecular sponge to miR-760, and decreased miR-760 expression. Moreover, it was found that the promotive effect of circPUM1 was mediated by regulating miR-760. Collectively, our findings suggest that circPUM1 promotes PCOS progression through sponging to miR-760. We may provide a promising therapeutic target for PCOS.


Asunto(s)
Regulación de la Expresión Génica , Células de la Granulosa/patología , MicroARNs/genética , Síndrome del Ovario Poliquístico/patología , ARN Circular/genética , Apoptosis , Proliferación Celular , Células Cultivadas , Progresión de la Enfermedad , Femenino , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Humanos , Hipoglucemiantes/farmacología , Insulina/farmacología , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/metabolismo
15.
Therapie ; 75(4): 327-333, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32425249

RESUMEN

According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Diabetes Mellitus/epidemiología , Hipoglucemiantes/administración & dosificación , Neumonía Viral/epidemiología , Animales , Infecciones por Coronavirus/fisiopatología , Diabetes Mellitus/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/farmacología , Insulina/administración & dosificación , Pandemias , Neumonía Viral/fisiopatología , Factores de Riesgo , Índice de Severidad de la Enfermedad
16.
Obesity (Silver Spring) ; 28(6): 1068-1074, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32352644

RESUMEN

OBJECTIVE: Epicardial adipose tissue (EAT) thickness is a marker of visceral fat and an emerging therapeutic target. Dapagliflozin, a selective sodium-glucose cotransporter 2 inhibitor, improves glucose control and induces moderate weight loss in patients with type 2 diabetes mellitus. Dapagliflozin has recently been shown to reduce cardiovascular risk. Nevertheless, whether dapagliflozin could reduce EAT thickness is unknown. METHODS: This hypothesis was tested in a 24-week, randomized, double-blind, placebo-controlled clinical trial in 100 patients with type 2 diabetes mellitus with BMI ≥ 27 kg/m2 and a hemoglobin A1c level ≤ 8% on metformin monotherapy. Individuals were randomly assigned to 2 groups to receive additional dapagliflozin up to 10 mg once daily or to remain on metformin up to 1,000 mg twice daily. Ultrasound-measured EAT thickness was measured at baseline, 12 weeks, and 24 weeks. RESULTS: In the dapagliflozin group, EAT decreased by 20% from baseline to 24 weeks, by 15% after 12 weeks, and by 7% between 12 and 24 weeks, respectively (P < 0.01 for all), whereas in the metformin group, there was a significant but smaller EAT reduction. There was no statistically significant correlation between EAT and body weight changes. CONCLUSIONS: Dapagliflozin causes a rapid and significant EAT reduction that could be independent of weight loss.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Obesidad/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Compuestos de Bencidrilo/farmacología , Método Doble Ciego , Femenino , Glucósidos/farmacología , Humanos , Hipoglucemiantes/farmacología , Masculino , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología
17.
Obesity (Silver Spring) ; 28(6): 1050-1061, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32441473

RESUMEN

OBJECTIVE: The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight. METHODS: Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long-term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results will be available in 2020/2021. For all trials, the primary end point is change from baseline to end of treatment in body weight. RESULTS: Participants have a mean age of 46.2 to 55.3 years, are mostly female (mean: 74.1%-81.0%), and have a mean BMI of 35.7 to 38.5 kg/m2 and a mean waist circumference of 113.0 to 115.7 cm. CONCLUSIONS: The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once weekly in a broad population. The trials will provide insights on WM in people with obesity with and without type 2 diabetes and on long-term follow-up.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptidos Similares al Glucagón/uso terapéutico , Hipoglucemiantes/uso terapéutico , Obesidad/tratamiento farmacológico , Método Doble Ciego , Femenino , Péptidos Similares al Glucagón/farmacología , Humanos , Hipoglucemiantes/farmacología , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
18.
Life Sci ; 256: 117853, 2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32470452

RESUMEN

AIMS: To investigate the diabetes-protective effect and weight-lowering potential of a novel long-acting triagonist at three metabolically related hormone receptors including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon receptors. MAIN METHODS: Triagonist were designed in an iterative manner from native GLP-1, GIP and Glucogan. Main peptide chain (termed TG peptides) and subsequently modified LTG peptides were synthesized via solid phase synthesis. In vitro receptor activity assay was performed to screen the TG peptide with most balanced potency on all three receptors. The in vitro biological activities of modified TG peptides were further investigated by albumin-binding measurement and proteolytic cleavage test. Subsequently, oral glucose tolerance test (OGTT), pharmacokinetic test and chronic study were subjected to the acute and long-term efficacy evaluation of selected fusion peptide, LTG-6. KEY FINDINGS: TG-8 exhibited equally aligned constituent efficacy and supraphysiological potency on corresponding receptor without cross-reactivity. Modified TG-8, termed LTG-6, exerted the great binding affinity for human serum albumin and the enhanced rational controlled-release of TG-8 in vitro. Further OGTT in different gene knockout mice and diabetic mice demonstrated the promising hypoglycemic and insulinotropic abilities of LTG-6. After long-term treatment for 8 weeks, LTG-6 was proved superior to co-agonists to decrease the body weight and %HbA1c, improve reverse dyslipidemia and glycemic control in the DIO models. SIGNIFICANCE: LTG-6, as a newly designed long-acting triagonist, holds potential to correct the obesity related metabolic disorders.


Asunto(s)
Diabetes Mellitus Experimental/prevención & control , Receptor del Péptido 1 Similar al Glucagón/agonistas , Péptidos/farmacología , Receptores de la Hormona Gastrointestinal/agonistas , Receptores de Glucagón/agonistas , Animales , Peso Corporal/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Células HEK293 , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Masculino , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/prevención & control , Ratones , Ratones Noqueados , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Péptidos/química , Ratas , Ratas Sprague-Dawley , Trombina/química
19.
Metabolism ; 109: 154265, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32446679

RESUMEN

BACKGROUND: Dementia is more prevalent among people with type 2 diabetes, but little is known regarding the influence of antidiabetic agents on this association. OBJECTIVE: This study assessed the impact of various antidiabetic agents on the risk of dementia among patients with Type 2 diabetes mellitus. METHODS: Relevant studies were retrieved from the PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases. Nine antidiabetic agents were included in the search. Data were pooled via network meta-analysis and meta-analysis. RESULTS: Nine studies were selected for the network meta-analysis with 530,355 individuals and 17 studies for the meta-analysis with 1,258,879 individuals. The analysis excluded glucagon-like peptide 1 (GLP-1) analogs and sodium-dependent glucose transporter 2 (SGLT-2) inhibitors due to the absence of relevant data. The use of dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, thiazolidinedione, and sulfonylurea was associated with a decreased risk of dementia in comparison to no treatment with antidiabetic agents (hazard ratio [HR] for DPP-4 inhibitors, 0.54; 95% confidence interval [CI], 0.38-0.74, HR for metformin, 0.75; 95% CI, 0.63-0.86; HR for sulfonylurea, 0.85; 95%CI, 0.73-0.98 and HR for thiazolidinedione, 0.70; 95% CI, 0.55-0.89, respectively). However, the node-splitting analysis showed the inconsistency of direct and indirect estimates in sulfonylurea (P = 0.042). DPP-4 inhibitors, metformin, thiazolidinedione, and sulfonylurea exhibited a significant impact on the risk of dementia in diabetics compared with insulin (HR, 0.35; 95%CI, 0.20-0.59, HR, 0.48; 95% CI, 0.30-0.77, HR, 0.45; 95% CI, 0.29-0.73 and HR, 0.55; 95% CI, 0.34-0.88, respectively). DPP-4 inhibitors also exhibited a protective effect on the risk of Alzheimer's dementia compared with the no treatment with antidiabetic agents (HR, 0.48; 95% CI, 0.25-0.92). The meta-analysis demonstrated a protective effect of using metformin and DPP-4 inhibitors on the risk of dementia (HR, 0.86; 95% CI, 0.74-1.00 and HR, 0.65; 95% CI, 0.55-0.76, respectively). Further analysis showed insulin was associated with an increased risk of Alzheimer's dementia (HR, 1.60; 95% CI, 1.13-2.26). Only two case-control studies mentioned GLP-1 analogs and SGLT-2 inhibitors, and the pooled ORs showed no evidence of an association with dementia (GLP-1 analogs: 0.71; 95% CI, 0.46-1.10 and SGLT-2 inhibitors: 0.74; 95% CI, 0.47-1.15). CONCLUSION: This analysis indicated that patients with type 2 diabetes under treatment with DPP-4 inhibitors presented with the lowest risk of dementia, followed by those treated with metformin and thiazolidinedione, while treatment with insulin was associated with the highest risk. For the increasing focus on the protective effect on dementia, further specific clinical studies are needed to evaluate the impact of GLP-1 analogs and SGLT-2 inhibitors on the risk of dementia.


Asunto(s)
Teorema de Bayes , Demencia/etiología , Hipoglucemiantes/farmacología , Metaanálisis en Red , Demencia/prevención & control , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Metformina/farmacología , Metformina/uso terapéutico , Sustancias Protectoras , Riesgo , Compuestos de Sulfonilurea/farmacología , Compuestos de Sulfonilurea/uso terapéutico , Tiazolidinedionas/farmacología , Tiazolidinedionas/uso terapéutico
20.
Mol Cell ; 79(1): 43-53.e4, 2020 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-32464093

RESUMEN

The physiological role of immune cells in the regulation of postprandial glucose metabolism has not been fully elucidated. We have found that adipose tissue macrophages produce interleukin-10 (IL-10) upon feeding, which suppresses hepatic glucose production in cooperation with insulin. Both elevated insulin and gut-microbiome-derived lipopolysaccharide in response to feeding are required for IL-10 production via the Akt/mammalian target of rapamycin (mTOR) pathway. Indeed, myeloid-specific knockout of the insulin receptor or bone marrow transplantation of mutant TLR4 marrow cells results in increased expression of gluconeogenic genes and impaired glucose tolerance. Furthermore, myeloid-specific Akt1 and Akt2 knockout results in similar phenotypes that are rescued by additional knockout of TSC2, an inhibitor of mTOR. In obesity, IL-10 production is impaired due to insulin resistance in macrophages, whereas adenovirus-mediated expression of IL-10 ameliorates postprandial hyperglycemia. Thus, the orchestrated response of the endogenous hormone and gut environment to feeding is a key regulator of postprandial glycemia.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Hiperglucemia/patología , Insulina/farmacología , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Tejido Adiposo/metabolismo , Animales , Glucemia/análisis , Gluconeogénesis/genética , Hiperglucemia/etiología , Hiperglucemia/metabolismo , Hipoglucemiantes/farmacología , Resistencia a la Insulina , Interleucina-10/fisiología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Noqueados , Periodo Posprandial , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Proteína 2 del Complejo de la Esclerosis Tuberosa/fisiología
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