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1.
J Ethnopharmacol ; 266: 113474, 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33068650

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba extract (GbE) is derived from a medicinal plant and suggested as a treatment for diabetic nephropathy (DN), but the mechanism was not clarified. AIM OF STUDY: The present study investigated whether GbE prevented DN via activation of heme oxygenase (HO)-1. MATERIALS AND METHODS: Streptozotocin-induced diabetic mice were fed a high-fat diet to generate DN. Human and murine podocytes were used for the in vitro study. RESULTS: GbE improved renal function via decreasing glomerular hypertrophy, the kidney/body weight ratio, and albuminuria in DN mice. GbE reversed the reduction of synaptopodin and nephrin and enhanced HO-1 expression in the kidneys of DN mice. GbE decreased the enhancement of TNF-α, IL-6, fibronectin, and lipid accumulation in the glomeruli of DN mice. GbE attenuated the uptake of oxidized low-density lipoprotein and reduced the production of ROS in high glucose-stimulated podocytes, and HO-1 inhibitor treatment abrogated the protective effects of GbE. Nuclear factor erythroid 2-related factor 2 (Nrf-2) siRNA significantly abolished the beneficial effects of GbE via decreased HO-1 expression and enhanced TNF-α and IL-6 levels. CONCLUSIONS: GbE protected podocytes against hyperglycemia and prevented the development of DN via Nrf-2/HO-1 activation. Our findings provide further mechanistic insight into the potential use of GbE in clinical DN.


Asunto(s)
Antiinflamatorios/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Extractos Vegetales/farmacología , Animales , Células Cultivadas , Diabetes Mellitus Experimental/complicaciones , Dieta Alta en Grasa , Hemo-Oxigenasa 1/metabolismo , Humanos , Hiperglucemia/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos DBA , Factor 2 Relacionado con NF-E2/metabolismo , Podocitos/efectos de los fármacos , Podocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estreptozocina
2.
J Ethnopharmacol ; 265: 113210, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32795501

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: One of the commonly prescribed 'anti-diabetic' polyherbal mixtures by European herbalists is made of Rubus fruticosus and Vaccinium myrtillus leaves, Potentilla erecta roots, Geum urbanum aerial parts and Phaseolus vulgaris pods. AIM OF THE STUDY: This study aimed to evaluate the phytochemical composition, antioxidant capacity, potential toxicity, hypoglycemic, hypolipidemic, nephroprotective and hepatoprotective activities of this polyherbal mixture decoction. MATERIALS AND METHODS: The phytochemical composition was evaluated using HPLC-UV. The antioxidant activity was assessed using the DPPH test. Potential toxicity was evaluated using the acute and sub-chronic oral toxicity method. Diabetes was induced in Wistar female rats with a single intraperitoneal injection of alloxan monohydrate (150 mg/kg). The animals whose blood glucose was >20 mmol/L for 14 consecutive days were considered diabetic. For the next 14 days, D-10 and D-20 groups were treated with the polyherbal mixture (10 and 20 g of dry plant material/kg, respectively). I and M were control groups treated with insulin glargine (13 IU/kg) and metformin (150 mg/kg), respectively. Healthy control (HC) and diabetic control (DC) groups were treated with water. The blood glucose level was measured on days 14, 21 and 28. Lipid profile analysis was done on day 28. Pancreas, kidney and liver histopathology was evaluated using the H&E and Masson's trichrome staining. The liver tissue was additionally tested for PAS-positive cells. RESULTS: The HPLC-UV analysis revealed the presence of quinic, gallic and caftaric acid, arbutin, rutin, trifolin, astragalin, hyperoside, isoquercetin and quercitrin. The antioxidant activity of the extract was higher than the reference's one (p < 0.01). Treatment with the polyherbal mixture (10 and 20 g/kg) has shown no toxic effects. No major decline in blood sugar was recorded in I and M groups compared to the DC one (22.86 ±â€¯2.58, 28.5 ±â€¯0.42 and 27.82 ±â€¯0.9 mmol/L, respectively). The polyherbal mixture lowered the blood glucose level to the normal value (8.64 ±â€¯4.09, 5.26 ±â€¯1.3 and 6.76 ±â€¯1.54 mmol/L in D-10, D-20 and HC groups, respectively). Furthermore, it decreased the levels of total cholesterol, triglycerides, VLDL, LDL, atherogenic and cardiovascular risk indices (p < 0.001) compared to the DC group. In addition, the extract restored histopathological changes of the pancreas, kidneys and liver to the healthy animal level. CONCLUSION: Treatment with the polyherbal mixture extract was more effective than the standard drugs (insulin and metformin) in the amelioration of hyperglycemia, hyperlipidemia, and histopathological changes of the pancreas, kidney and liver tissue.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hipolipemiantes/farmacología , Extractos Vegetales/farmacología , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Femenino , Hiperglucemia/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Hipolipemiantes/aislamiento & purificación , Insulina/farmacología , Riñón/efectos de los fármacos , Riñón/patología , Hígado/efectos de los fármacos , Hígado/patología , Metformina/farmacología , Páncreas/efectos de los fármacos , Páncreas/patología , Plantas Medicinales/química , Ratas , Ratas Wistar
3.
Phytomedicine ; 80: 153395, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33137599

RESUMEN

BACKGROUND: Curcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS). OBJECTIVE: We hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS. METHODS: In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements. RESULTS: Of 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial. CONCLUSIONS: Curcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.


Asunto(s)
Glucemia/análisis , Curcumina/uso terapéutico , Resistencia a la Insulina , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Adolescente , Adulto , Andrógenos/sangre , Deshidroepiandrosterona/sangre , Suplementos Dietéticos , Método Doble Ciego , Femenino , Hirsutismo/tratamiento farmacológico , Humanos , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/etiología , Insulina/sangre , Persona de Mediana Edad , Placebos , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Resultado del Tratamiento , Adulto Joven
4.
Adv Exp Med Biol ; 1307: 129-152, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32266607

RESUMEN

Diabetes mellitus is constantly increasing worldwide. Vascular complications are the most common in the setting of long-standing disease, claiming the greatest burden in terms of morbidity and mortality. Glucotoxicity is involved in vascular damage through different metabolic pathways, such as production of advanced glycation end-products, activation of protein kinase C, polyol pathway activation and production of reactive oxygen species. Vascular complications can be classified according to the calibre of the vessels involved as microvascular (such as diabetic retinopathy, nephropathy and neuropathy) or macrovascular (such as cerebrovascular, coronary and peripheral artery disease). Previous studies showed that the severity of vascular complications depends on duration and degree of hyperglycaemia and, as consequence, early trials were designed to prove that intensive glucose control could reduce the number of vascular events. Unfortunately, results were not as satisfactory as expected. Trials showed good results in reducing incidence of microvascular complications but coronary heart diseases, strokes and peripheral artery diseases were not affected despite optimal glycemia control. In 2008, after the demonstration that rosiglitazone increases cardiovascular risk, FDA demanded stricter rules for marketing glucose-lowering drugs, marking the beginning of cardiovascular outcome trials, whose function is to demonstrate the cardiovascular safety of anti-diabetic drugs. The introduction of new molecules led to a change in diabetes treatment, as some new glucose-lowering drugs showed not only to be safe but also to ensure cardiovascular benefit to diabetic patients. Empaglifozin, a sodium-glucose cotransporter 2 inhibitor, was the first molecule to show impressing results, followed on by glucagon-like peptide 1 receptor agonists, such as liraglutide. A combination of anti-atherogenic effects and hemodynamic improvements are likely explanations of the observed reduction in cardiovascular events and mortality. These evidences have opened a completely new era in the field of glucose-lowering drugs and of diabetes treatment in particular with respect to vascular complications.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2 , Hiperglucemia , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico
5.
J Assoc Physicians India ; 68(12[Special]): 55-59, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33247665

RESUMEN

Both hyperglycemia and hypoglycemia in hospitalized patients represent a major concern as they are associated with adverse outcomes-including increased rates of infection, longer hospital stay, and even death. Insulin therapy is the mainstay in the management of inpatient hyperglycemia. The traditional approach of sliding scale insulin (SSI) therapy for the temporary management of blood glucose levels in hospitalized patients, has now given way to basal-bolus insulin (BBI) therapy. This is owing to the BBI affording a better glycemic control in non-critical hospital settings as observed in multiple clinical studies using insulin glargine 100 U/mL (Gla-100) as the basal component. Furthermore, a string of clinical studies has also attested to Gla-100 being used effectively even in patients on corticosteroids, enteral or parenteral nutrition, and in perioperative settings. Hence, overall, the existing evidence would point to the growing role of BBI regimens centering around basal insulin like Gla-100 as an effective option with low safety concerns for insulin therapy in both hospitalized and out-patient settings in the treatment of patients with type 2 diabetes mellitus (T2DM).


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Hipoglucemia , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hiperglucemia/tratamiento farmacológico , Hipoglucemia/inducido químicamente , Hipoglucemiantes , Insulina , Insulina Glargina
6.
Cochrane Database Syst Rev ; 10: CD004730, 2020 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-33075159

RESUMEN

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.


Asunto(s)
Fibrosis Quística/complicaciones , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Administración Oral , Sesgo , Glucemia/análisis , Carbamatos/administración & dosificación , Fibrosis Quística/sangre , Diabetes Mellitus/sangre , Diabetes Mellitus/etiología , Ayuno/sangre , Humanos , Hiperglucemia/tratamiento farmacológico , Insulina Glargina/administración & dosificación , Insulina Isófana/administración & dosificación , Piperidinas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto
8.
J Card Surg ; 35(10): 2759-2767, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32939829

RESUMEN

OBJECTIVES: Hyperglycemia is associated with an increased risk of adverse cardiovascular outcomes, such as heart failure, coronary heart disease, stroke, and in-hospital mortality. For those receiving cardiac surgery, up to half develop hyperglycemia while 30% have a diagnosis of diabetes, which is defined by chronic hyperglycemia. Due to a prothrombic state and endovascular damage, patients with diabetes have a twofold increased risk of cardiovascular events. METHODS: Electronic literature search was done to identify articles that have discussed antidiabetic medications and how it is impacting the glycemia status as well as cardiovascular outcomes. No limits were placed on timing of the publication or type of the article. Key words and MeSH terms were used to conduct the search and the results are summarized in a narrative manner within each relevant section. RESULTS: Antidiabetic medications play a key role in lowering blood glucose levels to reduce adverse cardiovascular outcomes. However, it is a challenge to assess their cardiovascular safety due to confounding factors, such as age, obesity, smoking, hyperlipidemia, and high blood pressure. Further research in this field is required to understand this correlation closely. CONCLUSION: Optimizing blood glucose level during the perioperative period with correct medication and dose have a significant role in reducing morbidities. Measures should be taken to provide a safe blood glucose level for optimum outcomes.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/cirugía , Complicaciones de la Diabetes/complicaciones , Diabetes Mellitus/tratamiento farmacológico , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Atención Perioperativa , Complicaciones Posoperatorias/prevención & control , Humanos , Riesgo , Resultado del Tratamiento
10.
Phytomedicine ; 78: 153319, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32950951

RESUMEN

BACKGROUND: Inflammation and oxidative stress play essential roles in the occurrence and progression of diabetic cardiomyopathy (DCM). Isoliquiritigenin (ISL), a natural chalcone, exhibits strong anti-inflammatory and antioxidant activities. HYPOTHESIS/PURPOSE: In this study, we aimed to investigate the protective effects of ISL on DCM using high glucose (HG)-challenged cultured cardiomyocytes and streptozotocin (STZ)-induced diabetic mice. STUDY DESIGN AND METHODS: Embryonic rat heart-derived H9c2 cells challenged with a high concentration of glucose were used to evaluate the anti-inflammatory and antioxidant effects of ISL. STZ-induced diabetic mice were used to study the effects of ISL in DCM in vivo. Furthermore, cardiac fibrosis, hypertrophy, and apoptosis were explored both in vitro and in vivo. RESULTS: ISL effectively inhibited HG-induced hypertrophy, fibrosis, and apoptosis probably by alleviating the inflammatory response and oxidative stress in H9c2 cells. Results from in vivo experiments showed that ISL exhibited anti-inflammatory and antioxidant stress activities that were characterized by the attenuation of cardiac hypertrophy, fibrosis, and apoptosis, which resulted in the maintenance of cardiac function. The protective effects of ISL against inflammation and oxidative stress were mediated by the inhibition of mitogen-activated protein kinases (MAPKs) and induction of nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, respectively. CONCLUSION: Our results provided compelling evidence that ISL, by virtue of neutralizing excessive inflammatory response and oxidative stress, could be a promising agent in the treatment of DCM. Targeting the MAPKs and Nrf2 signaling pathway might be an effective therapeutic strategy for the prevention and treatment of DCM.


Asunto(s)
Antioxidantes/farmacología , Chalconas/farmacología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/farmacología , Apoptosis/efectos de los fármacos , Cardiotónicos/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/fisiopatología , Glucosa/metabolismo , Glucosa/farmacología , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/fisiopatología , Masculino , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Estreptozocina
11.
Yonsei Med J ; 61(9): 780-788, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32882762

RESUMEN

PURPOSE: This research was designed to investigate how miR-542-5p regulates the progression of hyperglycemia and hyperlipoidemia. MATERIALS AND METHODS: An in vivo model with diabetic db/db mice and an in vitro model with forskolin/dexamethasone (FSK/DEX)-induced primary hepatocytes and HepG2 cells were employed in the study. Bioinformatics analysis was conducted to identify the expression of candidate miRNAs in the liver tissues of diabetic and control mice. H&E staining revealed liver morphology in diabetic and control mice. Pyruvate tolerance tests, insulin tolerance tests, and intraperitoneal glucose tolerance test were utilized to assess insulin resistance. ELISA was conducted to evaluate blood glucose and insulin levels. Red oil O staining showed lipid deposition in liver tissues. Luciferase reporter assay was used to depict binding between miR-542-5p and forkhead box O1 (FOXO1). RESULTS: MiR-542-5p expression was under-expressed in the livers of db/db mice. Further in vitro experiments revealed that FSK/DEX, which mimics the effects of glucagon and glucocorticoids, induced cellular glucose production in HepG2 cells and in primary hepatocytes cells. Notably, these changes were reversed by miR-542-5p. We found that transcription factor FOXO1 is a target of miR-542-5p. Further in vivo study indicated that miR-542-5p overexpression decreases FOXO1 expression, thereby reversing increases in blood glucose, blood lipids, and glucose-related enzymes in diabetic db/db mice. In contrast, anti-miR-542-5p exerted an adverse influence on blood glucose and blood lipid metabolism, and its stimulatory effects were significantly inhibited by sh-FOXO1 in normal control mice. CONCLUSION: Collectively, our results indicated that miR-542-5p inhibits hyperglycemia and hyperlipoidemia by targeting FOXO1.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Hiperglucemia/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , MicroARNs/genética , Animales , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Regulación de la Expresión Génica , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Células Hep G2 , Hepatocitos/metabolismo , Humanos , Hiperglucemia/metabolismo , Hiperlipidemias/metabolismo , Resistencia a la Insulina , Metabolismo de los Lípidos , Hígado/metabolismo , Ratones , MicroARNs/metabolismo , MicroARNs/farmacología
12.
Ugeskr Laeger ; 182(29)2020 07 13.
Artículo en Danés | MEDLINE | ID: mdl-32734864

RESUMEN

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome corona virus 2. High age, hypertension, diabetes, and obesity are risk factors for severe COVID-19 with increased mortality. In this review, we discuss potential mechanisms by which diabetes and obesity modulate the host viral interactions and host-immune response. Glucose levels should be monitored rigorously, and patient-tailored aggressive treatment of hyperglycaemia is recommended, often with the use of insulin. Persons with diabetes and obesity are susceptible to severe outcomes from COVID-19.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Diabetes Mellitus/virología , Interacciones Microbiota-Huesped , Obesidad/complicaciones , Neumonía Viral/complicaciones , Betacoronavirus , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Diabetes Mellitus/metabolismo , Sistema Endocrino , Humanos , Hiperglucemia/tratamiento farmacológico , Insulina/uso terapéutico , Obesidad/metabolismo , Obesidad/virología , Pandemias , Neumonía Viral/inmunología , Neumonía Viral/metabolismo , Factores de Riesgo
13.
PLoS One ; 15(8): e0237660, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32841254

RESUMEN

This study evaluated the influence of type 2 diabetes mellitus on bone loss, bone repair and cytokine production in hyperglycemic rats, treated or not with metformin. The animals were distributed as follow: Non-Hyperglycemic (NH), Non Hyperglycemic with Ligature (NH-L), Treated Non Hyperglycemic (TNH), Treated Non Hyperglycemic with Ligature Treated (TNH-L), Hyperglycemic (H), Treated Hyperglycemic (TH), Hyperglycemic with Ligature (H-L), Treated Hyperglycemic with Ligature (TH-L). At 40th day after induction of hyperglycemia, the groups NH-L, TNH-L, H-L, TH-L received a ligature to induce periodontitis. On the 69th, the TNH, TNH-L, TH, TH-L groups received metformin until the end of the study. Bone repair was evaluated at histometric and the expression levels of Sox9, RunX2 and Osterix. Analysis of the ex-vivo expression of TNF-α, IFN-γ, IL-12, IL-4, TGF-ß, IL-10, IL-6 and IL-17 were also evaluated. Metformin partially reverse induced bone loss in NH and H animals. Lower OPG/RANKL, increased OCN and TRAP expression were observed in hyperglycemic animals, and treatment with metformin partially reversed hyperglycemia on the OPG/RANKL, OPN and TRAP expression in the periodontitis. The expression of SOX9 and RunX2 were also decreased by hyperglycemia and metformin treatment. Increased ex vivo levels of TNF-α, IL-6, IL-4, IL-10 and IL-17 was observed. Hyperglycemia promoted increased IL-10 levels compared to non-hyperglycemic ones. Treatment of NH with metformin was able to mediate increased levels of TNF-α, IL-10 and IL-17, whereas for H an increase of TNF-α and IL-17 was detected in the 24- or 48-hour after stimulation with LPS. Ligature was able to induce increased levels of TNF-α and IL-17 in both NH and H. This study revealed the negative impact of hyperglycemia and/or treatment with metformin in the bone repair via inhibition of transcription factors associated with osteoblastic differentiation.


Asunto(s)
Pérdida de Hueso Alveolar/prevención & control , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Hiperglucemia/complicaciones , Metformina/administración & dosificación , Periodontitis/prevención & control , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/metabolismo , Proceso Alveolar/citología , Proceso Alveolar/efectos de los fármacos , Proceso Alveolar/metabolismo , Proceso Alveolar/patología , Animales , Regeneración Ósea/efectos de los fármacos , Regeneración Ósea/genética , Diferenciación Celular/efectos de los fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hiperglucemia/inducido químicamente , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/metabolismo , Osteoblastos/fisiología , Periodontitis/etiología , Periodontitis/metabolismo , Ratas , Estreptozocina/toxicidad , Factores de Transcripción/metabolismo
16.
Nihon Yakurigaku Zasshi ; 155(4): 214-219, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-32612031

RESUMEN

The peel of Citrus kawachiensis (Kawachi Bankan), a citrus species grown in Ehime, Japan, is abundant in auraptene. Auraptene, a coumarin compound, have been shown to exert anti-inflammatory effects in peripheral tissues, but it was still unclear of the effect in the brain. Hyperglycemia and brain ischemia induce inflammation and oxidative stress and cause massive damage in the brain; therefore, we examined the anti-inflammatory and other effects of the dried peel powder of C. kawachiensis and auraptene in a hyperglycemia and global cerebral ischemia models. The C. kawachiensis treatment inhibited astroglial activation in the hippocampus and the hyperphosphorylation of tau protein in hippocampal neurons, and also relieved the suppression of neurogenesis in the dentate gyrus of the hippocampus in the type 2 diabetic db/db mice. The C. kawachiensis treatment inhibited microglial and astroglial activation, and neuronal cell death in the hippocampus of transient global cerebral ischemia mice. It was suggested that the dried peel powder of C. kawachiensis exerts anti-inflammatory and neuroprotective effects in the brain. We attempted to demonstrate the effect of auraptene in the brains in streptozotocin-induced hyperglycemic mice and transient global cerebral ischemia mice. Auraptene administration showed the similar effects as the peel of C. kawachiensis in the hippocampus of these mice models. These results suggested that auraptene have potential effects as a neuroprotective agent in the peel of C. kawachiensis.


Asunto(s)
Isquemia Encefálica , Citrus , Hiperglucemia , Fármacos Neuroprotectores , Daño por Reperfusión , Animales , Isquemia Encefálica/tratamiento farmacológico , Cumarinas/farmacología , Hipocampo , Hiperglucemia/tratamiento farmacológico , Japón , Ratones , Ratones Obesos , Fármacos Neuroprotectores/farmacología
18.
Diabetes Metab Syndr ; 14(5): 947-948, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32599534

RESUMEN

There is a desperate need to explore different insulin administration strategies, particularly in coronavirus disease 2019 (COVID-19) patients with hyperglycemic crisis. Noteworthily, diabetes mellitus (DM) and poorly controlled blood glucose increase the risk of mortality and severity of COVID-19. Intravenous (IV) insulin administration with hourly monitoring of blood glucose is the ideal approach in managing patients with hyperglycemic crisis, but it is not judicious to be applied in developing countries where shortage of personal protective equipment (PPE) is a major issue. Furthermore, increasing the probability of "already greater risks" for doctors or other healthcare workers contracting COVID-19 seems inappropriate. Thus, an alternative administration strategy and more moderate glucose monitoring to reduce the contact exposure of healthcare workers with COVID-19 patients, by ensuring appropriate blood glucose levels, needs to be performed in this critical pandemic era. Subcutaneous (SC) rapid-acting insulin analog administration could presumably be a solution to this contentious issue.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Neumonía Viral/complicaciones , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Manejo de la Enfermedad , Humanos , Hiperglucemia/epidemiología , Hiperglucemia/virología , Inyecciones Subcutáneas , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología
19.
Pediatr Blood Cancer ; 67(9): e28475, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32589365

RESUMEN

BACKGROUND: Hyperglycemia is a complication of induction chemotherapy in 10%-50% of pediatric patients with acute lymphoblastic leukemia (ALL). Though hyperglycemia in ALL patients is usually transient, it may be associated with adverse health outcomes. However, the risk factors for and consequences of hyperglycemia are poorly understood. We hypothesized that hyperglycemia significant enough to require insulin therapy during induction chemotherapy would be associated with increased morbidity and mortality in pediatric ALL patients during induction chemotherapy and in subsequent care. METHODS: We abstracted clinical and resource utilization data from the Pediatric Health Information System (PHIS) database utilizing ICD-9 codes and medication charges. We used logistic regression analysis to predict the development of hyperglycemia. The effects of hyperglycemia on binary and count adverse outcomes following induction chemotherapy were modeled using mixed-effect regression models. RESULTS: An increased risk of hyperglycemia requiring insulin was associated with older age, female sex, higher risk group and trisomy 21. Patients on insulin for hyperglycemia had increased mortality following induction chemotherapy. These patients were more likely to have subsequent infectious complications, need for bone marrow transplant, and risk of disease relapse. They also had greater length of inpatient stay, higher cost of care, and were more likely to require intensive care unit admission during induction chemotherapy. CONCLUSIONS: Hyperglycemia requiring insulin during induction chemotherapy in pediatric ALL is associated with an increased risk of short-term and long-term complications. Prospective studies are needed to analyze formal screening, preventive measures, and optimal management practices for hyperglycemia during ALL induction chemotherapy.


Asunto(s)
Hiperglucemia , Quimioterapia de Inducción , Insulina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Niño , Preescolar , Costos y Análisis de Costo , Femenino , Humanos , Hiperglucemia/inducido químicamente , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/economía , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/economía , Lactante , Insulina/administración & dosificación , Insulina/economía , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/economía
20.
Eur J Clin Invest ; 50(7): e13262, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32383239

RESUMEN

The Covid-19 pandemic confronted us with unknown clinical pictures, also in diabetology and endocrinology. Sharing clinical experiences is therefore of enormous importance. Actually, information about the care given in the Covid-19 ward (in contrast to that provided in the Emergency Room/ICU) is still sparse. The last weeks we built experience and gathered knowledge while giving hospital care to patients who had a pre-existent endocrine disease (and diabetes; most patients suffered from a type two diabetes). In our contribution we presented our insights obtained from this intensive period obtained in the Covid-19 ward.


Asunto(s)
Infecciones por Coronavirus/terapia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Neumonía Viral/terapia , Insuficiencia Suprarrenal/complicaciones , Insuficiencia Suprarrenal/tratamiento farmacológico , Bélgica , Betacoronavirus , Glucemia/metabolismo , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/metabolismo , Complicaciones de la Diabetes , Diabetes Insípida/complicaciones , Diabetes Insípida/terapia , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Manejo de la Enfermedad , Hemoglobina A Glucada/metabolismo , Unidades Hospitalarias , Hospitalización , Humanos , Hiperglucemia/etiología , Hiperglucemia/metabolismo , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/metabolismo
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