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1.
BMJ ; 367: l5887, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690574

RESUMO

Diabetes is a major and costly health concern worldwide, with high morbidity, disability, mortality, and impaired quality of life. The vast majority of people living with diabetes have type 2 diabetes. Historically, the main strategy to reduce complications of type 2 diabetes has been intensive glycemic control. However, the body of evidence shows no meaningful benefit of intensive (compared with moderate) glycemic control for microvascular and macrovascular outcomes important to patients, with the exception of reduced rates of non-fatal myocardial infarction. Intensive glycemic control does, however, increase the risk of severe hypoglycemia and incurs additional burden by way of polypharmacy, side effects, and cost. Additionally, data from cardiovascular outcomes trials showed that cardiovascular, kidney, and mortality outcomes may be improved with use of specific classes of glucose lowering drugs largely independently of their glycemic effects. Therefore, delivering evidence based, patient centered care to people with type 2 diabetes requires a paradigm shift and departure from the predominantly glucocentric view of diabetes management. Instead of prioritizing intensive glycemic control, the focus needs to be on ensuring access to adequate diabetes care, aligning glycemic targets to patients' goals and situations, minimizing short term and long term complications, reducing the burden of treatment, and improving quality of life.


Assuntos
Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Qualidade de Vida , Glicemia/análise , Glicemia/efeitos dos fármacos , Complicações do Diabetes/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normas , Humanos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Incidência , Metanálise como Assunto , Assistência Centrada no Paciente/métodos , Assistência Centrada no Paciente/normas , Guias de Prática Clínica como Assunto , Revisão Sistemática como Assunto , Resultado do Tratamento
2.
J Agric Food Chem ; 67(45): 12472-12480, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31642672

RESUMO

Brown macroalgae are an important source of polyphenols with multiple health functions. In this work, polyphenol extracts from Lessonia trabeculate were purified and investigated for the antidiabetic activity in vitro and in vivo. The purified polyphenol extracts exhibited good antioxidant activities, α-glucosidase and lipase inhibition activities (IC50 < 0.25 mg/mL). The HPLC-DAD-ESI-MS/MS analysis indicated that the compounds in polyphenol extracts were mainly phlorotannin derivatives, phenolic acid derivatives, and gallocatechin derivatives. In vivo, C57BL/6J rats treated with polyphenol extracts for 4 weeks had lower fasting blood glucose levels, insulin levels, as well as better serum lipid profiles and antioxidant stress parameters, compared with the diabetic control (DC) group. Histopathology revealed that polyphenol extracts preserved the architecture and function of the liver. Short-chain fatty acid contents in rats' fecal samples with polyphenols administration were significantly recovered as compared with the DC group. Furthermore, the gut microflora of rats was investigated with high-throughput 16S rRNA gene sequencing and results indicated that polyphenol extracts had a positive effect on regulating the dysbiosis of the microbial ecology in diabetic rats. All of the results from the study provided a scientific reference of the potentially beneficial effects of L. trabeculate polyphenols on diabetes management.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Feófitas/química , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Alga Marinha/química , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiologia , Dieta Hiperlipídica/efeitos adversos , Humanos , Hiperglicemia/metabolismo , Hiperglicemia/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Ratos , Estreptozocina/efeitos adversos
3.
Nature ; 574(7776): 63-68, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31554967

RESUMO

The gp130 receptor cytokines IL-6 and CNTF improve metabolic homeostasis but have limited therapeutic use for the treatment of type 2 diabetes. Accordingly, we engineered the gp130 ligand IC7Fc, in which one gp130-binding site is removed from IL-6 and replaced with the LIF-receptor-binding site from CNTF, fused with the Fc domain of immunoglobulin G, creating a cytokine with CNTF-like, but IL-6-receptor-dependent, signalling. Here we show that IC7Fc improves glucose tolerance and hyperglycaemia and prevents weight gain and liver steatosis in mice. In addition, IC7Fc either increases, or prevents the loss of, skeletal muscle mass by activation of the transcriptional regulator YAP1. In human-cell-based assays, and in non-human primates, IC7Fc treatment results in no signs of inflammation or immunogenicity. Thus, IC7Fc is a realistic next-generation biological agent for the treatment of type 2 diabetes and muscle atrophy, disorders that are currently pandemic.


Assuntos
Receptor gp130 de Citocina/metabolismo , Citocinas/síntese química , Citocinas/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Ligação Competitiva , Citocinas/química , Diabetes Mellitus Tipo 2/metabolismo , Desenho de Drogas , Fígado Gorduroso/prevenção & controle , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Incretinas/metabolismo , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Masculino , Camundongos , Músculo Esquelético/efeitos dos fármacos , Obesidade/metabolismo , Pâncreas/metabolismo , Fosfoproteínas/metabolismo , Engenharia de Proteínas , Receptores de Interleucina-6/metabolismo , Transdução de Sinais , Fatores de Transcrição , Ganho de Peso/efeitos dos fármacos
5.
DNA Cell Biol ; 38(10): 1134-1142, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433203

RESUMO

Diabetes mellitus is a complicated metabolic disease characterized by hyperglycemia. Diabetic nephropathy (DN) is a progressive kidney disease, which results in mortality in diabetic patients. The present study was designed to investigate the effect of applying spironolactone (S), captopril (C), and their combination (S+C) on some renal performance indices and microRNAs' (miRNAs) expression. A total of 35 two-month-old male Wistar rats were provided for the study. Intraperitoneal injection of freshly dissolved streptozotocin (60 mg/kg) in cold citrate buffer was used to induce diabetes. Blood samples were examined through calorimetry to assess serum concentrations of glucose, blood urea nitrogen (BUN), and creatinine. To measure the microalbuminuria and transforming growth factor-ß (TGF-ß) levels and to evaluate the miRNAs expression levels of the kidney tissue, the ELISA method and the real-time PCR were used. The obtained results serve as in vivo evidence for the positive relationship between miR-192 and TGF-ß levels in the DN rats. A significant increase and decrease were found for miR-29a/b/c and the miR-192 expression of DN after treatment with S, C, and S+C. TGF-ß levels and microalbuminuria of diabetic rats also increased. The results obtained from this research study suggest that S, C, and S + C can improve DN by targeting miR-192 and miR-29 family and changing their expression. These findings suggest that miR-192 and miRs-29a/b/c can be potential targets for DN remediation.


Assuntos
Captopril/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Espironolactona/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Diuréticos/farmacologia , Combinação de Medicamentos , Reposicionamento de Medicamentos , Hiperglicemia/induzido quimicamente , Hiperglicemia/genética , Hiperglicemia/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Ratos , Ratos Wistar , Estreptozocina/administração & dosagem , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento
6.
Postgrad Med ; 131(7): 423-437, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382796

RESUMO

Hyperglycemia on hospital admission is a common phenomenon in acute ischemic stroke patients and represents an independent predictor of poor clinical outcome with or without acute recanalization therapies (systemic thrombolysis or mechanical thrombectomy). Effective restoration of normoglycemia is considered to be beneficial, but conclusive evidence from randomized controlled clinical trials and specific recommendations are lacking. In addition, aggressive glucose control can be complicated by hypoglycemia leading to early neurological deterioration. We conducted a systematic literature review with the aim of addressing several questions: timing of glucose control, target range, type of insulin delivery, duration and practicability of glucose-lowering protocols. Special issues regarding mechanical thrombectomy and glycemic variability can then be investigated in future trials which are also being considered.


Assuntos
Isquemia Encefálica/terapia , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Acidente Vascular Cerebral/terapia , Glicemia/metabolismo , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Hospitalização , Humanos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hipoglicemia/induzido quimicamente , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Trombectomia , Terapia Trombolítica
7.
J Sci Food Agric ; 99(15): 6981-6988, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31414473

RESUMO

BACKGROUND: Diabetes mellitus is a serious chronic disease, characterized by hyperglycemia. This study administered either ß-mannanase-treated yeast cell autolysis supernatant (YCS) or yeast cell-wall residues after autolysis (YCR) to investigate their influence on the alleviation of diabetes in a diabetic mouse model. RESULTS: Application of either YCS or YCR led to body weight gain, blood glucose reduction, and an improvement in lipid composition in the diabetic mice. Administration of YCS was more effective in inhibiting oxidative stress than YCR. The expression of PPARα and CPT1α was enhanced, improving lipid biosynthesis, and Trx1 and HIF-1-α genes were downregulated due to the activation of thioredoxin following the interventions, indicating that the processes of lipid metabolism and oxidative stress were heavily involved in the reduction of diabetic characteristics following the interventions. The current study revealed that consumption of YCR also led to a reduction in hyperglycemia, this being associated with its richness in mineral elements, such as chromium and selenium. CONCLUSION: This study may highlight the potential of both YCS and YCR as functional ingredients in dietary formula for improving diabetic syndromes. © 2019 Society of Chemical Industry.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Saccharomyces cerevisiae/química , beta-Manosidase/química , Animais , Biocatálise , Glicemia/metabolismo , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Suplementos Nutricionais/análise , Humanos , Hiperglicemia/genética , Hiperglicemia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos , Minerais/análise , Estresse Oxidativo/efeitos dos fármacos , PPAR alfa/genética , PPAR alfa/metabolismo
8.
JAMA ; 322(4): 326-335, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31334795

RESUMO

Importance: Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown. Objectives: To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke. Design, Setting, and Participants: The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria. Interventions: Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity. Results: Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 529 [46%] women, 920 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08], P = .55; unadjusted risk difference, -0.83% [95% CI, -5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]). Conclusions and Relevance: Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT01369069.


Assuntos
Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Acidente Vascular Cerebral/complicações , Idoso , Isquemia Encefálica/complicações , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hiperglicemia/complicações , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Infusões Intravenosas , Injeções Subcutâneas , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
9.
Plant Foods Hum Nutr ; 74(3): 430-435, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302831

RESUMO

The beneficial health effects of apple consumption are well known, however, little is known about the potential of its phenolic fractions to inhibit α-glucosidases and thereafter to treat diseases related to the carbohydrate metabolism, such as postprandial hyperglycemia and diabetes. In the present study, the α-glucosidase inhibition and antioxidant activity of different phenolic fractions of apple were evaluated using the 2,2-diphenyl-1-picrylhydrazyl and hydroxyl radical scavenging activity. Moreover, the phenolic fractions were chemically characterized by LC-MS in order to identify the compounds responsible for the biological properties. The purified extract (not fractionated) had the highest α-glucosidase and hydroxyl radical inhibitions. The purified extract and fractions III and IV were more active against the enzyme activity than the positive control acarbose, the drug used by diabetic patients to treat postprandial hyperglycaemia. Our results show that apple phenolic extracts strongly inhibit α-glucosidase acitivity, validating their potential to be used in the management of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/farmacologia , Hiperglicemia/tratamento farmacológico , Malus/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Metabolismo dos Carboidratos , Fenóis/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/isolamento & purificação , alfa-Glucosidases/metabolismo
10.
Medicine (Baltimore) ; 98(28): e16255, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305406

RESUMO

RATIONALE: Hemichorea-hemiballism, a rare manifestation of non-ketotic hyperglycemia, characterized by involuntary arrhythmic motions involving one side of the body, results from focal lesions in the contralateral caudate nucleus and putamen. Hyperkinetic disorders can be complications of uncontrolled diabetes mellitus and should not be ignored. PATIENT CONCERNS: We present the case of a 39-year-old woman who presented to the emergency department with a 3-day history of left-sided hemichorea-hemiballism. She had type 2 diabetes mellitus with poor control and maintenance of regular hemodialysis. DIAGNOSES: The patient was diagnosed as hyperglycemia, normal ketone body and hemichorea-hemiballism based on laboratory examination, computed tomography (CT) scan, and brain magnetic resonance image (MRI). INTERVENTIONS: Intensive glycemic control via insulin injection was prescribed for correction of hyperglycemia. OUTCOMES: The unilateral involuntary movements subsided progressively over four weeks. The patient's hemichorea had completely resolved at the three-month follow-up. LESSONS: This unusual clinical presentation is often accompanied by severe hyperglycemia. Appropriate blood glycemic control is important. If physicians recognize and provide early treatment for this disease, it is usually treatable and has a good prognosis.


Assuntos
Coreia/complicações , Diabetes Mellitus Tipo 2/complicações , Discinesias/complicações , Hiperglicemia/complicações , Adulto , Coreia/diagnóstico , Coreia/tratamento farmacológico , Coreia/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Diagnóstico Diferencial , Discinesias/diagnóstico , Discinesias/tratamento farmacológico , Discinesias/fisiopatologia , Feminino , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia
11.
Phytother Res ; 33(7): 1921-1933, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31183921

RESUMO

This study evaluated the potential effectiveness of different doses of Eriomin® on hyperglycemia and insulin resistance associated with other metabolic biomarkers in prediabetic individuals. Prediabetes patients (n = 103, 49 ± 10 years) were randomly divided into four parallel groups: (a) Placebo; (b) Eriomin 200 mg; (c) Eriomin 400 mg; and (d) Eriomin 800 mg. Assessment of biochemical, metabolic, inflammatory, hepatic, renal, anthropometric markers, blood pressure, and dietary parameters were performed during 12 weeks of intervention. Treatment with all doses of Eriomin (200, 400, and 800 mg) had similar effects and altered significantly the following variables: blood glucose (-5%), insulin resistance (-7%), glucose intolerance (-7%), glycated hemoglobin (-2%), glucagon (-6.5%), C-peptide (-5%), hsCRP (-12%), interleukin-6 (-13%), TNFα (-11%), lipid peroxidation (-17%), systolic blood pressure (-8%), GLP-1 (+15%), adiponectin (+19%), and antioxidant capacity (+6%). Eriomin or placebo did not influence the anthropometric and dietary variables. Short-term intervention with Eriomin, at doses of 200, 400, or 800 mg/day, benefited glycemic control, reduced systemic inflammation and oxidative stress, and reversed the prediabetic condition in 24% of the evaluated patients.


Assuntos
Flavanonas/uso terapêutico , Hesperidina/uso terapêutico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Estado Pré-Diabético/tratamento farmacológico , Adulto , Glicemia/metabolismo , Citrus , Método Duplo-Cego , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Nanoscale ; 11(21): 10167-10171, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31112182

RESUMO

We have introduced a non-hormonal hyperglycemia treatment strategy by using an injectable glucose-responsive boronic acid- zwitterionic nanogel. The synthesized system, similar to an artificial liver, is capable of storing/releasing glucose at high/low blood glucose concentrations. In vivo performance revealed that the injection of the nanogels can effectively regulate blood glucose in type 1 diabetic rats for at least 6 hours.


Assuntos
Betaína/análogos & derivados , Glicemia/metabolismo , Ácidos Borônicos , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hiperglicemia , Nanoestruturas , Animais , Betaína/síntese química , Betaína/química , Betaína/farmacologia , Ácidos Borônicos/síntese química , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Géis , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Masculino , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Ratos , Ratos Sprague-Dawley
13.
Life Sci ; 230: 10-18, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31121175

RESUMO

AIMS: The evidence suggests that the hyperglycemia and hyperinsulinemia of diabetes mellitus (DM) are risk factors for the development of hepatocellular carcinoma (HCC). The aim of the present study was to examine the effect of streptozotocin (STZ)-induced DM on promoting diethylnitrosamine (DEN) induced HCC in male wistar rats. Further, we investigated the administration of (α)-and (ß)-asarone and metformin HCl on experimentally induced diabetic-hepatocellular carcinoma. MATERIALS AND METHODS: Diabetes was induced by single dose of STZ (55 mg/2 ml/kg b.w. i.p.) and HCC by single dose of DEN (200 mg/ml/kg b.w. i.p.). Another group received the STZ followed by DEN two weeks later to mimic diabetic-HCC. The combined dose of (α)-and (ß)-asarone (50 µg/1.5 ml/kg b.w. p.o. in the ratio of 1:1) and metformin HCl (250 mg/1.5 ml/kg b.w. p.o.) treatment was compared with the STZ + DEN group. The blood and liver samples were collected at the end of 12 and 18-weeks to study biochemical and histopathological changes in liver. KEY FINDINGS: The STZ induced diabetes promoted the tumor progression due to administration of DEN. The treatment of asarones and metformin significantly reduced the levels of glucose, glycosylated hemoglobin, liver dysfunction markers and tumor biomarkers along with an increase in level of insulin when compared to diabetic-HCC group. Histopathological examination indicated that asarones and metformin attenuate the inflammation, fibrosis, cirrhosis and development of spontaneous HCC. SIGNIFICANCE: The STZ can be used to promote the DEN induced HCC. Treatment with (α)-and (ß)-asarone attenuates the effect of STZ + DEN induced HCC akin to metformin.


Assuntos
Anisóis/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Metformina/farmacologia , Animais , Anisóis/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Dietilnitrosamina , Modelos Animais de Doenças , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Fígado/efeitos dos fármacos , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Metformina/metabolismo , Ratos , Ratos Wistar
14.
Horm Metab Res ; 51(5): 288-295, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31071733

RESUMO

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of calcium-vitamin D co­supplementation on insulin, insulin sensitivity, and glycemia. A systematic search was carried out in Web of Science, PubMed, EMBASE, Scopus, and Cochrane library without any language and time restriction up to 12 August 2018, to retrieve the RCTs, which examined the effect of calcium and vitamin D co-supplementation on fasting blood glucose (FBG), insulin, HOMA-B, HOMA-IR, and QUICKI. Meta-analyses were carried out using a random effects model, and I2 indexes were used to evaluate the heterogeneity. Search yielded 2225 publications. Twelve RCTs with 4395 patients were eligible. Results demonstrated that calcium and vitamin D co­supplementation had significantly reducing effects on FBG, HOMA-IR and circulating levels of insulin. As the subgroup analysis demonstrated, short-term (≤12 weeks) calcium and vitamin D co­supplementation had a significant reducing effect on FBG. However, beneficial effects of calcium and vitamin D co­supplementation on circulating level of insulin and HOMA-IR were seen in both short-term and long-term (>12 weeks) supplementations. Furthermore, we found that high doses of vitamin D and calcium co-supplementation (vitamin D≥2000 mg/day and calcium≥1000 mg/day) had significantly reducing effects on FBG, HOMA-IR and insulin. Present meta-analysis indicated the beneficial effects of high-dose and short-term combined vitamin D and calcium supplementation on insulin, insulin resistance and glycemia; however, further large-scale RCTs with adequate and multiple dosing schedules are needed.


Assuntos
Cálcio/uso terapêutico , Suplementos Nutricionais , Hiperglicemia/tratamento farmacológico , Resistência à Insulina , Insulina/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/uso terapêutico , Glicemia/metabolismo , Jejum/sangue , Humanos , Viés de Publicação
15.
Int J Mol Sci ; 20(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126115

RESUMO

Vascular risk factors, such as type 2 diabetes mellitus (T2DM), are associated with the increased risk of Alzheimer's disease. One of the common T2DM medications, dipeptidyl peptidase (DPP)-4 inhibitors, have a minimum risk for hypoglycemia and have recently been suggested to ameliorate ß-amyloid pathology. However, conflicting results have been reported regarding the effects of DPP-4 inhibition on cognitive function and tau pathology. Thus, we investigated whether inhibiting DPP-4 affects tau pathology and cognition in a mouse model of tauopathy with hyperglycemia. Male mice overexpressing the P301S mutant human microtubule-associated protein tau gene (PS19) were fed either a low or high-fat diet. PS19 mice were then administered either linagliptin, a DPP-4 inhibitor, or vehicle, from 6 weeks to 8 months of age. Linagliptin-treated mice exhibited higher levels of glucagon-like peptide-1 and decreased fasting blood glucose, compared with the vehicle-treated mice at 8 months. Linagliptin treatment significantly restored spatial reference memory and increased cerebral blood flow without affecting phosphorylation levels of tau or endothelial nitric oxide synthase (eNOS) in the brain. Linagliptin may ameliorate HFD-induced cognitive worsening in tauopathy, at least partially, by increasing cerebral perfusion via the eNOS-independent pathway.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Linagliptina/uso terapêutico , Tauopatias/tratamento farmacológico , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Humanos , Hiperglicemia/complicações , Hiperglicemia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tauopatias/complicações , Tauopatias/patologia
16.
BMC Res Notes ; 12(1): 207, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30947749

RESUMO

OBJECTIVE: Contemporary clinical guidelines endorsed that glycemic control is the ultimate goal in the management patients with diabetes. The aim of this study was to assess the prevalence of glycemic control and to identify predictors of poor glycemic control in patients with type 2 diabetes (T2D). A cross-sectional study was conducted among systematically selected 357 diabetic patients. Data were collected through direct patients' interviews and medical chart review. Binary logistic regression analyses were performed and analyzed using SPSS version 22.0. RESULTS: Participants' mean age was (± SD) 56.1 ± 11.6 years. Nearly four in five (77.9%) of the participants had comorbidities, mainly of hypertension, and 60.2% had diabetic complications, mainly diabetes neuropathy. Poor glycemic control was found in 68.3% of the participants with a mean (± SD) FBG of 174.1 ± 48.9 mg/dL. Being female gender, having greater body mass index and low medication adherence was significantly associated with poor glycemic control. In conclusion, the overall aspects of glycemic control level of patients were far from the standards. Being female, greater body mass index and poor medication adherence were predictors of poor glycemic control. In response to this finding, an aggressive intervention that targets in improving the glycemic control is required.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Neuropatias Diabéticas/diagnóstico , Hiperglicemia/diagnóstico , Hipertensão/diagnóstico , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/fisiopatologia , Etiópia , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Modelos Logísticos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Fatores Sexuais , Atenção Terciária à Saúde
17.
Int J Biol Macromol ; 131: 1162-1170, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30974142

RESUMO

Diabetes is a complicated endocrine and metabolic disorder, which has become an epidemic health issue worldwide. Fucoidan is extensively distributed in the brown algae and several marine invertebrates exhibiting diverse biological activities. In the present study, the physicochemical property of Sargassum fusiforme fucoidan (SFF) and its effects on streptozotocin (STZ)-induced diabetic mice and gut microbiota were investigated. Diabetes mice not only showed abnormal blood glucose, but also accompanied by multiple symptoms, such as gradual emaciation, decreased body weight, increased food and water intake. Compared with diabetic mice after 6-week treatment, administration of SFF significantly decreased the fasting blood glucose, diet and water intake. Furthermore, SFF attenuated the pathological change in the heart and liver, improved the liver function, and suppressed oxidative stress in STZ-induced diabetic mice. Simultaneously, SFF significantly altered the gut microbiota in the faeces of diabetic mice, decreased the relative abundances of the diabetes-related intestinal bacteria, which is a potential mechanism for relieving the symptoms of diabetes. Therefore, SFF might be considered as one of the promising complementary and alternative medicines for the management of diabetes mellitus in future.


Assuntos
Glicemia/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/etiologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Sargassum/química , Animais , Fenômenos Químicos , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Hiperglicemia/tratamento farmacológico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Metagenoma , Metagenômica/métodos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Análise Espectral , Estreptozocina/efeitos adversos , Transcriptoma
18.
Wien Klin Wochenschr ; 131(Suppl 1): 27-38, 2019 May.
Artigo em Alemão | MEDLINE | ID: mdl-30980148

RESUMO

Hyperglycemia significantly contributes to complications in patients with diabetes mellitus. While lifestyle interventions remain cornerstones of disease prevention and treatment, most patients with type 2 diabetes will eventually require pharmacotherapy for glycemic control. The definition of individual targets regarding optimal therapeutic efficacy and safety as well as cardiovascular effects is of great importance. In this guideline we present the most current evidence-based best clinical practice data for healthcare professionals.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2 , Hipoglicemiantes/uso terapêutico , Guias de Prática Clínica como Assunto , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperglicemia/tratamento farmacológico , Estilo de Vida
19.
BMC Res Notes ; 12(1): 212, 2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30961663

RESUMO

OBJECTIVE: To assess the self-care practices and associated factors among diabetic patients in West Ethiopia. RESULTS: A total of 252 study participants were included in the study, of this 54.8% were male. Of the participants more than half 150 (59.5%) had poor glycemic control and 153 (60.7%) of the participants had good self-care. Majority of the study participants 209 (82.9%) had adequate foot care and more than half 175 (69.4%) and 160 (63.5%) had adequate dietary plan and exercise management respectively. However of the total diabetic patients only 38 (15.1%) had adequate blood glucose testing practices. On multivariable logistic analysis poor self-care practices were more likely to occur among male patients (AOR = 5.551, 95% CI = 2.055-14.997, p = 0.001), patients living in rural area (AOR = 5.517, 95% CI = 2.184-13.938, p < 0.001), patients with duration of diabetes < 6 years (AOR = 41.023, 95% CI = 7.373-228.257, p < 0.001), patients with no access for self-monitoring blood glucose (AOR = 9.448, 95% CI = 2.198-40.617, p = 0.003), patients with poor knowledge about diabetes (AOR = 67.917, 95% CI = 8.212-561.686, p < 0.001) and patients with comorbidities (AOR = 18.621, 95% CI = 4.415-78.540, p < 0.001).


Assuntos
Automonitorização da Glicemia/estatística & dados numéricos , Diabetes Mellitus Tipo 2/diagnóstico , Conhecimentos, Atitudes e Prática em Saúde , Hiperglicemia/diagnóstico , Hipoglicemiantes/uso terapêutico , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Etiópia , Feminino , Educação em Saúde/estatística & dados numéricos , Humanos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia , Modelos Logísticos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Fatores Sexuais , Inquéritos e Questionários
20.
Biomed Res Int ; 2019: 2835152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984778

RESUMO

Traditionally, in many countries, various parts of the Adansonia digitata (A. digitata) tree have been used in the treatment of many clinical ailments including diarrhea and dysentery. The phytochemical screening has indicated that the leaf extract of A. digitata contains flavonoids, saponins, mucilage, steroids, and alkaloids. Thus, this paper aims to evaluate the hyperglycaemic and hypolipidaemic effects of methanolic extract of A. digitata leaves (200 mg/kg and 400 mg/kg) in diabetic rats. The extract was administered orally for six weeks in the streptozotocin (STZ)-induced diabetic rats. The treatment with the extract caused a significant reduction in the blood glucose, glycosylated hemoglobin, cholesterol, triglycerides, low-density lipoprotein (LDL), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) levels by 46.7%, 46.15%, 48.91%, 43%, 60%, 66%, 45.45%, and 30.4%, respectively, as compared to the diabetic group after the sixth week of treatment. The leaf extract also mitigated the decline of high-density lipoprotein (HDL) level, RBCs count, hemoglobin level, packed cell volume (PCV %), and erythropoietin concentration in diabetic rats by 31%, 33.25%, 24.72%, 51.42%, and 220.68% with respect to the diabetic group. Also, the extract maintained the level of antioxidant enzymes, catalase (CAT) and superoxide dismutase (SOD), and reduced glutathione (GSH) in the diabetic rats. It also reduced the elevation in the white blood corpuscles (WBC) count in the STZ-induced diabetic rats. Our study, therefore, indicates that methanolic extract of A. digitata leaf exerts strong antidiabetic and hypolipidaemic properties in a dose-dependent manner by improving the hematological properties and redox parameters in the experimental diabetic rats.


Assuntos
Adansonia/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Glicemia/efeitos dos fármacos , Catalase/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Humanos , Hiperglicemia/sangue , Hiperglicemia/patologia , Hiperlipidemias/sangue , Hiperlipidemias/patologia , Hipoglicemiantes/administração & dosagem , Interleucina-6/sangue , Malondialdeído/sangue , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos , Superóxido Dismutase/sangue , Fator de Necrose Tumoral alfa/sangue
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