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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
3.
Life Sci ; 235: 116858, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31505195

RESUMO

AIMS: The current study was conducted to investigate the potential protective effects of hesperidin and its possible mechanisms of action on pancreatic ß-cells in diabetes. MAIN METHODS: Male Sprague Dawley rats were made diabetic using 65 mg/kg intraperitoneal injection of streptozotocin, and then administered daily with 100 mg/kg of hesperidin over 4 weeks. On conclusion of the experiment, blood and pancreatic tissue were collected to determine the function of ß-cells, apoptosis, oxidative stress, ER stress, and inflammation. KEY FINDINGS: Treatment of diabetic rats with hesperidin, significantly decreased fasting blood glucose and food intake, along with increased body weight, serum and pancreatic insulin levels, and pancreatic-duodenal homeobox-1 (PDX-1) protein expression. The beneficial roles of hesperidin on diabetic pancreatic ß-cells exhibited an increment in antioxidant SOD and GPx activities, and a decrement in nitrotyrosine as well as malondialdehyde (MDA) levels. Additionally, the elevated concentration of TNF-α and expressions of ER stress maker GRP78 and CHOP proteins in the pancreas of diabetic rats were significantly diminished by hesperidin treatment. Furthermore, hesperidin effectively modulated expressions of apoptosis-regulatory proteins in diabetic rat pancreas, as revealed by upregulating anti-apoptotic Bcl-xL; with a concomitant downregulating pro-apoptotic Bax, cleaved caspase-3, and inhibiting the activation of DNA repair protein poly (ADP-ribose) polymerase (PARP). SIGNIFICANCE: Collectively, these findings suggest that hesperidin may have the potential to protect pancreatic ß-cells and improve their function by suppressing oxidative and ER stress, along with activating its antioxidant, anti-inflammatory, and anti-apoptotic effects.


Assuntos
Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hesperidina/farmacologia , Células Secretoras de Insulina/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Ingestão de Alimentos/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Homeodomínio/biossíntese , Inflamação , Insulina/sangue , Insulina/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Superóxido Dismutase/metabolismo , Transativadores/biossíntese , Fator de Transcrição CHOP/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo
4.
Medicine (Baltimore) ; 98(36): e17081, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490412

RESUMO

OBJECTIVE: The purpose of this study was to assess the efficacy and hypoglycemic risk of sitagliptin versus that of GLP-1 receptor agonists in the management of obese/overweight patients with T2DM. METHODS: EMBASE, PubMed, Cochrane Library, and ClinicalTrials.gov were searched; randomized controlled trials comparing the efficacy of sitagliptin versus that of GLP-1 receptor agonists in obese/overweight patients with T2DM were included. The mean BMI of participants for each study was ≥30 kg/m. We conducted a meta-analysis according to the methods specified in the Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.1 software was used to perform the meta-analysis. The Cochrane Q test and I statistics were used to estimate the heterogeneity among studies. The results are expressed as the mean difference (MD) or risk ratio (RR) with 95% confidence intervals. RESULTS: A total of 8 eligible studies were included in our meta-analysis. Compared with GLP-1 receptor agonists, sitagliptin was less effective at reducing HbA1c (0.42 [0.27, 0.56]), FPG (0.78 [0.36, 1.19]), PPG (2.61 [1.35, 3.87]), and body weight (1.42 [0.71, 2.14]). Conversely, there were no significant differences in SBP reduction (0.38 [-1.14, 1.89]), DBP reduction (-0.30 [-1.00, 0.39]), and hypoglycemic risk (1.09 [0.50, 2.35]). CONCLUSION: For obese/overweight patients, sitagliptin may exert a less potent effect on HbA1C, FPG, PPG, and weight reduction than GLP-1 receptor agonists, but these drugs had a similar efficacy in reducing blood pressure; furthermore, there was no significant difference in hypoglycemic risk.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Obesidade/complicações , Fosfato de Sitagliptina/uso terapêutico , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/farmacologia , Fosfato de Sitagliptina/farmacologia
5.
Arch Endocrinol Metab ; 63(4): 376-384, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365624

RESUMO

OBJECTIVE: To test the influence of oral fructose and glucose dose-response solutions in blood glucose (BG), glucagon, triglycerides, uricaemia, and malondialdehyde in postprandial states in type 1 diabetes mellitus (T1DM) patients. SUBJECTS AND METHODS: The study had a simple-blind, randomized, two-way crossover design in which T1DM patients were selected to receive fructose and glucose solutions (75g of sugars dissolved in 200 mL of mineral-water) in two separate study days, with 2-7 weeks washout period. In each day, blood samples were drawn after 8h fasting and at 180 min postprandial to obtain glucose, glucagon, triglycerides, uric acid, lactate, and malondialdehyde levels. RESULTS: Sixteen T1DM patients (seven men) were evaluated, with a mean age of 25.19 ± 8.8 years, a mean duration of disease of 14.88 ± 4.73 years, and glycated hemoglobin of 8.13 ± 1.84%. Fructose resulted in lower postprandial BG levels than glucose (4.4 ± 5.5 mmol/L; and 12.9 ± 4.1 mmol/L, respectively; p < 0.01). Uric acid levels increased after fructose (26.1 ± 49.9 µmol/L; p < 0.01) and reduced after glucose (-13.6 ± 9.5 µmol/L; p < 0.01). The malondialdehyde increased after fructose (1.4 ± 1.6 µmol/L; p < 0.01) and did not change after glucose solution (-0.2 ± 1.6 µmol/L; p = 0.40). Other variables did not change. CONCLUSIONS: Fructose and glucose had similar sweetness, flavor and aftertaste characteristics and did not change triglycerides, lactate or glucagon levels. Although fructose resulted in lower postprandial BG than glucose, it increased uric acid and malondialdehyde levels in T1DM patients. Therefore it should be used with caution. ClinicalTrials.gov registration: NCT01713023.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Frutose/metabolismo , Glucose/metabolismo , Período Pós-Prandial/efeitos dos fármacos , Edulcorantes/metabolismo , Adolescente , Adulto , Glicemia/análise , Glicemia/efeitos dos fármacos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Feminino , Frutose/farmacologia , Glucose/farmacologia , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Projetos Piloto , Método Simples-Cego , Soluções/farmacologia , Edulcorantes/farmacologia , Paladar/efeitos dos fármacos , Triglicerídeos/sangue , Ácido Úrico/sangue , Adulto Jovem
6.
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
7.
Rev Med Suisse ; 15(659): 1426-1430, 2019 Aug 21.
Artigo em Francês | MEDLINE | ID: mdl-31436057

RESUMO

Type 1 diabetes (T1D) management is still complex. Some drugs have been proposed as adjunctive treatment to insulin for type 1 diabetes but results are not encouraging. Sodium-glucose cotransporter 2 (SGLT2) inhibitors act independently of insulin and initial proof-of-concept studies related to their use in T1D led to larger phase 3 trials. Several trials have demonstrated some beneficial and consistent effects as HbA1c, body weight and insulin dose reductions, and lesser glycaemic excursions. Nevertheless, adverse events were also reported, especially a higher rate of diabetic ketoacidosis when using gliflozins in T1D. Balance between positive and negative effects must be carefully studied in the near future with data from real-life and large trials dedicated to this potential new help in T1D.


Assuntos
Diabetes Mellitus Tipo 1 , Inibidores do Transportador 2 de Sódio-Glicose , Glicemia/efeitos dos fármacos , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cetoacidose Diabética/induzido quimicamente , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
8.
Medicine (Baltimore) ; 98(35): e17008, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464958

RESUMO

Urinary kallidinogenase may assist recovery acute ischemic stroke. This study evaluated the effect of urinary kallidinogenase on National Institute of Health Stroke Scale (NIHSS) score, modified Rankin scale (mRS) score, and fasting glucose levels in patients with acute ischemic stroke (AIS) combined with diabetes mellitus and impaired fasting glucose.Patients with AIS and abnormal glucose metabolism were enrolled in this prospective cohort study and divided into 2 groups. The human urinary kallidinogenase (HUK) group were treated with urinary kallidinogenase and standard treatment; the control group received standard treatment. NIHSS scores, mRS scores, and fasting blood glucose were evaluated and compared.A total of 113 patients were included: 58 in the HUK group and 55 in the control group. NIHSS scores decreased with treatment in both groups (time effect P < .05), but were lower in the HUK group (main effect P = .026). The mRS score decreased in both groups from 10 until 90 days after treatment (time effect P < .05); the 2 groups were similar (main effect, P = .130). Blood glucose levels decreased in both groups 10 days after treatment (time effect, P < .05), but there was no significant treatment effect (main effect, P = .635). Multivariate analysis showed blood uric acid >420 µmol/L (odds ratio [OR]: 0.053, 95% confidence interval [CI]: 0.008-0.350; P = .002) and application of HUK (OR: 0.217, 95% CI: 0.049-0.954; P = .043) were associated with 90% NIHSS recovery. Baseline NIHSS score was independently associated with poor curative effect.Urinary kallidinogenase with conventional therapy significantly improved NIHSS scores in patients with AIS. Urinary kallidinogenase also showed a trend toward lower fasting blood glucose levels, although the level did not reach significance.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Calicreínas Teciduais/uso terapêutico , Adulto , Idoso , Glicemia/efeitos dos fármacos , Isquemia Encefálica/etiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Feminino , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia
9.
BMJ ; 366: l4894, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462492

RESUMO

OBJECTIVE: To evaluate if the lowest target level for glycated haemoglobin (HbA1c) of <6.5% is associated with lower risk for retinopathy and nephropathy than less tight control in children and adults with type 1 diabetes. DESIGN: Population based cohort study. SETTING: Swedish National Diabetes Registry, 1 January 1998 to 31 December 2017. PARTICIPANTS: 10 398 children and adults with type 1 diabetes followed from diagnosis, or close thereafter, until end of 2017. MAIN OUTCOME MEASURES: Relative risk (odds ratios) for retinopathy and nephropathy for different mean levels of HbA1c. RESULTS: Mean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years, and mean HbA1c level was 8.0% (63.4 mmol/mol). After adjustment for age, sex, duration of diabetes, blood pressure, blood lipid levels, body mass index, and smoking, the odds ratio for mean HbA1c <6.5% (<48 mmol/mol) compared with 6.5-6.9% (48-52 mmol/mol) for any retinopathy (simplex or worse) was 0.77 (95% confidence interval 0.56 to 1.05, P=0.10), for preproliferative diabetic retinopathy or worse was 3.29 (0.99 to 10.96, P=0.05), for proliferative diabetic retinopathy was 2.48 (0.71 to 8.62, P=0.15), for microalbuminuria or worse was 0.98 (0.60 to 1.61, P=0.95), and for macroalbuminuria was 2.47 (0.69 to 8.87, P=0.17). Compared with HbA1c levels 6.5-6.9%, HbA1c levels 7.0-7.4% (53-57 mmol/mol) were associated with an increased risk of any retinopathy (1.31, 1.05 to 1.64, P=0.02) and microalbuminuria (1.55, 1.03 to 2.32, P=0.03). The risk for proliferative retinopathy (5.98, 2.10 to 17.06, P<0.001) and macroalbuminuria (3.43, 1.14 to 10.26, P=0.03) increased at HbA1c levels >8.6% (>70 mmol/mol). The risk for severe hypoglycaemia was increased at mean HbA1c <6.5% compared with 6.5-6.9% (relative risk 1.34, 95% confidence interval 1.09 to 1.64, P=0.005). CONCLUSIONS: Risk of retinopathy and nephropathy did not differ at HbA1c levels <6.5% but increased for severe hypoglycaemia compared with HbA1c levels 6.5-6.9%. The risk for severe complications mainly occurred at HbA1c levels >8.6%, but for milder complications was increased at HbA1c levels >7.0%.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Hemoglobina A Glicada/análise , Hipoglicemia/complicações , Adolescente , Adulto , Glicemia/análise , Glicemia/efeitos dos fármacos , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Retinopatia Diabética/sangue , Retinopatia Diabética/etiologia , Feminino , Seguimentos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologia , Adulto Jovem
10.
Internist (Berl) ; 60(9): 903-911, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31375850

RESUMO

BACKGROUND: Inhibitors of sodium-glucose cotransporters type 2 (SGLT-2) are a class of oral antidiabetic drugs with a novel specific mode of action in the kidneys. OBJECTIVE: The effects of SGLT-2 inhibitors on cardiovascular (CV) and renal endpoints in outcome trials with type 2 diabetes patients. MATERIAL AND METHODS: Differential analysis and interpretation of the results of outcome trials with the SGLT-2 inhibitors empagliflozin, canagliflozin and dapagliflozin in type 2 diabetes mellitus. RESULTS: In the EMPA-REG OUTCOME trial, empagliflozin demonstrated a significant reduction in major cardiac adverse events (MACE), hospitalization for heart failure (HHI), renal endpoints, CV and total mortality vs. placebo in >7000 patients with type 2 diabetes and established CV disease over 3.1 years. In the CANVAS program, canagliflozin demonstrated a significant reduction of MACE, HHI and renal endpoints vs. placebo in >10,000 patients with type 2 diabetes and high CV risk over 2.4 years. In the CREDENCE trial, canagliflozin demonstrated a significant reduction of a combined renal endpoint and CV endpoints vs. placebo in >4000 patients with type 2 diabetes and established kidney disease with albuminuria over 2.6 years. In the DECLARE-TIMI 58 trial, dapagliflozin demonstrated a significant reduction in a combined endpoint of CV death and HHI vs. placebo in >17,000 patients with type 2 diabetes and established CV disease or with multiple CV risk factors over 3.1 years. CONCLUSION: Outcome trials with SGLT-2 inhibitors have collectively demonstrated cardioprotective and nephroprotective effects in patients with type 2 diabetes and high CV risk. The use of SGLT-2 inhibitors is recommended in current guidelines and consensus statements as primary combination partners for metformin in patients with type 2 diabetes and established CV disease, high CV risk, heart failure or kidney disease.


Assuntos
Canagliflozina/uso terapêutico , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Nefropatias/fisiopatologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Avaliação de Resultados (Cuidados de Saúde) , Guias de Prática Clínica como Assunto , Transportador 2 de Glucose-Sódio/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Resultado do Tratamento
11.
Expert Opin Investig Drugs ; 28(9): 741-747, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31398075

RESUMO

Introduction: Type 2 diabetes is a complex metabolic disorder defined by hyperglycemia which occurs because of impaired insulin secretion and sensitivity. There is an ongoing need to develop novel therapies that are effective and safe with minimal side effects and long-term durability. TTP399 is a hepatoselective, glucokinase activator with potential for treating type 2 diabetes. Areas covered: This is a review of the available data regarding the mechanism of action and the pharmacokinetics of TTP399. The efficacy and safety of the drug for treatment of type 2 diabetes will also be examined with an emphasis on the results of a randomized, controlled phase 2 study. Expert opinion: TTP399 could offer significant advantages over currently available therapies for type 2 diabetes. It successfully lowers glucose without side effects such as hypoglycemia, weight gain or dyslipidemia. Larger trials are required to understand long-term efficacy and safety of this medication in various patient populations and to elucidate its effect on the pathologic processes underpinning type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Glucoquinase/efeitos dos fármacos , Glucoquinase/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Fígado/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Medicine (Baltimore) ; 98(30): e16575, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348290

RESUMO

BACKGROUND: Dapagliflozin, a novel inhibitor of sodium-glucose cotransporter-2 (SGLT-2), lowers blood glucose level by specifically inhibiting the activity of SGLT-2. Previous studies showed efficacy and safety of dapagliflozin combined with other antihyperglycemic agents in type 2 diabetes (T2DM), however, there are few studies for dapagliflozin as monotherapy. The aim of this study was to assess the efficacy and safety of dapagliflozin as a monotherapy in T2DM and provide theoretical basis for clinical rational use of drugs. METHODS: We did a systematic review and meta-analysis of randomized, placbo-controlled clinical studies in patients with type 2 diabetes. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database through October 2018, we also manually screened list of references to the previous meta-analysis of dapagliflozin in the treatment of type 2 diabetes. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. A meta-analysis was conducted by using RevMan 5.3 software. RESULTS: Six randomized controlled trials (RCTs) including 2033 patients were analyzed. Compared with placebo, dapagliflozin monotherapy was associated with a reduction in glycosylated hemoglobin A1c (HbA1c) (weighted mean difference [WMD]: -0.60%; 95% confidence interval [CI]: -0.67%, -0.52%; P < .00001), fasting plasam glucose (FPG) (WMD: -1.30 mmol/L; 95% CI: -1.52, -1.08; P < .00001), and body weight (WMD: -1.50 kg; 95% CI: -1.67, -1.32; P < .00001). Dapagliflozin was associated with an increased risk of urinary tract infections (relative risk [RR]: 1.74; 95% CI: 1.21, 2.49; P = .003) and genital tract infections (RR: 3.52; 95% CI: 2.06, 6.03; P < .00001). CONCLUSIONS: Dapagliflozin monotherapy was well tolerated and effective in reducing the level of HbA1c, FPG, and body weight in patients with T2DM without increasing hypoglycaemia, although it may increase the risk of urinary tract infections and genital tract infections. This meta-analysis provides an evidence for the treatment in patients with T2DM. However, more randomized clinical evidences are still needed to verify the results.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Hemoglobina A Glicada , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
13.
High Blood Press Cardiovasc Prev ; 26(4): 345-350, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31352663

RESUMO

INTRODUCION: Treatment strategies for patients with pre-hypertension and low-moderate cardiovascular (CV) risk may include nutraceutical compounds (NCs). AIM: To investigate the efficacy and safety of a new-generation of NC in lowering BP values and improving metabolic profile, in a group of hyper-cholesterolemic subjects with pre-hypertension. METHODS: 131 subjects with pre-hypertension (systolic BP 130-139 mmHg and/or diastolic BP 85-89 mmHg) without organ damage and history of CV diseases were enrolled. 66 subjects were treated with a once-daily oral formulation of a NC (red yeast rice, Berberine, Coenzyme Q10, folic acid and chrome) added to diet for 3 months, while 65 patients followed a diet only. Differences in serum total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG), glycemia, creatine phosphokinase (CPK), aspartate aminotransferase (AST) alanine aminotransferase (ALT) and body mass index (BMI) were evaluated. RESULTS: At the end of treatment, significant reductions of TC, LDLC, TG glucose levels were observed in both treatment groups, while HDLC values increased in the active treatment group only. A greater reduction of TC, LDLC and glycemia was observed in the treatment group. TG levels were not different within the two groups. BP and BMI levels remained unchanged, as well AST, ALT; CPK slightly increased in both groups, but it remained in the normal range. CONCLUSIONS: In patients with pre-hypertension, NC supplementation was safe, well tolerated and effective in improving lipid pattern and glucose levels and in preventing the progression to overt hypertension.


Assuntos
Anti-Hipertensivos/uso terapêutico , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais , Hipercolesterolemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Pré-Hipertensão/tratamento farmacológico , Idoso , Anti-Hipertensivos/efeitos adversos , Biomarcadores/sangue , Glicemia/metabolismo , Suplementos Nutricionais/efeitos adversos , Progressão da Doença , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/diagnóstico , Hipoglicemiantes/efeitos adversos , Hipolipemiantes/efeitos adversos , Itália , Masculino , Pessoa de Meia-Idade , Pré-Hipertensão/diagnóstico , Pré-Hipertensão/fisiopatologia , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
14.
Am J Vet Res ; 80(8): 743-755, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31339769

RESUMO

OBJECTIVE: To evaluate the clinicopathologic, hemodynamic, and echocardiographic effects of short-term administration of anti-inflammatory dosages of prednisolone to systemically normal cats. ANIMALS: 10 cats with allergic dermatitis and 10 healthy control cats. PROCEDURES: Cats with allergic dermatitis were randomly allocated to 2 groups and received 2 dosages of prednisolone (1 and 2 mg/kg/d, PO, for 7 days) in a crossover design followed by 9-day tapering and 14-day washout periods. Each prednisolone-treated cat was matched to a healthy control cat on the basis of sex, neuter status, age (± 1 year), and body weight (± 10%). Control cats received no treatment during the 35-day observation period. Clinicopathologic, echocardiographic, and hemodynamic variables were measured at baseline (day 0) and predetermined times during and after prednisolone administration and compared within and between the 2 treatment groups. RESULTS: Prednisolone-treated cats had expected clinicopathologic alterations (mild increases in neutrophil and monocyte counts and serum concentrations of albumin, cholesterol, and triglycerides) but systolic arterial blood pressure; blood glucose, serum potassium, and cardiac biomarker concentrations; urinary sodium excretion; and echocardiographic variables did not differ significantly from baseline at any time. Statistically significant, albeit clinically irrelevant, increases in blood glucose and N-terminal pro-B-type natriuretic peptide concentrations were observed between baseline and the prednisolone pharmacokinetic steady state (7 days after initiation) only when the 2-mg/kg dosage was administered. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated short-term oral administration of anti-inflammatory dosages of prednisolone did not cause relevant hemodynamic, echocardiographic, or diabetogenic effects in systemically normal cats with allergic dermatitis.


Assuntos
Anti-Inflamatórios/farmacologia , Gatos , Glucocorticoides/farmacologia , Prednisolona/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Doenças do Gato/tratamento farmacológico , Dermatite/tratamento farmacológico , Dermatite/veterinária , Ecocardiografia/efeitos dos fármacos , Ecocardiografia/veterinária , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Hemodinâmica/efeitos dos fármacos , Masculino , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Estudos Prospectivos , Distribuição Aleatória
15.
Clin Drug Investig ; 39(8): 805-819, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31317516

RESUMO

Glucagon-like peptide-1 receptor analogues/agonists (GLP-1RAs) are well established as effective adjuncts to lifestyle modification in the treatment of type 2 diabetes (T2D) as monotherapy or in combination with oral glucose-lowering drugs ± insulin. The six subcutaneous GLP-1RA formulations (i.e. twice-daily exenatide, once-daily liraglutide and lixisenatide, and once-weekly dulaglutide, exenatide and semaglutide) currently available in the EU and USA have many similarities, but also some unique features and properties. By stimulating GLP-1 receptors, GLP-1RAs increase insulin secretion and suppress glucagon release in a glucose-dependent manner, thereby improving clinical and patient-reported outcomes related to glycaemic control and weight. They also have been shown to reduce, or at least not increase, the risk of major cardiovascular outcomes. GLP-1RAs are generally well tolerated, with gastrointestinal and injection-site reactions being the most troublesome drug-related adverse events, and are associated with a very low intrinsic risk of hypoglycaemia. Treatment with GLP-1RAs should be customized to meet the clinical needs and personal preferences of the individual.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Administração Oral , Glicemia/efeitos dos fármacos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas
16.
Orv Hetil ; 160(31): 1207-1215, 2019 Aug.
Artigo em Húngaro | MEDLINE | ID: mdl-31352807

RESUMO

Type 2 diabetes - due to its natural course - should be considered as a progressive chronic disease. Owing to this fact, antihyperglycemic treatment should be continuously increased stepwise in order to achieve proper glycemic control. Lifestyle modification should be initiated immediately after manifestation, shortly followed by metformin monotherapy, and later, dual or triple combinations and, finally, injectable derivatives - only insulin in the past - should be used for appropriate glycemic control. Guidelines about treatment approach of patients with type 2 diabetes unequivocally emphasize and describe in detail the need of treatment intensification, in other words, stepwise escalation in clinical practice. In the last couple of years, evidences provided that step down therapy, simplification of complex treatment regimens should also be considered in certain cases. This approach was generally called de-escalation in antihyperglycemic treatment which should be considered in patients with type 2 diabetes 1) after bariatric (metabolic) surgery; 2) with significant weight reduction irrespective of its origin; 3) with complex insulin regimens where re-evaluation of this treatment was missed; 4) with continuously decreasing renal function; 5) among elderly patients with comorbidities; 6) in social deprivation. In this article, data about therapeutic de-escalation of antihyperglycemic treatment in patients with type 2 diabetes and first experiences with this treatment approach are summarized. Orv Hetil. 2019; 160(31): 1207-1215.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Idoso , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/farmacologia , Conduta do Tratamento Medicamentoso , Metformina/administração & dosagem , Resultado do Tratamento
17.
Life Sci ; 232: 116622, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271767

RESUMO

AIMS: This study was designed to compare the effects of empagliflozin monotherapy and its combination with metformin on glucose and lipid modulations in T2DM mice. MAIN METHODS: Nine-week-old male C57BLKS/J db/db mice (n = 32) were used as T2DM model, and their age-matched C57BLKS/J db/m mice (n = 8) were used as normal control. A total of 32 db/db mice were randomly divided into four groups (n = 8/group): the DMT1 group, treated with metformin (250 mg/kg/day); the DMT2 group, treated with metformin (250 mg/kg/day) plus empagliflozin (10 mg/kg/day); the DMT3 group, treated with empagliflozin (10 mg/kg/day); the T2DM control group (DM), received 0.5% Natrosol. The db/m mice received same administration as DM group. KEY FINDINGS: After four-week treatments, compared with T2DM control (DM), the empagliflozin or its combination with metformin dramatically increased the levels of plasma HDL-C (139.6% and 154.9%, respectively), with significant decrease in plasma TC (22.9% and 13.7%, respectively) and plasma TG (26% and 19.7%, respectively) and in hepatic TG (30.3% and 28.6%, respectively). The protein expressions of SREBP1c (75.3% and 54.0%, respectively) and APOC-III (51.2% and 50.2%, respectively) were reduced, while CPT1A (304.0% and 221.4%, respectively) and ApoA1 levels (90.0% and 85.3%, respectively) were enhanced. Although both interventions improve above-mentioned lipid homeostasis, there were no statistic differences between two groups (p > 0.05). SIGNIFICANCE: Our study demonstrated that current dose of combination therapy may have no higher amelioration than empagliflozin monotherapy for glucose and lipid metabolism in male T2DM mice when it followed a treatment shorter than that expected during clinical treatment.


Assuntos
Compostos Benzidrílicos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/farmacologia , Animais , Compostos Benzidrílicos/metabolismo , Glicemia/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada/métodos , Glucose/metabolismo , Glucosídeos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metformina/metabolismo , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Resultado do Tratamento
18.
Life Sci ; 231: 116538, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176776

RESUMO

Apoptosis is a complicated process that involves activation of a series of intracellular signaling. Tissue injuries from diabetes mellitus mostly occur as a consequence of higher rate of apoptosis process due to activation of a series of molecular mechanisms. Several classes of anti-hyperglycaemic agents have been developed which could potentially modulate the apoptotic process resulting in fewer tissue damages. Novel types of anti-hyperglycaemic medications such as sodium glucose cotransporters-2 inhibitors, glucagon like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have shown to provide potent anti-hyperglycaemic effects, but their influences on diabetes-induced apoptotic injuries is largely unknown. Therefore, in the current study, we reviewed the published data about the possible effects of these anti-hyperglycaemic agents on apoptosis in diabetic milieu as well as in cancer cells.


Assuntos
Apoptose/efeitos dos fármacos , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Glicemia/efeitos dos fármacos , Surdez/tratamento farmacológico , Surdez/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Inibidores da Dipeptidil Peptidase IV/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Peptídeos Semelhantes ao Glucagon/agonistas , Humanos , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
19.
Life Sci ; 231: 116566, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31201846

RESUMO

AIMS: Diabetes mellitus can cause cognitive impairments, a state between normal aging and dementia. Effective clinical interventions are urgently needed to prevent or treat this complication. Liraglutide as a glucagon-like peptide 1 analog has been shown to exert memory-enhancing and neuroprotective effects on neurodegenerative diseases. This study aims to investigate the neuroprotective effects of liraglutide in streptozotocin (STZ)-induced diabetic mice with cognitive deficits. METHODS: Male C57BL/6J mice were intraperitoneal injected with STZ (65 mg/kg body weight daily for 5 days) to induce type 1 diabetes model. Then the mice were treated with liraglutide (250 mg/kg/day, for 6 weeks) or saline. Weekly changes of body weight and fasting blood glucose were measured. Cognitive performance was evaluated by Morris water maze test. The ultrastructure of hippocampus was observed by transmission electron microscope. The superoxide dismutase activities and malondialdehyde levels in the hippocampus were detected by biochemistry assay. Apoptosis-related proteins and phosphoinositide 3-kinase (PI3K)/protein kinase-B (Akt) signaling were detected by Western blotting. KEY FINDINGS: We found that STZ-induced diabetic mice exhibited impaired learning and memory, ultrastructure damage of hippocampal neurons and synapses, exacerbated oxidative stress and neuronal apoptosis, as compared to the control mice. These effects were attenuated by the treatment with liraglutide. Furthermore, liraglutide reversed diabetes-induced alterations in PI3K/Akt signaling pathway that plays an essential role in modulating neuronal survival, apoptosis and plasticity. SIGNIFICANCE: These data suggest that the neuroprotective effects of liraglutide on diabetes-induced cognitive impairments are associated with the improvements of hippocampal synapses and inhibition of neuronal apoptosis.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Complicações do Diabetes/tratamento farmacológico , Liraglutida/farmacologia , Animais , Apoptose/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Cognição/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipoglicemiantes/farmacologia , Liraglutida/metabolismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/efeitos adversos , Sinapses/efeitos dos fármacos , Sinapses/fisiologia
20.
Food Chem Toxicol ; 131: 110562, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31181236

RESUMO

Brown seaweed Sargassum confusum (C. Agardh) has been used in traditional Chinese medicine to treat a variety of diseases. The aim of the present study was to evaluate the anti-diabetic effect of oligosaccharides from brown seaweed S. confusum (SCO). The anti-diabetic effect of SCO was evaluated in vivo using high-fat/high-sucrose fed hamsters. Molecular mechanisms of modulating gene expression of specific members of insulin signaling pathways were determined. The components of the intestinal microflora in diabetic animals were also analyzed by high-throughput 16S rRNA gene sequencing. And it was found that SCO had a sequence of sulfated anhydrogalactose and methyl sulfated galactoside units. Fasting blood glucose levels were significantly decreased after SCO administration. Histology showed that SCO could protect the cellular architecture of the liver. SCO could also significantly increase the relative abundance of Lactobacillus and Clostridium XIVa and decrease that of Allobaculum, Bacteroides and Clostridium IV. The active role of SCO in anti-diabetic effect was revealed by its regulation of insulin receptor substrate 1/phosphatidylinositol 3-kinase and c-Jun N-terminal kinase pathways. These results suggested that SCO might be used as a functional material to regulate gut microbiota in obese and diabetic individuals.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Oligossacarídeos/uso terapêutico , Sargassum/química , Animais , Bactérias/genética , Sequência de Bases , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Dieta da Carga de Carboidratos , Dieta Hiperlipídica , Hipoglicemiantes/isolamento & purificação , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Mesocricetus , Oligossacarídeos/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/uso terapêutico , RNA Ribossômico 16S/genética , Alga Marinha/química
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