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1.
Nutrients ; 13(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205413

RESUMO

The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake.


Assuntos
Acarbose/administração & dosagem , Diabetes Mellitus Tipo 2/microbiologia , Dieta , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Idoso , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , DNA Bacteriano/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Sacarose Alimentar/administração & dosagem , Fezes/microbiologia , Feminino , Inibidores de Glicosídeo Hidrolases , Humanos , Japão , Masculino , Pessoa de Meia-Idade
2.
Sci Rep ; 11(1): 4839, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649485

RESUMO

To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The study population of Beijing Community Diabetes Study (BCDS) were type 2 diabetes (T2DM) living in 21 communities in Beijing. All patients received comprehensive intervention in accordance with the Chinese guidelines for the prevention and treatment of diabetes. Professors in endocrinology from top tier hospitals regularly visited the communities for consultations, which was a feature of this study. A total of 1797 T2DM in BCDS study had complete screening data, including blood glucose, blood pressure, lipid profiles and acarbose continuous therapy. After 10-year follow-up, the risks of CVD outcomes were assessed according to whether patients had received acarbose therapy or not. All patients were followed-up to assess the long-term effects of the multifactorial interventions. At baseline, compared with the acarbose therapy free in T2DM, there was no significant difference in achieving the joint target control in patients with acarbose therapy. From the beginning of 8th year follow-up, the joint target control rate in patients with acarbose therapy was significantly higher than that of acarbose therapy free. During the 10-year follow-up, a total of 446 endpoint events occurred, including all-cause death, cardiovascular events, cerebrovascular events. The incidences of myocardial infarction (from the 4th year of follow-up) and all-cause death (from the 2nd year of follow-up) in patients who received acarbose therapy were significantly lower than that of acarbose therapy free respectively. In Cox multivariate analyses, there were significant differences in incidences of myocardial infarction and all-cause death between afore two groups during the 10-year follow-up, and the adjusted HRs were 0.50 and 0.52, respectively. After multifactorial interventions, T2DM with acarbose therapy revealed significant reductions of myocardial infarction and all-cause death. The long-term effects of with acarbose therapy on improving joint target control might be one of the main reasons of myocardial infarction and all-cause death reduction.Trial Registration: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.


Assuntos
Acarbose/administração & dosagem , Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Infarto do Miocárdio , Idoso , China/epidemiologia , Complicações do Diabetes/mortalidade , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Estudos Retrospectivos
3.
Clin Pharmacol Drug Dev ; 10(10): 1225-1230, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33606918

RESUMO

The purpose of this study was to determine whether the reference formulation and test formulation of acarbose are bioequivalent among healthy Chinese subjects based on evaluation of the pharmacodynamic end point. Two clinical trials with acarbose were conducted: study A, a pilot study (n = 12; 50 and 100 mg), and study B, a pivotal study (n = 60; 50 mg). In study A, there was a dose-dependent relationship between 50 mg acarbose and 100 mg acarbose and a significant difference compared with sucrose alone. In study B, after logarithmic conversion, a linear mixed-effects model was used to analyze the maximum serum glucose value and area under the serum glucose-time curve from 0 to 2 hours. The geometric mean ratios (test formulation/reference formulation) were 92.68% and 95.70%, with 90% confidence intervals of 84.08%-102.17% and 84.21%-108.76%, respectively, falling between 80.00% and 125.00%. According to the geometric least-squares mean, the test formulation (or reference formulation) was statistically significantly different as a single sucrose (P < .001). The effective dose of acarbose in healthy Chinese volunteers was 50 mg. The reference and test formulations were bioequivalent.


Assuntos
Acarbose/administração & dosagem , Acarbose/sangue , Povo Asiático , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Inibidores de Glicosídeo Hidrolases/sangue , Adulto , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Voluntários Saudáveis , Humanos , Masculino , Projetos Piloto , Equivalência Terapêutica , Adulto Jovem
4.
Clin Pharmacol Drug Dev ; 10(10): 1242-1247, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33580745

RESUMO

The safety of a novel modified-release oral capsule with orlistat and acarbose (MR-OA) was investigated in 67 obese middle-aged White men with a body mass index of 32 to 40 kg/m2 or 30 to 32 kg/m2 plus waist circumference >102 cm. The purpose of this investigation was to compare MR-OA with the existing conventional orlistat regarding systemic safety defined as plasma orlistat concentration at the end of the treatment period of 14 days. Participants took the MR-OA fixed-dose combination formulation 3 times a day together with a major meal. Three different doses of MR-OA were evaluated-60/20, 90/30, and 120/40 (mg orlistat/mg acarbose)-as well as 1 reference group who received the conventional orlistat, Xenical, with 120 mg of orlistat. Blood plasma was sampled on days 1 and 14. The orlistat plasma concentrations of the MR-OA dose showed a delayed absorption and were lower compared with conventional orlistat at the end of the study. All doses were safe and well tolerated without any unexpected adverse events and no serious adverse events. The delay in the rise of orlistat plasma concentration indicates that the modified-release properties of the MR-OA formulation are effective. The systemic exposure of orlistat resulting from MR-OA was similar, albeit a bit lower than the conventional orlistat with 120 mg of orlistat. We can therefore assume that the safety profile regarding the orlistat moiety of MR-OA is comparable to the conventional orlistat and a promising approach for weight control in obese patients. Further clinical evaluation is underway.


Assuntos
Acarbose/administração & dosagem , Fármacos Antiobesidade/administração & dosagem , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Obesidade/tratamento farmacológico , Orlistate/administração & dosagem , Redução de Peso/efeitos dos fármacos , Acarbose/efeitos adversos , Acarbose/sangue , Administração Oral , Adulto , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/sangue , Combinação de Medicamentos , Seguimentos , Inibidores de Glicosídeo Hidrolases/efeitos adversos , Inibidores de Glicosídeo Hidrolases/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Orlistate/efeitos adversos , Orlistate/sangue , Redução de Peso/fisiologia
5.
J Clin Pharm Ther ; 46(3): 814-819, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33462825

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Acarbose can efficiently block glucose absorption in the intestine as an alpha-glucosidase inhibitor. It is currently manufactured in several oral dosage forms, with the most common types being tablets and chewable tablets. The acarbose tablet (Glucobay® , 50 mg, Bayer) package insert gives instructions for either directly swallowing or chewing then swallowing. This study compared the pharmacodynamic effects of a single formulation of acarbose tablets under these two different administration routes. METHODS: This randomized, crossover study enrolled 24 healthy subjects who were instructed to chew (C group) or swallow (S group) the acarbose tablet. Glucose levels were monitored in subjects for up to 4 h following administration of 75 g of sucrose to establish a baseline firstly, after which subjects in the C and S groups were administered 50- or 100- mg of acarbose along with 75 g of sucrose. Then, subjects entered a 1-week washout period before being crossed over to the alternate dosing route. RESULTS AND DISCUSSION: Compared with the S group, the C group had a lower maximum concentration of serum glucose (Cmax ) and areas under the concentration-time curve (AUC0-2 , AUC0-1.5 ). In addition, the maximum reduction in serum glucose (ΔCmax ) and the reduction in the AUC (AUEC0-1.5 ) were both increased in the S group. This occurred at both the 50 mg and 100 mg dosages. These results indicate that fluctuations in blood glucose were lower following chewing of the acarbose tablet. Both administration routes exhibited similar safety and tolerance profiles. WHAT IS NEW AND CONCLUSION: In summary, chewing acarbose tablets appears to induce a superior glycaemic-controlling effect compared with swallowing them directly, at least with a single dose. It will be important to inform both clinicians and patients about these differences between the two administrations so that informed clinical decisions can be made, as numerous patients with diabetes are inclined to directly swallow acarbose tablets for convenience.


Assuntos
Acarbose/administração & dosagem , Acarbose/farmacologia , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Inibidores de Glicosídeo Hidrolases/farmacologia , Comprimidos/química , Acarbose/farmacocinética , Adolescente , Adulto , Área Sob a Curva , Glicemia/efeitos dos fármacos , Índice de Massa Corporal , China , Estudos Cross-Over , Deglutição/fisiologia , Relação Dose-Resposta a Droga , Feminino , Inibidores de Glicosídeo Hidrolases/farmacocinética , Voluntários Saudáveis , Humanos , Masculino , Mastigação/fisiologia , Pessoa de Meia-Idade , Adulto Jovem
6.
J Clin Pharm Ther ; 46(2): 492-503, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33325562

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Acarbose is a poorly absorbed α-glucosidase inhibitor that acts locally in the intestinal tract. Therefore, the evaluation of its bioequivalence (BE) should be based on pharmacodynamic (PD) rather than pharmacokinetic (PK) endpoints. Currently, there is no consensus on the best method for acarbose BE evaluation. The optimal protocol design regarding dosing time/dose and PD parameters requires further exploration. The aim of the study was to identify an optimum protocol for establishing acarbose BE in healthy Chinese volunteers using PD endpoints. METHODS: Three pilot studies were conducted in healthy Chinese subjects. Study 1 was an open, randomized, two-period crossover study using the reference (R) drug at the dose of 1 × 50 mg. Study 1 aimed to determine appropriate dosing time by comparing the PD effect of acarbose between two administration methods. One method was concomitant administration of sucrose and acarbose, and another method was acarbose administration 10 min before sucrose. Study 2 was an open, randomized, three-period crossover study. Subjects were given the R drug at the dose of 1 × 50 mg, 2 × 50 mg or 3 × 50 mg in a random sequence. The aim of Study 2 was to identify a reasonable dose of acarbose in the BE study. Study 3 was conducted with an open, randomized, three-period crossover design using the test (T) or R drug in an R-T-R sequence at the dose of 2 × 50 mg. Study 3 aimed to compare the BE between the R and T drug and determine intra-individual variation. Twelve subjects were recruited in Study 1, Study 2 and Study 3, respectively, with a one-week washout period. Serum glucose and insulin concentrations were determined after sucrose administration (baseline) and sucrose/acarbose co-administration. RESULTS AND DISCUSSION: In Study 1, no significant differences in PD parameters were found between the two administration methods. The results of Study 2 revealed that the optimal dose was between 1 × 50 mg and 2 × 50 mg. The comparison of PD parameters indicated that the rectifying method could distinguish between different formulations. Study 3 showed that the geometric mean ratios of Cmax, r , AUC0-2 h, r and AUC0-4 h, r were 90.06%, 84.55% and 84.21%, respectively, using the rectifying method. The 90% CIs of Cmax, r were within acceptance limits (80.00%-125.00%), whereas that of AUC0-2 h, r and AUC0-4 h, r were out of the range. The intra-individual variation was approximately 21% for R formulation. Based on the variation, the number of subjects needed to identify formulation differences in the pivotal study would be 55 with 90% power at the 5% level of significance. WHAT IS NEW AND CONCLUSION: The results from our study manifested that a randomized, balanced, two-way crossover design was eligible to evaluate acarbose BE. The appropriate dosing time was concomitant administration of sucrose and acarbose, and the optimal dose was 2 × 50 mg. The rectifying method exhibited preferable sensitivity and applicability in acarbose BE evaluation. A practical sample size of the pivotal study would be 55. These results may help to provide new insights into the protocol design of acarbose BE study.


Assuntos
Acarbose/farmacologia , Protocolos Clínicos/normas , Inibidores de Glicosídeo Hidrolases/farmacologia , Acarbose/administração & dosagem , Acarbose/farmacocinética , Adulto , Área Sob a Curva , Glicemia , China , Estudos Cross-Over , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Inibidores de Glicosídeo Hidrolases/farmacocinética , Humanos , Insulina/sangue , Masculino , Taxa de Depuração Metabólica , Sacarose/administração & dosagem , Equivalência Terapêutica , Adulto Jovem
7.
Food Funct ; 11(7): 6476-6486, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32627774

RESUMO

Extracts of Cyclopia species are used as food ingredients. In vitroα-glucosidase (AG) inhibition by ultrafiltered C. genistoides extract, fractions enriched in xanthones (XEF) and benzophenones (BEF), as well as mangiferin, isomangiferin, 3-ß-d-glucopyranosyliriflophenone (I3G) and 3-ß-d-glucopyranosyl-4-O-ß-d-glucopyranosyliriflophenone (IDG) was determined with acarbose as positive control. XEF was more potent than the extract and BEF (IC50 = 43.3, 95.5 and 205.7 µg mL-1, respectively). Compounds demonstrated potency in the descending order: acarbose (IC50 = 44.3 µM) > mangiferin (102.2 µM) > isomangiferin (119.8 µM) > I3G (237.5 µM) > IDG (299.4 µM). The combination index (CI) was used to determine synergism (CI < 0.7) as demonstrated for combinations of acarbose with XEF, BEF or the respective compounds at 50% and 75% effect levels. The greatest potential acarbose dose reductions (>six-fold) across all effect levels were calculated for combinations of acarbose with mangiferin or isomangiferin, explaining the greater acarbose dose reduction potential of XEF vs. BEF. The effect of batch-to-batch variation (n = 10) of raw plant material on AG inhibition was quantified at a fixed concentration (160 µg mL-1). XEFs (xanthone content = 223-481 g kg-1) achieved AG inhibition of 63-72%, whereas BEFs (benzophenone content = 114-251 g kg-1) achieved AG inhibition of 26-34%, with weak linear correlation (R2 < 0.43) between target compound content of the fractions and their achieved AG inhibition. Thus, extract fractions of C. genistoides, enriched in xanthones and benzophenones, show potential in reducing the effective dose of acarbose required to prevent postprandial hyperglycaemia.


Assuntos
Acarbose/administração & dosagem , Cyclopia (Planta)/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/farmacologia , Benzofenonas/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Hiperglicemia/prevenção & controle , Xantonas/farmacologia
8.
Acupunct Med ; 38(5): 335-342, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32297559

RESUMO

BACKGROUND: Previous studies have reported that electroacupuncture (EA) induces a glucose-lowering effect by improving insulin resistance (IR) and reduces plasma free fatty acid (FFA) levels in rats with steroid-induced insulin resistance (SIIR). In addition, EA can activate cholinergic nerves and stimulate endogenous opioid peptides to lower plasma glucose in streptozotocin-induced hyperglycemic rats. The aim of this study was to investigate the glucose-lowering effects of 15 Hz EA at bilateral ST36 in combination with acarbose (ACA). We hypothesized that EA combined with ACA would produce a stronger glucose-lowering effect than ACA alone. METHODS: In this study, normal Wistar rats and SIIR rats were randomly divided into two groups: ACA and ACA + EA. To explore the potential mechanisms underlying the glucose-lowering effect, plasma FFA/insulin and insulin transduction signal pathway proteins were assayed. RESULTS: Combined ACA + EA treatment had a greater glucose-lowering effect than ACA alone in normal Wistar rats (-45% ± 3% vs -19% ± 3%, p < 0.001) and SIIR model rats (-43% ± 2% vs -16% ± 6%, p < 0.001). A significant reduction in plasma FFA levels, improvement in homeostatic model assessment of IR (HOMA-IR) index (-48.9% ± 4.0%, p < 0.001) and insulin sensitivity index (102% ± 16.9%, p < 0.001), and significant increases in insulin receptor substrate 1, glucose transporter 4, and peroxisome proliferator-activated receptor γ protein expressions in skeletal muscle, were also observed in the ACA + EA group of SIIR rats. CONCLUSION: Combined EA and ACA therapy had a greater glucose-lowering effect than ACA monotherapy; this combined therapy could be more effective at improving IR in SIIR rats, which may be related to a reduction in plasma FFA levels and an elevation of insulin signaling proteins. Whether this combined therapy has an effect in type 2 diabetes mellitus (T2DM) patients still needs to be explored.


Assuntos
Acarbose/administração & dosagem , Eletroacupuntura , Hiperglicemia/terapia , Resistência à Insulina , PPAR gama/metabolismo , Esteroides/efeitos adversos , Animais , Terapia Combinada , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Humanos , Hiperglicemia/etiologia , Hiperglicemia/genética , Hiperglicemia/metabolismo , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , PPAR gama/genética , Ratos , Ratos Wistar
9.
J Diabetes Investig ; 11(4): 896-905, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32020731

RESUMO

AIMS/INTRODUCTION: This secondary analysis of the 24-week SMART study examined the efficacy of add-on saxagliptin or acarbose to metformin across different patient subgroups with type 2 diabetes mellitus, based on baseline characteristics. MATERIALS AND METHODS: Randomized patients (n = 481) were classified into subgroups based on their baseline age (<65, ≥65 years), body mass index (BMI; <24, 24-<28, ≥28 kg/m2 ), glycated hemoglobin (HbA1c; <8%, 8-<9%, 9-<10%, ≥10%) and renal function (creatinine clearance 50-<80, ≥80 mL/min). Treatment effects on primary outcome (HbA1c) and key secondary outcomes of fasting plasma glucose (FPG), 2-h postprandial glucose and homeostatic model assessment of ß-cell function were assessed across patient subgroups. RESULTS: For saxagliptin, reductions in HbA1c from baseline to week 24 were consistent across different subgroups regardless of baseline age, body mass index, HbA1c and renal function (range -0.66 to -1.16%). Saxagliptin was associated with consistent reductions in FPG (-0.60 to -1.33 mmol/L) and 2-h postprandial glucose (-0.48 to -1.95 mmol/L) across the majority of subgroups studied. The efficacy of acarbose on FPG attenuated progressively with increasing baseline HbA1c (+0.86 to -1.43 mmol/L); an increase from baseline FPG was observed in patients with HbA1c >9%. The effect of acarbose on postprandial glucose was also variable (+0.23 to -3.38 mmol/L). CONCLUSIONS: As add-on to metformin, both saxagliptin and acarbose reduced HbA1c regardless of baseline HbA1c, age, body mass index and renal function; however, only saxagliptin was effective at a stable glycemic control (FPG and PPG). The efficacy of acarbose on FPG and PPG was significantly attenuated in patients with higher baseline HbA1c (≥8%).


Assuntos
Acarbose/administração & dosagem , Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptídeos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Metformina/administração & dosagem , Adamantano/administração & dosagem , Idoso , Glicemia/efeitos dos fármacos , China , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Controle Glicêmico/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Resultado do Tratamento
10.
Diabetes Technol Ther ; 22(4): 256-264, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31638433

RESUMO

Background: Acarbose (ACA) can effectively reduce the postprandial blood glucose and has similar antidiabetic effects as metformin (MET). To our knowledge, few studies have compared the effect of ACA or MET on glucose fluctuations. In the present study, we explored the effect of ACA or MET combined with premixed insulin (INS) on glycemic control and glycemic variability (GV). Methods: This was an open-label randomized trial that was conducted in type 2 diabetic patients taking premixed insulin. The patients were assigned to 12 weeks of MET (n = 62) or ACA (n = 62) treatment combined with INS. The main outcomes were changes in GV and glycosylated hemoglobin A1c (HbA1c) compared with baseline. Results: Compared with baseline, several GV indices (standard deviation [SD], mean amplitude of glycemic excursions [MAGE]) and blood glucose control indices (mean glucose [MG], time in range [TIR] and HbA1c) were both significantly improved in INS+ACA and INS+MET after 12-week therapy. However, coefficient of variation (CV) was significantly reduced in INS+ACA but not in INS+MET. Moreover, compared with INS+MET, INS+ACA led to a more pronounced percentage change from baseline in CV (26.3% [1.7%-44.6%] vs. 11.9% [-7.0% to 29.9%], P = 0.022), MAGE (40.5% [20.1%-60.5%] vs. 25.2% [-2.1% to 43.4%], P = 0.007) and SD (38.6% [25.2%-57.9%] vs. 30.1% [10.8%-46.5%], P = 0.041). Conclusion: Both MET and ACE combined with INS effectively reduced blood glucose. Compared with MET, ACA combined with INS reduced GV.


Assuntos
Acarbose/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Metformina/administração & dosagem , Idoso , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Controle Glicêmico , Índice Glicêmico , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Resultado do Tratamento
11.
Drug Des Devel Ther ; 13: 2769-2776, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31496653

RESUMO

OBJECTIVE: This study aimed to investigate the changes in inflammatory biomarkers between newly diagnosed type 2 diabetes (T2DM) patients under one-year acarbose treatments and those under metformin managements. METHODS: Seventy patients with newly diagnosed T2DM and 32 volunteers with normal glucose tolerance (normal controls, NCs) were enrolled. Seventy patients with T2DM were randomly assigned to two subgroups and treated with acarbose (n=34) or metformin (n=36) for 1 year. Blood glucose, insulin, glycosylated hemoglobin (A1C), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and inflammatory biomarker levels (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-2 (IL-2), and ferritin) were detected at 0, 6 and 12 months. RESULTS: After adjusting for sex, the waist-to-hip ratio (WHR) and body mass index (BMI), higher fasting plasma glucose (FPG), standard meal test 1/2 hr and 2 hr glucose, TG, TC, LDL-C, IL-6, TNF-α, IL-2 and ferritin levels were observed in T2DM group than in NCs (P<0.05). After 6 months of treatment, TNF-α levels were significantly decreased in both subgroups, and IL-6 and ferritin levels were significantly decreased after 12 months (P<0.05). However, no significant differences in the IL-6, TNF-α and ferritin levels were observed between the two subgroups. Moreover, significantly higher IL-6 and TNF-α levels were detected in the T2DM group than in NCs after 12 months of treatment (P<0.05). CONCLUSION: Patients with newly diagnosed T2DM exhibited a marked chronic inflammatory state characterized by increased IL-6, TNF-α, IL-1ß, IL-2 and ferritin levels. After 1 year of treatment with acarbose or metformin, IL-6, TNF-α, IL-1ß and ferritin levels were significantly decreased compared with the baseline. The anti-inflammatory effects of acarbose and metformin were comparable and required a long-term treatment (1 year), but the characteristics were different. Further investigations are needed to determine whether this effect was independent of the hypoglycemic effects.


Assuntos
Acarbose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inflamação/tratamento farmacológico , Metformina/uso terapêutico , Acarbose/administração & dosagem , Adulto , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/administração & dosagem , Inflamação/sangue , Inflamação/diagnóstico , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade
12.
BMC Geriatr ; 19(1): 241, 2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470806

RESUMO

BACKGROUND: Postprandial hypotension (PPH) occurs frequently in the elderly and patients with type 2 diabetes, and lacks a satisfactory treatment. Gastric distension and the α-glucosidase inhibitor, acarbose, may attenuate the postprandial fall in blood pressure (BP) by complementary mechanisms. We aimed to determine whether gastric distension and acarbose have additive effects to attenuate the fall in BP induced by oral sucrose. METHODS: Ten healthy older adults (74.0 ± 1.4 yr) had measurements of BP and superior mesenteric artery (SMA) blood flow for 120 min after receiving either (i) the 'study drink' of 100 g sucrose in 300 mL of water (control treatment), (ii) a 300 mL water 'preload' 15 min before the 'study drink' (distension treatment), (iii) 100 mg acarbose dissolved in the 'study drink' (acarbose treatment) or (iv) a 300 ml water 'preload' 15 min before 100 mg acarbose dissolved in the 'study drink' (acarbose and distension treatment). RESULTS: The area under the curve (AUC)0-120min for mean arterial pressure (MAP) was greater (P = 0.005) and the maximum fall in MAP was less (P = 0.006) during treatments with acarbose. Gastric distension did not affect the MAP-AUC0-120min response to acarbose (P = 0.44) and there was no effect of gastric distension alone (P = 0.68). Both acarbose treatments attenuated the rise in SMA blood flow (P = 0.003), whereas gastric distension had no effect. CONCLUSIONS: In healthy older adults, acarbose (100 mg), but not gastric distension, attenuates the fall in BP and rise in SMA blood flow after oral sucrose. The observations support the use of acarbose, but not gastric distension, to attenuate a postprandial fall in BP. TRIAL REGISTRATION: The study was retrospectively registered at ( ACTRN12618000152224 ) on February 02nd 2018.


Assuntos
Acarbose/administração & dosagem , Pressão Sanguínea/fisiologia , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Hipotensão/terapia , Período Pós-Prandial/fisiologia , Sacarose/administração & dosagem , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Terapia Combinada/métodos , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Feminino , Absorção Gástrica/efeitos dos fármacos , Absorção Gástrica/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Hipotensão/sangue , Masculino , Período Pós-Prandial/efeitos dos fármacos , Estudos Retrospectivos
13.
Adv Mater ; 31(27): e1901103, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31112631

RESUMO

Ionic liquids (ILs) and deep eutectic solvents have shown great promise in drug delivery applications. Choline-based ILs, in particular choline and geranic acid (CAGE), have been used to enhance the transdermal delivery of several small and large molecules. However, detailed studies outlining the design principles of ILs for transdermal drug delivery are still lacking. Using two model drugs of differing hydrophilicities, acarbose and ruxolitinib and 16 ILs, the dependence of skin penetration on the chemical properties of ILs is examined. First, the impact of ion stoichiometry on skin penetration of drugs is assessed using CAGE, which evidences that a molar ratio of 1:2 of choline to geranic acid yields the highest delivery. Subsequently, variants of CAGE are prepared using anions with structural similarity to geranic acid and cations with structural similarity to choline at a ratio of 1:2. Mechanistic studies reveal that the potency of ILs in enhancing transdermal drug delivery correlates inversely with the inter-ionic interactions as determined by 2D NMR spectroscopy. Using this understanding, a new IL is designed, and it provides the highest delivery of ruxolitinib of all ILs tested here. Overall, these studies provide a generalized framework for optimizing ILs for enhancing skin permeability.


Assuntos
Acarbose/administração & dosagem , Ácidos Carboxílicos/química , Portadores de Fármacos/química , Líquidos Iônicos/química , Pirazóis/administração & dosagem , Administração Cutânea , Animais , Colina/química , Cobaias , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Nitrilas , Permeabilidade , Pirimidinas , Pele/metabolismo , Solventes/química , Terpenos/química
14.
mSphere ; 4(1)2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728281

RESUMO

Acarbose is a safe and effective medication for type 2 diabetes that inhibits host glucoamylases to prevent starch digestion in the small intestines and thus decrease postprandial blood glucose levels. This results in an increase in dietary starch in the distal intestine, where it becomes food for the gut bacterial community. Here, we examined the effect of acarbose therapy on the gut community structure in mice fed either a high-starch (HS) or high-fiber diet rich in plant polysaccharides (PP). The fecal microbiota of animals consuming a low dose of acarbose (25 ppm) was not significantly different from that of control animals that did not receive acarbose. However, a high dose of acarbose (400 ppm) with the HS diet resulted in a substantial change to the microbiota structure. Most notably, the HS diet with a high dose of acarbose lead to an expansion of the Bacteroidaceae and Bifidobacteriaceae and a decrease in the Verrucomicrobiaceae (such as Akkermansia muciniphila) and the Bacteroidales S24-7. Once acarbose treatment ceased, the community composition quickly reverted to mirror that of the control group, suggesting that acarbose does not irreversibly alter the gut community. The high dose of acarbose in the PP diet resulted in a distinct community structure with increased representation of Bifidobacteriaceae and Lachnospiraceae Short-chain fatty acids (SCFAs) measured from stool samples were increased, especially butyrate, as a result of acarbose treatment in both diets. These data demonstrate the potential of acarbose to change the gut community structure and increase beneficial SCFA output in a diet-dependent manner.IMPORTANCE The gut microbial community has a profound influence on host physiology in both health and disease. In diabetic individuals, the gut microbiota can affect the course of disease, and some medications for diabetes, including metformin, seem to elicit some of their benefits via an interaction with the microbiota. Here, we report that acarbose, a glucoamylase inhibitor for type 2 diabetes, changes the murine gut bacterial community structure in a reversible and diet-dependent manner. In both high-starch and high-fiber diet backgrounds, acarbose treatment results in increased short-chain fatty acids, particularly butyrate, as measured in stool samples. As we learn more about how human disease is affected by the intestinal bacterial community, the interplay between medications such as acarbose and the diet will become increasingly important to evaluate.


Assuntos
Acarbose/administração & dosagem , Bactérias/efeitos dos fármacos , Dieta , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Animais , Bactérias/genética , Bacteroidaceae/efeitos dos fármacos , Butiratos/análise , Fibras na Dieta/metabolismo , Ácidos Graxos Voláteis/análise , Fezes/química , Fezes/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S , Amido/metabolismo
15.
Pharmacoepidemiol Drug Saf ; 28(4): 500-506, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30724413

RESUMO

PURPOSE: The objective of this study was to investigate the association between the administration of dipeptidyl peptidase-4 (DPP-4) inhibitors (cumulative duration, timing, and individual substance) and the risk of arthralgia by using a nationwide database with two methodological approaches including cohort and nested case-control study designs. METHODS: Using Taiwan's National Health Insurance Research Database, we identified patients who were newly prescribed with DPP-4 inhibitors, thiazolidinediones (TZDs), or acarbose between 1 March 2009 and 31 December 2012. The exposure of studied drugs was categorized into five exclusive categories: DPP-4 inhibitor, TZD, acarbose, combined use, or non-use, and assessed in a time-varying manner. Time-dependent Cox proportional hazard models were used to estimate the association between DPP-4 inhibitors and the risk of arthralgia. Particularly, we tested the impact of different cumulative duration, timing, and individual substance of DPP-4 inhibitors use on risk of arthralgia. A corresponding nested case-control study using conditional logistic regression was conducted to verify this association. RESULTS: An increased risk of arthralgia was observed during the first year after initiating DPP-4 inhibitors (adjusted Hazard Ratio = 1.35; 95% confidence interval [CI], 1.04-1.75) but the risk declined with cumulative use. This duration-response relation was not found in TZDs use and acarbose use. In the nested case-control study, there was a slightly increased risk of arthralgia (aOR = 1.08; 95% CI, 1.04-1.12) associated with current DPP-4 inhibitor use. CONCLUSION: A relatively higher risk of arthralgia was associated with the initial administration of DPP-4 inhibitors, however, the risk declined among long-term users.


Assuntos
Artralgia/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Hipoglicemiantes/efeitos adversos , Acarbose/administração & dosagem , Acarbose/efeitos adversos , Idoso , Artralgia/induzido quimicamente , Estudos de Casos e Controles , Estudos de Coortes , Bases de Dados Factuais/estatística & dados numéricos , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Taiwan/epidemiologia , Tiazolidinedionas/administração & dosagem , Tiazolidinedionas/efeitos adversos , Fatores de Tempo
16.
Aging Cell ; 18(2): e12898, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30688027

RESUMO

To follow-up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log-rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%-11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2-(2-hydroxyphenyl) benzothiazole (HBX), and INT-767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose-control drugs in humans.


Assuntos
Acarbose/farmacologia , Envelhecimento Saudável/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Acarbose/administração & dosagem , Acarbose/análise , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Mutantes
17.
J Cell Biochem ; 120(1): 425-438, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30191607

RESUMO

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/uso terapêutico , Quercetina/análogos & derivados , alfa-Amilases/sangue , Acarbose/administração & dosagem , Acarbose/uso terapêutico , Aloxano/administração & dosagem , Aloxano/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glicemia/metabolismo , Proteína C-Reativa/análise , Domínio Catalítico , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Lipase/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Quercetina/administração & dosagem , Quercetina/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Ratos , alfa-Amilases/antagonistas & inibidores
18.
Metab Syndr Relat Disord ; 16(7): 336-341, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29912623

RESUMO

BACKGROUND AND AIMS: Saxagliptin as one of dipeptidyl peptidase-4 (DPP-4) inhibitors can effectively improve glycaemic control in type 2 diabetes mellitus, and nesfatin-1 is regarded as a very important factor in regulating feeding behavior and energy homeostasis. In this trial, we observed the effect of saxagliptin on regulating nesfatin-1 secretion and ameliorating insulin resistance and metabolic profiles in type 2 diabetes mellitus. METHODS: One hundred two type 2 diabetes participants (M/F = 48/54) were investigated. Fifty-one (M/F = 24/27) of them as the treatment group were treated with oral glucose-lowering agents including saxagliptin, the other 51 (M/F = 24/27) as the control group were treated with oral glucose-lowering agents excluding any DPP-4 inhibitors. The parameters of serum nesfatin-1, C-peptide, homeostasis model assessment-ß (HOMA-ß) function, HOMA insulin resistance (HOMA-IR), glycosylated hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), body mass index (BMI), and blood pressure (BP) at baseline, month 3, 6, and 12 were observed and compared respectively. RESULTS: Saxagliptin significantly upregulated nesfatin-1 secretion (P < 0.001 at 3-, 6-, and 12-months vs. baseline), increased serum C-peptide (P < 0.05, 0.001, and 0.001 at 3-, 6-, and 12-months vs. baseline), improved HOMA-IR and function of HOMA-ß (P < 0.001 at 3-, 6-, and 12-months vs. baseline) and metabolic profiles (P < 0.001 with HbA1c at 3-, 6- and 12-months; P < 0.001 with LDL-C at 6- and 12-months; P < 0.001 and 0.01 with HDL-C at 6- and 12-months vs. baseline), declined BMI (P < 0.05 at 6- and 12-months vs. baseline) and BP (P < 0.001 with systolic BP (SBP), and mean BP at 6- and 12-months, P < 0.01 with diastolic BP at 6- and 12-months vs. baseline). CONCLUSIONS: Saxagliptin could upregulate nesfatin-1 secretion and ameliorate insulin resistance and metabolic profiles in type 2 diabetes mellitus. Saxagliptin had the potential to play fundamental by upregulating nesfatin-1 secretion besides lowering glucose by inhibiting the degradation of glucagon-like peptide-1.


Assuntos
Adamantano/análogos & derivados , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptídeos/farmacologia , Resistência à Insulina , Metaboloma/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Acarbose/administração & dosagem , Adamantano/administração & dosagem , Adamantano/farmacologia , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dipeptídeos/administração & dosagem , Feminino , Seguimentos , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Nucleobindinas , Regulação para Cima/efeitos dos fármacos
20.
Pak J Pharm Sci ; 31(3(Special)): 1103-1107, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29735458

RESUMO

The goal of diabetic drug treatment is to stabilize the blood sugar for a long time to close to the normal level, to correct the metabolic disorder and eliminate the symptoms. At present, glimepiride has become commonly used drugs for the treatment of diabetes with obesity. Compared with metformin, acarbose and rosiglitazone, glimepiride has different mechanisms of drug action, clinical combination showed synergistic hypoglycemic effect, good clinical curative effect. So, we use three treatments to study as group A (glimepiride and metformin); group B (glimepiride and acarbose); Group C (glimepiride and rosiglitazone). From the analysis of drug economics, glimepiride and metformin scheme is better, has the lowest cost per unit cost effect. From the comparison of scheme is efficient, the best curative effect is rosiglitazone plus glimepiride, effective rate as 96.7%. At the same time, the drug can be rationally used to reduce the occurrence of some drug-induced diseases and adverse drug reactions.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Farmacoeconomia , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/uso terapêutico , Acarbose/administração & dosagem , Acarbose/economia , Acarbose/uso terapêutico , Adulto , Glicemia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/administração & dosagem , Metformina/economia , Metformina/uso terapêutico , Pessoa de Meia-Idade , Rosiglitazona/administração & dosagem , Rosiglitazona/economia , Rosiglitazona/uso terapêutico , Compostos de Sulfonilureia/economia
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