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BACKGROUND: In preclinical studies, bitter compounds, including quinine, stimulate secretion of glucoregulatory hormones [e.g., glucagon-like peptide-1 (GLP-1)] and slow gastric emptying, both key determinants of postprandial glycemia. A greater density of bitter-taste receptors has been reported in the duodenum than the stomach. Thus, intraduodenal (ID) delivery may be more effective in stimulating GI functions to lower postprandial glucose. OBJECTIVE: We compared effects of intragastric (IG) and ID quinine [as quinine hydrochloride (QHCl)] administration on the plasma glucose response to a mixed-nutrient drink and relations with gastric emptying, plasma C-peptide (reflecting insulin secretion), and GLP-1. METHODS: Fourteen healthy men [mean ± SD age: 25 ± 3 y; BMI (in kg/m2): 22.5 ± 0.5] received, on 4 separate occasions, in double-blind, randomly assigned order, 600 mg QHCl or control, IG or ID, 60 min (IG conditions) or 30 min (IG conditions) before a mixed-nutrient drink. Plasma glucose (primary outcome) and hormones were measured before, and for 2 h following, the drink. Gastric emptying of the drink was measured using a 13C-acetate breath test. Data were analyzed using repeated-measures 2-way ANOVAs (factors: treatment and route of administration) to evaluate effects of QHCl alone and 3-way ANOVAs (factors: treatment, route-of-administration, and time) for responses to the drink. RESULTS: After QHCl alone, there were effects of treatment, but not route of administration, on C-peptide, GLP-1, and glucose (P < 0.05); QHCl stimulated C-peptide and GLP-1 and lowered glucose concentrations (IG control: 4.5 ± 0.1; IG-QHCl: 3.9 ± 0.1; ID-control: 4.6 ± 0.1; ID-QHCl: 4.2 ± 0.1 mmol/L) compared with control. Postdrink, there were treatment × time interactions for glucose, C-peptide, and gastric emptying, and a treatment effect for GLP-1 (all P < 0.05), but no route-of-administration effects. QHCl stimulated C-peptide and GLP-1, slowed gastric emptying, and reduced glucose (IG control: 7.2 ± 0.3; IG-QHCl: 6.2 ± 0.3; ID-control: 7.2 ± 0.3; ID-QHCl: 6.4 ± 0.4 mmol/L) compared with control. CONCLUSIONS: In healthy men, IG and ID quinine administration similarly lowered plasma glucose, increased plasma insulin and GLP-1, and slowed gastric emptying. These findings have potential implications for lowering blood glucose in type 2 diabetes. This study was registered as a clinical trial with the Australian New Zealand Clinical Trials at www.anzctr.org.au as ACTRN12619001269123.
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Glicemia , Esvaziamento Gástrico , Quinina/farmacologia , Adulto , Austrália , Bebidas , Peptídeo C/metabolismo , Método Duplo-Cego , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Insulina , Masculino , Nutrientes , Período Pós-Prandial , Adulto JovemRESUMO
BACKGROUND: We conducted a systematic review and meta-analysis to assess the effects of statin therapy on serum vitamin D concentrations. MATERIALS AND METHODS: We searched multiple databases including PubMed, MEDLINE, Web of Science and Google Scholar from inception to May 2016, for studies on the effects of statin treatment on serum vitamin D concentration. Quantitative data synthesis used random-effects models meta-analysis, with sensitivity analysis conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. The systematic review's registration number was CRD42016035974. RESULTS: In all, seven of 644 studies met our selection criteria including three randomized controlled trials (RCT), three observational cohort studies and one case-control study. Across RCTs, treatment with statins was associated a significant increase in serum vitamin D concentrations [weighted mean difference (WMD) 2·71 ng/mL, 95% CI 0·19-5·24, I2 62·1%). Across studies of non-RCT design, statins treatment was associated with a decrease in vitamin D concentrations (WMD -0·70 ng/mL, 95% CI -1·20 to -0·20, I2 56·3%). These findings were robust in sensitivity analyses. CONCLUSIONS: This meta-analysis was inconclusive on the effects of statins on vitamin D, with conflicting directions of the effects from interventional and observational studies. The suggested favourable effects from RCTs need to be confirmed in larger studies with extended follow-up in order to determine the possible health benefits.
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Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Vitamina D/sangue , HumanosRESUMO
UNLABELLED: Fasting during the month of Ramadan is a religious rituals of all healthy adult Muslims. However, there is no clear agreement on the effects of Ramadan fasting on cardiovascular disease. Comorbidities and factors such as age, gender, health status, daily duration of fasting, food intake before and after fasting may impact on a fasting individual's cardiometabolic risk. This review was undertaken to assess the effects of Ramadan fasting on: the incidence of cardiovascular disease during the month of Ramadan; the clinical status of patients with stable cardiac disease; and any alterations in cardiometabolic risk profile. METHODS: A systematic search was undertaken for studies that investigated the impact of Ramadan fasting on cardiovascular outcomes and risk factors. Electronic databases including MEDLINE, Scopus and Web of Knowledge were searched from 1982 up to 2014. The incidence of acute cardiac illness during Ramadan fasting was similar when compared to non-fasting days. Ramadan fasting is associated with elevations in high-density lipoprotein cholesterol (HDL-c), and reductions in low-density lipoprotein cholesterol (LDL-c) and total cholesterol (T-chol). However, the lipid profile of diabetic patients deteriorated significantly during Ramadan fasting. In addition, Ramadan fasting lowers body weight, body fat percentage and BMI (body mass index). However, the relationship between weight reduction and loss of body fat is not studied. The majority of patients with stable cardiac illness can opt for Ramadan fasting safely. However, the long term effects of Ramadan fasting on cardiovascular outcomes and risk factors remains uncertain, and the apparent discordant effects in individuals with and without diabetes mellitus merits further study.
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Intraduodenal quinine, in the dose of 600 mg, stimulates glucagon-like peptide-1 (GLP-1), cholecystokinin and insulin; slows gastric emptying (GE); and lowers post-meal glucose in men. Oral sensitivity to bitter substances may be greater in women than men. We, accordingly, evaluated the dose-related effects of quinine on GE, and the glycaemic responses to, a mixed-nutrient drink in females, and compared the effects of the higher dose with those in males. A total of 13 female and 13 male healthy volunteers received quinine-hydrochloride (600 mg ('QHCl-600') or 300 mg ('QHCl-300', females only) or control ('C'), intraduodenally (10 mL bolus) 30 min before a drink (500 kcal, 74 g carbohydrates). Plasma glucose, insulin, C-peptide, GLP-1, glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin were measured at baseline, for 30 min after quinine alone, and then for 2 h post-drink. GE was measured by 13C-acetate breath-test. QHCl-600 alone stimulated insulin, C-peptide and GLP-1 secretion compared to C. Post-drink, QHCl-600 reduced plasma glucose, stimulated C-peptide and GLP-1, and increased the C-peptide/glucose ratio and oral disposition index, while cholecystokinin and GIP were less, in females and males. QHCl-600 also slowed GE compared to C in males and compared to QHCl-300 in females (p < 0.05). QHCl-300 reduced post-meal glucose concentrations and increased the C-peptide/glucose ratio, compared to C (p < 0.05). Magnitudes of glucose lowering and increase in C-peptide/glucose ratio by QHCl-600 were greater in females than males (p < 0.05). We conclude that quinine modulates glucoregulatory functions, associated with glucose lowering in healthy males and females. However, glucose lowering appears to be greater in females than males, without apparent differential effects on GI functions.
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Esvaziamento Gástrico , Quinina , Humanos , Feminino , Masculino , Quinina/farmacologia , Glicemia , Peptídeo C , Nutrientes , Insulina , Glucose , Colecistocinina , Polipeptídeo Inibidor Gástrico , Peptídeo 1 Semelhante ao GlucagonRESUMO
Objectives: Although early childhood dental caries (ECC) have the same general etiology as other types of caries, predisposing factors are not well elucidated. This study aimed to investigate the effect of salivary alpha-amylase (sAA) activity, body mass index (BMI), dietary habits, and oral hygiene on ECC. Methods: This cross-sectional study was performed on 38 ECC-affected and 41 caries-free children, aged 36 to 72 months. Upon the parents' consent, 3 mL of non-stimulated saliva was collected from the participants to measure the level of sAA activity through spectrophotometry. Additionally, parents/caretakers completed a structured questionnaire about demographic factors, oral hygiene, and consumption of sugar-containing foods. BMI, BMI z-scores, and percentile data were calculated by using an online calculator. The independent variables were dichotomized and tested through chi-square test, followed by a stepwise logistic regression, by using SPSS software (α = 0.05). Results: The sAA activity was significantly higher in caries-free children (P ≤ 0.001). However, the mean BMI was not significantly different between the two groups (P=0.49). Brushing and other measured dietary habits were significantly associated with the development of ECC (P ≤ 0.001). According to the results of the logistic regression, sAA activity was shown to be a predictor for ECC development (Odds ratio (95% confidence interval): 0.9 (0.95-0.98)). Conclusion: Children with inherently lower levels of sAA activity were more susceptible to dental caries. Improper nutritional habits and poor oral health care could exacerbate the risk of ECC.
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CONTEXT: The bitter substance quinine modulates the release of a number of gut and gluco-regulatory hormones and upper gut motility. As the density of bitter receptors may be higher in the duodenum than the stomach, direct delivery to the duodenum may be more potent in stimulating these functions. The gastrointestinal responses to bitter compounds may also be modified by sex. BACKGROUND: We have characterized the effects of intragastric (IG) versus intraduodenal (ID) administration of quinine hydrochloride (QHCl) on gut and pancreatic hormones and antropyloroduodenal pressures in healthy men and women. METHODS: 14 men (26â ±â 2 years, BMI: 22.2â ±â 0.5 kg/m2) and 14 women (28â ±â 2 years, BMI: 22.5â ±â 0.5 kg/m2) received 600 mg QHCl on 2 separate occasions, IG or ID as a 10-mL bolus, in randomized, double-blind fashion. Plasma ghrelin, cholecystokinin, peptide YY, glucagon-like peptide-1 (GLP-1), insulin, glucagon, and glucose concentrations and antropyloroduodenal pressures were measured at baseline and for 120 minutes following QHCl. RESULTS: Suppression of ghrelin (Pâ =â 0.006), stimulation of cholecystokinin (Pâ =â 0.030), peptide YY (Pâ =â 0.017), GLP-1 (Pâ =â 0.034), insulin (Pâ =â 0.024), glucagon (Pâ =â 0.030), and pyloric pressures (Pâ =â 0.050), and lowering of glucose (Pâ =â 0.001) were greater after ID-QHCl than IG-QHCl. Insulin stimulation (Pâ =â 0.021) and glucose reduction (Pâ =â 0.001) were greater in females than males, while no sex-associated effects were found for cholecystokinin, peptide YY, GLP-1, glucagon, or pyloric pressures. CONCLUSION: ID quinine has greater effects on plasma gut and pancreatic hormones and pyloric pressures than IG quinine in healthy subjects, consistent with the concept that stimulation of small intestinal bitter receptors is critical to these responses. Both insulin stimulation and glucose lowering were sex-dependent.
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Grelina , Quinina , Colecistocinina , Método Duplo-Cego , Ingestão de Energia , Feminino , Motilidade Gastrointestinal , Glucagon , Peptídeo 1 Semelhante ao Glucagon , Glucose , Humanos , Insulina , Masculino , Hormônios Pancreáticos , Peptídeo YY , Quinina/farmacologiaRESUMO
Bitter substances are contained in many plants, are often toxic and can be present in spoiled food. Thus, the capacity to detect bitter taste has classically been viewed to have evolved primarily to signal the presence of toxins and thereby avoid their consumption. The recognition, based on preclinical studies (i.e., studies in cell cultures or experimental animals), that bitter substances may have potent effects to stimulate the secretion of gastrointestinal (GI) hormones and modulate gut motility, via activation of bitter taste receptors located in the GI tract, reduce food intake and lower postprandial blood glucose, has sparked considerable interest in their potential use in the management or prevention of obesity and/or type 2 diabetes. However, it remains to be established whether findings from preclinical studies can be translated to health outcomes, including weight loss and improved long-term glycaemic control. This review examines information relating to the effects of bitter substances on the secretion of key gut hormones, gastric motility, food intake and blood glucose in preclinical studies, as well as the evidence from clinical studies, as to whether findings from animal studies translate to humans. Finally, the evidence that bitter substances have the capacity to reduce body weight and/or improve glycaemic control in obesity and/or type 2 diabetes, and potentially represent a novel strategy for the management, or prevention, of obesity and type 2 diabetes, is explored.
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Agentes Aversivos/farmacologia , Glicemia/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Motilidade Gastrointestinal/efeitos dos fármacos , Paladar/fisiologia , Animais , Diabetes Mellitus Tipo 2/metabolismo , Digestão/efeitos dos fármacos , Hormônios Gastrointestinais/metabolismo , Trato Gastrointestinal/metabolismo , Humanos , Obesidade/metabolismo , Período Pós-Prandial , Pesquisa Translacional Biomédica , Redução de Peso/efeitos dos fármacosRESUMO
OBJECTIVES: Metabolic syndrome (MetS) represents a clustering of metabolic abnormalities that are associated with an increased risk of type 2 diabetes and cardiovascular disease. We aimed to evaluate the effects of sesame oil enriched with vitamin E (vit E), sesame oil alone and sunflower oil on lipid profile, fasting blood glucose (FBG), malondialdehyde (MDA), high-sensitivity C-reactive protein (Hs-CRP), homeostatic model assessment (HOMA-IR), and blood pressure (BP) in patients with MetS. SUBJECTS: Overall, 75 individuals with MetS (aged 30-70 years) participated in this randomized, single-blind controlled trial. Patients were randomly allocated to: (1) Group A (n = 25): sesame oil (30 ml/day) enriched with vit E (400 mg/day), (2) Group B (n = 25): sesame oil (30 ml/day), (3) Group C (n = 25): sunflower oil (30 ml/day). Anthropometric data, dietary intake, blood pressure, and biochemical markers, including fasting serum lipids, FBG, serum insulin, MDA, and hs-CRP were measured at baseline and at week 8. RESULTS: In individuals in the sesame oil enriched with vit E group (Group A), there were significant reductions in serum total cholesterol (TC), triglycerides (TG), FBG, HOMA-IR, MDA, hs-CRP, high-density lipoprotein (HDL-C) systolic and diastolic BP (for all the comparison p < 0.02). Similarly, in Group B (taking sesame oil alone), TC, TG, FBG, HOMA-IR, MDA, systolic and diastolic BP were significantly improved (for all the comparison p < 0.025), while there were no significant changes in serum HDL (baseline = 35.9 ± 7.2 mg/dL vs. 36.4 ± 6.2 mg/dL, p = 0.432) and hs-CRP (baseline = 4.38 ± 1.34 mg/dL vs. week 8 = 3.96 ± 1.7 mg/dL, p = 0.057) in second group. No significant changes in any of the studied clinical and anthropometric data were found in Group C (on sunflower oil). CONCLUSION: Sesame oil (±vit E) was shown to beneficially affect several cardiometabolic indices (including lipids, FBG, BP, HOMA-IR, and MDA) in patients with MetS.
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Doenças Cardiovasculares/prevenção & controle , Síndrome Metabólica/tratamento farmacológico , Óleo de Gergelim/administração & dosagem , Vitamina E/administração & dosagem , Adulto , Idoso , Glicemia/análise , Pressão Sanguínea , Proteína C-Reativa/análise , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Jejum , Feminino , Humanos , Resistência à Insulina , Lipídeos/sangue , Masculino , Malondialdeído/sangue , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Fatores de Risco , Método Simples-CegoRESUMO
INTRODUCTION: The aim of the study was to undertake a systematic review and meta-analysis of prospective studies to determine the effect of magnesium (Mg) supplementation on C-reactive protein (CRP). Design: Systematic review and meta-analysis of randomised controlled trials (RCTs). MATERIAL AND METHODS: Data sources: PubMed-Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched (up until December 2016). Eligibility criteria: Randomized controlled trials evaluating the impact of Mg supplementation on CRP. We used random effects models meta-analysis for quantitative data synthesis. For sensitivity analysis was used the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. Main outcome: Level of CRP after Mg supplementation. RESULTS: From a total of 96 entries identified via searches, eight studies were included in the final selection. The meta-analysis indicated a significant reduction in serum CRP concentrations following Mg supplementation (weighted mean difference (WMD) -1.33 mg/l; 95% CI: -2.63 to -0.02, heterogeneity p < 0.123; I2 = 29.1%). The WMD for interleukin 6 was -0.16 pg/dl (95% CI: -3.52 to 3.26, heterogeneity p = 0.802; I2 = 2.3%), and 0.61 mg/dl (95% CI: -2.72 to 1.48, p = 0.182, heterogeneity p = 0.742; I2 = 6.1%) for fasting blood glucose. These findings were robust in sensitivity analyses. Random-effects meta-regression revealed that changes in serum CRP levels were independent of the dosage of Mg supplementation (slope: -0.004; 95% CI: -0.03, 0.02; p = 0.720) or duration of follow-up (slope: -0.06; 95% CI: -0.37, 0.24; p = 0.681). CONCLUSIONS: This meta-analysis suggests that Mg supplementation significantly reduces serum CRP level. RCTs with a larger sample size and a longer follow-up period should be considered for future investigations to give an unequivocal answer.
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BACKGROUND: To evaluate the effect of vitamin D supplementation on C-reactive protein (CRP) through a systematic review and meta-analysis of randomized control trials (RCTs). METHODS: PubMed-Medline, SCOPUS, Google Scholar and Web of Science databases were searched (up until April 2016) to identify RCTs evaluating the impact of vitamin D supplementation on CRP. We used random effects models (using DerSimonian-Laird method) as well as the generic inverse variance methods for quantitative data synthesis. For sensitivity analysis, we applied leave-one-out approach. To examine the heterogeneity we used I2 index. Registration code: CRD42016036932. RESULTS: Among 1274 search items, 24 studies met the inclusion criteria in the final evaluation. Pooling the data together indicated a non-significant decrease in CRP level following administration of vitamin D (weighted mean difference [WMD] -0.26(mg/l), (95% CI -0.75 to 0.22, N = 26 arms, heterogeneity p = 0.042; I2 54.2%). The WMDs for IL6 was 0.67 pg/ml, (95% CI 0.29 to 1.06, N = 16 arms, heterogeneity p = 0.234; I2 19.1%), 0.43 pg/ml, (95% CI 0.08 to 1.05, N = 26 arms, heterogeneity p = 0.120; I2 42.1%), for IL10, and -0.11 pg/ml, (95% CI -0.53 to 0.30, N = 12 arms, heterogeneity p = 0.423; I2 9.2%) for TNF-α, 4.03 pg/ml, (95% CI 3.50 to 4.57, N = 3 arms, heterogeneity p = 0.752; I2 8.1%) for adiponectin. Sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS: This study provided evidence that vitamin D supplementation had no impact on serum CRP, IL10, and TNF-α, while significantly increased serum IL6. We recommend RCTs with longer period of follow-up time (12 months) for future studies to provide explicit results.
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We conducted this systematic review and meta-analysis of prospective studies to determine the effect of probiotic administration on serum C-reactive protein (CRP) concentrations. We searched PubMed-Medline, Web of Science, the Cochrane, and Google Scholar databases (until May 2016) to identify prospective studies evaluating the impact of probiotic administration on CRP. We used a random effects models and generic inverse variance methods to synthesize quantitative data, followed by a leave-one-out method for sensitivity analysis. The systematic review registration number was: CRD42016039457. From a total of 425 entries identified via searches, 20 studies were included in the final analysis. The meta-analysis indicated a significant reduction in serum CRP following probiotic administration with a weighted mean difference (WMD) of -1.35 mg/L, (95% confidence interval (CI) -2.15 to -0.55, I² 65.1%). The WMDs for interleukin 10 (IL10) was -1.65 pg/dL, (95% CI -3.45 to 0.14, I² 3.1%), and -0.45 pg/mL, (95% CI -1.38 to 0.48, I² 10.2%) for tumor necrosis factor alpha (TNF-α). These findings were robust in sensitivity analyses. This meta-analysis suggests that probiotic administration may significantly reduce serum CRP while having no significant effect on serum IL10 and TNF-α.
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Proteína C-Reativa/metabolismo , Probióticos/administração & dosagem , Bases de Dados Factuais , Humanos , Interleucina-10/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/sangueRESUMO
Aim: to systematically review and conduct a meta-analysis of randomized controlled trials investigating the impact of vitamin D supplementation on endothelial function. Method: We searched PubMed-Medline, SCOPUS, Web of Science and Google Scholar (until June 2016) to detect prospective studies evaluating the impact of vitamin D supplementation on endothelial function indexes. We used random effects models (using DerSimonian-Laird method) and generic inverse variance methods to synthesize quantitative data. We used the leave-one-out method for sensitivity analysis. To quantitatively assess the heterogeneity we used the I2 index. Systematic review registration: CRD42016039329. Results: From a total of 213 entries identified, 12 studies were appropriate for inclusion into the final analysis. The meta-analysis indicated a significant enhancement in flow-mediated dilation (FMD) following D supplementation (vitamin D intervention group versus control group 1.27 %, (95% CI 0.20 to 2.34, N = 11 arms, heterogeneity p = 0.054; I2 51.2 %). These findings were robust in sensitivity analyses. Conclusions: This meta-analysis suggested that vitamin D supplementation may improve endothelial function. Randomized control trials with a longer-term follow-up are warranted to clarify the existing controversies and shed light on the potential underlying mechanisms.
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AIM: To undertake a systematic review and meta-analysis of prospective studies to determine the effect of conjugated linoleic acids (CLAs) supplementation on serum C-reactive protein (CRP). METHOD: PubMed-Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched (up until May 2016) to identify prospective studies evaluating the impact of CLAs supplementation on serum CRP. Random-effects models meta-analysis was used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. Systematic review registration: CRD42016038945. RESULTS: From a total of 85 entries identified via searches, 14 studies were included in the final selection. The meta-analysis indicated a significant increase in serum CRP concentrations following supplementation with CLAs (weighted mean difference [WMD] 0.63 mg/dL, 95% confidence interval [95% CI] 0.13-1.13, N=21 arms, heterogeneity P=.026; I2 =52.3%). These findings were robust in sensitivity analyses. Random-effects meta-regression revealed that changes in serum CRP levels were independent of the dosage of CLAs supplementation (slope: -0.02; 95% CI: -0.10, 0.12; P=.889) or duration of follow-up (slope: 0.271; 95% CI: -0.05, 0.59; P=.098). CONCLUSIONS: This meta-analysis suggests that CLA supplementation is associated with an increase in plasma CRP concentrations and a reduction in serum adiponectin concentrations, which indicates that CLA supplements have a proinflammatory effect. Randomized control trials with larger sample size and a longer follow-up period may be required for future investigations to provide an unequivocal answer.
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Proteína C-Reativa/metabolismo , Ácidos Linoleicos Conjugados/farmacologia , Suplementos Nutricionais , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
AIM: To undertake a systematic review and meta-analysis of prospective clinical studies to determine the effect of bile acid sequestrants (BAS) on lipid profile and blood glucose concentrations. METHOD: PubMed-Medline, Web of Science, Cochrane Database and Google Scholar databases were searched (up until August 2016) to identify prospective studies evaluating the impact of BASs on the cardio-metabolic profile. Random effects model meta-analysis was used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. Systematic review registration: CRD42016035973. RESULTS: From a total of 769 entries identified, 15 studies were included in the final analysis. The meta-analysis indicated a significant reduction in fasting serum triglyceride concentrations following treatment with BASs (weighted mean difference [WMD] 0.54mg/dL, 95% CI 0.43 to 0.65, heterogeneity p=0.021; I2 54.2%, n=11 studies). The WMDs for total serum cholesterol (TC) was -1.18mg/dL (95% CI -1.30 to -1.06, heterogeneity p=0012; I2 63.1%, n=11 studies), 0.126mg/dL (95% CI 0.02 to 0.22, heterogeneity p=0.231; I2 43.2%, n=11 studies) for HDL-cholesterol, and -0.24mg/dL (95% CI -0.35 to -0.14, heterogeneity p=0.562; I2 23.1%, n=10 studies) for LDL-cholesterol, and -2.10mg/dL (95% CI -2.84 to -1.36, heterogeneity p=0.200; I2 42.6%, n=11 studies) fasting blood glucose (FBG) and -0.83% (95% CI -1.08 to -0.57, heterogeneity p=0.856; I2 20.9%, n=11 studies) for HbA1c. These findings were robust in sensitivity analyses. CONCLUSIONS: This meta-analysis suggests that therapy with BAS significantly improves HDL-C, LDL-C, and glycemic markers including fasting blood glucose, HbA1c levels, while deteriorating triglyceride levels.
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Resinas de Troca Aniônica/farmacologia , Glicemia/análise , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Ácidos e Sais Biliares/antagonistas & inibidores , Feminino , Humanos , Masculino , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
AIM: To undertake a systematic review and meta-analysis of randomized controlled trials of the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy on serum C-reactive protein (CRP) concentrations. METHOD: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched for the period up until March 16, 2016. Prospective studies evaluating the impact of GLP-1 RAs on serum CRP were identified. A random effects model (using the DerSimonian-Laird method) and generic inverse variance methods were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. Random effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential moderator. International Prospective Register for Systematic Reviews (PROSPERO) number CRD42016036868. RESULTS: Meta-analysis of the data from 7 treatment arms revealed a significant reduction in serum CRP concentrations following treatment with GLP-1 RAs (WMD -2.14 (mg/dL), 95% CI -3.51, -0.78, P=0.002; I2 96.1%). Removal of one study in the meta-analysis did not change the result in the sensitivity analysis (WMD -2.14 (mg/dL), 95% CI -3.51, -0.78, P=0.002; I2 96.1%), indicating that our results could not be solely attributed to the effect of a single study. Random effects meta-regression was performed to evaluate the impact of potential moderator on the estimated effect size. Changes in serum CRP concentration were associated with the duration of treatment (slope -0.097, 95% CI -0.158, -0.042, P<0.001). CONCLUSIONS: This meta-analysis suggests that GLP-1 RAs therapy causes a significant reduction in CRP.
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Proteína C-Reativa/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Exenatida , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hemoglobinas Glicadas/análise , Humanos , Liraglutida/uso terapêutico , Peptídeos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Peçonhas/uso terapêuticoRESUMO
BACKGROUND: The sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of oral hypoglycemic agents. We undertake a systematic review and meta-analysis of prospective studies to determine the effect of SGLT2 on blood pressure (BP) among individuals with type 2 diabetes mellitus. METHODS AND RESULTS: PubMed-Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched to identify trial registries evaluating the impact of SGLT2 on BP. Random-effects models meta-analysis was used for quantitative data synthesis. The meta-analysis indicated a significant reduction in systolic BP following treatment with SGLT2 (weighted mean difference -2.46 mm Hg [95% CI -2.86 to -2.06]). The weighted mean differences for the effect on diastolic BP was -1.46 mm Hg (95% CI -1.82 to -1.09). In these subjects the weighted mean difference effects on serum triglycerides and total cholesterol were -2.08 mg/dL (95% CI -2.51 to -1.64) and 0.77 mg/dL (95% CI 0.33-1.21), respectively. The weighted mean differences for the effect of SGLT2 on body weight was -1.88 kg (95% CI -2.11 to -1.66) across all studies. These findings were robust in sensitivity analyses. CONCLUSIONS: Treatment with SGLT2 glucose cotransporter inhibitors therefore has beneficial off-target effects on BP in patients with type 2 diabetes mellitus and may also be of value in improving other cardiometabolic parameters including lipid profile and body weight in addition to their expected effects on glycemic control. However, our findings should be interpreted with consideration for the moderate statistical heterogeneity across the included studies.
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Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Túbulos Renais Proximais/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Benzidrílicos/administração & dosagem , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Canagliflozina/administração & dosagem , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Glucosídeos/administração & dosagem , Humanos , Hipoglicemiantes/efeitos adversos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/fisiopatologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Transportador 2 de Glucose-Sódio/metabolismo , Tiofenos/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To investigate changes in adiposity and cardio-metabolic risk profile following Roux-en-Y gastric bypass in patients of Middle Eastern ethnicity with severe obesity. METHODS: This prospective cohort study involved 92 patients who met the indications of bariatric surgery. Post-procedure markers of obesity and cardiometabolic profile were monitored regularly for a year. RESULTS: Mean body mass index decreased by 29.5% from 41.9 to 29.5 kg/m2 between baseline and 12-mo follow-up, while mean fat mass decreased by 45.9% from 64.2 kg to 34.7 kg. An improvement was also observed in the gluco-metabolic profile with both fasting glucose and HbA1c substantially decreasing (P < 0.001). CONCLUSION: The present study shows the short to medium term (1 year) health benefits of bariatric surgery for patients of Middle Eastern ethnicity.
RESUMO
BACKGROUND: Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. OBJECTIVE: We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. METHODS: The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. RESULTS: Of the 10568 eligible participants, 48.0% (n=5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p<0.001). The association between TL and kidney function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (ß-coefficient= -0.012, p=0.056). CONCLUSION: The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.
RESUMO
Metabolic syndrome (MetS) is currently diagnosed by the co-presence of at least three of the five following abnormalities: abdominal obesity, dysglycaemia, elevated serum triglycerides, low high-density cholesterol (HDL) and finally elevated blood pressure. Metabolic syndrome increases the risk of developing cardiovascular disease and diabetes. This review is on the associations between MetS and vascular endothelial growth factor (VEGF). VEGF induces migration and proliferation of endothelial cells (ECs), increases vascular permeability and has a role in tumor growth, adipose tissue expansion, age-related macular degeneration and diabetic retinopathy. Circulating levels of VEGFs are elevated in obese individuals and it has also been suggested that VEGF is secreted from adipose tissues, especially from intra-abdominal adipose tissue. There is abundant evidence to support that poor glycemic control in diabetic patients is associated with increased plasma VEGF, which in turn may cause hypertension and several vascular complications in diabetic patients. Circulating VEGF levels are increased in children and young adults with type 1 diabetes mellitus and middle-aged diabetic patients with proliferative retinopathy. It has been revealed that plasma VEGF increases in patients with hyperlipidemia and may trigger the development of atherosclerosis. It can be concluded that there is a positive association between VEGF and components of MetS. Because of the importance of this relationship, more investigations are needed in this field.