Association of Thiazide-Type Diuretics With Glycemic Changes in Hypertensive Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.
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SUBMITTER: Zhang X
PROVIDER: S-EPMC8031670 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Single-nucleotide polymorphisms (SNPs) in NEDD4L may influence the ability of the NEDD4L protein to reduce epithelial sodium channel expression. A variant in NEDD4L, rs4149601, was associated with antihypertensive response and cardiovascular outcomes during treatment with thiazide diuretics and ?-blockers in a Swedish population. We sought to further evaluate associations between NEDD4L polymorphisms, blood pressure response and cardiovascular outcomes with thiazide diuretics and ?-blockers.Four SNPs, rs4149601, rs292449, rs1008899 and rs75982813, were genotyped in 767 patients from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) clinical trial and association was assessed with blood pressure response to hydrochlorothiazide and atenolol. One SNP, rs4149601, was also genotyped in 1345 patients from the International Verapmil SR Trandolapril Study (INVEST), and association was examined with adverse cardiovascular outcomes relative to hydrochlorothiazide treatment.Significant associations or trends were found between rs4149601, rs292449, rs75982813 and rs1008899 and decreases in blood pressure in whites on hydrochlorothiazide, and a significant association was observed with increasing copies of the GC rs4149601-rs292449 haplotype and greater blood pressure response to hydrochlorothiazide in whites (P = 0.0006 and 0.006, SBP and DBP, respectively). Significant associations were also seen with rs4149601 and an increased risk for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide [P = 0.022, odds ratio (95% confidence interval) = 10.65 (1.18-96.25)].NEDD4L rs4149601, rs292449 and rs75982813 may be predictors for blood pressure response to hydrochlorothiazide in whites, and NEDD4L rs4149601 may be a predictor for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide.
| S-EPMC3756535 | biostudies-literature
Project description:PurposeThiazide diuretics are the most common origin of drug-induced hyponatremia. However, population-based studies on clinical outcomes are lacking. We therefore explored the time course and absolute risk of thiazide-associated hospitalization due to hyponatremia in Sweden.MethodsPopulation-based case-control study including patients hospitalized with a principal diagnosis of hyponatremia (n = 11,213) compared with controls (n = 44,801). Linkage of registers was used to acquire data. Multivariable regression was applied to explore time-dependent associations between thiazide diuretics and hospitalization due to hyponatremia. Attributable risks were calculated assessing the disease burden attributable to thiazides.ResultsIndividuals initiating thiazide treatment were exposed to an immediate increase in risk for hospitalization with adjusted odds ratio (aOR) (95% CI) of 48 (28-89). The associations gradually declined reaching an aOR of 2.9 (2.7-3.1) for individuals treated for longer than 13 weeks. The attributable risk of hyponatremia-associated hospitalization due to thiazides of any treatment length was 27% (3095/11,213). Among 806 patients initiating treatment < 90 days before hospitalization, hyponatremia could be attributed to thiazides in 754. Based on nationwide data, 616,678 individuals were initiated on thiazides during the 8-year study period suggesting an absolute risk of 0.12% (754/661,678) for subsequent hospitalization with a main diagnosis of hyponatremia.ConclusionsThiazide diuretics attributed to more than one in four individuals hospitalized due to hyponatremia. The risk increase was very pronounced during the first month of treatment and then gradually declined, without returning to normal. However, the absolute risk for the development of hyponatremia demanding hospitalization may for most individuals be modest.
| S-EPMC8184529 | biostudies-literature
Project description:OBJECTIVES:Thiazide diuretics are one of the first choice antihypertensives but not optimally utilised because of concerns regarding their adverse effects on glucose metabolism. The Diuretics In the Management of Essential hypertension (DIME) study was designed, for the first time, to assess the risk for type 2 diabetes mellitus in patients with essential hypertension during antihypertensive treatment with low-dose thiazide diuretics compared to those not treated with diuretics. DESIGN:Multicentre, unblinded, pragmatic, randomised, controlled trial with blinded assessment of end points and intention-to-treat analysis that was started in 2004 and finished in 2012. SETTING:Hypertension clinics at 106 sites in Japan, including general practitioners' offices and teaching hospitals. PARTICIPANTS:Non-diabetic patients with essential hypertension. INTERVENTIONS:Antihypertensive treatment with low-dose thiazide diuretics at 12.5?mg/day of hydrochlorothiazide or equivalent (Diuretics group) or that without thiazide diuretics (No-diuretics group). MAIN OUTCOME:The primary outcome was new onset of type 2 diabetes diagnosed according to WHO criteria and the criteria of Japanese Society of Diabetes. RESULTS:1130 patients were allocated to Diuretics (n=544) or No-diuretics group (n=586). Complete end point information was collected for 1049 participants after a median follow-up of 4.4?years. Diabetes developed in 25 (4.6%) participants in the Diuretics group, as compared with 29 (4.9%) in the No-diuretics group (HR 0.93; 95% CI 0.55 to 1.58; p=0.800). CONCLUSIONS:Antihypertensive treatment with thiazide diuretics at low doses may not be associated with an increased risk for new onset of type 2 diabetes. This result might suggest safety of use of low doses of thiazide diuretics. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov NCT00131846.
| S-EPMC4120409 | biostudies-literature
Project description:We performed a meta-analysis to evaluate the efficacy of alprostadil in the treatment of hypertensive nephropathy. Seven online databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure [CNKI] database, Wanfang Data Knowledge Service Platform, VIP Information Resource Integration Service Platform [cqVIP], and China Biology Medicine Disc [SinoMed]) were searched from inception to January 31, 2022, and a set of clinical indicators for hypertensive nephropathy was selected. The main indicators were 24-h urinary protein, serum creatinine, endogenous serum creatinine clearance rate, blood urea nitrogen, cystatin C, and mean arterial pressure. The methodological quality of the included trials was analyzed using a risk of bias assessment according to the Cochrane Manual guidelines, and a meta-analysis was performed. A random-effects model was implemented to pool the results. A total of 20 randomized controlled trials involving 1441 patients with hypertensive nephropathy were included in this review. Our findings showed that alprostadil had a positive effect on 24-h urinary protein (mean difference [MD] = -0.79, 95% confidence interval [CI] [-1.16, -0.42], P < 0.0001), serum creatinine (MD = -13.83, 95% CI [-19.34, -8.32], P < 0.00001), endogenous serum creatinine clearance rate (MD = 6.09, 95% CI [3.59, 8.59], P < 0.00001), blood urea nitrogen (MD = -6.42, 95% CI [-8.63, -4.21], P < 0.00001), cystatin C (MD = -0.26, 95% CI [-0.34, -0.18], P < 0.00001), and mean arterial pressure levels(MD = -13.65, 95% CI [-16.08, -11.21], P < 0.00001). Compared to conventional treatment alone, alprostadil combined with conventional treatment can improve renal function in patients with hypertensive nephropathy more effectively. However, additional large-scale, multicenter, rigorously designed randomized controlled trials are needed to verify these results. This is the first meta-analysis to evaluate the efficacy of alprostadil for hypertensive nephropathy, and the results may guide clinical practice.
| S-EPMC9135256 | biostudies-literature
Project description:Aims/introductionAlthough mounting evidence has suggested an inverse association between the intake of whole grains and glycemic control, findings from randomized controlled trials are still conflicting. The current study was carried out to evaluate the effect of medium/long-term whole grain intake on glycemic control in metabolic syndrome and healthy populations.Materials and methodsA literature search was carried out to identify qualified studies up to July 2021. The effects of whole grain consumption on glycemic control were calculated using a fixed effects model. Subgroup analysis was used to study whether grouping factors were important influencing factors of heterogeneity between research results.ResultsA total of 32 randomized controlled trials with 2,060 participants were included in the analyses. Whole grain consumption showed a significant inverse regulatory effect on fasting glucose concentration, but no significant effect was found for other glycemic measures, such as fasting insulin, homeostatic model assessment for insulin resistance, glycated hemoglobin and 2-h glucose, in the pooled analysis. Through subgroup analyses, a significant decrease in fasting glucose concentration was observed for studies with a higher whole grain dose, with participants of normal glycemia, and with mixed types of whole grain.ConclusionsMedium-/long-term whole grain intake reduced the fasting glucose concentration compared with similar refined foods. Appropriate intervention dose and accurate population selection might be the key links for whole grain consumption to exert its glycemic control effect.
| S-EPMC9623515 | biostudies-literature
Project description:PurposeOur meta-analysis was undertaken to evaluate the efficacy and safety of nebivolol compared with other second-generation β blockers for hypertensive patients.MethodsWe searched PubMed, the Cochrane Library, EMBASE, and Clinical Trials.gov databases for randomized controlled trials (RCTs). The efficacy endpoints included systolic blood pressure (SBP), diastolic blood pressure (DBP), reduction of SBP and DBP, heart rate (HR), and adverse events (AEs).FindingsEight RCTs with 1514 patients met the inclusion criteria. HR was significantly lower in patients receiving other second-generation β blockers compared with patients receiving nebivolol. There was no difference the reduction of blood pressure (SBP and DBP) or the reduction of SBP or DBP between the groups. The incidence of AEs was lower in patients taking nebivolol compared with patients taking other second-generation β blockers.ConclusionsNo significant difference was demonstrated between nebivolol and other second-generation β blockers in the reduction of blood pressure, SBP, and DBP. The tolerability of nebivolol was significantly better compared with other second-generation β blockers, and nebivolol was also associated with a stable HR and a lower risk of AEs compared with other second-generation β blockers.
| S-EPMC7588777 | biostudies-literature
Project description:BackgroundPrevious clinical trials indicate that probiotic consumption may improve blood glucose control, however, results from randomized trials on glycemic control have been inconsistent.ObjectiveTo investigate the effects of probiotics on glycemic control in a systematic review and meta-analysis of randomized controlled trials.Data sourcesPubMed, Embase, Cochrane Library, and Clinicaltrial.gov through October 2014.Data extraction and synthesisTwo independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using a random-effects model and expressed as mean differences (MD) with 95% CI. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2).ResultsSeventeen randomized controlled trials were included, in which 17 fasting blood glucose (n = 1105), 11 fasting plasma insulin (n = 788), 8 homeostasis model assessment of insulin resistance (n = 635) comparisons were reported. Probiotic consumption, compared with placebo, significantly reduced fasting glucose (MD = -0.31 mmol/L; 95% CI 0.56, 0.06; p = 0.02), fasting plasma insulin (MD = -1.29 ?U/mL; 95% CI -2.17, -0.41; p = 0.004), and HOMA-IR (MD = 0.48; 95% CI -0.83, -0.13; p = 0.007).ConclusionsProbiotic consumption may improve glycemic control modestly. Modification of gut microbiota by probiotic supplementation may be a method for preventing and control hyperglycemia in clinical practice.
| S-EPMC4498615 | biostudies-literature
Project description:BACKGROUND:The popularity of internet as an area of research has grown manifold over the years. Given its rapid development and increasing coverage worldwide, internet-based interventions seem to offer a promising option to ameliorate huge burdens brought by type 2 diabetes mellitus. However, studies conducted by different researchers have provided contradictory results on the effect of internet-based interventions in glycemic control. OBJECTIVE:This meta-analysis aims to summarize currently available evidence and evaluate the overall impact of internet-based interventions on glycemic management of type 2 diabetic patients. METHODS:A systematic literature search was performed in PubMed, ScienceDirect, and Web of Science. Randomized controlled trials that used glycosylated hemoglobin values as the outcome measure of glycemic control were considered. Risk of bias and publication bias were evaluated. RESULTS:Of the 492 studies, 35 were included in meta-analysis, and results indicated that the weighted mean difference (WMD) between usual care and internet-based interventions at endpoint was -0.426% (95% CI -0.540 to -0.312; P<.001). Subgroup analyses revealed that intervention duration ≤3 months yielded optimal performance (WMD -0.51%; 95% CI -0.71 to -0.31; P<.001). Combined mobile and website interventions were substantially superior to solely Web-based and mobile-based interventions in glycemic control (combined WMD -0.77%, 95% CI -1.07 to -0.47; P<.001; Web only: WMD -0.48%; 95% CI -0.71 to -0.24, P<.001; mobile only WMD -0.31%, 95% CI -0.49 to -0.14; P<.001). Furthermore, the effect of interventions with automated feedbacks was similar to those with manual feedbacks, and studies with internet-based educational contents were more effective in glycemic control. The assessment revealed a low risk of bias. CONCLUSIONS:In conclusion, utilization of internet-based intervention is beneficial for patients with type 2 diabetes mellitus, and taking full advantage of this type of intervention may substantially reduce the incidence of complications and improve quality of life. TRIAL REGISTRATION:International Prospective Register of Systematic Reviews (PROSPERO): CRD42017058032; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=58032 (Archived by WebCite at http://www.webcitation.org/6yY7eQNHr).
| S-EPMC5962831 | biostudies-other
Project description:BackgroundPrior meta-analyses measuring thiazide-induced glycemic change have demonstrated an increased risk of incident diabetes; however, this measure's definition has changed over time.AimTo determine the magnitude of change in fasting plasma glucose (FPG) for thiazide diuretics.Data sourcesA research librarian designed and conducted searches in Medline®, EMBASE, and EBM Reviews-Cochrane Central Register of Controlled Trials (inception through July 2018) and International Pharmaceutical Abstracts (inception to December 2014).Study selectionRandomized, controlled trials comparing a thiazide or thiazide-like diuretic to any comparator reporting FPG were identified. Trials enrolling < 50 participants, those with a follow-up period of < 4 weeks, and conference abstracts were excluded.Data extractionIndependent duplicate screening of citations and full-text articles, data extraction, and assessment of risk of bias was conducted.Data synthesisNinety-five studies were included (N = 76,608 participants), with thiazides compared with placebo, beta-blockers, calcium channel blockers, renin-angiotensin-aldosterone-system inhibitors, potassium-sparing diuretic, and others alone or in combination. Thiazide diuretics marginally increased FPG (weighted mean difference 0.20 mmol/L (95% CI 0.15-0.25); I2 = 84%) (1 mmol/L = 18 mg/dL). Results did not change substantially when considering dose or duration, comparing thiazides with placebo or an active comparator, or using thiazides as monotherapy or combination therapy, even when combined with a potassium-correcting agent.ConclusionThiazide diuretics have a small and clinically unimportant impact on FPG.
| S-EPMC7280437 | biostudies-literature
Project description:Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response.
| S-EPMC4915478 | biostudies-literature