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Clinical Nutrition (Edinburgh, Scotland) Dec 2023Diabetes mellitus is a risk factor for muscle loss and sarcopenia. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) or "gliflozins" are one of the newest... (Review)
Review
Diabetes mellitus is a risk factor for muscle loss and sarcopenia. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) or "gliflozins" are one of the newest anti-hyperglycemic drugs. They reduce blood glucose levels by inhibiting renal glucose reabsorption in the early proximal convoluted tubule. Various randomized trials showed that SGLT2i have cardio-protective and reno-protective action. SGLT2i also affect body composition. They usually decrease body fat percentage, visceral and subcutaneous adipose tissue. However, regarding the muscle mass, there are conflicting findings some studies showing detrimental effects and others showed neutral or beneficial effects. This issue is extremely important not only because of the wide use of SGLT2i around globe; but also skeletal muscle mass consumes large amounts of calories during exercise and is an important determinant of resting metabolic rate and skeletal muscle loss hinders energy consumption leading to obesity. In this systematic review, we extensively reviewed the experimental and clinical studies regarding the impact of SGLT2i on muscle mass and related metabolic alterations. Importantly, studies are heterogeneous and there is unmet need to highlight the alterations in muscle during SGLT2i use.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Sarcopenia; Glucose; Sodium; Symporters
PubMed: 37862820
DOI: 10.1016/j.clnu.2023.10.004 -
Carcinogenesis Feb 2024Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have... (Meta-Analysis)
Meta-Analysis
Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69-0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Androgens; Follow-Up Studies; Cohort Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Prospective Studies; Genotype; Organic Anion Transporters; Solute Carrier Organic Anion Transporter Family Member 1B3
PubMed: 37856781
DOI: 10.1093/carcin/bgad075 -
Journal of the American Pharmacists... 2024The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of diabetic ketoacidosis (DKA). As more drugs of this class are approved and their indications are expanded, this serious adverse effect has been increasingly reported.
OBJECTIVE
This review evaluated observational studies to inform the prevalence of SGLT2-inhibitor-associated DKA compared with other antihyperglycemic agents.
METHODS
A systematic review was conducted in PubMed and EMBASE until 19 July 2022 (PROSPERO: CRD42022385425). We included published retrospective cohort active comparator/new user (ACNU) and prevalent new user studies assessing SGLT2-inhibitor-associated DKA prevalence in adult patients with type 2 diabetes mellitus (T2DM) against active comparators. We excluded studies which lacked 1:1 propensity score matching. The JBI Checklist for Cohort Studies guided the risk-of-bias assessments. Meta-analysis was conducted based on the inverse variance method in R software.
RESULTS
Sixteen studies with a sample of 2,956,100 nonunique patients met the inclusion criteria. Most studies were conducted in North America (n = 9) and adopted the ACNU design (n = 15). Meta-analysis of 14 studies identified 33% higher DKA risk associated with SGLT2 inhibitors (HR = 1.33, 95% CI: 1.14-1.55, P < 0.01). Meta-regression analysis identified the study location (P = 0.02), analysis principle (P < 0.001), exclusion of chronic comorbidities (P = 0.007), and canagliflozin (P = 0.04) as significant moderator variables.
CONCLUSIONS
Despite limitations related to heterogeneity, generalizability, and misclassification, the results of this study show that SGLT2 inhibitors increase the prevalence of DKA among adult T2DM patients in the real world. The findings supplement evidence from randomized controlled trials (RCTs) and call for continued vigilance.
Topics: Adult; Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Ketoacidosis; Prevalence; Sodium-Glucose Transporter 2; Nimustine; Diabetes Mellitus, Type 2; Hypoglycemic Agents
PubMed: 37844733
DOI: 10.1016/j.japh.2023.10.010 -
Clinical Laboratory Oct 2023Acinetobacter baumannii produce biofilm and efflux pumps. This systematic review study aimed to provide new strategies to inhibit the efflux pumps and biofilm in A.... (Review)
Review
BACKGROUND
Acinetobacter baumannii produce biofilm and efflux pumps. This systematic review study aimed to provide new strategies to inhibit the efflux pumps and biofilm in A. baumannii using nanoparticles.
METHODS
In this research, analyses from 2000 to February 24, 2022, were performed by the Statement of Preferred Reporting Items for Systematic Reviews (PRISMA). Keywords include Acinetobacter baumannii (A. baumannii) AND (biofilm) AND (anti-biofilm activity) AND (nanoparticles) AND (solid lipid NPS) AND (lipid nanocarriers), and in other searches include Acinetobacter baumannii (A. baumanni) AND (efflux pumps) AND (nanoparticles) AND (solid lipid NPS) AND (lipid nanocarriers). Searches were conducted in English databases, including Science Direct, PubMed, Scopus, Ovid, and Cochrane.
RESULTS
At first, 136 studies were extracted, but after removing duplicates, 116 cases remained for further analysis. After evaluating the title and abstract of each study, 95 unrelated studies were excluded. The remaining 25 studies were reviewed based on full texts. Considering the inclusion/exclusion criteria, 19 studies were selected. In this study, metal nanoparticles were the most used nanoparticles for anti-biofilm and efflux pump purposes, and among these nanoparticles, silver nanoparticles (AgNPs) contributed the most.
CONCLUSIONS
The present study shows that nanoparticles have potential and significant effects in inhibiting biofilm and efflux pumps in A. baumannii isolates, which researchers can consider in light of the increasing prevalence of antibiotic resistance.
Topics: Humans; Anti-Bacterial Agents; Membrane Transport Proteins; Acinetobacter baumannii; Metal Nanoparticles; Silver; Biofilms; Lipids; Microbial Sensitivity Tests; Drug Resistance, Multiple, Bacterial; Bacterial Proteins
PubMed: 37844038
DOI: 10.7754/Clin.Lab.2023.230227 -
Expert Opinion on Pharmacotherapy 2023This study assessed the clinical safety and efficacy of bexagliflozin, a sodium-glucose cotransporter 2(SGLT2) inhibitor, in managing glycemia among patients with type 2... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This study assessed the clinical safety and efficacy of bexagliflozin, a sodium-glucose cotransporter 2(SGLT2) inhibitor, in managing glycemia among patients with type 2 diabetes mellitus (T2DM).
AREAS COVERED
We examined RCTs with T2DM comparing the clinical effectiveness and safety of 20 mg once daily oral dose of bexagliflozin with placebo for managing glycemia till 28 May 2023, published on databases like ClinicalTrials.gov, PubMed, Embase, and Cochrane Library. Furthermore, reduction of body weight, fasting plasma sugarr(FPG), systolic blood pressure (SBP) and the percentage of individuals who achieved glycated hemoglobin (HbA1c) of < 7% from baseline were also evaluated. The Review Manager 5 was utilized to investigate the retrieved data.
EXPERT OPINION
We involved eight RCTs. Bexagliflozin was significantly superior in reducing HbA1c[least squares mean difference(LSMD) = -0.45,95% confidence interval (CI =-0.55 to -0.34, < 0.00001], FPG [LSMD= -1.37, 95%CI =-1.73 to -1.00, < 0.00001], body weight (LSMD= -1.77, 95%CI =-2.44 to-1.10, < 0.00001), and SBP(LSMD= -4.11,95%CI = -6.18 to -2.03, = 0.0001) in comparison to placebo. The safety outcomes of bexagliflozin were consistent with the placebo arm. This study concluded that bexagliflozin seems to be a promising oral anti-diabetic drug for enhancing glycemic management in adult patients with T2DM.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glycated Hemoglobin; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Body Weight; Glucose; Sodium
PubMed: 37817422
DOI: 10.1080/14656566.2023.2269854 -
Journal of Psychopharmacology (Oxford,... Nov 2023Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the magnitude and consistency of the findings are unknown. We address this by systematically reviewing in vivo imaging evidence for dopamine measures in MDD and meta-analysing these where there are sufficient studies.
METHODS
Studies investigating the dopaminergic system using positron emission tomography or single photon emission computed tomography in MDD and a control group were included. Demographic, clinical and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted.
RESULTS
We identified 43 studies including 662 patients and 801 controls. Meta-analysis of 38 studies showed no difference in mean or mean variability of striatal D receptor availability ( = 0.06, = 0.620), or combined dopamine synthesis and release capacity ( = 0.19, = 0.309). Dopamine transporter (DAT) availability was lower in the MDD group in studies using DAT selective tracers ( = -0.56, = 0.006), but not when tracers with an affinity for serotonin transporters were included ( = -0.21, = 0.420). Subgroup analysis showed greater dopamine release ( = 0.49, = 0.030), but no difference in dopamine synthesis capacity ( = -0.21, = 0.434) in the MDD group. Striatal D receptor availability was lower in patients with MDD in two studies.
CONCLUSIONS
The meta-analysis indicates striatal DAT availability is lower, but D receptor availability is not altered in people with MDD compared to healthy controls. There may be greater dopamine release and lower striatal D receptors in MDD, although further studies are warranted. We discuss factors associated with these findings, discrepancies with preclinical literature and implications for future research.
Topics: Humans; Dopamine; Depressive Disorder, Major; Tomography, Emission-Computed, Single-Photon; Positron-Emission Tomography; Receptors, Dopamine D2; Dopamine Plasma Membrane Transport Proteins
PubMed: 37811803
DOI: 10.1177/02698811231200881 -
Seizure Nov 2023Epilepsy is a common neurological disorder in children. Numerous studies have demonstrated the association between SCN1A polymorphisms and risk of epilepsy in adults,... (Meta-Analysis)
Meta-Analysis
Epilepsy is a common neurological disorder in children. Numerous studies have demonstrated the association between SCN1A polymorphisms and risk of epilepsy in adults, but their role in epilepsy in children has just gained traction and results have remained inconsistent. In this work, we performed a systematic review and meta-analysis to assess the association between SCN1A polymorphisms and risk for epilepsy in children. A systematic literature search was performed in PubMed, Scopus, Web of Science, China National Knowledge Internet, Wanfang and VIP databases to identify eligible studies up to June 2023. Quantitative data synthesis was then performed under five genetic models: dominant, recessive, homozygous, heterozygous, and allele. Five studies involving 1380 subjects were included in the meta-analysis. Among many SCN1A polymorphisms reported, only rs2298771 was repeatedly studied in these reports. Pooled analysis demonstrated that there was no significant association between the polymorphism and risk of epilepsy in children (P>0.05). In conclusion, SCN1A rs2298771 polymorphism was not significantly associated with the risk of epilepsy in children.
Topics: Adult; Humans; Child; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; NAV1.1 Voltage-Gated Sodium Channel; Epilepsy; China
PubMed: 37741152
DOI: 10.1016/j.seizure.2023.09.012 -
Seizure Oct 2023Bumetanide, an inhibitor of the sodium-potassium-chloride cotransporter-1, has been suggested as an adjunct to phenobarbital for treating neonatal seizures.
BACKGROUND
Bumetanide, an inhibitor of the sodium-potassium-chloride cotransporter-1, has been suggested as an adjunct to phenobarbital for treating neonatal seizures.
METHODS
A systematic review of animal and human studies was conducted to evaluate the efficacy and safety of bumetanide for neonatal seizures. PubMed, Embase, CINAHL and Cochrane databases were searched in March 2023.
RESULTS
26 animal (rat or mice) studies describing 38 experiments (28 in-vivo and ten in-vitro) and two human studies (one RCT and one open-label dose-finding) were included. The study designs, methods to induce seizures, bumetanide dose, and outcome measures were heterogeneous, with only 4/38 experiments being in animal hypoxia/ischaemia models. Among 38 animal experiments, bumetanide was reported to have antiseizure effects in 21, pro-seizure in six and ineffective in 11. The two human studies (n = 57) did not show the benefits of bumetanide as an add-on agent to phenobarbital in their primary analyses, but one study reported benefit on post-hoc analysis. Overall, hearing impairment was detected in 5/37 surviving infants in the bumetanide group vs. 0/13 in controls. Four of the five infants with hearing impairment had received aminoglycosides concurrently. Other adverse effects reported were diuresis, mild-to-moderate dehydration, hypotension, and electrolyte disturbances. The studies did not report on long-term neurodevelopment. The certainty of the evidence was very low.
CONCLUSION
Animal data suggest that bumetanide has inconsistent effects as an antiseizure medication in neonates. Data from human studies are scarce and raise some concerns regarding ototoxicity when given with aminoglycosides. Well conducted studies in animal models of hypoxic-ischaemic encephalopathy are urgently needed. Future RCTs, if conducted in human neonates, should have an adequate sample size, assess neurodevelopment, minimize using aminoglycosides, be transparent about the potential ototoxicity in the parent information sheet, conduct early hearing tests and have trial-stopping rules that include hearing impairment as an outcome.
Topics: Infant, Newborn; Infant; Humans; Rats; Mice; Animals; Bumetanide; Ototoxicity; Sodium Potassium Chloride Symporter Inhibitors; Solute Carrier Family 12, Member 2; Seizures; Epilepsy; Phenobarbital; Infant, Newborn, Diseases; Aminoglycosides; Hearing Loss; Anticonvulsants
PubMed: 37690372
DOI: 10.1016/j.seizure.2023.09.007 -
Genes Aug 2023Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs)...
Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs) contribute to the occurrence of metformin side effects. The aim of the present study was to identify intronic genetic variants modifying the occurrence of metformin side effects and to replicate them in individuals with T2DM and in women with PCOS. We performed Next Generation Sequencing (Illumina Next Seq) of 115 SNPs in a discovery cohort of 120 metformin users and conducted a systematic literature review. Selected SNPs were analysed in two independent cohorts of individuals with either T2DM or PCOS, using 5'-3'exonucleaseassay. A total of 14 SNPs in the organic cation transporters (OCTs) showed associations with side effects in an unadjusted binary logistic regression model, with eight SNPs remaining significantly associated after appropriate adjustment in the discovery cohort. Five SNPs were confirmed in a combined analysis of both replication cohorts but showed different association patterns in subgroup analyses. In an unweighted polygenic risk score (PRS), the risk for metformin side effects increased with the number of risk alleles. Intronic SNPs in the OCT cluster contribute to the development of metformin side effects in individuals with T2DM and in women with PCOS and are therefore of interest for personalized therapy options.
Topics: Female; Humans; Polymorphism, Single Nucleotide; Metformin; Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Introns; Membrane Transport Proteins; Polycystic Ovary Syndrome
PubMed: 37628660
DOI: 10.3390/genes14081609 -
International Journal of Molecular... Jul 2023Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various... (Review)
Review
Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.
Topics: Animals; Aquaporins; Water; Homeostasis; Brain; Seizures
PubMed: 37569297
DOI: 10.3390/ijms241511923