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Aging Cell Jul 2023Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains... (Meta-Analysis)
Meta-Analysis Review
Emerging evidence has shown that leukocyte telomere length (LTL) is associated with various health-related outcomes, while the causality of these associations remains unclear. We performed a systematic review and meta-analysis of current evidence from Mendelian randomization (MR) studies on the association between LTL and health-related outcomes. We searched PubMed, Embase, and Web of Science up to April 2022 to identify eligible MR studies. We graded the evidence level of each MR association based on the results of the main analysis and four sensitive MR methods, MR-Egger, weighted median, MR-PRESSO, and multivariate MR. Meta-analyses of published MR studies were also performed. A total of 62 studies with 310 outcomes and 396 MR associations were included. Robust evidence level was observed for the association between longer LTL and increased risk of 24 neoplasms (the strongest magnitude for osteosarcoma, GBM, glioma, thyroid cancer, and non-GBM glioma), six genitourinary and digestive system outcomes of excessive or abnormal growth, hypertension, metabolic syndrome, multiple sclerosis, and clonal hematopoiesis of indeterminate potential. Robust inverse association was observed for coronary heart disease, chronic kidney disease, rheumatoid arthritis, juvenile idiopathic arthritis, idiopathic pulmonary fibrosis, and facial aging. Meta-analyses of MR studies suggested that genetically determined LTL was associated with 12 neoplasms and 9 nonneoplasm outcomes. Evidence from published MR studies supports that LTL plays a causal role in various neoplastic and nonneoplastic diseases. Further research is required to elucidate the underlying mechanisms and to bring insight into the potential prediction, prevention, and therapeutic applications of telomere length.
Topics: Humans; Mendelian Randomization Analysis; Arthritis, Rheumatoid; Glioma; Hypertension; Telomere; Genome-Wide Association Study; Polymorphism, Single Nucleotide
PubMed: 37232505
DOI: 10.1111/acel.13874 -
The Journal of Clinical Endocrinology... Dec 2023Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women...
PURPOSE
Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS
We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS
Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSION
AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
Topics: Humans; Female; Adult; Polycystic Ovary Syndrome; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipose Tissue; Insulin; Cytokines; Obesity; Inflammation; Glucose
PubMed: 37329216
DOI: 10.1210/clinem/dgad356 -
Drugs Oct 2023Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs).
OBJECTIVE
The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA).
METHODS
Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry ( http://www.
CLINICALTRIALS
gov ) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework.
RESULTS
Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04-5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.
CONCLUSIONS
There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles.
Topics: Humans; Anticonvulsants; Cannabidiol; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Epilepsies, Myoclonic; Fenfluramine; Pharmaceutical Preparations
PubMed: 37695433
DOI: 10.1007/s40265-023-01936-y -
The Journal of Clinical Endocrinology... Jan 2024Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women. (Meta-Analysis)
Meta-Analysis
CONTEXT
Polycystic ovary syndrome (PCOS) affects more than 1 in 10 women.
OBJECTIVE
As part of the 2023 International PCOS Guidelines update, comparisons between combined oral contraceptive pills (COCP), metformin, and combination treatment were evaluated.
DATA SOURCES
Ovid Medline, Embase, PsycINFO, All EBM, and CINAHL were searched.
STUDY SELECTION
Women with PCOS included in randomized controlled trials (RCTs).
DATA EXTRACTION
We calculated mean differences and 95% CIs regarding anthropometrics, metabolic, and hyperandrogenic outcomes. Meta-analyses and quality assessment using GRADE were performed.
DATA SYNTHESIS
The search identified 1660 publications; 36 RCTs were included. For hirsutism, no differences were seen when comparing metformin vs COCP, nor when comparing COCP vs combination treatment with metformin and COCP. Metformin was inferior on free androgen index (FAI) (7.08; 95% CI 4.81, 9.36), sex hormone binding globulin (SHBG) (-118.61 nmol/L; 95% CI -174.46, -62.75) and testosterone (0.48 nmol/L; 95% CI 0.32, 0.64) compared with COCP. COCP was inferior for FAI (0.58; 95% CI 0.36, 0.80) and SHBG (-16.61 nmol/L; 95% CI -28.51, -4.71) compared with combination treatment, whereas testosterone did not differ. Metformin lowered insulin (-27.12 pmol/L; 95% CI -40.65, -13.59) and triglycerides (-0.15 mmol/L; 95% CI -0.29, -0.01) compared with COCP. COCP was inferior for insulin (17.03 pmol/L; 95% CI 7.79, 26.26) and insulin resistance (0.44; 95% CI 0.17, 0.70) compared with combination treatment.
CONCLUSIONS
The choice of metformin or COCP treatment should be based on symptoms, noting some biochemical benefits from combination treatment targeting both major endocrine disturbances seen in PCOS (hyperinsulinemia and hyperandrogenism).
Topics: Female; Humans; Metformin; Polycystic Ovary Syndrome; Contraceptives, Oral, Combined; Hypoglycemic Agents; Testosterone; Insulins
PubMed: 37554096
DOI: 10.1210/clinem/dgad465 -
The Journal of Clinical Endocrinology... May 2024Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of... (Meta-Analysis)
Meta-Analysis
CONTEXT
Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Inositol may have insulin sensitizing effects; however, its efficacy in the management of PCOS remains indeterminate.
OBJECTIVE
To inform the 2023 international evidence-based guidelines in PCOS, this systematic review and meta-analysis evaluated the efficacy of inositol, alone or in combination with other therapies, in the management of PCOS.
DATA SOURCES
Medline, PsycInfo, EMBASE, All EBM, and CINAHL from inception until August 2022.
STUDY SELECTION
Thirty trials (n = 2230; 1093 intervention, 1137 control), with 19 pooled in meta-analyses were included.
DATA EXTRACTION
Data were extracted for hormonal, metabolic, lipids, psychological, anthropometric, reproductive outcomes, and adverse effects by 1 reviewer, independently verified by a second.
DATA SYNTHESIS
Thirteen comparisons were assessed, with 3 in meta-analyses. Evidence suggests benefits for myo-inositol or D-chiro-inositol (DCI) for some metabolic measures and potential benefits from DCI for ovulation, but inositol may have no effect on other outcomes. Metformin may improve waist-hip ratio and hirsutism compared to inositol, but there is likely no difference for reproductive outcomes, and the evidence is very uncertain for body mass indexI. Myo-inositol likely causes fewer gastrointestinal adverse events compared with metformin; however, these are typically mild and self-limited.
CONCLUSION
The evidence supporting the use of inositol in the management of PCOS is limited and inconclusive. Clinicians and their patients should consider the uncertainty of the evidence together with individual values and preferences when engaging in shared decision-making regarding the use of inositol for PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Inositol; Female; Practice Guidelines as Topic; Insulin Resistance; Evidence-Based Medicine
PubMed: 38163998
DOI: 10.1210/clinem/dgad762 -
Journal of the American Association of... Aug 2023Psyllium is a natural, predominantly soluble fiber that forms a viscous gel when hydrated and is not digested or fermented. In the small intestine, psyllium gel... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psyllium is a natural, predominantly soluble fiber that forms a viscous gel when hydrated and is not digested or fermented. In the small intestine, psyllium gel increases chyme viscosity, slowing the degradation and absorption of nutrients. Psyllium has a significant effect in patients with metabolic syndrome and type-2 diabetes on glycemic control, while lowering serum cholesterol in hypercholesterolemic patients. Some randomized controlled studies have shown that psyllium also facilitates weight loss in overweight and obese participants.
OBJECTIVES
A comprehensive review and meta-analysis assessing psyllium's impact on body weight, body mass index (BMI), and waist circumference in overweight and obese participants.
DATA SOURCES
A comprehensive search was performed (Medline, Scopus, Cochrane Database) through March 21, 2022, using search terms to identify randomized, controlled, clinical studies designed to assess weight loss in overweight and obese participants over at least 2 months. Data were analyzed using the inverse variance method with random effects models.
CONCLUSIONS
Six studies meeting inclusion criteria were identified (total n = 354). The meta-analysis showed that psyllium, dosed just before meals (mean dose 10.8 g/day, mean duration 4.8 months), was effective for decreasing body weight (MD = -2.1 kg [95% confidence interval [CI]: -2.6 to -1.6]; p < .001), BMI (MD = -0.8 kg/m 2 [95% CI: -1.0 to -0.6]; p < .001) and waist circumference (MD = -2.2 cm [95% CI: -2.9 to -1.4]; p < .001) in overweight and obese populations.
IMPLICATIONS FOR PRACTICE
Gel-forming nonfermented psyllium fiber, dosed just before meals, is effective in facilitating weight loss in overweight and obese participants.
Topics: Humans; Body Weight; Obesity; Overweight; Psyllium; Weight Loss
PubMed: 37163454
DOI: 10.1097/JXX.0000000000000882 -
Environmental Pollution (Barking, Essex... Sep 2023Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific... (Meta-Analysis)
Meta-Analysis Review
Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific phthalate metabolites have been associated with an increased risk of cardiometabolic diseases. The aim of this study was to assess the association between phthalate exposure and the metabolic syndrome in the general population. A comprehensive literature search was performed in four databases (Web of Science, Medline, PubMed, and Scopus). We included all the observational studies that evaluate the association between phthalate metabolites and the metabolic syndrome available until January 31st, 2023. Pooled Odds Ratios (OR) and their 95% confidence intervals were calculated by using the inverse-variance weighted method. Nine cross-sectional studies and 25,365 participants aged from 12 to 80 were included. Comparing extreme categories of phthalate exposure, the pooled ORs for the metabolic syndrome were: 1.08 (95% CI, 1.02-1.16, I = 28%) for low molecular weight phthalates, and 1.11 (95% CI, 1.07-1.16, I = 7%) for high molecular weight phthalates. For individual phthalate metabolites, the pooled ORs that achieved statistical significance were: 1.13 (95% CI, 1.00-1.27, I = 24%) for MiBP; 1.89 (95% CI, 1.17-3.07, I = 15%) for MMP in men; 1.12 (95% CI, 1.00-1.25, I = 22%) for MCOP; 1.09 (95% CI, 0.99-1.20, I = 0%) for MCPP; 1.16 (95% CI, 1.05-1.28, I = 6%) for MBzP; and 1.16 (95% CI, 1.09-1.24, I = 14%) for DEHP (including ΣDEHP and its metabolites). In conclusion, both low molecular weight and high molecular weight phthalates were associated with an 8 and 11% higher prevalence of the MetS, respectively. The exposure to six specific phthalate metabolites was associated with a higher prevalence of the MetS.
Topics: Male; Humans; Metabolic Syndrome; Environmental Pollutants; Cross-Sectional Studies; Phthalic Acids; Plastics; Environmental Exposure
PubMed: 37328121
DOI: 10.1016/j.envpol.2023.121957 -
Diabetology & Metabolic Syndrome Oct 2023Metabolic syndrome (MetS) is a group of metabolic abnormalities characterised by hypertension, central obesity, dyslipidaemia and dysregulation of blood glucose,... (Review)
Review
BACKGROUND
Metabolic syndrome (MetS) is a group of metabolic abnormalities characterised by hypertension, central obesity, dyslipidaemia and dysregulation of blood glucose, associated with the risk of diabetes, cardiovascular disease and overall mortality. The presence of elevated liver enzymes may precede the development of MetS, with alterations of the liver being observed that are directly related to metabolic problems. The study aims to provide the best evidence on the association between liver enzymes (ALT, AST, GGT) and MetS by determining the effect size of these biomarkers.
METHODS
A systematic review and meta-analysis of studies indexed in PubMed and Scopus databases were performed. Study quality was assessed using the STROBE tool. The Grade Pro tool was used to evaluate the evidence, and the quantitative synthesis was performed using RevMan (Cochrane Collaboration).
RESULTS
Seventeen articles comparing liver enzyme concentrations between 76,686 with MetS (MetS+) and 201,855 without MetS (MetS-) subjects were included. The concentration of ALT, AST and GGT in the MetS + subjects was significantly higher than in the control group 7.13 IU/L (CI95% 5.73-8.54; p < 0.00001; I = 96%), 2.68 IU/L (CI95% 1.82-3.54; p < 0.00001; I = 96%) and 11.20 IU/L (CI95% 7.11-15.29; p < 0.00001; I = 96%), respectively.
CONCLUSIONS
The evaluation of the relationship of liver enzymes in the pathophysiological process of MetS could lead to new insights into early diagnosis.
PubMed: 37899468
DOI: 10.1186/s13098-023-01200-z -
Sleep Science (Sao Paulo, Brazil) Jun 2023Shift work can cause circadian cycles disturbances and misaligns the endogenous rhythms. The physiological variables are driven by the circadian system and, its... (Review)
Review
Shift work can cause circadian cycles disturbances and misaligns the endogenous rhythms. The physiological variables are driven by the circadian system and, its misalignment, can impair the metabolic functions. Thus, the main objective of this study was to evaluate the metabolic alterations as a result of shift work and night work reported in articles published in the last 5 years, using the eligibility criteria both gender and indexed articles in English language. In order to execute this work, we perform a systematic review according to PRISMA guidelines and searched about Chronobiology Disorders and Night Work, both related to metabolism, in Medline, Lilacs, ScienceDirect and Cochrane. Cross-sectional, cohort and experimental studies with low risk of bias were included. We found a total of 132 articles, and, after the selection process, 16 articles remained to be analyzed. It was observed that shift work can cause circadian misalignment and, consequently, some metabolic parameters alterations such as an impaired glycemic control and insulin functioning, cortisol phase release, cholesterol fractions imbalance, changes in morphological indexes and melatonin secretion. There are some limitations, such as heterogenicity in used databases and the 5 years restriction period, because the effects of sleep disturbance may have been reported earlier. In conclusion, we suggest that shift work interferes with the sleep-wake cycle and eating patterns, which cause crucial physiological alterations that, together, can lead to metabolic syndrome.
PubMed: 37425967
DOI: 10.1055/s-0043-1770798 -
Frontiers in Endocrinology 2023MetS is associated with greater morbidity and mortality in relation to a number of malignancies, but its association with ovarian cancer remains contested. The present... (Meta-Analysis)
Meta-Analysis
BACKGROUND
MetS is associated with greater morbidity and mortality in relation to a number of malignancies, but its association with ovarian cancer remains contested. The present study was a systematic review and meta-analysis of case-control and cohort studies examining the association between MetS and ovarian cancer risk.
METHODS
The study was registered on the PROSPERO platform in January 2023 (CRD42023391830). Up until February 13, 2023, a complete search was undertaken in PubMed, EMBASE, Web of Science, the Cochrane Library, and ClinicalTrials. On the basis of inclusion and exclusion criteria, eligible studies for meta-analysis were screened to determine the association between MetS and ovarian cancer risk.
RESULTS
Five studies were included in total, including three cohort studies and two case-control studies. Meta-analysis showed no significant correlation between metabolic syndrome and ovarian cancer (OR=1.29, 95% CI: 0.90-1.84). Significant heterogeneity (I = 92.6, P<0.05) existed between the included studies. We performed a subgroup analysis of the risk of bias and showed that only unadjusted stratification of risk of bias for smoking (OR= 3.19, 95% CI: 2.14-4.76) and hysterectomy (OR= 3.19, 95% CI: 2.14-4.76) demonstrated a relationship between metabolic syndrome and ovarian cancer risk. The meta-regression analysis revealed that smoking and hysterectomy excision were substantially linked with heterogeneity (p < 0.05).
CONCLUSION
Our research revealed no statistically significant association between MetS and ovarian cancer risk. The prevalence of metabolic syndrome has highlighted the need of enhancing and controlling women's metabolic health. However, the evaluation of metabolic syndrome as a cancer risk factor may be deceptive and etiologically uninformative.
Topics: Female; Humans; Metabolic Syndrome; Ovarian Neoplasms; Risk Factors; Smoking
PubMed: 37693347
DOI: 10.3389/fendo.2023.1219827