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PloS One 2023To uncover the effect of GLP-1 receptor agonists (GLP-1 RAs) on the visceral- and hepatic fat content of adults. (Meta-Analysis)
Meta-Analysis
The effects of GLP-1 receptor agonists on visceral fat and liver ectopic fat in an adult population with or without diabetes and nonalcoholic fatty liver disease: A systematic review and meta-analysis.
AIM
To uncover the effect of GLP-1 receptor agonists (GLP-1 RAs) on the visceral- and hepatic fat content of adults.
METHODS
PubMed, EMBASE, Cochrane Library, and Web of Science were searched from inception until November 2022. Randomized controlled trials (RCTs) of GLP-1Ras was extracted, including reports of effects on visceral adipose tissue and hepatic fat content in individuals with type 2 diabetes, non-type 2 diabetes, NAFLD (non-alcoholic fatty liver disease), and non-NAFLD. Meta-analyses used random-effects models.
RESULTS
1736 individuals in the 30 qualified RCTs were included, comprising 1363 people with type 2 diabetes and 318 with NFLD. GLP-1 RAs reduced visceral adipose tissue (standard mean difference [SMD] = -0.59, 95% CI [-0.83, -0.36], P<0.00001) and hepatic fat content (weighted mean difference [WMD] = -3.09, 95% CI [-4.16, -2.02], P<0.00001) compared to other control treatment. Subgroup analysis showed that GLP-1Ras dramatically decreased visceral fat in patients with type 2 diabetes (SMD = -0.49, 95% CI [-0.69, -0.29] P<0.00001), NAFLD (SMD = -0.99, 95% CI [-1.64, -0.34] P = 0.003), non-type 2 diabetes (SMD = -1.38, 95% CI [-2.44, -0.32] P = 0.01), and non-NAFLD (SMD = -0.53, 95% CI [-0.78, -0.28] P<0.0001). GLP-1Ras reduced the liver fat level of type 2 diabetes (WMD = -3.15, 95% CI [-4.14, -2.15] P<0.00001), NAFLD (WMD = -3.83, 95% CI [-6.30, -1.37] P = 0.002), and type 2 diabetes with NAFLD (WMD = -4.27, 95% CI [-6.80, -1.74] P = 0.0009), while showed no impact on the hepatic fat content in non-Type 2 diabetes (WMD = -12.48, 95% CI [-45.19, 20.24] P = 0.45).
CONCLUSIONS
LP-1 RAs significantly reduce visceral- and liver fat content in adults.
Topics: Adult; Humans; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Intra-Abdominal Fat; Non-alcoholic Fatty Liver Disease
PubMed: 37616255
DOI: 10.1371/journal.pone.0289616 -
Gynecological Endocrinology : the... Dec 2023In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To... (Review)
Review
In recent years, new combined oral contraceptives (COCs) have become available, representing an advance in terms of individualization and compliance by users. To provide recommendations regarding COCs: formulations, use, efficacy, benefits and safety. For these recommendations, we have used the modified Delphi methodology and carried out a systematic review of studies found in the literature and reviews performed in humans, published in English and Spanish in Pubmed, Medline and advanced medicine and computer networks until the year 2021, using the combination of terms: 'oral contraceptives', 'estroprogestins' and 'combined oral contraceptives'. Regarding the estrogen component, initially switching from mestranol (the pro-drug of ethinylestradiol) to ethinylestradiol (EE) and then reducing the EE dose helped reduce side effects and associated adverse events. Natural estradiol and estradiol valerate are already available and represent a valid alternative to EE. The use of more potent 19-nortestosterone-derived progestins, in order to lower the dose and then the appearance of non-androgenic progestins with different endocrine and metabolic characteristics, has made it possible to individualize the prescription of COC according to the profile of each woman. Advances in the provision of new COCs have improved the risk/benefit ratio by increasing benefits and reducing risks. Currently, the challenge is to tailor contraceptives to individual needs in terms of safety, efficacy, and protection of female reproductive health.
Topics: Female; Humans; Contraceptives, Oral, Combined; Progestins; Latin America; Ethinyl Estradiol; Estrogens; Women's Health
PubMed: 37857350
DOI: 10.1080/09513590.2023.2271072 -
Cureus Aug 2023Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, especially in people with obesity, dyslipidemia, type 2 diabetes mellitus (T2DM),... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, especially in people with obesity, dyslipidemia, type 2 diabetes mellitus (T2DM), and metabolic syndrome. Weight loss and dietary modifications are established first-line treatments for NAFLD. Currently, there is no approved drug for NAFLD; however, pioglitazone and vitamin E have shown some beneficial effects. This systematic review covers the comparative efficacies of vitamin E, pioglitazone, and vitamin E plus pioglitazone. As of December 2022, the sources for prior literature review included PubMed, PubMed Central, and Medline. We included studies assessing the efficacy of pioglitazone, vitamin E, and vitamin E plus pioglitazone in improving liver histology, liver markers, and lipid profile when compared to other interventions in patients with NAFLD/non-alcoholic steatohepatitis (NASH). Review materials include randomized control trials (RCTs), traditional reviews, systematic reviews, meta-analyses, and observational studies on human participants published within the last five years in the English language. Studies on animals, pediatric populations, and with insufficient data were excluded from the review. Two authors scanned and filtered articles independently and later performed quality checks. A third reviewer resolved any conflicts. The risk of bias was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for systematic reviews, the Cochrane Risk of Bias Tool for RCTs, and the Scale for the Assessment of Narrative Review Articles for Traditional Reviews. A total of 21 articles were shortlisted. The results showed that pioglitazone and vitamin E are effective in reducing steatosis, inflammation, and ballooning, reducing liver markers, but there seem to be conflicting data on fibrosis resolution. Pioglitazone decreases triglycerides and increases high-density lipoproteins. One study has suggested that pioglitazone has superior efficacy to vitamin E in fibrosis reduction and vitamin E plus pioglitazone has superior efficacy than pioglitazone alone for NASH resolution. However, these conclusions require further validation through extensive analysis and additional research. In conclusion, diabetic patients with NAFLD can be given pioglitazone, and non-diabetic patients with NAFLD can be given vitamin E.
PubMed: 37719477
DOI: 10.7759/cureus.43635 -
Psychological Medicine Aug 2023Impaired brain metabolism may be central to schizophrenia pathophysiology, but the magnitude and consistency of metabolic dysfunction is unknown. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Impaired brain metabolism may be central to schizophrenia pathophysiology, but the magnitude and consistency of metabolic dysfunction is unknown.
METHODS
We searched MEDLINE, PsychINFO and EMBASE between 01/01/1980 and 13/05/2021 for studies comparing regional brain glucose metabolism using FDG-PET, in schizophrenia/first-episode psychosis controls. Effect sizes (Hedges ) were pooled using a random-effects model. Primary measures were regional absolute and relative CMRGlu in frontal, temporal, parietal and occipital lobes, basal ganglia and thalamus.
RESULTS
Thirty-six studies (1335 subjects) were included. Frontal absolute glucose metabolism (Hedge's = -0.74 ± 0.54, = 0.01; = 67%) and metabolism relative to whole brain ( = -0.44 ± 0.34, = 0.01; = 55%) were lower in schizophrenia controls with moderate heterogeneity. Absolute frontal metabolism was lower in chronic ( = -1.18 ± 0.73) first-episode patients ( = -0.09 ± 0.88) and controls. Medicated patients showed frontal hypometabolism relative to controls (-1.04 ± 0.26) while metabolism in drug-free patients did not differ significantly from controls. There were no differences in parietal, temporal or occipital lobe or thalamic metabolism in schizophrenia controls. Excluding outliers, absolute basal ganglia metabolism was lower in schizophrenia controls (-0.25 ± 0.24, = 0.049; = 5%). Studies identified reporting voxel-based morphometry measures of absolute FDG uptake (eight studies) were also analysed using signed differential mapping analysis, finding lower FDG uptake in the left anterior cingulate gyrus ( = -4.143; = 0.007) and the left inferior orbital frontal gyrus ( = -4.239; = 0.02) in schizophrenia.
CONCLUSIONS
We report evidence for hypometabolism with large effect sizes in the frontal cortex in schizophrenia without consistent evidence for alterations in other brain regions. Our findings support the hypothesis of hypofrontality in schizophrenia.
Topics: Humans; Glucose; Schizophrenia; Fluorodeoxyglucose F18; Brain; Positron-Emission Tomography
PubMed: 35730361
DOI: 10.1017/S003329172200174X -
Archives of Endocrinology and Metabolism Nov 2023FGF21 is a hormone produced primarily by the liver with several metabolic functions, such as induction of heat production, control of glucose homeostasis, and regulation... (Meta-Analysis)
Meta-Analysis Review
FGF21 is a hormone produced primarily by the liver with several metabolic functions, such as induction of heat production, control of glucose homeostasis, and regulation of blood lipid levels. Due to these actions, several laboratories have developed FGF21 analogs to treat patients with metabolic disorders such as obesity and diabetes. Here, we performed a systematic review and meta-analysis of randomized controlled trials that used FGF21 analogs and analyzed metabolic outcomes. Our search yielded 236 articles, and we included eight randomized clinical trials in the meta-analysis. The use of FGF21 analogs exhibited no effect on fasting blood glucose, glycated hemoglobin, HOMA index, blood free fatty acids or systolic blood pressure. However, the treatment significantly reduced fasting insulinemia, body weight and total cholesterolemia. None of the included studies were at high risk of bias. The quality of the evidence ranged from moderate to very low, especially due to imprecision and indirection issues. These results indicate that FGF21 analogs can potentially treat metabolic syndrome. However, more clinical trials are needed to increase the quality of evidence and confirm the effects seen thus far.
Topics: Humans; Blood Glucose; Metabolic Diseases; Metabolic Syndrome; Obesity; Diabetes Mellitus
PubMed: 37948566
DOI: 10.20945/2359-4292-2022-0493 -
Women's Health (London, England) 2024Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including... (Review)
Review
Polycystic ovary syndrome is a common reproductive endocrine condition that affects women of fertile age and is characterized by three main features, including hyperandrogenism, chronic anovulation, and polycystic ovaries. In addition, half of women with polycystic ovary syndrome have insulin resistance, and obesity or overweight, type 2 diabetes, hypertension, and hyperlipidemia are the most common metabolic abnormalities affecting (30%) women with polycystic ovary syndrome. Weight loss is regarded as the first-line treatment as it can potentially improve polycystic ovary syndrome parameters (androgen levels, menstrual cyclicity, lipid and glucose metabolism). However, achieving and maintaining weight loss can be challenging, and pharmacological agents could be essential to achieve optimal glycemic control and improve the endocrine disturbance associated with polycystic ovary syndrome. Glucagon-like peptide-1 receptor agonist has been demonstrated as monotherapy or in combination with metformin for managing obesity and insulin resistance associated with polycystic ovary syndrome. Yet, its effect on endocrine and metabolic parameters remains elusive, and further research is needed to close the gap. The aim is to evaluate the efficacy of glucagon-like peptide-1 receptor agonist monotherapy and/or a combined treatment between glucagon-like peptide-1 receptor agonist and metformin for improving anthropometric measurements, endocrine and metabolic parameters in lean and obese women with polycystic ovary syndrome. A systematic review of longitudinal cohort studies was conducted across databases including Ovid Medline, PubMed Central, and Cochrane Library between 2015 and 2022. Eligible studies included participants with polycystic ovary syndrome diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health criteria. A total of eight studies including 486 patients with polycystic ovary syndrome were analyzed. The mean age was between 18 and 45 years with mean follow-up period between 12 and 32 weeks. In all these studies, results were comparable for the reduction in body mass index, waist circumference, fat mass, and visceral fat mass; however, it was more in combination therapy versus comparator. In conclusion, glucagon-like peptide-1 receptor agonists effectively reduce body weight and improve some of the endocrine and metabolic parameters of polycystic ovary syndrome. A combined treatment with glucagon-like peptide-1 receptor agonist and metformin had significant effects on weight loss and favorable results on endocrine and metabolic parameters, yet further research is needed to discover the long-term safety of combined therapy in women diagnosed with polycystic ovary syndrome and obesity or overweight.
Topics: Female; Humans; Infant; Male; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor Agonists; Insulin Resistance; Longitudinal Studies; Metformin; Obesity; Overweight; Polycystic Ovary Syndrome; United States; Weight Loss
PubMed: 38444070
DOI: 10.1177/17455057241234530 -
Probiotics and Antimicrobial Proteins Aug 2023Heart failure (HF) is a global pandemic with increasing prevalence and mortality rates annually. Its main cause is myocardial infarction (MI), followed by rapid cardiac... (Meta-Analysis)
Meta-Analysis
Anti-Inflammatory, Antioxidant, Metabolic and Gut Microbiota Modulation Activities of Probiotic in Cardiac Remodeling Condition: Evidence from Systematic Study and Meta-Analysis of Randomized Controlled Trials.
Heart failure (HF) is a global pandemic with increasing prevalence and mortality rates annually. Its main cause is myocardial infarction (MI), followed by rapid cardiac remodeling. Several clinical studies have shown that probiotics can improve the quality of life and reduce cardiovascular risk factors. This systematic review and meta-analysis aimed to investigate the effectiveness of probiotics in preventing HF caused by a MI according to a prospectively registered protocol (PROSPERO: CRD42023388870). Four independent evaluators independently extracted the data using predefined extraction forms and evaluated the eligibility and accuracy of the studies. A total of six studies consisting of 366 participants were included in the systematic review. Probiotics are not significant in intervening left ventricular ejection fraction (LVEF) and high-sensitivity C-reactive protein (hs-CRP) when compared between the intervention group and the control group due to inadequate studies supporting its efficacy. Among sarcopenia indexes, hand grip strength (HGS) showed robust correlations with the Wnt biomarkers (p < 0.05), improved short physical performance battery (SPPB) scores were also strongly correlated with Dickkopf-related protein (Dkk)-3, followed by Dkk-1, and sterol regulatory element-binding protein 1 (SREBP-1) (p < 0.05). The probiotic group showed improvement in total cholesterol (p = 0.01) and uric acid (p = 0.014) compared to the baseline. Finally, probiotic supplements may be an anti-inflammatory, antioxidant, metabolic, and intestinal microbiota modulator in cardiac remodeling conditions. Probiotics have great potential to attenuate cardiac remodeling in HF or post-MI patients while also enhancing the Wnt signaling pathway which can improve sarcopenia under such conditions.
Topics: Humans; Antioxidants; Gastrointestinal Microbiome; Quality of Life; Stroke Volume; Hand Strength; Sarcopenia; Ventricular Remodeling; Ventricular Function, Left; Randomized Controlled Trials as Topic; Probiotics; Anti-Inflammatory Agents
PubMed: 37349622
DOI: 10.1007/s12602-023-10105-2 -
BMC Endocrine Disorders Jul 2023Childhood obesity is one of the main concerns of public health. Considering its long-term adverse health effect, various studies investigated the effect of drug therapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Childhood obesity is one of the main concerns of public health. Considering its long-term adverse health effect, various studies investigated the effect of drug therapy on anthropometric parameters and provided mixed results. In this systematic review and meta-analysis, we aimed to determine the effect of Orlistat on anthropometrics and biochemical parameters in children and adolescents.
MATERIALS AND METHODS
The databases of PubMed, Scopus, and Web of Science were searched until September 2022. Experimental and semi-experimental studies were included if they evaluated the effect of Orlistat on obesity-related parameters in children and reported the before and after anthropometric values. A revised Cochrane risk-of-bias (Rob2) was used to evaluate the methodological quality. STATA software version 16.0 was used for the meta-analysis of the random-effect model.
RESULTS
Of 810 articles retrieved in the initial search, four experimental and two semi-experimental studies were selected for systematic review. The result of the meta-analysis of experimental studies indicated the significant effect of Orlistat on waist circumference (SMD: -0.27, 95% CI: -0.47, -0.07) and serum insulin level (SMD: -0.89, 95% CI: -1.52, 0.26). However, there were no significant effects of orlistat on body weight, body mass index, lipid profile, and serum glucose level.
CONCLUSION
The present meta-analysis showed the significant effect of Orlistat on the reduction of waist circumference and insulin level in overweight and obese adolescents. However, due to the paucity of studies included in the meta-analysis, more prospective studies with longer duration and more sample sizes will be needed in this age group.
Topics: Child; Adolescent; Humans; Orlistat; Anti-Obesity Agents; Prospective Studies; Pediatric Obesity; Lactones; Insulins
PubMed: 37420181
DOI: 10.1186/s12902-023-01390-7 -
Cureus Nov 2023Type 2 diabetes mellitus (T2DM) is a worldwide epidemic that is only increasing as the years progress, and as of 2019, affecting over 37 million. T2DM is a chronic... (Review)
Review
Type 2 diabetes mellitus (T2DM) is a worldwide epidemic that is only increasing as the years progress, and as of 2019, affecting over 37 million. T2DM is a chronic condition caused by reduced insulin secretion and increased insulin resistance. Due to insulin not operating at optimal conditions, blood glucose rises and remains high, thus disturbing metabolic hemostasis. Many complications can arise from T2DM, such as coronary vascular disease, kidney damage, eye damage, and, quite significantly, dementia. It is theorized that dementia from T2DM stems from the fact that the brain is susceptible to hyperglycemic conditions, which are promoted by the increase in insulin resistance of target cells in the central nervous system. This directly affects cognitive processes and memory, which correlates to decreased temporal and front lobes volume. The risk of diabetic complications can be minimized with therapeutic interventions such as oral-antidiabetic (OAD) agents and insulin. Several OADs are on the market, but the first-line agent is metformin, a biguanide that decreases glucose production and increases insulin sensitivity. This paper aims to determine if currently prescribed OADs can help slow cognitive decline and reduce the risk and incidence of dementia as a complication of T2DM. Studies found that, for the most part, all OADs except sulfonylureas (SU) significantly slowed the decline of cognitive function and reduced the risk and incidence of dementia. SU's were shown to increase the risk of dementia in most studies. Of all the OADs, thiazolidinediones may be the most beneficial drug class for reducing the risk of dementia in T2DM patients. Future research should focus on whether early intervention with specific classes of OADs can not only improve glycemic control, leading to decreased hyperglycemia but also prevent the build-up of damaged brain tissue and help to reduce the risk and incidence of dementia in patients with T2DM.
PubMed: 38152822
DOI: 10.7759/cureus.49515 -
International Journal of Antimicrobial... Sep 2023Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment... (Review)
Review
Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment responses. This systematic review, conducted according to PRISMA guidelines, aimed to evaluate the concentration-effect relationship. In vitro/in vivo studies had to contain information on the infection model, PZA dose and concentration, and microbiological outcome. Human studies had to present information on PZA dose, measures of drug exposure and maximum concentration, and microbiological response parameter or overall treatment outcome. A total of 34 studies were assessed, including in vitro (n = 2), in vivo (n = 3) and clinical studies (n = 29). Intracellular and extracellular models demonstrated a direct correlation between PZA dose of 15-50 mg/kg/day and reduction in bacterial count between 0.50-27.7 log CFU/mL. Consistent with this, higher PZA doses (>150 mg/kg) were associated with a greater reduction in bacterial burden in BALB/c mice models. Human pharmacokinetic studies displayed a linear positive correlation between PZA dose (i.e. 21.4-35.7 mg/kg/day) and drug exposure (AUC range 220.6-514.5 mg·h/L). Additionally, human studies confirmed a dose-effect relationship, with an increased 2-month sputum culture conversion rate at AUC/MIC targets of 8.4-11.3 with higher exposure/susceptibility ratios leading to greater efficacy. A 5-fold variability in AUC was observed at PZA dose of 25 mg/kg. A direct concentration-effect relationship and increased treatment efficacy with higher PZA exposure to susceptibility ratios was observed. Taking into account variability in drug exposure and treatment response, further studies on dose optimisation are justified.
Topics: Animals; Mice; Humans; Pyrazinamide; Mycobacterium tuberculosis; Tuberculosis; Antitubercular Agents; Mice, Inbred BALB C; Microbial Sensitivity Tests
PubMed: 37419292
DOI: 10.1016/j.ijantimicag.2023.106914