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1.
A missense variant in SLC12A3 gene enhances aberrant splicing causing Gitelman syndrome.
Law, CY, Lui, DTW, Lau, E, Woo, CSL, Chang, JYC, Leung, EKH, Lee, ACH, Lee, CH, Woo, YC, Chow, WS, et al
Clinica chimica acta; international journal of clinical chemistry. 2025;:119924
Abstract
Gitelman syndrome (GS) is the most prevalent genetic tubulopathy characterized by several electrolyte abnormalities, including hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis, and hyperreninemic hyperaldosteronism. These features are caused by a bi-allelic mutation in the SLC12A3 gene. In this report, we present a case of GS in an asymptomatic woman who incidentally exhibited hypokalemia during an antenatal check-up. Her biochemical profile was consistent with GS. Genetic analysis revealed two heterozygous variants in trans, namely, NM_001126108.2:c.625C>T; p.(Arg209Trp) and c.965C>T; p.(Ala322Val). The c.625C>T; p.(Arg209Trp) variant has previously been experimentally confirmed as a loss-of-function (LOF) variant. However, the functional impact of the c.965C>T variant, located at the 5 prime end of exon 8, has not been fully elucidated. Through the utilization of both complementary DNA (cDNA) and minigene analysis, we confirmed that the c.965C>T variant can generate two distinct cDNA transcripts. The first transcript carries a missense mutation, p.(Ala322Val) in the full SLC12A3 transcript, while the second transcript consists of an in-frame deletion of both exons 7 and 8 in the SLC12A3 transcript, in which may result in the loss of transmembrane regions 5 - 6 involved in chloride transport. Our findings provide insights into the intricate mechanisms of splicing, highlighting how a variant in one exon can remotely influence the transcription of an upstream exon, as observed with the variant in exon 8 impacting the transcription of exon 7.
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2.
Association between metabolic syndrome and the risk of Parkinson's disease: a meta-analysis.
Zhong, Y, Wang, TH, Huang, LJ, Hua, YS
BMC neurology. 2024;(1):313
Abstract
BACKGROUND There is still a lack of knowledge about the relationship between metabolic syndrome (MetS) and Parkinson's disease (PD). This study aimed to determine whether MetS increases PD risk. METHODS To identify relevant clinical studies, databases such as PubMed, Embase, and the Cochrane Library were searched in depth from the inception of databases until March 31, 2024. The study evaluated the correlation between MetS and the likelihood of developing PD through the computation of aggregated relative risks (RR) and their respective 95% confidence intervals (CIs) utilizing selnRR and lnRR. RESULTS Seven studies were included in our systematic review. The meta-analysis revealed that patients with MetS have a 0.3-fold increased risk of developing PD (p = 0.001). Furthermore, the analysis revealed a positive correlation between central obesity and the incidence of PD, with an RR of 1.19 (95% CI, 1.16-1.22; p = 0.001), as well as a greater risk of PD in patients with elevated blood pressure, with an RR of 1.13 (95% CI, 1.07-1.19; p = 0.001); elevated serum triglyceride levels, with an RR of 1.09 (95% CI, 1.02-1.15; p = 0.001); lower serum HDL cholesterol levels, with an RR of 1.21 (95% CI, 1.15-1.28; p = 0.001); and elevated plasma fasting glucose levels, with an RR of 1.18 (95% CI, 1.11-1.26; p = 0.001). CONCLUSION MetS can contribute to the incidence of Parkinson's disease, with individual components of MetS demonstrating comparable effects.
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Research progress on the effects of sodium-glucose linked transporter 2 inhibitors on multiple metabolic disorders in metabolic syndrome.
Xu, C, Cai, X, Qiu, X, Zhao, L
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences. 2024;(3):382-389
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Abstract
Metabolic syndrome is a complex group of metabolic disorders with an increasing global incidence rate, posing a serious threat to human health. Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drug. SGLT2 inhibitors not only lower blood glucose level in a non-insulin-dependent manner by inhibiting glucose reabsorption by renal proximal convoluted tubular epithelial cell to promote urinary glucose excretion, but also by improving islet β cell function, reducing inflammatory responses, and inhibiting oxidative stress. In addition, SGLT2 inhibitors can reduce body weight through osmotic diuresis and increase fat metabolism; reduce blood pressure by inhibiting excessive activation of sympathetic nervous system and by improving vascular function. They can also improve blood lipids by increasing degradation of triacylglycerol; reduce blood uric acid by promoting uric acid excretion in kidney and intestine, and by reducing uric acid synthesis. This article reviews the effects and mechanisms of SGLT2 inhibitors on multiple metabolic disorders in metabolic syndrome and explores their potential application in metabolic syndrome treatment.
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4.
Potential therapeutic effects of baicalin and baicalein.
Sabry, K, Jamshidi, Z, Emami, SA, Sahebka, A
Avicenna journal of phytomedicine. 2024;(1):23-49
Abstract
OBJECTIVE Baicalin and baicalein are natural flavonoids reported for the first time from Scutellaria baicalensis Georgi. Recently, attention has been paid to these valuable flavonoids due to their promising effects. This paper aims to have a comprehensive review of their pharmacological effects. MATERIALS AND METHODS An extensive search through scientific databases including Scopus, PubMed, and ISI Web of Science was established. RESULTS According to literature, these compounds have been mainly effective in the treatment of neurological and neurodegenerative diseases, hepatic and cardiovascular disorders, metabolic syndrome, and cancers through anti-inflammatory and antioxidant pathways. Induction of apoptosis and autophagy, and inhibition of migration and metastasis are the main mechanisms for their cytotoxic and antitumor activities. Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are their main hepatoprotective mechanisms. Inhibiting the development of cardiac fibrosis and reducing inflammation, oxidative stress, and apoptosis are also the mechanisms suggested for cardioprotective activities. Decreasing the accumulation of inflammatory mediators and improving cognitive function and depressive-like behaviours are the main mechanisms for neurological and neurodegenerative activities. CONCLUSION The findings suggest the therapeutic potential of baicalin and baicalein. However, complementary research in different in vitro and in vivo models to investigate their mechanisms of action as well as clinical trials to evaluate their efficacy and safety are suggested.
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Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study.
Neglia, D, Caselli, C, Maffei, E, Cademartiri, F, Meloni, A, Bossone, E, Saba, L, Lee, SE, Sung, JM, Andreini, D, et al
Circulation. Cardiovascular imaging. 2024;(7):e016481
Abstract
BACKGROUND We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease. METHODS Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm3) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization. RESULTS In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P=0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P<0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P=0.018) together with family history, baseline percent atheroma volume, and rapid PP. CONCLUSIONS In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411.
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Metabolic syndrome and its association with physical activity in Sudanese early adolescents - Khartoum state, Sudan: An observational study.
Elfaki, FA, Mukhayer, AIG, Moukhyer, ME, Chandika, RM, Khalafalla, HE, Kremers, SPJ
Medicine. 2024;(23):e38242
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Abstract
The growing prevalence of overweight/obesity in adolescents highlights the significance of studying metabolic syndrome (MetS) in increasingly sedentary adolescents. To date, no study in Sudan has examined the association between MetS and physical activity (PA) among adolescents. This study aimed to assess the association between MetS and its components and PA among Sudanese early adolescents. A cross-sectional assessment was conducted from to 2018 to 2019 on a sample of 921 primary school students from Khartoum State, Republic of Sudan. MetS was defined according to the International Diabetes Federation criteria and a standardized questionnaire was used to assess PA. Metabolic equivalents of task were calculated, and levels of different intensities of PA (tertiles) were identified accordingly. The association between PA and MetS and its components was assessed using a logistic regression model. The participants comprised 388 boys and 533 girls with a mean age of 12.59 ± 1.21 years. The prevalence of MetS was significantly higher in subjects in the 1st PA tertile (least active) than in the 2nd and 3rd (most active) tertiles of PA, and this difference was observed in both boys and girls. After adjusting for other study factors, the odds of MetS among adolescents in the 1st PA tertile were 7 times higher than those in the highest PA tertile (adjusted odds ratio = 7.01, 95% confidence interval: 1.48, 32.99). A physically inactive lifestyle was associated with higher odds of MetS and its components, especially waist circumference and triglyceride levels, in Sudanese early adolescents. This study highlights the importance of promoting PA in this age group.
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Use of a Micronutrient Cocktail to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults with Obesity: A Randomized, Double-Blinded Pilot Clinical Trial.
Perva, IT, Simina, IE, Bende, R, Motofelea, AC, Chirita Emandi, A, Andreescu, N, Sima, A, Vlad, A, Sporea, I, Zimbru, C, et al
Medicina (Kaunas, Lithuania). 2024;(8)
Abstract
Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.
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Enteral Nutrition in Operated-On Gastric Cancer Patients: An Update.
Triantafillidis, JK, Papakontantinou, J, Antonakis, P, Konstadoulakis, MM, Papalois, AE
Nutrients. 2024;(11)
Abstract
It is well established that the preoperative nutritional status of gastric cancer (GC) patients significantly affects the prognosis of the operated patients, their overall survival, as well as the disease-specific survival. Existing data support that preoperative assessment of nutritional status and early correction of nutritional deficiencies exert a favorable effect on early postoperative outcomes. A variety of relevant indices are used to assess the nutritional status of GC patients who are candidates for surgery. The guidelines of almost all international organizations recommend the use of oral enteral nutrition (EN). Oncologically acceptable types of gastrectomy and methods of patient rehabilitation should take into account the expected postoperative nutritional status. The majority of data support that perioperative EN reduces complications and hospital stay, but not mortality. Oral EN in the postoperative period, albeit in small amounts, helps to reduce the weight loss that is a consequence of gastrectomy. Iron deficiency with or without anemia and low serum levels of vitamin B12 are common metabolic sequelae after gastrectomy and should be restored. EN also significantly helps patients undergoing neoadjuvant or adjuvant antineoplastic therapy. The occurrence of the so-called "postgastrectomy syndromes" requires dietary modifications and drug support. This review attempts to highlight the benefits of EN in GC patients undergoing gastrectomy and to emphasize the type of necessary nutritional management, based on current literature data.
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Gut microbiota in insulin resistance: a bibliometric analysis.
Tian, W, Liu, L, Wang, R, Quan, Y, Tang, B, Yu, D, Zhang, L, Hua, H, Zhao, J
Journal of diabetes and metabolic disorders. 2024;(1):173-188
Abstract
BACKGROUND Insulin resistance (IR) is considered the pathogenic driver of diabetes, and can lead to obesity, hypertension, coronary artery disease, metabolic syndrome, and other metabolic disorders. Accumulating evidence indicates that the connection between gut microbiota and IR. This bibliometric analysis aimed to summarize the knowledge structure of gut microbiota in IR. METHODS Articles and reviews related to gut microbiota in IR from 2013 to 2022 were retrieved from the Web of Science Core Collection (WoSCC), and the bibliometric analysis and visualization were performed by Microsoft Excel, Origin, R package (bibliometrix), Citespace, and VOSviewer. RESULTS A total of 4 749 publications from WoSCC were retrieved, including 3 050 articles and 1 699 reviews. The majority of publications were from China and USA. The University Copenhagen and Shanghai Jiao Tong University were the most active institutions. The journal of Nutrients published the most papers, while Nature was the top 1 co-cited journal, and the major area of these publications was molecular, biology, and immunology. Nieuwdorp M published the highest number of papers, and Cani PD had the highest co-citations. Keyword analysis showed that the most frequently occurring keywords were "gut microbiota", "insulin-resistance", "obesity", and "inflammation". Trend topics and thematic maps showed that serum metabolome and natural products, such as resveratrol, flavonoids were the research hotspots in this field. CONCLUSION This bibliometric analysis summarised the hotspots, frontiers, pathogenesis, and treatment strategies, providing a clear and comprehensive profile of gut microbiota in IR. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s40200-023-01342-x.
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Interventions in preconception and pregnant women at risk of gestational diabetes; a systematic review and meta-analysis of randomised controlled trials.
Quotah, OF, Andreeva, D, Nowak, KG, Dalrymple, KV, Almubarak, A, Patel, A, Vyas, N, Cakir, GS, Heslehurst, N, Bell, Z, et al
Diabetology & metabolic syndrome. 2024;(1):8
Abstract
BACKGROUND Women at risk of gestational diabetes mellitus (GDM) need preventative interventions. OBJECTIVE To evaluate targeted interventions before and during pregnancy for women identified as being at risk of developing GDM. METHODS Systematic review and meta-analysis conducted following PRISMA guidelines. MEDLINE, EMBASE and the Cochrane Library in addition to reference and citation lists were searched to identify eligible randomised controlled trials (RCTs) utilising risk stratification during the preconception period or in the first/early second trimester. Screening and data extraction were carried out by the authors independently. Quality assessment was conducted based on the Cochrane risk-of-bias tool. Random effects meta-analysis and narrative synthesis were performed. RESULTS Eighty-four RCTs were included: two during preconception and 82 in pregnancy, with a pooled sample of 22,568 women. Interventions were behavioural (n = 54), dietary supplementation (n = 19) and pharmacological (n = 11). Predictive factors for risk assessment varied; only one study utilised a validated prediction model. Gestational diabetes was reduced in diet and physical activity interventions (risk difference - 0.03, 95% CI 0.06, - 0.01; I2 58.69%), inositol (risk difference - 0.19, 95% CI 0.33, - 0.06; I2 92.19%), and vitamin D supplements (risk difference - 0.16, 95% CI 0.25, - 0.06; I2 32.27%). Subgroup analysis showed that diet and physical activity interventions were beneficial in women with ≥ 2 GDM risk factors (risk difference - 0.16, 95% CI 0.25, - 0.07; I2 11.23%) while inositol supplementation was effective in women with overweight or obesity (risk difference - 0.17, 95% CI 0.22, - 0.11; I2 0.01%). Effectiveness of all other interventions were not statistically significant. CONCLUSIONS This review provides evidence that interventions targeted at women at risk of GDM may be an effective strategy for prevention. Further studies using validated prediction tools or multiple risk factors to target high-risk women for intervention before and during pregnancy are warranted.
