Metabolic Parameters Research Articles

The effects of different doses of single‐ and dual‐wavelength whole‐body photobiomodulation on metabolic parameters in obese mice

AbstractPhotobiomodulation (PBM) shows beneficial effects on obesity‐related alterations. It is not known if dual‐ is more beneficial than single‐wavelength, nor the dose–response effect of such treatments. The effects of different doses of single‐ and dual‐wavelength whole‐body PBM on metabolic parameters in obese mice were evaluated. Male Swiss albino mice were fed with standard (Chow) or a cafeteria (CAF) diet and allocated into Sham (lights off), and PBM (whole‐body blanket (140 cm2) composed of 20 LED clusters, 2.14 mW/cm2/cluster, for 67 or 133 s: 1 or 2 J per cluster; 20 and 40 J total energy; and 0.143 and 0.286 J/cm2) with 660 nm (660), 850 (850) nm, or 660 nm + 850 nm (660/850). CAF induced insulin resistance that was inhibited in 660–1, 660–2, 850–1, and 660/850–2. CAF increased serum total cholesterol that was inhibited in 660–1, 660–2, 850–1, 660/850–1, and 660/850–2. There were no PBM‐induced changes in other variables assessed. The effects of whole‐body PBM in metabolic paraments in obese mice were wavelength and dose dependent: increasing the dose for 660 did not affect the outcomes; increasing the dose for 850 negatively affected the outcomes, and increasing the dose for 660/850 was mostly beneficial on the outcomes.

Uric Acid-HDL Ratio as Predictor of Major Cardiovascular Events in Very High Cardiovascular Risk Patients Treated with High-Intensity Statin Therapy

Introduction: Uric acid levels are positively correlated with cardiovascular disease. High Density Lipoprotein (HDL) cholesterol plays a role in suppressing blood oxidation reactions and protecting vascular endothelial cells. The combination of these two metabolic parameters, the Uric Acid-HDL Ratio (UHR) makes it a very useful predictor marker for metabolic disorders. Statins are known to be the gold standard for raising HDL cholesterol. Some types of statins are also known to reduce serum uric acid levels by involving pleiotropic actions. The aim of this study was to determine baseline UHR as a predictor of MACE after administration of high-intensity statins.Objectives: The Objective of this study was to determine baseline UHR as a predictor of MACE after administration of high-intensity statins.Methods: This study was conducted at the cardiac center of Dr Zainal Abidin Regional General Hospital. This study is an observational study with a prospective cohort design. The target population was patients classified as patients with very high cardiovascular risk and using consecutive sampling techniques.Results: During the study period, a total of 82 patients with ischemic heart disease with very high cardiovascular risk met the inclusion and exclusion criteria. Of these, 49 patients (59.8%) were identified as having major cardiovascular events (MACE) while the remaining 33 patients (40.2%) did not had MACE. The results of this study are that statin therapy may not significantly affect the uric acid-HDL ratio in the context of major cardiovascular events.Conclusions: The uric acid-HDL ratio had no significant predictive ability for major cardiovascular events in patients with very high cardiovascular risk who were treated with high-intensity statin therapy.

CORRELATION OF LEPTIN AND ADIPONECTIN LEVELS WITH METABOLIC AND HORMONAL PROFILES IN PCOS PATIENTS: A COMPARATIVE STUDY WITH NORMAL CONTROLS

Objective: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder characterized by metabolic and reproductive abnormalities, including insulin resistance and hyperandrogenism. Leptin and adiponectin, two adipokines involved in metabolic regulation, are known to be dysregulated in PCOS. This study aims to investigate the correlation between leptin and adiponectin levels and their association with metabolic and hormonal profiles in PCOS patients compared to healthy controls. Methods: A prospective, observational study was conducted involving 120 women diagnosed with PCOS and 50 healthy controls. Leptin and adiponectin levels were measured using enzyme-linked immunosorbent assay (ELISA). The adiponectin-to-leptin ratio (ALR) was calculated, and correlations with BMI, LH/FSH ratio, and other metabolic parameters were analyzed. Data were analyzed using appropriate statistical methods. Results: Leptin levels were significantly higher in the PCOS group compared to controls (25.34 ng/ml vs. 11.16 ng/ml, p<0.0001), while adiponectin levels were significantly lower (2.93 mcg/ml vs. 21.44 mcg/ml, p<0.0001). The adiponectin-to-leptin ratio was markedly reduced in PCOS patients (0.13 vs. 2.05, p<0.0001). A significant correlation was observed between the adiponectin/leptin ratio and the LH/FSH ratio (r = 0.2138, p = 0.019). Conclusion: This study highlights the dysregulation of leptin and adiponectin in PCOS, suggesting their potential role in metabolic and reproductive dysfunction. The adiponectin-to-leptin ratio emerges as a promising biomarker for insulin resistance and metabolic risk in PCOS patients.

Impact of Gut Microbiome Interventions on Glucose and Lipid Metabolism in Metabolic Diseases: A Systematic Review and Meta-Analysis

Background: The gut microbiome is increasingly recognized as a key player in metabolic health, influencing glucose and lipid metabolism through various mechanisms. However, the efficacy of gut microbiota-targeted interventions, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet-based treatments, remains unclear for specific metabolic outcomes. In this study, the aim was to evaluate the impact of these interventions on the glucose and lipid parameters in individuals with metabolic diseases such as diabetes mellitus (DM), obesity, and metabolic syndrome. Methods: This systematic review and meta-analysis included 41 randomized controlled trials that investigated the effects of gut microbiota-targeted treatments on metabolic parameters such as fasting glucose, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. A comprehensive search was conducted using databases like PubMed, Google Scholar, and Scopus, focusing on interventions targeting the gut microbiota. A meta-analysis was performed using random-effects models, with effect sizes calculated for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool. Results: Gut microbiota-targeted interventions significantly reduced fasting glucose, HbA1c, HOMA-IR, total cholesterol, LDL-C, and triglycerides, with moderate heterogeneity observed across studies. The interventions also led to modest increases in HDL-C levels. Probiotic and synbiotic interventions showed the most consistent benefits in improving both glucose and lipid profiles, while FMT yielded mixed results. Short-term interventions showed rapid microbial shifts but less pronounced metabolic improvements, whereas longer-term interventions had more substantial metabolic benefits. Conclusions: In this study, it is demonstrated that gut microbiota-targeted interventions can improve key metabolic outcomes, offering a potential therapeutic strategy for managing metabolic diseases. However, the effectiveness of these interventions varies depending on the type, duration, and population characteristics, highlighting the need for further long-term studies to assess the sustained effects of microbiota modulation on metabolic health.

Visseral Lipectomy Improves Metabolic Syndrome Parameters and Adipokines in a Rat Model of Metabolic Syndrome Induced by Monosodium Glutamate.

Metabolic syndrome (MetS) includes abdominal obesity, hypertension, insulin resistance, and dyslipidemia. Research has indicated that reducing excess visceral fat has positive effects on inflammation and insulin resistance. We examined whether visceral lipectomy modifies the effects of MetS parameters and adipocytokine levels. Each group included 15 newborn male rats: control+sham (C+S), metabolic syndrome+sham (MetS+S), and metabolic syndrome+visceral lipectomy (MetS+VL). On postnatal days 0, 2, 4, 6, 8, and 10, subcutaneous injections of monosodium glutamate (MSG) (4g/mg) were administered to induce MetS. The control group received saline injection. The rats underwent sham surgery or lipectomy on the 120th day of life. Two months post-surgery, tests were performed to check lipid and insulin levels as well as the Lee index, HOMA-IR, serum adiponectin (ADP), resistin, interleukin-6 (IL6), leptin, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) levels. These findings showed that the Lee index (p = 0.001), insulin resistance (p = 0.002), and hyperinsulinemia (p = 0.009) were significantly improved in the MetS+VL group compared to those in the MetS+S group. The lipid profile was unaffected by visceral lipectomy. Furthermore, visceral lipectomy normalized MetS-induced adipokine imbalance. The decrease in the Lee index and improvement in hyperinsulinemia suggest that visceral lipectomy may benefit impaired glucose metabolism. Although visceral lipectomy has no apparent effect on the lipid profile, positive effects on adipokine levels by reducing various inflammatory markers including resistin, IL6, leptin, TNF-α, and CRP. These findings indicate that visceral lipectomy may have therapeutic potential for MetS. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Proposed shorter duration protocols for measuring resting energy expenditure utilizing whole-room indirect calorimetry.

Sixty minutes is currently the shortest testing duration for 24-h resting energy expenditure (24-h REE) utilizing whole-room indirect calorimetry. Show that recalculated 30-min extrapolated 24-h REE from previously published 60-min metabolic data are valid. Propane consumption linearity was determined through an 8-h combustion test. Thereafter, metabolic data for 24-h extrapolated ventilation rates of oxygen (VO2; l/d), carbon dioxide (VCO2; l/d), respiratory quotient (RQ; VCO2/VO2), and REE (MJ/d) from ten 60-min propane combustion tests were recalculated to reflect a 30-min testing duration. A similar analysis was performed utilizing data from 60-min subject metabolic measurements within a whole-room indirect calorimeter (4597 liters) specific for measuring resting energy expenditure (REE). Statistical (p < 0.05) comparisons between recalculated and original 60-min metabolic data were determined by SPSS (version 29). Propane consumption during a combustion test was found to be linear for up to 8-h. Furthermore, no differences existed between propane stoichiometry and combustion for any of the extrapolated 24-h metabolic parameters when recalculated from 60-min propane combustion data to reflect a 30-min duration. Finally, similar results were obtained for all recalculated subject metabolic data. Recalculated extrapolated 24-h metabolic data derived from a 30-min testing duration appear to be valid. This suggests that whole-room indirect calorimetry could be an adjunct for various weight loss or other programs where accurate metabolic measurements are required.

Treatment of hypothalamic obesity with GLP-1 analogs

Abstract Introduction Congenital and acquired damage to hypothalamic nuclei or neuronal circuits controlling satiety and energy expenditure results in hypothalamic obesity (HO). To date, successful weight loss and satiety has only been achieved in a limited number of affected patients across multiple drug trials. Glucagon-like peptide-1 (GLP-1) acts via central pathways that are independent from the hypothalamus to induce satiety. GLP-1 receptor agonists (GLP-1RAs) may provide an alternative approach to treating HO. Methods We performed a comprehensive search in Medline, google scholar, and clinical trials registries (ClinicalTrials.gov; clinicaltrialsregister.eur). This non-systematic literature review was conducted to identify scientific papers published from January 2005 to February 2024, using the Pubmed and Embase databases. Key words used were GLP-1, GLP-1 receptor agonist, hypothalamic obesity, suprasellar tumor, and craniopharyngioma. Results Our search identified 7 case studies, 5 case series and 2 published clinical trials relating to the use of GLP-1RAs in HO. All case studies demonstrated weight loss and improved metabolic function. In contrast, results from case series were variable, with some showing no weight loss, and others demonstrating moderate to significant weight loss and improved metabolic parameters. In the “ECHO” clinical trial, nearly half the subjects randomized to weekly exenatide showed reduced BMI. Paradoxically, BMI reduction was greater in patients with more extensive hypothalamic injuries. Conclusion GLP-1RAs potentially offer a new approach to treating HO. There is a need to stratify patients who are more likely to respond. Further RCTs are required to determine their efficacy either in isolation or combined with other therapies.

Efficacy of levothyroxine monotherapy in achieving clinical euthyroidism and its impact on weight loss in women with hypothyroidism and obesity.

In light of research indicating that normal TSH levels do not necessarily reflect clinical euthyroidism in hypothyroid patients, and given the patient dissatisfaction with levothyroxine (LT4) monotherapy, we evaluate the response to weight loss treatment in patients with obesity and primary hypothyroidism who are euthyroid under LT4 therapy, with a focus on weight and metabolic parameters. The retrospective study included 138 subjects with obesity (BMI ≥ 30kg/m2), 69 women with hypothyroidism on levothyroxine, and 69 age- and BMI-matched women without thyroid disease. Secondary causes of obesity, medications that may affect thyroid functions and metabolic parameters, chronic and oncological disease, pregnancy, TSH outside the reference range, follow-up periods of less than one year, and bariatric surgery were the exclusion criteria. Patients' characteristics and metabolic responses to weight reduction treatment consisting of calorie restriction, moderate exercise, and metformin if needed were evaluated. TSH and fT4 levels were higher, and fT3 and T3/T4 ratios were lower all within the reference ranges in hypothyroid women. They were less insulin resistant. Both patient' groups experienced a significant decrease in body weight, BMI, and atherogenic index of plasma (AIP) during the follow-up (p = 0.001). Insulin resistance was not changed. The groups' body weight, BMI, HOMA-IR, and AIP changes were similar at the end of the study (p = 0.876, p = 0.850, p = 0.555, p = 0.293). The results suggest that achieving euthyroid status via levothyroxine monotherapy in hypothyroid women leads to weight loss responses comparable to those in women with normal thyroid. This supports the effectiveness of current hypothyroidism treatment strategies, emphasizing TSH level normalization, in achieving clinical euthyroidism concerning weight loss outcomes.

Assessment of Glecaprevir/Pibrentasvir Treatment’s Influence on Biochemical and Metabolic Markers in Patients with Chronic Hepatitis

Background/Objectives: Liver function tests (LFT) are essential for diagnosing and monitoring liver status in patients with chronic hepatitis. In addition, tracking the systemic implications reflected in the changes in metabolic parameters is essential for correctly managing the cases. This study addresses the critical gap in the literature by evaluating the effects of glecaprevir/pibrentasvir on key liver function markers (AST, ALT, GGT, TB) and metabolic parameters (TC, TG, HbA1c) in patients with chronic hepatitis C (CHC). Moreover, this study will evaluate the impact of glecaprevir/pibrentasvir on A2MG, which provides insights into its effects on liver fibrosis. Awareness of these effects is critical for the optimal management of patients during and following antiviral therapy to ensure that therapeutic success does not come at the expense of overall liver and metabolic health. These parameters should be monitored as they supply clinicians with essential data, informing treatment more accurately and ensuring a holistic approach in CH patients. Methods: This study consists of 104 patients with chronic hepatitis C treated with glecaprevir/pibrentasvir and monitored from January to June 2024. Assessments comprised standard liver markers, lipid profiles, glycated hemoglobin, and alpha-2-macroglobulin, as well as specific non-invasive tests of liver injury. Results: 95.2% of the patients experienced a sustained virologic response. Biochemical markers and total cholesterol values were significantly decreased with glecaprevir/pibrentasvir therapy. Non-significant elevations in total bilirubin and glycated hemoglobin support the drug’s favorable tolerability profile. Conclusions: In the treatment of chronic hepatitis C patients, glecaprevir/pibrentasvir therapy leads to normalization in biochemical markers (AST, ALT, and GGT), as well as in total cholesterol.

Effectiveness of metformin in combination with intranasal insulin for the treatment of metabolic and hormonal disturbances in adult male rats with metabolic syndrome induced by impaired breastfeeding

BACKGROUND: Limiting or temporally stopping breastfeeding can lead to the development of metabolic syndrome in adulthood, which requires the development of approaches for its prevention and correction. One such approach is treatment with metformin or intranasal insulin. Since the targets of these agents differ and may complement each other, it has been suggested that their combined use could be effective. AIM: To study the effect of a four-week co-administration of metformin (orally, 120 mg/kg/day) and intranasal insulin (1.2 IU/kg/day) in male rats with metabolic syndrome, induced by breastfeeding disruption on postnatal days 19–21, on their metabolic and hormonal parameters. MATERIALS AND METHODS: The study treatment was compared with monotherapy using the same drugs. RESULTS: It was found that adult male rats with disrupted breastfeeding developed obesity, dyslipidemia, hyperleptinemia, impaired glucose tolerance, and a reduction in the number of β-cells and the area of pancreatic islets, which are characteristic of metabolic syndrome. Long-term treatment with metformin and its combination with intranasal insulin partially or fully normalized body weight, abdominal fat, and metabolic and hormonal parameters, with the restorative effect of combination treatment on such parameters as body weight, fat mass, glucose tolerance, and blood glycated hemoglobin levels being more pronounced than with metformin alone. CONCLUSIONS: The results of the study support the use of a combination of metformin and intranasal insulin to normalize metabolic and hormonal parameters in metabolic syndrome induced by breastfeeding disruption in early days of life.

Safety and Effectiveness of a 4-Week Diet on Low-Carb Ready-to-Eat Ketogenic Products as Preoperative Care Treatment in Patients Scheduled for Metabolic and Bariatric Surgery

Before metabolic and bariatric surgery (MBS), moderate weight loss and liver left lateral section (LLLS) volume reduction are desirable. Low-carb ketogenic diet-induced weight loss before MBS has been shown to have beneficial effects on the reduction in body weight (BW) and LLLS. However, the nutritional protocol of low-carb ketogenic diet may be hard to keep for prolonged periods due to the lack of sweet taste. Furthermore, transitioning to a low-carb ketogenic diet can cause people to crave foods that are restricted in the ketogenic diet, such as cookies, bread, pasta, and bagels. Therefore, many ready-to-eat low-carb ketogenic products (RLCKP) that mimic carbohydrate-rich foods despite a low-carb composition have been provided to make it easier for the patients to adopt a low-carb lifestyle. To date, there are no studies describing the dietary protocol for efficient and safe use of pre-operative RLCKP in terms of weight and LLLS volume reduction in patients with obesity scheduled for MBS. Therefore, the aim of this study was to assess the safety and effectiveness of a 4-week diet using RLCKP in reducing BW and LLLS volume in patients with obesity scheduled for MBS. Patients with obesity (n = 42) with a mean body mass index (BMI) of 42.4 ± 9.2 kg/m2 scheduled for MBS underwent a 4-week preoperative RLCKP diet intervention. Their weight, LLLS volume, and biochemical and metabolic parameters were measured before and after the diet. Patient compliance was assessed by the presence of ketonuria and weight loss. Qualitative methods (5-point Likert questionnaire) were used to measure diet acceptability and side effects. All patients completed the study. We observed highly significant decreases in BW (−6.5%, p &lt; 0.001), and LLLS volume (−22.3%, p &lt; 0.001) and an amelioration of patient clinical status. All patients showed a high frequency of acceptability and compliance in following the diet. No adverse side effects were reported. Based on our findings, we were able to support the hypothesis that a 4-week preoperative RLCKP diet is safe and effective in reducing BW, and LLLS volume in patients with obesity scheduled for MBS.

Cardiometabolic risk factors of post-bariatric patients two years after COVID-19 pandemic onset: a longitudinal study.

The COVID-19 pandemic's prolonged extension may have had a long-term negative impact on weight and metabolic parameters associated with the effectiveness of bariatric surgery. The aim of this study was to assess the impact of the COVID-19 pandemic on cardiometabolic risk markers and weight outcomes of post-bariatric patients. This is a longitudinal study carried out with patients who underwent bariatric surgery before the COVID-19 pandemic. Anthropometric, lipid, glycemic profile, blood pressure, eating behavior and physical activity parameters obtained through face-to-face consultations from 2019 to 2022 were evaluated. An increase in BMI (p = 0.001), percentage of weight gain (p < 0.001), postoperative weight regain rate (p = 0.002), fasting blood glucose (p < 0.001), and glycosylated hemoglobin (p < 0.001) was identified. There were reductions in the percentages of excess weight loss (p = 0.001) and physically active individuals (p = 0.016). These changes were only triggered after the pandemic years. Uncontrolled eating, emotional eating, and physical inactivity were identified as risk factors for weight gain during the pandemic. Prepandemic weight regain rate was risk factor for increased fasting blood glucose. Two years after the pandemic onset, the study participants exhibited increased rates of weight regain, reduced excess weight loss, and an increase in fasting blood glucose and glycosylated hemoglobin parameters.

Abstract 4138745: Blockade of Mineralocorticoid Receptor by Esaxerenone Improves Insulin Sensitivity in Obese Mice

Background: Aldosterone regulates blood pressure and electrolyte balance. However, overactivation of the mineralocorticoid receptor (MR) and elevated aldosterone levels are implicated in the pathogenesis of cardiometabolic disorders, though the underlying mechanisms are not fully understood. In this study, we investigated whether a novel, non-steroidal selective MR blocker, esaxerenone, ameliorates the development of metabolic disorders in obese mice models and examined the underlying mechanism. Methods: Esaxerenone (3 mg/kg/day) was orally administered to high-fat diet (HFD)-fed C57BL/6J or normal chow-fed db/db mice. Metabolic parameters, tissue morphology, and effects of esaxerenone on insulin sensitivity were assessed. Gene expression and insulin signaling, determined by Akt phosphorylation, were examined using quantitative RT-PCR and western blotting, respectively. In in-vitro experiments, insulin targets cell lines such as 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes were used. Insulin-responsive cells were treated with 10 nM or 100 nM esaxerenone or eplerenone for 30 minutes before 4-hour 1000 nM aldosterone stimulation. Insulin signaling was assessed 15 minutes after stimulation with 17 nM insulin. Results: Esaxerenone improved insulin sensitivity (P&lt;0.05) without altering metabolic parameters in HFD-induced obese and db/db mice. Esaxerenone suppressed fat accumulation, adipocyte size, and liver lipid droplets compared with the vehicle-treated group (P&lt;0.01). In adipose tissue, esaxerenone reduced macrophage infiltration (P&lt;0.01) and the expression of inflammatory molecules (P&lt;0.05). In in-vitro experiments, aldosterone significantly decreased the expression levels of PPARγ and adiponectin in 3T3-L1 adipocytes. Moreover, aldosterone attenuated insulin-induced Akt phosphorylation in 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes in a dose-dependent manner (P&lt;0.01). Pretreatment with esaxerenone reversed the effect of aldosterone, whereas eplerenone, an MR antagonist, did not show a similar effect at the same dose. Conclusion: Inhibition of MR by esaxerenone improved insulin sensitivity in HFD-induced obese and genetically diabetic mice. The reduction of inflammation and fat accumulation and enhancement of insulin signaling were suggested to be underlying mechanisms. Esaxerenone might be a beneficial therapeutic approach for managing metabolic disorders.

Metabolic Effects of Sodium Thiosulfate During Resuscitation from Trauma and Hemorrhage in Cigarette-Smoke-Exposed Cystathionine-γ-Lyase Knockout Mice

Background: Acute and chronic pre-traumatic cigarette smoke exposure increases morbidity and mortality after trauma and hemorrhage. In mice with a genetic deletion of the H2S-producing enzyme cystathione-γ-lyase (CSE−/−), providing exogenous H2S using sodium thiosulfate (Na2S2O3) improved organ function after chest trauma and hemorrhagic shock. Therefore, we evaluated the effect of Na2S2O3 during resuscitation from blunt chest trauma and hemorrhagic shock on CSE−/− mice with pre-traumatic cigarette smoke (CS) exposure. Since H2S is well established as being able to modify energy metabolism, a specific focus was placed on whole-body metabolic pathways and mitochondrial respiratory activity. Methods: Following CS exposure, the CSE−/− mice underwent anesthesia, surgical instrumentation, blunt chest trauma, hemorrhagic shock for over 1 h (target mean arterial pressure (MAP) ≈ 35 ± 5 mmHg), and resuscitation for up to 8 h comprising lung-protective mechanical ventilation, the re-transfusion of shed blood, fluid resuscitation, and continuous i.v. noradrenaline (NoA) to maintain an MAP ≥ 55 mmHg. At the start of the resuscitation, the mice randomly received either i.v. Na2S2O3 (0.45 mg/gbodyweight; n = 14) or the vehicle (NaCl 0.9%; n = 11). In addition to the hemodynamics, lung mechanics, gas exchange, acid–base status, and organ function, we quantified the parameters of carbohydrate, lipid, and protein metabolism using a primed continuous infusion of stable, non-radioactive, isotope-labeled substrates (gas chromatography/mass spectrometry) and the post-mortem tissue mitochondrial respiratory activity (“high-resolution respirometry”). Results: While the hemodynamics and NoA infusion rates did not differ, Na2S2O3 was associated with a trend towards lower static lung compliance (p = 0.071) and arterial PO2 (p = 0.089) at the end of the experiment. The direct, aerobic glucose oxidation rate was higher (p = 0.041) in the Na2S2O3-treated mice, which resulted in lower glycemia levels (p = 0.050) and a higher whole-body CO2 production rate (p = 0.065). The mitochondrial respiration in the heart, kidney, and liver tissue did not differ. While the kidney function was comparable, the Na2S2O3-treated mice showed a trend towards a shorter survival time (p = 0.068). Conclusions: During resuscitation from blunt chest trauma and hemorrhagic shock in CSE−/− mice with pre-traumatic CS exposure, Na2S2O3 was associated with increased direct, aerobic glucose oxidation, suggesting a switch in energy metabolism towards preferential carbohydrate utilization. Nevertheless, treatment with Na2S2O3 coincided with a trend towards worsened lung mechanics and gas exchange, and, ultimately, shorter survival.

Evaluation of the Tobacco Heating System (THS) During Closed Lower Limb Fracture Healing in Trauma Smokers’ Patients

BACKGROUND: Since 1976, it's been recognized that increased cigarette consumption correlates with decreased bone density, hindering fracture healing and leading to prolonged hospitalization. Although prior research has shown the relatively less harmful effects of electronic nicotine delivery systems (ENDS) on bone cells in lab settings and animal models, clinical evidence regarding their impact on fracture healing remains scarce. This study aims to investigate whether switching to a tobacco heating system (THS) post-orthopedic surgery improves outcomes for smoking patients during tibia or femur fracture healing over a 6-month period. METHODS: The study is a prospective, open-label, non-parallel, single-center trial involving 150 patients from a Level 1 Trauma center, Germany, diagnosed and treated for closed tibia, closed femur shaft, or closed distal femur fractures (according to AO/OTA: 41A2-41C3, 42A-C, 43A-C, 32A-C, 33A2-3, 33B-C). Participants will be categorized into three groups based on smoking behavior: smokers (no intervention), THS (participants switching from cigarettes to THS), and ex-smokers (participants abstaining from cigarettes or ENDS during the study). Clinical, radiological, and laboratory data will be collected during preoperative and postoperative assessments at 6, 12, 18, and 24 weeks. The primary outcome will be the serum concentration of N-terminal propeptide procollagen type 1, a bone formation marker. Secondary outcomes include bone metabolism, healing, immunological, blood count, and clinical parameters. Approval for the study protocol and consent declarations was obtained from the ethics committee of the medical faculty of Eberhard Karls University (724/2022BO1). DISCUSSION: The study results will provide evidence that switching to THS previous orthopedic intervention improves clinical outcomes during closed tibia or femur fracture healing in smokers’ patients due to reduced bone resorption rate consequent to the diminished activity of cigarette smoke-activated osteoclast.

Association between depression and diabetes among American adults using NHANES data from 2005 to 2020.

Depression impairs self-management in diabetic patients, exacerbates insulin resistance, and elevates glycated hemoglobin (HbA1c) levels, thereby increasing diabetes risk. This study analyzed data from 30,386 participants in the National Health and Nutrition Examination Survey (NHANES), assessing depression severity using the 9-item Patient Health Questionnaire (PHQ-9) and evaluating diabetes status through clinical markers such as HbA1c, random blood glucose, and fasting blood glucose. Participants were stratified by depression severity and diabetes status to examine the relationship between depression and diabetes risk. We applied descriptive statistics, logistic regression models, subgroup analyses, and restricted cubic spline (RCS) modeling to explore this association. The results revealed that greater depression severity was significantly associated with increased diabetes incidence, elevated HbA1c, fasting glucose, and insulin levels. Multivariate regression analysis confirmed a consistent positive correlation between depression severity and diabetes risk. Subgroup analyses further identified significant relationships between depression and various demographic and behavioral factors, including gender, race, BMI, smoking status, and prediabetic conditions. Additionally, the RCS model demonstrated a clear increase in diabetes risk with rising PHQ-9 scores. In conclusion, our study demonstrates that the severity of depression is positively correlated with the risk of diabetes, and this association may be closely linked to various glycemic and lipid metabolic parameters.

Abstract 4125587: Vasomotor function and its regulation by perivascular adipose tissue in metabolic syndrome vary depending on severity and combination of metabolic parameters

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. Because perivascular adipose tissue (PVAT) regulates arterial tone by releasing vasorelaxing/vasocontracting factors, the effects of PVAT on vasomotor function have been heterogeneously reported. Various PVAT functions can result from the severity or combination of metabolic parameters in MetS. Therefore, we compared the effects of mesenteric arterial PVAT on the nitric oxide-dependent vasorelaxation response among the three metabolic syndrome (MetS) model strains. We compared male OLETF, Zucker fatty (ZF), and SHRSPZF (SPZF) rats aged 20 weeks to lean controls, LETO, ZF +/+ , and Wistar-Kyoto (WKY) rats. To determine the effects of PVAT on vasodilators, we used organ bath techniques to assay nitroprusside-induced relaxation of isolated mesenteric arterial ring preparations with intact or removed PVAT. The waist circumference to length ratio in OLETF and ZF rats was higher than that in SPZF rats, and the systolic blood pressure was higher in SPZF rats than in the other groups. In the serum, there was no significant difference in triglyceride levels. Still, glucose and thiobarbituric acid reactive substance levels were higher in OLETF and SPZF rats than in ZF rats. Relaxation in ZF rats did not change compared to that in ZF +/+ rats and the presence of PVAT. In contrast, relaxation in OLETF rats was lower than in LETO rats, and there was no difference between the presence and absence of PVAT. However, relaxation in SPZF rats was lower than in WKY rats, and relaxation increased to the same level as in WKY rats in the presence of PVAT. This study unveils novel insights, suggesting that high serum glucose and oxidative stress cause arterial dysfunction, whereas high blood pressure induces PVAT functional changes. These findings underscore the complex interplay between metabolic disorders and vascular health, potentially paving the way for more targeted interventions in patients with MetS.

Systematic Review and Meta-Analysis of Sclerocarya birrea on Metabolic Disorders: Evidence from Preclinical Studies

Background/Objectives: Metabolic disorders, including diabetes, obesity, and cardiovascular diseases, are significant global health issues. Nutraceuticals, such as Sclerocarya birrea (SB), known for its high polyphenol content, are increasingly explored for managing these conditions. This study aims to evaluate the antihyperglycemic, hypolipidemic, and antihypertensive effects of SB in animal models to understand its potential as a natural intervention for metabolic diseases. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. Searches across databases like PubMed, Web of Science, Embase, and Scopus identified studies using SB in animal models of metabolic disorders. Inclusion criteria were studies with SB intervention, control groups, and quantitative measures of metabolic parameters. The study was registered with INPLASY (INPLASY2024100031). Results: The meta-analysis revealed that SB significantly reduces blood glucose levels in diabetic animal models. Acute administration of SB showed a pooled standardized mean difference (SMD) of −7.13 (95% CI: −11.44 to −2.83) at 1 h and −9.75 (95% CI: −15.92 to −3.59) at 2–4 h post-administration. Chronic administration indicated a non-significant reduction in glucose levels (SMD: −5.69, 95% CI: −16.38 to 5.01). Conclusions: SB appears to have the potential for reducing blood glucose levels and may offer benefits for other cardiometabolic risk factors, including lipid profiles and oxidative stress. However, variability in the results underscores the need for further research, including standardized animal studies and clinical trials, to confirm these effects and clarify the mechanisms by which SB may impact metabolic disorders.

Dapagliflozin alleviates high-fat-induced obesity cardiomyopathy by inhibiting ferroptosis.

Dapagliflozin (Dapa) is a novel hypoglycaemic agent with multiple cardiovascular protective effects, and it is widely used in treatment of heart failure patients, but whether it can improve obese phenotype of heart failure and its mechanism is still unclear. Ferroptosis is an iron dependent form of cell death and has been proved to be an important role in heart failure. The aim of this study is to determine whether Dapa improves obesity-related heart failure by regulating ferroptosis in high-fat diet rats. Male SD rats were fed a high-fat diet for 12 weeks and confirmed of obese heart failure by metabolic parameters and cardiac ultrasound. Being overweight by 20% compared with the normal group, with elevated systolic blood pressure and abnormal levels of insulin and blood lipid (TG and LDL-c), is recognized as obesity. The obese rats with reduced EF, FS, and E/A shown on ultrasound are defined as the obese heart failure (OHF) group. Histological tests confirmed the more pronounced cardiac fibrosis, mitochondrial volume and collagen deposition in OHF group. Dapa treatment effectively reduced body weight, INS, ISI/IRI index, TG and HDL-C levels (P < 0.05). Also, Dapa administration can slightly decrease the SBP and DBP levels; however, there was no statistical difference among those four groups. Furthermore, Dapa treatment can significantly improve high-fat induced systolic and diastolic dysfunction via regulating cardiac histological abnormalities, including less obvious mitochondrial swelling, muscle fibre dissolution and collagen deposition. Additionally, genes from the OHF group were used by GO enrichment analysis, and it shows that ferroptosis metabolic pathway participated in the development of obese phenotype of heart failure. More importantly, Dapa significantly inhibited Fe2+ and MDA levels (P < 0.05), but augmented GSH content (P < 0.05). In addition, the mRNAs and protein expression of some important regulators of ferroptosis, like GPX4, SLC7A11, FTH1 and FPN1, were all decreased after Dapa intervention. Dapa improved high-fat induced obese cardiac dysfunction via regulating ferroptosis pathway.

Real-world evidence of effectiveness and safety of pasireotide in the treatment of acromegaly: a systematic review and meta-analysis.

Pasireotide long-acting release (PAS-LAR) is a second-generation somatostatin receptor ligand (SRL) approved for acromegaly treatment. This meta-analysis aimed to evaluate the real-world effectiveness and safety of PAS-LAR in patients with acromegaly resistant to first-generation somatostatin receptor ligands (fgSRL). A systematic literature search was conducted in PubMed and Web of Science for real-world studies on PAS-LAR in acromegaly published between 2014 and 2023. Random-effects meta-analyses were performed on biochemical control rates, tumor shrinkage, and metabolic parameters. Twelve studies comprising 409 patients were included. The pooled rate of insulin-like growth factor 1 (IGF-1) control was 57.9% [95% CI: 48.4-66.8] and the percentage of patients with tumor shrinkage was 33.3% [95%CI: 19.7-50.4]. Significant reductions were observed in growth hormone standardized mean difference (SMD) 0.6 ng/mL [95% CI: 0.3 to 1.0] and IGF-1 levels SMD 0.9 ULN [95% CI: 0.4 to 1.4]. However, as expected, a worsening in glucose metabolism was noted as an increase in fasting glucose SMD - 0.8mg/dL [95% CI: -1.0 to -0.5, p < 0.01], glycated hemoglobin SMD - 0.5% [95% CI: -0.7 to -0.2]. and type 2 diabetes mellitus prevalence SMD - 11.5% (95% CI: -17.5 to -5.5). PAS-LAR demonstrated higher effectiveness in real-world settings, with over 60% of patients achieving IGF-1 control compared to the around 30% efficacy observed in clinical trials. These findings suggest that PAS-LAR is an effective option for acromegaly patients resistant to fgSRL, but careful monitoring of glucose levels is essential. The high heterogeneity observed across studies emphasizes the need for identifying PAS-LAR response biomarkers to set-up individualized treatment approaches for optimizing patient outcomes.