Metabolism-related Parameters Research Articles

Metformin modulates the TXNIP-NLRP3-GSDMD pathway to improve diabetic bladder dysfunction

To validate the therapeutic efficacy of metformin on diabetic bladder dysfunction (DBD) and further elucidate whether the TXNIP-NLRP3-GSDMD axis serves as a target for metformin in ameliorating DBD. C57BL/6J mice were induced with diet-induced obesity by being fed a high-fat diet (HFD) for 16 weeks. After establishing the model, the mice were treated with metformin for 4 weeks, and their glucose metabolism-related parameters were assessed. Urine spot assays and urodynamic measurements were conducted to reflect the bladder function and urinary behavior in mice, while histological examination was performed to observe morphological changes. Western blot analysis was employed to measure the expression levels of pyroptotic factors such as TXNIP, NLRP3, GSDMD, and tight junction proteins. Metformin treatment significantly improved glucose tolerance and insulin sensitivity in mice. Moreover, it showed promise in decreasing urinary spot occurrence, reducing urination frequency, alleviating non-voiding contractions, and stabilizing peak urinary pressure. Following metformin therapy, mice displayed restored epithelial fold structure, increased thickness of the muscular layer, substantial decrease in muscle fiber content, notably reduced levels of TXNIP and GSDMD proteins in the metformin-treated group compared to the DBD group, and restored expression of tight junction proteins Zo-1, Claudin-1, and Occludin. Metformin ameliorates urothelial cells damage in DBD mice by inhibiting TXNIP generation and reducing NLRP3 and GSDMD production.

Osilodrostat treatment in patients with Cushing's disease of Asian or non-Asian origin: a pooled analysis of two Phase III randomized trials (LINC 3 and LINC 4).

Cushing's disease is associated with increased morbidity and mortality. Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained mean urinary free cortisol (mUFC) normalization in Cushing's disease patients in two Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734). Here, we evaluate the efficacy and safety of osilodrostat in Cushing's disease in patients of Asian origin compared with patients of non-Asian origin. Pooled data from LINC 3 and LINC 4 were analyzed. Outcomes were evaluated separately for Asian and non-Asian patients. For the analysis, 210 patients were included; 56 (27%) were of Asian origin. Median (minimum-maximum) osilodrostat dose was 3.8 (1-25) and 7.3 (1-47) mg/day in Asian and non-Asian patients, respectively. mUFC control was achieved at weeks 48 and 72 in 64.3% and 68.1% of Asian and 68.2% and 75.8% of non-Asian patients. Improvements in cardiovascular and metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life were similar in both groups. Most common adverse events (AEs) were adrenal insufficiency (44.6%) in Asian and nausea (45.5%) in non-Asian patients. AEs related to hypocortisolism and pituitary tumor enlargement occurred in more Asian (58.9% and 21.4%) than non-Asian patients (40.3% and 9.1%). Of Asian and non-Asian patients, 23.2% and 13.6%, respectively, discontinued because of AEs. Asian patients with Cushing's disease generally required numerically lower osilodrostat doses than non-Asian patients to achieve beneficial effects. Hypocortisolism-related AEs were reported in more Asian than non-Asian patients. Together, these findings suggest that Asian patients are more sensitive to osilodrostat than non-Asian patients.

Low doses of acetyl trihexyl citrate plasticizer promote adipogenesis in hepatocytes and mice.

Accumulating epidemiological evidence underscores the association between pervasive environmental factors and an increased risk of metabolic diseases. Environmental chemicals, recognized disruptors of endocrine and metabolic processes, may contribute to the global prevalence of metabolic disorders, including obesity. Acetyl tributyl citrate (ATHC), categorized as a citric acid ester plasticizer, serves as a substitute for di-(2-ethylhexyl) phthalate (DEHP) in various everyday products. Despite its widespread use and the increasing risk of exposure in humans and animals due to its high leakage rates, information regarding the safety of exposure to environmentally relevant doses of ATHC remains limited. This study aimed to investigate the potential impact of ATHC exposure on metabolic homeostasis. Both in vivo and in vitro exposure models were used to characterize the effects induced by ATHC exposure. C57BL/6J male mice were subjected to a diet containing ATHC for 12weeks, and metabolism-related parameters were monitored and analyzed throughout and after the exposure period. Results indicated that sub-chronic dietary exposure to ATHC induced an increase in body fat percentage, elevated serum lipid levels, and increased lipid content in the liver tissue of mice. Furthermore, the effect of ATHC exposure on murine hepatocytes were examined and results indicated that ATHC significantly augmented lipid levels in AML12 hepatocytes, disrupting energy homeostasis and altering the expression of genes associated with fatty acid synthesis, uptake, oxidation, and secretion pathways. Conclusively, both in vivo and in vitro results suggest that exposure to low levels of ATHC may be linked to an elevated risk of obesity and fatty liver in mice. The potential implications of ATHC on human health warrant comprehensive evaluation in future studies.

Effects of dietary protein level on liver lipid deposition, bile acid profile and gut microbiota composition of growing pullets

The current study investigated the effects of dietary crude protein (CP) level on the liver lipid metabolism, gut microbiota, and bile acids (BA) profiles of growing pullets. Roman growing pullets (N = 180, 13-wk-old) were divided into 3 treatments groups with 6 replicates in each group and 10 hens in each replicate and provided 3 different dietary CP level diet treatments. The diet treatments included: a high-protein diet (15.5% CP, HP group), a medium-protein diet (14.5% CP, MP group), and a low-protein diet (13.5% CP, LP group). Compared with HP group, LP group significantly increased the lipid contents in the body (such as Breast intramuscular fat [BIMF], Leg intramuscular fat [LIMF], Percentage of abdominal fat [PAF], liver triglyceride [TG] and liver cholesterol [TC]), and the lipid metabolism-related parameters in serum (such as cholesterol (TC), high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], very low density lipoprotein [VLDL]), and the mRNA expression of lipid metabolism-related genes (such as fatty acid synthase [FAS], CCAAT/enhancer binding protein β [C/EBPβ], and fatty acid translocase [FAT/CD6]) (P < 0.05). In addition, LP group significantly reduced the contents of lithocholic acid (LCA), isoLCA, and ursodesoxycholic acid (UDCA), and increased the deoxycholic acid (DCA) content compared with HP group (P < 0.05). The effects of LCA on lipid deposition were confirmed in chicken preadipocyte cell line (CPI), in which LCA supplementation significantly decreased the relative expression of PPARγ, FAS, acyl-CoA carboxylase (ACC) and SREBP-1c (P < 0.05). Correlation analysis further revealed a significant association between BA profiles and lipid metabolism-related parameters. Furthermore, 16S rRNA gene sequencing indicated that dietary protein level can significantly affect the richness, diversity, and composition of cecal microbiota in growing pullets. LP group significantly increased the abundance of Bacteroidetes and significantly decreased the abundance of Firmicutesa compared with the HP group. In summary, low protein diet in growing pullets influence the liver lipid metabolism through changing the gut microbiota and liver BA metabolism.

Molecular Signaling Effects behind the Spontaneous Soleus Muscle Activity Induced by 7-Day Rat Hindlimb Suspension.

The elimination of ground reaction force (support withdrawal) vastly affects slow postural muscles in terms of their regulation and structure. One of the effects of support withdrawal in this study was an immediate postural muscle inactivation, followed by the daily gradual development of spontaneous activity of the slow postural soleus muscle in response to rat hindlimb suspension to mimic space flight. The origin of this activity is somewhat akin to muscle spasticity after spinal cord injuries and is the result of KCC2 content decline in the spinal cord's motor neurons. However, the physiological consequences of unloading-induced spontaneous activity remain unexplored. We have conducted an experiment with the administration of a highly specific KCC2 activator during 7-day unloading. For this experiment, 32 male Wistar rats were divided into 4 groups: C+placebo, C+CLP-290 (100 mg/kg b w), 7HS+placebo, and 7HS+CLP-hindlimb-suspended group with CLP-290 administration (100 mg/kg b w). The soleus muscles of the animals were dissected and analyzed for several proteostasis- and metabolism-related parameters. CLP-290 administration to the unloaded animals led to the upregulation of AMPK downstream (p-ACC) and mTOR targets (p-p70S6k and p-4E-BP) and an enhanced PGC1alpha decrease vs. the 7HS group, but neither prevented nor enhanced atrophy of the soleus muscle or myofiber CSA.

Dietary Bacillus species modulate lipid metabolism-related parameters, growth, water quality, and bacterial load in Nile tilapia (Oreochromis niloticus )

This study examined the impact of supplementing Bacillus spp. mixtures at concentrations of 0.2 g/kg (PRO-0.2) and 0.5 g/kg (PRO-0.5) on Nile tilapia (Oreochromis niloticus) for 90 days. Fish groups receiving PRO-0.2 and PRO-0.5 exhibited significantly lower water ammonia levels than the control group, in linear and quadratic patterns. Furthermore, their length and weight increased exponentially over time, peaking at the end of the experiment. After 90 days, the PRO-0.5 group displayed the highest mean weight gain. Additionally, both the PRO-0.2 and PRO-0.5 groups had the lowest food conversion ratios and highest protein efficiency ratios in a linear pattern. They also showed improved liver function, as indicated by lower levels of liver enzyme (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) compared to the control group. In terms of the lipid profile, the PRO-0.2 and PRO-0.5 groups had significantly lower serum levels of low-density lipoprotein, triglycerides, in linear and quadratic patterns, and cholesterol compared to the control group, with no significant differences in cholesterol levels. High-density lipoprotein increased significantly in both PRO-0.2 and PRO-0.5 groups after 90 days, following a linear pattern. Hepatic alkaline phosphatase levels decreased in both the PRO-0.2 and PRO-0.5 groups, following a significant linear pattern over time. After 30 days, the expression of hepatic fatty acid binding protein 3 (fabp3) significantly decreased in the PRO-0.5 group. Intestinal cluster of differentiation 36 (cd36) and fabp3 expression markedly increased, with cd36 showing the greatest rise. After 90 days, hepatic cd36 expression became prominent in both PRO-0.2 and PRO-0.5 groups. Expression of fas was significantly downregulated in both the PRO-0.2 and PRO-0.5 groups. Notably, hepatic lipoprotein lipase (lpl) expression significantly increased in the supplementation groups after 30 days but decreased significantly after 90 days. Overall, this study highlights the positive impact of dietary mixtures of Bacillus spp. on various aspects, including water quality, growth performance, feed utilization, survivability, expression of lipid metabolism-related genes, lipid profile, body composition, and bacterial load in both water and fish bodies.

Value of serum iron and urine neutrophil gelatinase-associated lipocalin in predicting the mortality of critically ill patients with sepsis.

We aimed to investigate the association of iron metabolism-related parameters with 60-day mortality in critically ill patients with sepsis. Serum or urine concentrations of iron metabolism-related parameters on intensive care unit admission were measured in a prospective cohort of 133 eligible patients with sepsis according to the Sepsis-3 criteria, and these values were compared between survivors and nonsurvivors, categorized according to their 60-day survival status. Cox regression analyses were performed to examine the association between iron parameters and 60-day mortality. Kaplan-Meier methods were used to illustrate the differences in survival between different iron parameters. Of the 133 patients included in the study, 61 (45.8%) had died by day 60. After adjusting for confounding variables, higher concentrations of serum iron (cut-off 9.5 μmol/mL) and higher concentrations of urine neutrophil gelatinase-associated lipocalin (uNGAL; cut-off 169.3 ng/mL) were associated with a significantly greater risk of death in the Cox regression analysis. These two biomarkers combined with Sequential Organ Failure Assessment (SOFA) scores increased the area under the receiver operating characteristic (AUROC) curve to 0.85. These findings suggest that higher concentrations of serum iron and uNGAL are each associated with higher 60-day mortality, and they add significant accuracy to this prediction in combination with SOFA. Abbreviations: uNGAL: urine neutrophil gelatinase-associated lipocalin; ICU: intensive care unit; SOFA: Sequential Organ Failure Assessment; APACHE II: the Acute Physiology and Chronic Health Evaluation II; ELISA: enzyme-linked immunosorbent assay; HR: hazard ratio; CIs: confidence intervals; WBC: white blood cell; TBIL: total bilirubin.

Restless leg syndrome as a complication of primary hyperparathyroidism: insights from a retrospective study.

Restless leg syndrome (RLS) is an invalidating neurological disorder with a complex, largely unknown pathophysiology. While RLS is observed in Parkinson's disease and in renal failure, idiopathic cases are common. Limited reports associate RLS with parathyroid hormone (PTH). This study analyzes a cohort of patients with primary hyperparathyroidism (PHPT) and chronic post-surgical hypoparathyroidism (hypo PTH), to investigate RLS prevalence, and associated risk factors. Ninety-five patients (54 PHPT, 41 hypo PTH) were consecutively enrolled at the bone metabolism outpatient clinic. The revised IRLSSG diagnostic criteria were used to diagnose RLS, with assessments conducted through face-to-face interviews and neurological examination. When RLS was confirmed, the RLS severity scale was applied. Retrospective records included calcium-phosphate metabolism-related parameters, surgery details, renal lithiasis, fragility fractures, and densitometric features (T-score). RLS was diagnosed in 22.2% PHPT patients, compared to 4.9% of patients with hypo PTH (p = 0.02). Of RLS diagnosed patients, 91.7% had a history of parathyroidectomy, compared to 47.6% of patients without RLS (p = 0.01). Most of the operated patients reported that surgery determined an improvement of symptoms; however, mean score severity of RLS at our evaluation was 15/40, defined as moderate. PTH and calcium levels were not statistically associated to the presence of RLS. Our study suggests that PHPT may be one of the etiologies of RLS. Parathyroidectomy alleviates symptoms in the vast majority of the cases but does not remove them.

From NAFLD to MASLD: Meta-analysis and systematic review of NAFLD patients in Turkiye in terms of metabolic profile and MASLD potential.

Non-alcoholic Fatty Liver Disease (NAFLD) is both a cause and a consequence of metabolic disturbances. Consequently, the disease term has recently changed to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Turkiye is one of the leading countries with high incidences of diseases such as diabetes, obesity, metabolic syndrome, and fatty liver. This study aims to identify the metabolic parameters and MASLD potential of NAFLD in Turkiye. All NAFLD studies conducted in Turkiye were systematically searched using the keywords "fatty liver disease" AND " Turkiye " on PubMed, Scopus, and Web of Science databases. A total of 2653 articles were scanned, and 120 studies were eligible for meta-analysis. The metabolic parameters were meta-analyzed from a broad perspective. According to the meta-analysis results, there were significant increases in waist circumferences (mean difference: 10.90, p<0.00001), HOMA-IR (mean difference: 2.13, p<0.00001), aspartate aminotransferase (AST) (mean difference: 17.82, p<0.00001), systolic blood pressure (SBP) (mean difference: 5.86, p<0.00001), and C-reactive protein (CRP) levels (mean difference: 0.95, p<0.00001). These parameters are representative biochemical findings of disturbed glucose metabolism, lipid profile, blood pressure, and acute phase response mechanisms. Furthermore, the analysis of all related parameters commonly found among the articles confirmed these metabolic dysfunctions. NAFLD is a metabolic disease that encompasses multiple pathways related to glucose and lipid metabolism, vascular function, inflammation, and acute phase responses. Additionally, our results suggest that Turkish NAFLD patients identified in previous studies mostly have MASLD. This is the first meta-analysis study indicating changes in metabolism-related parameters with a cumulative meta-analysis of all Turkish NAFLD studies.

Efficacy of lumbar and abdominal muscle rehabilitation training on degree of osteoporosis, pain and anxiety in elderly patients with osteoporotic vertebral compression fracture after PKP and compliance analysis.

To explore the rehabilitation effect and compliance of lumbar and abdominal muscle rehabilitation training in patients with osteoporotic vertebral compression fracture (OVCF) after percutaneous balloon vertebroplasty (PKP). A total 177 elderly patients with OVCF were divided into rehabilitation group (n = 104) and control group (n = 73) according to whether they received psoas and abdominal muscle rehabilitation training for 3 months after PKP. The differences of general data, orthopaedic rehabilitation, prognosis and bone metabolism were compared between the two groups. All the patients were divided into compliance group (68 cases) and non-compliance group (36 cases) according to compliance. Orthopaedic rehabilitation indicators, prognostic indicators of PKP, and bone metabolism-related parameters were collected for analysis of Chi-square test and Logistic regression. ROC curve was used to analyze the predictive value of bone metabolism related indicators in the compliance of lumbar and abdominal muscle rehabilitation training. There was no significant difference in the general data between the rehabilitation training group and the control group (All p > 0.05). Compared with the control group, the Berg balance scale score was significantly increased, while the Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) score and the proportion of new fractures were significantly decreased in the rehabilitation training group (All p < 0.05). Compared with the control group, the bone mineral density (BMD) T value, osteocalcin (OCN) and 25-hydroxyvitamin D (25 (OH) D) levels were significantly increased and the levels of type I N-propeptide (P1NP) and β-isomerized C-terminal telopeptides (β-CTX) were significantly decreased in the rehabilitation training group compared with the control group (All p < 0.05). Chi-square test and Logistic regression analysis showed that age > 75 years, severe anxiety, severe pain and postoperative complications were significantly associated with the compliance of psoas and abdominal muscle rehabilitation training in patients with OVCF after PKP. ROC curve analysis showed that BMD T value, OCN, P1NP, β-CTX, or 25-OH-D levels predicted the AUC of rehabilitation training compliance in patients with OVCF after PKP were 0.821, 0.835, 0.736, 0.715, and 0.748, respectively. Rehabilitation training of lumbar and abdominal muscles can significantly improve the efficacy of PKP, reduce the degree of osteoporosis and improve the prognosis of patients with OVCF. Age, anxiety, pain and postoperative complications were independent risk factors affecting the compliance of psoas and abdominal rehabilitation training in patients with OVCF after PKP.

The Role of Phosphatidylethanolamine N-Methyltransferase (PEMT) and Its Waist-Hip-Ratio-Associated Locus rs4646404 in Obesity-Related Metabolic Traits and Liver Disease

In previous genome-wide association studies (GWAS), genetic loci associated with obesity and impaired fat distribution (FD) have been identified. In the present study, we elucidated the role of the PEMT gene, including the waist–hip-ratio-associated single nucleotide polymorphism rs4646404, and its influence on obesity-related metabolic traits. DNA from 2926 metabolically well-characterized subjects was used for genotyping. PEMT expression was analyzed in paired visceral (vis) and subcutaneous (sc) adipose tissue (AT) from a subset of 574 individuals. Additionally, PEMT expression was examined in vis, sc AT and liver tissue in a separate cohort of 64 patients with morbid obesity and liver disease. An in vitro Pemt knockdown was conducted in murine epididymal and inguinal adipocytes. Our findings highlight tissue-specific variations in PEMT mRNA expression across the three studied tissues. Specifically, vis PEMT mRNA levels correlated significantly with T2D and were implicated in the progression of non-alcoholic steatohepatitis (NASH), in contrast to liver tissue, where no significant associations were found. Moreover, sc PEMT expression showed significant correlations with several anthropometric- and metabolic-related parameters. The rs4646404 was associated with vis AT PEMT expression and also with diabetes-related traits. Our in vitro experiments supported the influence of PEMT on adipogenesis, emphasizing its role in AT biology. In summary, our data suggest that PEMT plays a role in regulating FD and has implications in metabolic diseases.

The association of lipid metabolism and sarcopenia among older patients: a cross-sectional study

Sarcopenia has become a heavy disease burden among the elderly. Lipid metabolism was reported to be involved in many degenerative diseases. This study aims to investigate the association between dysregulated lipid metabolism and sarcopenia in geriatric inpatients. This cross-sectional study included 303 patients aged ≥ 60, of which 151 were diagnosed with sarcopenia. The level of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), homocysteine (HCY), BMI, and fat percentage, were compared between sarcopenia and non-sarcopenia patients. The Spearman correlation coefficient was used to estimate the association between sarcopenia and the level of lipid metabolism. To determine risk factors related to sarcopenia, a multivariate logistic regression analysis was carried out. Risk prediction models were constructed based on all possible data through principal component analysis (PCA), Logistic Regression (LR), Support Vector Machine (SVM), k-Nearest Neighbor (KNN), and eXtreme Gradient Boosting (XGboost). We observed rising prevalence of sarcopenia with increasing age, decreasing BMI, and fat percentage (p < 0.001, Cochran Armitage test). Multivariate logistic regression analysis revealed sarcopenia’s risk factors, including older age, male sex, lower levels of BMI, TC, and TG, and higher levels of LDL and HCY (p < 0.05). The sarcopenia risk prediction model showed the risk prediction value of sarcopenia, with the highest area under the receiver operating curve (AUC) of 0.775. Our study provided thorough insight into the risk factors associated with sarcopenia. It demonstrated that an increase in lipid metabolism-related parameters (BMI, TG, TC), within normal reference ranges, may be protective against sarcopenia. The present study can illuminate the direction and significance of lipid metabolism-related factors in preventing sarcopenia.

THU032 Osilodrostat Is Effective And Well Tolerated In Patients Of Asian And Non-Asian Origin With Cushing's Disease: A Pooled Analysis From LINC 3 And LINC 4

Abstract Disclosure: P.J. Snyder: Consulting Fee; Self; Teva Pharmaceutical Industries Ltd. B.M. Biller: Consulting Fee; Self; HRA Pharmaceuticals, Recordati, Sparrow, Xeris Pharmaceuticals (Strongbridge). M. Fleseriu: Consulting Fee; Self; Recordati, Sparrow, Xeris Pharmaceuticals (Strongbridge), HRA Pharmaceuticals. Grant Recipient; Self; Recordati, Sparrow, Xeris Pharmaceuticals (Strongbridge). R. Pivonello: Consulting Fee; Self; Novartis Pharmaceuticals, Recordati, Corcept Therapeutics, Pfizer, Inc., Bresmed Health Solutions, Damor Farmaceutici, S&amp;R Farmaceutici, Organon Italia, Siunergos Pharma, Biohealth Italia. Research Investigator; Self; Novartis Pharmaceuticals, Recordati, Xeris Pharmaceuticals (Strongbridge), Corcept Therapeutics, Takeda, Neurocrine Biosciences, Camurus AB, Pfizer, Inc., Merck Serono, IBSA. E.J. Lee: None. R. Leelawattana: None. J.H. Kim: None. R. Walia: None. Y. Yu: None. Z. Liao: None. A. Piacentini: Employee; Self; Recordati. A.M. Pedroncelli: Employee; Self; Recordati. A. Shimatsu: Consulting Fee; Self; Recordati. Speaker; Self; Recordati. Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, has demonstrated rapid and sustained normalization of cortisol in two Phase III studies (LINC 3, NCT02180217; LINC 4, NCT02697734) in patients (pts) with Cushing’s disease (CD). Relative osilodrostat bioavailability is estimated to be 20% higher in pts of Asian origin than other ethnicities, and body weight is not a major determinant of this difference. This analysis of the LINC 3 and LINC 4 studies evaluated the efficacy and safety of osilodrostat in pts of Asian and non-Asian origin with CD. Methods: Data were pooled from the LINC 3 and LINC 4 Phase III studies. LINC 3 comprised a 48-week (W) core phase, including an 8W randomized withdrawal for eligible pts. LINC 4 included a 12W, double-blind, placebo-controlled period and 36W of open-label osilodrostat. Both studies had an optional extension. Efficacy and safety outcomes were evaluated separately in pts of Asian and non-Asian origin. Periods where pts received placebo were excluded. Results: In total, 56/210 (27%) pts were of Asian origin, enrolled in China (n=16), South Korea (n=14), Japan (n=9), Thailand (n=9), India (n=7) and USA (n=1). Most non-Asian pts were Caucasian (n=138/154, 90%). Median (min−max) osilodrostat dose was 3.8 (1−25) and 7.3 mg/day (1−47) in pts of Asian and non-Asian origin, respectively. mUFC control was achieved at W48 and W72 in 64.3% and 68.1% of Asian pts and in 68.2% and 75.8% of non-Asian pts, respectively. Improvements from baseline in most cardiovascular and metabolic-related parameters and in physical manifestations of hypercortisolism were similar across both groups during osilodrostat treatment. Osilodrostat was well tolerated; the most common investigator-reported adverse events (AEs) in Asian pts were adrenal insufficiency (44.6%), nausea (33.9%) and decreased appetite (26.8%), and in non-Asian pts, nausea (45.5%), fatigue (40.9%) and headache (39.0%). The most common serious AE in Asian and non-Asian pts was adrenal insufficiency (5.4% and 5.2%, respectively). Hypocortisolism-related AEs occurred in 58.9% of Asian pts and 40.3% of non-Asian pts, most commonly reported by the investigator as adrenal insufficiency (44.6% and 22.1%). AEs related to pituitary tumor enlargement occurred in 21.4% of Asian and 9.1% of non-Asian pts. AEs related to arrhythmogenic potential and QT prolongation were infrequent in all pts. Conclusions: Osilodrostat demonstrated similar beneficial effects in Asian and non-Asian pts in terms of mUFC control and improvements in cardiovascular and metabolic-related parameters and physical manifestations of hypercortisolism. The mean dose to achieve beneficial effects was lower in pts of Asian than non-Asian origin. Osilodrostat was generally well tolerated in Asian and non-Asian pts; AEs related to hypocortisolism and pituitary enlargement were reported more frequently in Asian than non-Asian pts. Presentation: Thursday, June 15, 2023

Clinical Evaluation of the Eurosets Trilly Oxygenator During Cardiopulmonary Bypass in a Pediatric Population.

The equipment selected for cardiopulmonary bypass (CPB) in pediatric cardiac surgery critically influences the safety, efficiency, efficacy and pathophysiological impact in perioperative use and the post-operative outcome. In this report, we present a single-center retrospective analysis of the clinical efficacy, efficiency and safety of the Trilly oxygenator (Eurosets Srl, Medolla, MO, Italy), which has an integrated arterial filter. It has a blood flow capacity of 500 to 3500ml/min, an AAMI index of 4.000ml / min, and a static fill prime (oxygenating module + heat exchanger) of 130 ml. We used this device on 42 pediatric patients who underwent repair of various congenital heart defects with cardiopulmonary bypass. Pre- and intraoperative patient data were collected for the evaluation of gas transfer and metabolic parameters in relation to blood flow, temperature and hematologic profiles. The mean age of the patients was 8.07 ± 2.9 years. Eight patients had cyanotic heart disease, 7 had chromosomal abnormalities and 9 had previously undergone cardiac surgery. The STAT Mortality Category Score was distributed as follows: Cat. 1 (37.5%), Cat. 2 (35%), Cat. 3 (5%), Cat. 4 (22.5%), Cat. 5 (0%). The mean bodyweight was 29.03 ± 8.25 kg and the blood flow rate was 2664.88 ± 508.43 ml / min. The mean cardiopulmonary bypass time was 95±51.4 min and the cross-clamp time was 37±34.6 min. The mean gas transfer values were as follows: partial pressure of oxygen, post oxygenator, 224.7±28 mmHg; partial pressure of carbon dioxide, post oxygenator, 42±4 mmHg; oxygen delivery 356.9± 88.8 ml/min/m2; carbon dioxide transfer, 52.81± 1.98 mmHg, mixed venous saturation 77.78 %; and mean hematocrit value 29.0±4 %. The Trilly oxygenator was effective in terms of oxygen uptake, carbon dioxide removal, and heat exchange in a pediatric population undergoing cardiopulmonary bypass. This retrospective analysis showed that the Trilly is both safe and effective in clinical practice without iatrogenic problems.

Prevalence and factors associated with metabolic syndrome in first hospitalization for major depression disorder patients

Major depressive disorder (MDD) is a common and socially burdensome psychiatric disorder with a causal and complex relationship with metabolic syndrome (MetS), which is often co-morbid. However, the prevalence and risk factors for MetS in patients with MDD are inconclusive. The purpose of this study is to investigate the prevalence and factors influencing MetS in first hospitalization MDD patients. A total of 981 MDD patients were included. Sociodemographic and general clinical data were collected from the patients, while metabolism-related parameters were also measured, and psychological symptoms were assessed. Our study found that the prevalence of MetS in the study population was 9.68%. MDD patients with MetS had higher levels of metabolism-related parameters and more severe psychological symptoms. We identified risk factors for MetS and its severity separately: age of onset of MDD, more severe depressive symptoms, and higher thyroid stimulating hormone (TSH) levels were risk factors for the development of MetS, whereas higher TSH levels were risk factors for the severity of MetS. Our results suggest that MetS is not highly prevalent in MDD patients, but certain risk factors may increase its likelihood and severity, and that these findings could be beneficial for clinical intervention and care of MetS.

Comparison of Possible Changes in Oxidative Stress, DNA Damage, and Inflammatory Markers in Children/Adolescents Diagnosed with Sluggish Cognitive Tempo and Children/Adolescents Diagnosed with Attention-Deficit/Hyperactivity Disorder.

Background: There has been a debate on whether sluggish cognitive tempo (SCT) differs from attention-deficit/hyperactivity disorder (ADHD). Although there have been many studies on metabolic parameters in relation to ADHD, no similar studies have been conducted on patients with SCT. We investigated whether there are differences between SCT and ADHD in terms of these factors. Subjects and Methods: Sixty-two participants with ages ranging from 11 to 18 who have diagnosis of ADHD (33 subjects) and SCT (29 subjects) were included in this study. The parents of all participants completed the 48-item Conners' Parent Rating Scale (CPRS) and the Barkley Child Attention Scale (BCAS) forms, and all participants' blood was taken to compare metabolic, oxidative stress, and antioxidant status of the SCT and ADHD groups. A child and adolescent psychiatrist interviewed the parents and children to assess the diagnosis of SCT and ADHD using standard diagnostic procedures. Results: In the comparison between the SCT and ADHD groups in terms of metabolic parameters, statistically significant differences were found in terms of total oxidant status, total antioxidant status, Oxidative Stress Index, total thiol, native thiol, disulfide, interleukin (IL)-1β, IL-6, and DNA damage (p < 0.05), but not in terms of tumor necrosis factor-α (p > 0.05). Conclusions: Our data showed that these two disorders may be different, but we believe that the data that indicate their differences remain inconclusive overall, but this study may be a potential pathway for future research.

Two weeks daily intake of anthocyanin-rich New Zealand blackcurrant extract enhances whole-body fat oxidation during supine rest in healthy males

Introduction: Increase in exercise-induced fat oxidation has been observed with a 2-week daily intake of New Zealand blackcurrant (NZBC) extract. We examined for supine rest the effects of a 2-week daily intake of NZBC extract on physiological and metabolic parameters in relation to body fat%.Methods: Healthy active men (n=16, age: 24.1±6.0 yr, body mass: 78.2±15.6 kg, BMI: 24.7±4.2 kg·m-2) volunteered. NZBC extract (210 mg of anthocyanins) was consumed with breakfast with a14-day washout. The final ingestion was 2 hours before testing. Physiological and metabolic responses were measured during supine rest (2x10 min), and observations with the lowest 10-minute ventilation were analyzed. Bioelectrical impedance analysis was used to measure body fat%.Results: During supine rest, a 14-day daily intake of NZBC extract had no effect on heart rate, minute ventilation, oxygen uptake, carbon dioxide production, and energy expenditure. However, a 14-day daily intake of NZBC extract decreased the respiratory exchange ratio (baseline: 0.840±0.045, 14-day: 0.820±0.058, P=0.03), increased fat oxidation (baseline: 0.079±0.03, 14-day: 0.088±0.043 g·min-1, P=0.05), and decreased carbohydrate oxidation (baseline: 0.178±0.067, 14-day: 0.143±0.071 g·min-1, P=0.03) during supine rest. Nine of the 16 participants had increased fat oxidation by over 10% during supine rest. For those nine participants, the increases were 26±16%. We did not observe a significant correlation between body fat% and absolute and percentual changes in fat oxidation.Conclusions: In a healthy male cohort, daily intake of New Zealand blackcurrant extract for two weeks was able to increase fat oxidation during supine rest. Daily intake of New Zealand blackcurrant extract may be an effective anthocyanin-rich supplement for managing body composition and body weight.Keywords: New Zealand blackcurrant; anthocyanins; metabolic equivalent; rest; fat oxidation; respiratory exchange ratio

Incidence and Factors Associated with Hyperglycemia in Patients with First Hospitalization for Major Depression Disorder: A Large Cross-Sectional Sample.

Major depressive disorder (MDD) is a mood disorder characterized by persistent spontaneous depression and has a high rate of disability and mortality. There is a complex relationship between MDD and disorders of glucose metabolism, and our study aimed to investigate the prevalence and risk factors for hyperglycemia in patients with MDD who were hospitalized for the first times. A total of 981 first-time inpatients with MDD were recruited, socio-demographic information, anthropometric data, and biochemical parameters were collected for each participant. The 17-item Hamilton Assessment Scale for Depression (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive Syndrome Scale (PSS), and Clinical General Impressions Inventory-Severity of Illness (CGI-SI) scores were used to assess patients' clinical symptoms. The prevalence of hyperglycemia was 9.28% among patients with MDD who were hospitalized for the first time. Compared to the non-hyperglycemic subgroup, patients in the hyperglycemic subgroup were found to have more extensive and significant demographic and clinical characteristics, higher levels of metabolism-related parameters, and more severe psychological and psycho-pathological symptoms. Age, thyroid stimulating hormone (TSH), triglycerides (TG) were risk factors for hyperglycemia in MDD patients, while course of disease was a protective factor. The study findings suggest that the prevalence of hyperglycemia is not high in patients with MDD who are hospitalized for the first time. The risk variables for predicting hyperglycemia include age, TSH and TG. The above three factors and course of disease have good combined diagnostic ability for hyperglycemia.

Profiles and diagnostic value of intestinal microbiota in schizophrenia patients with metabolic syndrome.

It is widely thought that the intestinal microbiota plays a significant role in the pathogenesis of metabolic disorders. However, the gut microbiota composition and characteristics of schizophrenia patients with metabolic syndrome (MetS) have been largely understudied. Herein, we investigated the association between the metabolic status of mainland Chinese schizophrenia patients with MetS and the intestinal microbiome. Fecal microbiota communities from 115 male schizophrenia patients (57 with MetS and 58 without MetS) were assessed by 16S ribosomal RNA gene sequencing. We assessed the variations of gut microbiome between both groups and explored potential associations between intestinal microbiota and parameters of MetS. In addition, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on the KEGG database was used to predict the function of intestinal microbiota. We also conducted Decision Tree Analysis to develop a diagnostic model for the MetS in patients with schizophrenia based on the composition of intestinal microbiota. The fecal microbial diversity significantly differed between groups with or without MetS (α-diversity (Shannon index and Simpson index): p=0.0155, p=0.0089; β-diversity: p=0.001). Moreover, the microbial composition was significantly different between the two groups, involving five phyla and 38 genera (p<0.05). In addition, a significant correlation was observed between the metabolic-related parameters and abundance of altered microbiota including HDL-c (r2=0.203, p=0.0005), GLU (r2=0.286, p=0.0005) and WC (r2=0.061, p=0.037). Furthermore, KEGG pathway analysis showed that 16 signaling pathways were significantly enriched between the two groups (p<0.05). Importantly, our diagnostic model based on five microorganisms established by decision tree analysis could effectively distinguish between patients with and without MetS (AUC = 0.94). Our study established the compositional and functional characteristics of intestinal microbiota in schizophrenia patients with MetS. These new findings provide novel insights into a better understanding of this disease and provide the theoretical basis for implementing new interventional therapies in clinical practice.

Gender, Obesity, Fat Distribution and 25-Hydroxyvitamin D.

Background and Objectives: Obesity is a worldwide disease associated with systemic complications. In recent years, there has been growing interest in studying vitamin D but data related to obese subjects are still poor. AIM: The aim of this study was to evaluate the relationship between obesity degree and 25-hydroxyvitamin D [25(OH)D] levels. Materials and Methods: We recruited 147 Caucasian adult obese patients (BMI > 30 Kg/m2; 49 male; median age 53 years), and 20 overweight subjects as control group (median age 57 years), who had been referred to our Obesity Center of Chieti (Italy) between May 2020 and September 2021. Results: The median BMI was 38 (33-42) kg/m2 for obese patients and 27 (26-28) kg/m2 for overweight patients. 25(OH)D concentrations were lower in the obese population compared to the overweight population (19 ng/mL vs. 36 ng/mL; p < 0.001). Considering all obese subjects, a negative correlation was observed between 25(OH)D concentrations and obesity-related parameters (weight, BMI, waist circumference, fat mass, visceral fat, total cholesterol, LDL cholesterol) and glucose metabolism-related parameters. 25(OH)D was also negatively correlated with blood pressure. Conclusions: Our data confirmed the inverse relationship between obesity and blood concentration of 25(OH)D and highlighted how 25(OH)D levels decrease in the presence of glucose and lipid metabolism alterations.