Colchicine effect on biomarkers of cardiac remodelling and atherosclerosis in ST-elevation myocardial infarction: A randomized controlled trial.

AIMS: Owing to its underlying inflammatory nature, atherosclerotic cardiovascular disease remains the leading global cause of mortality, particularly post-ST-elevation myocardial infarction (STEMI), a condition with significant risk for further cardiovascular events and mortality. This study aimed to investigate colchicine's effect on inflammation, cardiac remodelling and atherosclerotic risk in STEMI patients. METHODS: We conducted a randomized controlled study on 88 STEMI patients undergoing percutaneous coronary intervention. Eligible patients were randomly assigned to 1 of 2 groups. The control group received the guideline-directed medical therapy for STEMI, and the test group received guideline-directed medical therapy and 0.5 mg colchicine twice daily for 3 months. The soluble suppressor of tumorigenicity (sST2), interleukin-1ß, lipid profile parameters, triglyceride (TG)/high-density lipoprotein (HDL-C) ratio levels and left ventricular ejection fraction were evaluated for patients at baseline and the end of the 3 months. RESULTS: No significant effects were reported for colchicine on sST2, interleukin-1ß levels or left ventricular ejection fraction. Colchicine significantly lowered TG levels vs. controls, 134 (46-353) vs. 176 (72-825) respectively, P = .02, as well as TG/HDL-C ratio levels, 4.16 (2.75-5.24) vs. 5.11 (3.51-8.33),` respectively, P = .024. sST2 levels of the studied cohort were positively correlated with their TG/HDL-C ratio levels (R = .459, P < .001) at the end of follow-up. CONCLUSION: Our study highlights a promising impact of colchicine on atherosclerosis and cardiac remodelling factors in STEMI patients. Colchicine significantly reduced TG levels and TG/HDL-C ratio and was safe and well tolerated. Larger long-term studies powered to assess clinical outcomes of remodelling are necessary to confirm its beneficial effects in STEMI. GOV REGISTRATION ID: NCT06054100.

A novel long non-coding RNA connects obesity to impaired adipocyte function.

BACKGROUND: Long non-coding RNAs (lncRNAs) can perform tasks of key relevance in fat cells, contributing, when defective, to the burden of obesity and its sequelae. Here, scrutiny of adipose tissue transcriptomes before and after bariatric surgery (GSE53378) granted identification of 496 lncRNAs linked to the obese phenotype. Only expression of linc-GALNTL6-4 displayed an average recovery over 2-fold and FDR-adjusted p-value <0.0001 after weight loss. The aim of the present study was to investigate the impact on adipocyte function and potential clinical value of impaired adipose linc-GALNTL6-4 in obese subjects. METHODS: We employed transcriptomic analysis of public dataset GSE199063, and cross validations in two large transversal cohorts to report evidence of a previously unknown association of adipose linc-GALNTL6-4 with obesity. We then performed functional analyses in human adipocyte cultures, genome-wide transcriptomics, and untargeted lipidomics in cell models of loss and gain of function to explore the molecular implications of its associations with obesity and weight loss. RESULTS: The expression of linc-GALNTL6-4 in human adipose tissue is adipocyte-specific and co-segregates with obesity, being normalized upon weight loss. This co-segregation is demonstrated in two longitudinal weight loss studies and two cross-sectional samples. While compromised expression of linc-GALNTL6-4 in obese subjects is primarily due to the inflammatory component in the context of obesity, adipogenesis requires the transcriptional upregulation of linc-GALNTL6-4, the expression of which reaches an apex in terminally differentiated adipocytes. Functionally, we demonstrated that the knockdown of linc-GALNTL6-4 impairs adipogenesis, induces alterations in the lipidome, and leads to the downregulation of genes related to cell cycle, while propelling in adipocytes inflammation, impaired fatty acid metabolism, and altered gene expression patterns, including that of apolipoprotein C1 (APOC1). Conversely, the genetic gain of linc-GALNTL6-4 ameliorated differentiation and adipocyte phenotype, putatively by constraining APOC1, also contributing to the metabolism of triglycerides in adipose. CONCLUSIONS: Current data unveil the unforeseen connection of adipocyte-specific linc-GALNTL6-4 as a modulator of lipid homeostasis challenged by excessive body weight and meta-inflammation.

Spinal Cord Injury Risk in Open Repair for Descending Thoracic and Thoracoabdominal Aneurysm.

Objective: In open repair for descending thoracic aortic aneurysm (DTAA) or thoracoabdominal aortic aneurysm (TAAA), the influence of re-interventions on spinal cord injury (SCI) remains unclear. This study evaluated the relationships between re-interventions, atherosclerosis, and SCI. Methods: We retrospectively reviewed 78 patients who underwent open surgical repair for DTAA or TAAA between April 2011 and May 2023. The associations of SCI with (i) re-interventions with a history of endovascular therapy and graft replacement and (ii) atherosclerotic factors, including monocyte count, triglyceride levels (TG), and intra-aortic plaques, were examined. Results: The rates of SCI complications and 30-day mortality were both 3.8% (3/78). There was no significant difference between the incidence of SCI in the re-intervention and first-time intervention groups (p >0.90). However, patients with protruding plaque on computed tomography (CT) were more affected by SCI than those without (13.3% vs. 1.6%, p = 0.034). Univariate analysis revealed that SCI was associated with increased monocyte count, TG, protruding plaques on CT, and intraoperative blood loss. Conclusion: Re-interventions for DTAA and TAAA showed no association with the development of SCI under appropriate protective measures. The implicated risk factors may be atherosclerosis factors such as elevated monocyte count, TG, and protruding plaques on CT.

Efficacy and safety of olezarsen in lowering apolipoprotein C-III and triglycerides in healthy Japanese Americans.

BACKGROUND: Olezarsen is a GalNAc3-conjugated, hepatic-targeted antisense oligonucleotide that lowers apolipoprotein C-III (apoC-III) and triglyceride levels. The efficacy and safety of olezarsen has not previously been studied in ethnically diverse American populations. The aim of this study is to assess the effect of olezarsen in healthy Japanese Americans. METHODS: A randomized, placebo-controlled, double-blind phase 1 study was performed in 28 healthy Japanese American participants treated with olezarsen in single-ascending doses (SAD; 30, 60, 90 mg) or multiple doses (MD; 60 mg every 4 weeks for 4 doses). The primary, secondary, and exploratory objectives were safety and tolerability, pharmacokinetics, and effects of olezarsen on fasting serum triglycerides and apoC-III, respectively. RESULTS: There were 20 participants (16 active:4 placebo) in the SAD part of the study, and 8 participants (6 active:2 placebo) in the MD part of the study. For the primary endpoint, no serious adverse events or clinically relevant laboratory abnormalities were reported. The majority of olezarsen plasma exposure occurred within 24 h post-dose. In the SAD cohorts at Day 15 the percentage reduction in apoC-III/TG was - 39.4%/ - 17.8%, - 60.8%/ - 52.7%, and - 68.1%/ - 39.2% in the 30, 60 and 90 mg doses, respectively, vs 2.3%/44.5% increases in placebo. In the MD cohort, at Day 92 the percentage reduction in apoC-III/TG was - 81.6/ - 73.8% vs - 17.2/ - 40.8% reduction in placebo. Favorable changes were also present in VLDL-C, apoB and HDL-C. CONCLUSIONS: Single- and multiple-dose administration of olezarsen was safe, was well tolerated, and significantly reduced apoC-III and triglyceride levels in healthy Japanese Americans.

Pancreatitis polygenic risk score is independently associated with all-cause acute pancreatitis risk in the UK Biobank.

BACKGROUND AND AIM: Acute pancreatitis (AP) is a complex disease most commonly caused by gallstones, alcohol intake, or hypertriglyceridemia. Even in subjects with hypertriglyceridemia, the risk of AP is heterogeneous. Identifying individuals with a high genetic susceptibility to AP could contribute to a better risk stratification in the clinic. This study aimed to determine if a weighted polygenic risk score (PRS) of common variants in pancreatitis susceptibility genes can independently predict all-cause AP incidence in the general population. METHODS: A weighted PRS was calculated for 484 932 individuals from the UK Biobank, including 3346 individuals who developed AP during follow-up. The PRS included eight single nucleotide polymorphisms in known pancreatitis susceptibility genes. RESULTS: Individuals with a pancreatitis PRS above the 90th percentile had a 1.21-fold (1.03-1.43; P = 0.02) increased risk of AP compared with those with a pancreatitis PRS below the 90th percentile. When comparing individuals in the third tertile versus the first tertile, the risk of AP was 1.13-fold (1.00-1.28; P = 0.06) higher. Individuals with both a high triglyceride (TG) level and a high pancreatitis PRS (third tertile) had a 2.31-fold (1.83-2.93; P = 3.4 × 10-12) increased risk of AP compared with those with a low pancreatitis PRS and a low TG level (first tertile). Overall, the association between pancreatitis PRS and incident AP was independent of baseline TG level. CONCLUSIONS: Results of this study suggest that the accumulation of common variants in pancreatitis susceptibility genes is associated with all-cause AP incidence. Pancreatitis PRS could help clinicians identify patients who may be at higher risk of AP and who may benefit from more aggressive treatment.

Maternal Lipids in Pregnancy and Later Life Dyslipidemia: The POUCHmoms Longitudinal Cohort Study.

OBJECTIVE: Maternal lipid levels increase in normal pregnancies. Here, we examine whether pregnancies with the highest total cholesterol, low-density lipoprotein (LDL) or triglyceride levels or the lowest high-density lipoprotein (HDL) levels predict future dyslipidemia post-pregnancy. DESIGN: Longitudinal cohort study. SETTING: Five communities in Michigan, USA. SAMPLE: Pregnant women (n = 649) with blood lipid levels measured at mid-pregnancy in the Pregnancy Outcomes and Community Health (POUCH) Study and at the POUCHmoms Study follow-up, 7-15 years later. METHODS: Maternal mid-pregnancy lipid levels were defined as 'high' (upper quartile of triglycerides ≥ 216 mg/dL, LDL ≥ 145 mg/dL and total cholesterol ≥ 256 mg/dL) or 'low' (lower quartile, HDL < 58 mg/dL) using whole sample lipid distributions. At follow-up, dyslipidemia was classified by the clinical cutoffs of triglycerides and total cholesterol ≥ 200 mg/dL, LDL ≥ 130 mg/dL and HDL < 50 mg/dL. Weighted regression models estimated the risk of dyslipidemia at follow-up in relation to pregnancy lipid levels, adjusted for baseline confounders. MAIN OUTCOME MEASURE: Dyslipidemia later in life. RESULTS: Mid-pregnancy triglycerides, LDL, and total cholesterol levels at the upper quartile were associated with at least threefold increase in the risk of abnormal triglycerides, LDL and total cholesterol levels later in life. Women with low mid-pregnancy HDL levels had just over a twofold increased risk of abnormally low HDL levels at follow-up. These associations persisted following adjustment for covariates, i.e. demographics, lifestyle, and years of follow-up. CONCLUSIONS: Higher mid-pregnancy LDL, total cholesterol and triglycerides and lower levels of HDL may signal future dyslipidemia risk and the need for closer lipid monitoring to ensure timely interventions that can attenuate cardiovascular disease risk.

Separation of triacylglycerol (TAG) isomers by cyclic ion mobility mass spectrometry.

Triacylglycerols (TAGs), a major lipid class in foods and the human body, consist of three fatty acids esterified to a glycerol backbone. They can occur in various isomeric forms, including sn-positional, cis/trans configurational, acyl chain length, double bond positional, and mixed type isomers. Separating isomeric mixtures is of great interest as different isomers can have distinct influence on mechanisms, such as digestibility, oxidative stability, or lipid metabolism. However, TAG isomer separation remains challenging with established analytical methodologies such as liquid-chromatography coupled to mass spectrometry (LC-MS). In this study, we developed a method with cyclic ion mobility mass spectrometry (cIMS-MS) for the separation and identification of all types of TAG isomers. First, the influence of different adducts (Li+, NH4+, Na+, and K+) on the separation was studied. Overall, it was concluded that the sodium adduct is the best choice to efficiently separate all types of TAG isomers. In addition, trends were found in the influence of specific structural features on the drift time order. An order of relative influence (from high to low) was established; (1) degree of unsaturation of the fatty acid(s) on an exterior position (if the total degree of unsaturation(s) is equal in both TAGs), (2) acyl chain length on the exterior positions, (3) cis/trans configuration, and (4) double bond (DB)-position. Finally, various cIMS-MS strategies were developed for the separation of mixtures containing four, five, and six isomers. To conclude, the developed methods can be used for separation of complex mixtures of TAG isomers and have great potential to be expanded to isomers of similar types of lipids such as di- and monoacylglycerols. This study also shows the potential of cIMS-MS to be used for the application on real TAG samples.

The effect of the modified Atkins diet and anti-seizure medications on lipid marker levels in adults with epilepsy.

OBJECTIVES: Some anti-seizure medications (ASMs) are known to induce liver enzymes and impact lipid values that include total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglyceride (TG). In addition, use of ketogenic diet therapies, including the modified Atkins diet (MAD), has also influenced lipids. Here, we explored the combined impact of enzyme inducing ASMs (EIASMs) and MAD on lipid values in adults with epilepsy. METHODS: Diet-naïve adults with epilepsy who began MAD were divided into three groups based on ASM use: EIASMs, non-EIASMs, and those on no ASMs. Demographic information, epilepsy-specific clinical history, anthropometrics and lipid values were obtained through retrospective chart review at baseline and after a minimum of 12 months of MAD use. RESULTS: Forty-two adults on MAD had baseline and follow up 12-month lipid outcomes. There was a significant increase in median levels of TC, LDL, non-HDL, and HDL after 12 months of MAD use. There was no change in median levels of TG. When separated according to ASM category, adults on non-EIASMs showed significant elevations in TC, HDL, and LDL after 12 months of MAD use. In contrast, adults on EIASMs only showed a significant increase in HDL after 12 months of MAD use. DISCUSSION: The increase in atherogenic cholesterol levels observed after 12 months of MAD use was most pronounced in adults with epilepsy on non-EIASMs and not observed in adults with epilepsy on EIASMs despite a higher proportion of abnormal cholesterol levels at baseline in those on EIASMs.

Relationship between triglyceride-glucose index and carotid artery plaques in ischemic stroke patients: Based on blood pressure status, sex, and age.

BACKGROUND: Numerous studies have shown that the triglyceride-glucose (TyG) index is a reliable substitute marker for insulin resistance. Nevertheless, its correlation with carotid artery plaques (CAPs) among patients with ischemic stroke (IS) remains to be elucidated. METHODS: 9248 IS patients hospitalized at the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine were grouped according to the quartiles of TyG index. Patients were further stratified by blood pressure status, sex, age and hypertension control status. Employing logistic regression to examine the connection between the TyG index and CAPs.Additionally, analyzing the receiver operating characteristic (ROC) curve to evaluate the predictive value of the TyG index for CAPs. RESULTS: Participants with an elevated TyG index had an increased prevalence of CAPs. The TyG index was positively correlated with CAPs (OR: 1.26, CI: 1.14-1.40, P<0.001). Compared with normal blood pressure and prehypertensive patients, the TyG index was markedly correlated with CAPs among hypertensive patients (OR: 1.29, 95% CI: 1.15-1.44, P<0.001). Females had a higher OR value than males(OR: 1.31, 95% CI: 1.11-1.54, P=0.001 versus OR: 1.24, 95% CI: 1.09-1.41, P=0.001). Older patients (>60 years) had a higher OR value than their middle-aged counterparts (≤60 years) (OR: 1.35; 95% CI: 1.16-1.58, P<0.001 versus OR: 1.20; 95% CI: 1.05-1.37, P=0.007). Patients with poorly-controlled hypertension had a higher OR value than patients with well-controlled hypertension(OR: 1.36; 95% CI: 1.14-1.63, P=0.001 versus OR: 1.24; 95% CI: 1.07-1.44, P=0.003). After adjusting for potential confounding factors, the area under the ROC curve (AUC) value in the overall population, sex-stratified group, hypertensive patients and hypertension control status-stratified group were all above 0.7 (P<0.01), demonstrating good forecasting capability. CONCLUSIONS: In IS patients, the TyG index was significantly associated with CAPs. Additionally, this correlation was more pronounced in hypertensive patients, females, older individuals and patients with poorly-controlled hypertension.

Impact of omega-3 fatty acids supplementation on lipid levels in pregnant women with previous pregnancy losses: a retrospective longitudinal study.

Objective: This research aims to investigate the impact of omega-3 fatty acids supplementation on the lipid levels of pregnant women who have experienced pregnancy losses. Methods: This retrospective study analyzed data from pregnant women with previous pregnancy losses from two medical centers. Their lipid profiles were measured at least twice during pregnancy. According to the use of omega-3 soft gel capsules, participants were divided into the omega-3 group and the control group. We assessed the relationship between omega-3 fatty acids supplementation and longitudinal lipid levels during pregnancy using generalized estimating equations (GEE). Subsequently, we conducted subgroup analyses to delineate the profile of beneficiaries who received omega-3 fatty acids based on body mass index (BMI), age, menstrual regularity, number of previous pregnancy losses, number of previous live births, and educational level. Results: The omega-3 group included 105 participants, while the control group comprised 274 participants. Women in the omega-3 group started supplementation between 3.43 and 17.14 weeks of gestation. According to GEE analysis, supplementing omega-3 fatty acids significantly reduced triglyceride (TG) levels during pregnancy (adjusted ß = -0.300, 95% CI -0.445 to -0.154, p < 0.001). No associations between omega-3 fatty acids supplementation and total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) levels were observed. Subgroup analyses revealed that omega-3 fatty acids supplementation was related to a reduction in TG levels among pregnant women with age of ≤35 years, a normal BMI (18.5-24.9 kg/m2), 1-2 previous pregnancy losses, no previous live births, or an educational level above high school. Conclusion: Supplementation with omega-3 fatty acids may significantly reduce TG levels, yet it does not seem to improve TC, LDL-C, or HDL-C levels in pregnant women with previous pregnancy losses.

Pulmonary Hypertension in Hemodialysis Patients and Its Determinants: A Hospital Based Cross-Sectional Study.

Purpose: Pulmonary hypertension (PH) is a serious complication in hemodialysis patients, which is associated with a significantly increased risk of morbidity and mortality. The present study aims to investigate PH frequency and associated factors in patients undergoing maintenance hemodialysis. Patients and Methods: This cross-sectional study was conducted in the hemodialysis department of the Shandong Provincial Third Hospital, China, from January 2016 to December 2022. A total of 167 consecutive patients who underwent regular hemodialysis treatment for at least three months were included in the study. Patients with a systolic pulmonary artery pressure (sPAP) value >35 mmHg at rest were considered to have PH. The relationship between PH and various demographic, laboratory, and echocardiographic parameters was evaluated. Results: A total of 93 patients (55.7%) were diagnosed with PH. Multivariate logistic regression analysis indicated that low serum levels of albumin (OR 0.89, 95% CI 0.82-0.98, p = 0.017), low serum levels of triglycerides (OR 0.32, 95% CI 0.15-0.69, p = 0.003), and high right atrial diameter (OR 1.19, 95% CI 1.04-1.37, p = 0.011) were significantly associated with an increased risk of PH. Conclusion: PH is a common finding in hemodialysis patients and is independently associated with serum levels of albumin, serum levels of triglyceride, and right atrial diameter; this suggests that evaluating these non-invasive and relatively easily available parameters may be useful in identifying patients with a high risk of PH. However, further studies are required to confirm these findings.

Optimizing the Extraction of Bioactive Compounds (Polyphenols, Lipids, and Alpha-Tocopherol) from Almond Okara to Unlock Its Potential as Functional Food.

Almond okara, a by-product of almond milk production, is rich in bioactive components, such as polyphenols, lipids, and alpha-tocopherol, making it a valuable functional food ingredient. This work aimed to investigate its composition while exploring two main aspects: (i) the impact of extraction time, solid-to-solvent ratio, ethanol concentration, and temperature on polyphenol recovery, and (ii) the quantification of okara's triglycerides (TG) and alpha-tocopherol contents. The polyphenols' optimal extraction conditions were 90 min, a 1:30 solid-to-solvent ratio (w/v), 50% ethanol, and 60 °C. These conditions achieved a total polyphenol yield of 523 mg GAE, tannin yield of 340 mg GAE, total flavonoid yield of 548 mg CE, and a total antioxidant capacity of 779 mg AAE per 100 g dry okara. The Peleg model effectively described the extraction kinetics. Additionally, TG levels, quantified by UHE/LPSFC-APCI-MS, in okara were comparable to those in almonds, and alpha-tocopherol levels, quantified by LC-UV, were 14,400 µg/100 g in almonds and 15,600 µg/100 g in okara. These findings highlight the potential of okara as a valuable resource, with a straightforward, scalable, and cost-effective solid-liquid extraction (SLE) method for polyphenols and a supercritical fluid extraction method for TG, for use in the functional food, nutraceutical, and cosmetic industries.

Strong associations between fasting lipids and glucose concentrations and ALT levels strengthened with increasing ALT quantiles.

BACKGROUND: A persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population. METHODS: A cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence. RESULTS: The associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and - 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles. CONCLUSIONS: The dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs.

Impact of excessive abdominal obesity on brain microstructural abnormality in schizophrenia.

Significant evidence links obesity and schizophrenia (SZ), but the brain associations are still largely unclear. 48 people with SZ were divided into two subgroups: patients with lower waist circumference (SZ-LWC: n = 24) and patients with higher waist circumference (SZ-HWC: n = 24). Healthy controls (HC) were included for comparison (HC: n = 27). Using tract-based spatial statistics, we compared fractional anisotropy (FA) of the whole-brain white matter skeleton between these three groups (SZ-LWC, SZ-HWC, HC). Using Free Surfer, we compared whole-brain cortical thickness and the selected subcortical volumes between the three groups. FA of widespread white matter and the mean cortical thickness in the right temporal lobe and insular cortex were significantly lower in the SZ-HWC group than in the HC group. The FA of regional white matter was significantly lower in the SZ-LWC group than in the HC group. There were no significant differences in mean subcortical volumes between the groups. Additionally, the cognitive performances were worse in the SZ-HWC group, who had more severe triglycerides elevation. This study provides evidence for microstructural abnormalities of white matter, cortical thickness and neurocognitive deficits in SZ patients with excessive abdominal obesity.

Prevalence of metabolic syndrome and its risk factors among newly diagnosed type 2 diabetes mellitus patients - A hospital-based cross-sectional study.

Context: Metabolic syndrome (MetS) raises the chance of cerebrovascular accidents and cardiovascular illness in type 2 diabetes mellitus (T2DM) individuals. Early identification of MetS allows for suitable prophylactic and treatment strategies to reduce the risks. Aim: To estimate the prevalence of MetS and its risk factors in T2DM individuals. Settings and Design: This cross-sectional study investigated MetS and its component's prevalence among newly diagnosed T2DM at the tertiary care hospital. Methods and Material: The study was conducted from January 2022 to December 2022 and included 300 participants above 18 years, with most being men (55%, 165), and using the World Health Organization (WHO) STEPS questionnaire for assessing selected risk factors. Along with blood glucose, different components of MetS were assessed, that is serum triglyceride (TG) level, serum high-density lipoprotein (HDL) level, blood pressure (BP) and waist circumference (WC), as per the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) criteria. Statistical Analysis Used: Data analysis includes mean and standard deviation (SD) for numerical variables with an unpaired t-test to compare means and percentage and proportions for categorical variables with the Chi-square test for the associations. Multivariate logistic regression was used for assessing the predictors of MetS. Results: The prevalence of components of MetS, that is obesity, hypertension (HTN), TG and HDL components, was 64.0% (192), 45.7% (137), 46.0% (138) and 30% (90), respectively. Overall, MetS was 57% (170). Moderate activity of 150 min/week, sitting/reclining, WC, diastolic BP, TG and HDL had a significant association with MetS. Conclusions: MetS was highly associated with newly diagnosed T2DM with obesity being the most common component.

Excess Triglycerides in Very Low-Density Lipoprotein (VLDL) Estimated from VLDL-Cholesterol could be a Useful Biomarker of Metabolic Dysfunction Associated Steatotic Liver Disease in Patients with Type 2 Diabetes.

AIMS: We report that small dense low-density lipoprotein cholesterol (sdLDL-C) levels are sensitive biomarkers of metabolic dysfunction-associated steatotic liver disease (MASLD). Since triglyceride (TG)-rich very low-density lipoprotein (VLDL) is a precursor of sdLDL and is overproduced by MASLD, the composition of VLDL may be more directly associated with MAFLD than sdLDL-C or plasma TG. To identify TG-rich VLDL, this author proposed "Excess TG" and examined its association with MASLD. METHODS: Patients with type 2 diabetes (n=1295), excluding fasting hypertriglyceridemia (TG ≥ 400 mg/dL) and heavy drinkers were examined. Liver steatosis and visceral fat area (VFA) were evaluated using CT. VLDL-C was calculated as the total C minus direct LDL-C minus HDL-C. The average VLDL-TG level can be estimated using VLDL-C×5, according to the principle of the Friedewald equation for LDL-C. Thus, VLDL-TG was estimated as VLDL-C×5, and Excess TG was calculated as plasma TG minus VLDL-C×5. RESULTS: Patients with MASLD were younger, more likely to be men and drinkers, and had higher VFA, TG, sdLDL-C, and excess TG, while VLDL-C was comparable. Excess TG was found to be the most sensitive lipid parameter for identifying MASLD, independent of sdLDL-C, TG, TG/VLDL-C, and VFA. The odds ratios for MASLD were 2.4-, 3.7-, and 3.9-fold higher for Excess TG ranges of 0-24, 25-49, and ≥ 50 mg/dL, respectively, relative to ＜0 mg, and a close relationship remained significant after adjustment for lipid- and adiposity-related parameters. CONCLUSIONS: Excess TG in VLDL was strongly associated with MASLD beyond TG and sdLDL-C levels, which may reflect the presence of TG-rich VLDL.

Pharmacokinetics and Safety of Pemafibrate in Patients with both Dyslipidemia and Severe Renal Impairment: A Phase 4 Study.

AIMS: Per the package insert, pemafibrate was contraindicated for use in patients with severe renal impairment despite its biliary excretion. To validate this, we evaluated the pharmacokinetics and safety of pemafibrate for 12 weeks in patients with hypertriglyceridemia and renal impairment. METHODS: In this phase 4, multicenter, placebo-controlled, double-blind, parallel-group, comparative study, 21 patients were randomly assigned to pemafibrate 0.2 mg/day or placebo within Groups A (estimated glomerular filtration rate [eGFR] ＜30 mL/min/1.73m2 without hemodialysis; pemafibrate n=4; placebo, n=2), B (hemodialysis; pemafibrate, n=4; placebo, n=1), and C (eGFR ≥ 30 and ＜60 mL/min/1.73m2 without hemodialysis; pemafibrate, n=8; placebo, n=2) for 12 weeks. Area under the concentration vs time curve within the dosing interval (τ) (AUCτ) of pemafibrate was measured after 12-week administration. RESULTS: The AUCτ (geometric mean) of pemafibrate was 7.333 and 7.991 ng·h/mL in Groups A+B and C, respectively; in Groups A+B to C at 12 weeks, the geometric mean ratio of pemafibrate AUCτ was 0.92 (90% confidence interval [CI]: 0.62, 1.36). The upper limit of the 90% CI was ≤ 2.0 (predetermined criterion). There was no consistent trend in the AUCτ and maximum plasma concentration of pemafibrate with/without statin use. Renal impairment degree did not affect the incidence of adverse events. No safety concerns were observed. CONCLUSION: Pemafibrate repeated administration in patients with severe renal impairment did not increase pemafibrate exposure.

Psychotropic medication and hepatobiliary health: Ultrasound observations on patients with schizophrenia.

OBJECTIVE: This study sought to examine the association between antipsychotic drug use and hepatobiliary health based on serum markers and ultrasound observations on a sample of patients with schizophrenia compared to age and gender matched healthy controls. METHODS: The 120 patients with schizophrenia and 60 control subjects had their blood drawn to measure liver function tests and underwent hepatobiliary ultrasonography to determine hepatobiliary lesions. Liver function tests included total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Standardized cross-sectional images of the liver and kidneys were obtained from patients and controls, and analyses were stratified by length of taking psychotropic medication among those with schizophrenia. Liver echo attenuation coefficients, liver-kidney ratios, and liver fat content were determined. RESULTS: Psychotropic drug use was associated with greater liver burden and liver lesions in patients with schizophrenia compared to controls. The levels of TC, TG, ALT and AST in patients with schizophrenia were also all significantly higher among patients with schizophrenia. Long-term psychotropic medication was associated with increased levels of fatty liver in patients compared with controls. Levels of TC, TG, ALT and AST were all significantly higher in the long-term psychotropic medication use group than in the short-term group. Liver echo attenuation coefficient, liver-kidney ratio, and liver fat content were also higher in the long-term medication use group compared to the short-term group. CONCLUSION: Antipsychotic drug use, particularly long-term use, is associated with increased liver burden in patients with schizophrenia, impaired lipid metabolism, increased liver lesions and fat content.

Serum Selenium Levels and Lipid Profile: A Systematic Review and Meta-analysis of Observational Studies.

Selenium is a trace element with pivotal roles in metabolic processes. Studies suggested that selenium deficiency could lead to impaired lipid profiles. However, inconsistent results have been reported regarding the association between serum selenium concentrations and lipid profile (triglycerides, LDL, HDL, VLDL, and total cholesterol). Thus, we aimed to review the correlation between them. A systematic literature search was conducted in PubMed, Embase, Web of Science, Scopus, and Google Scholar until 31 December 2023. The relevant correlation coefficients were used as desired effect sizes to assess the correlation between selenium level and lipid profile. Among 8291 records found in the primary search, 47 and 34 articles were included in the systematic review and meta-analysis, respectively. All included studies were observational investigations and had acceptable quality. Our results failed to reach strong evidence supporting the correlation between serum selenium level and lipid profiles, except for HDL, which showed a weak correlation among both adults (r = 0.1 [0.03:0.17]; I2 = 71%) and pediatrics (r = 0.08 [0.03:0.14]; I2 = 38%). Subgroup analyses based on gender did not reveal a significant or strong correlation with selenium levels (except for total cholesterol in males (r = 0.12 [0.01:0.22]; I2 = 52%)). The results did not change after the sensitivity analysis. Although some previous studies have suggested that selenium deficiency could lead to impaired lipid profile, the findings of this study indicate no strong correlation between serum selenium levels and lipid profile.

Impact of Serum Triglyceride Levels on Severity and Outcomes in Acute Biliary Pancreatitis: A Retrospective Cohort Study.

Background Acute biliary pancreatitis (ABP), a major inflammatory illness, is primarily caused by gallstone blockage of the common bile duct. The pathophysiology of ABP has been linked to serum triglyceride (TG) levels, suggesting a potential role for TG in predicting disease severity. Objective The research objective was to investigate the association between serum TG levels and the severity of ABP. Methodology This retrospective cohort study sought to determine the relationship between blood TG levels and the severity of ABP. It was conducted at Lady Reading Hospital in Peshawar, Pakistan, from September 2023 to March 2024. A total of 530 ABP patients were divided into two groups based on their TG levels: normal (<150 mg/dl) and elevated (≥150 mg/dl). Clinical data were gathered, including demographics, comorbidities, laboratory results, severity ratings (APACHE II and Ranson's criteria), and clinical outcomes. Descriptive statistics, Chi-square tests, and multivariate logistic regression were used in the statistical analysis. Results Patients with elevated TG levels (n=130) demonstrated higher median Ranson's criteria (3.24 vs. 2.53, p<0.001) and APACHE II scores (10.53 vs. 8.73, p<0.001) compared to those with normal TG levels (n=400). Elevated TG levels were associated with increased severity of ABP, with ORs of 2.41 (95% CI: 1.23-4.74) for mild vs. severe ABP. Clinical outcomes such as ICU admission (21.54% vs. 3.25%, p<0.001), mortality (6.15% vs. 0.50%, p<0.001), and pancreatic necrosis (10.77% vs. 1.25%, p<0.001) were significantly worse in the elevated TG group. Conclusion Elevated serum TG levels (≥150 mg/dl) are independently associated with increased severity of ABP, as indicated by higher severity scores and poorer clinical outcomes.