Low-density Lipoprotein Triglycerides Research Articles

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure.

Cardiovascular disease is the cause of physical infirmity and thousands of deaths annually. Typically, during heart failure, cardiomyocyte mitochondria falter in terms of energy production and metabolic processing. Additionally, inflammation and the accumulation of non-contractile fibrous tissue contribute to cardiac malfunction. Melatonin, an endogenously produced molecule, experimentally reduces the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. The current review critically analyzes published data related to the experimental use of melatonin to forestall coronary artery pathologies. Collectively, these studies document melatonin's anti-atherosclerotic actions in reducing LDL oxidation and triglyceride levels, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging destructive reactive oxygen species, preventing the proliferation and invasion of arterial smooth muscle cells into the lesioned area, restricting the ingrowth of blood vessels from the vasa vasorum, and solidifying the plaque cap to reduce the chance of its rupture. Diabetic hyperglycemia, which aggravates atherosclerotic plaque formation, is also inhibited by melatonin supplementation in experimental animals. The potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans should be seriously considered by performing clinical trials using this multifunctional molecule.

A novel fully human anti-NT-ANGPTL3 antibody from phage display library exhibits potent ApoB, TG, and LDL-C lowering activities in hyperlipidemia mice.

Dyslipidemia is characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and TG-rich lipoprotein (TGRLs) in circulation, and is closely associated with the incidence and development of cardiovascular disease. Angiopoietin-like protein 3 (ANGPTL3) deficiency has been identified as a cause of familial combined hypolipidemia in humans, which allows it to be an important therapeutic target for reducing plasma lipids. Here, we report the discovery and characterization of a novel fully human antibody F1519-D95aA against N-terminal ANGPTL3 (NT-ANGPTL3), which potently inhibits NT-ANGPTL3 with a KD as low as 9.21 nM. In hyperlipidemic mice, F1519-D95aA shows higher apolipoprotein B (ApoB) and TG-lowering, and similar LDL-C reducing activity as compared to positive control Evinacumab (56.50% vs 26.01% decrease in serum ApoB levels, 30.84% vs 25.28% decrease in serum TG levels, 23.32% vs 22.52% decrease in serum LDLC levels, relative to vehicle group). Molecular docking and binding energy calculations reveal that the F1519-D95aA-ANGPTL3 complex (10 hydrogen bonds, -65.51 kcal/mol) is more stable than the Evinacumab-ANGPTL3 complex (4 hydrogen bonds, -63.76 kcal/mol). Importantly, F1519-D95aA binds to ANGPTL3 with different residues in ANGPTL3 from Evinacumab, suggesting that F1519-D95aA may be useful for the treatment of patients resistant to Evinacumab. In conclusion, F1519-D95aA is a novel fully human anti-NT-ANGPTL3 antibody with potent plasma ApoB, TG, and LDL-C lowering activities, which can potentially serve as a therapeutic agent for hyperlipidemia and relevant cardiovascular diseases.

STUDY OF THE EFFICACY OF THE LEKHANIYA GHANAVATI IN THE MANAGEMENT OF HYPERLIPIDAEMIA IN DM-2 [BSL<250MG/DL

Hyperlipidaemia is emerging big problem in present society, which is now increasing day by day because of sedentary lifestyle of people, consumption of junk food, aerated cold drink, high level of stress are further deterioting the condition. Hyperlipidaemia is major cause in major illness such as HTN, obesity, acute MI, IHD, CCF& DM-2 (<250mg/dl) Previous study of hyperlipidaemia shows that reduction of fraction lipid level reduces rate of morbidity in individual with DM-2 (<250mg/dl), HTN, CAD. In ayurveda Hyperlipidaemia shows close resemblance with Medoroga as per Ayurveda. Lekhniya Gana is specifically indicated in ayurveda literature for management of Medoroga. In current case study 54 yrs female K/C/O DM -2(<250mg/dl) came with gross elevation of total cholesterol, triglycerides,LDL,VLDL levels.Lekhaniya Gana vati with proper pathya aahar was advised to patients for 2 months. Highly significant reduction was observed in total cholesterol level, triglycerides LDL, VLDL levels.

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.

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. 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. 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. Excess TG in VLDL was strongly associated with MASLD beyond TG and sdLDL-C levels, which may reflect the presence of TG-rich VLDL.

Genetic association of serum lipids and lipid-modifying targets with endometriosis: Trans-ethnic Mendelian-randomization and mediation analysis.

Prior observational research identified dyslipidemia as a risk factor for endometriosis (EMS) but the causal relationship remains unestablished due to inherent study limitations. Genome-wide association study data for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC) from European (EUR) and East Asian (EAS) ancestries were sourced from the Global Lipids Genetics Consortium. Multi-ancestry EMS data came from various datasets. Univariable Mendelian randomization (MR) examined causal links between serum lipids and EMS. Multivariable and mediation MR explored the influence of seven confounding factors and mediators. Drug-target MR investigates the association between lipid-lowering target genes identified in positive results and EMS. The primary method was inverse-variance weighted (IVW), with replication datasets and meta-analyses reinforcing causal associations. Sensitivity analyses included false discovery rate (FDR) correction, causal analysis using summary effect estimates (CAUSE), and colocalization analysis. IVW analysis in EUR ancestry showed a significant causal association between TG and increased EMS risk (OR = 1.112, 95% CI 1.033-1.198, P = 5.03×10-3, PFDR = 0.03), supported by replication and meta-analyses. CAUSE analysis confirmed unbiased results (P < 0.05). Multivariable and mediation MR revealed that systolic blood pressure (Mediation effect: 7.52%, P = 0.02) and total testosterone (Mediation effect: 10.79%, P = 0.01) partly mediated this relationship. No causal links were found between other lipid traits and EMS (P > 0.05 & PFDR > 0.05). In EAS ancestry, no causal relationships with EMS were detected (P > 0.05 & PFDR > 0.05). Drug-target MR indicated suggestive evidence for the influence of ANGPTL3 on EMS mediated through TG (OR = 0.798, 95% CI 0.670-0.951, P = 0.01, PFDR = 0.04, PP.H4 = 0.85%). This MR study in EUR ancestry indicated an increased EMS risk with higher serum TG levels.

Effects of waste-based concentrates from broiler farm on physico-chemical qualities and blood profile of landrace pigs.

The study aimed to determine the effect of giving concentrate protein from closed-house (CP-CH) broiler farm waste in rations on the meat quality (physical-chemical) and blood profile of landrace crossbreed pigs. The study used a completely randomized design (CRD) with 3 treatments and 4 replications with 12 finisher-phase landrace pigs with an average body weight of 63.42 ± 2.39 kg. The treatments were: A (control): use of 0% CP-CH + 24% CP-152 concentrate; B: 12% CP-CH + 12% CP-152 concentrate; and C: 24% CP-CH + 0% CP-152 concentrate. The research parameters were meat quality (physical-chemical meat) and blood lipid profile [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TGs)]. The results showed that treatment group B obtained physical meat quality (pH, drip loss, cooking loss, and water holding capacity) and meat chemical quality (moisture, protein, fat, and ash content) that were almost the same as the control (p > 0.05). By administering 24% CP-CH + 0% CP-152 (C) concentrate, there was a significant decrease in the physical and chemical quality of crossbreed landrace pigs (p < 0.05). Administration of CP-CH at 12%-24% did not affect total cholesterol, HDL, LDL, or blood TGs in landrace-crossbreed pigs. Giving 12% CP-CH (B) obtained meat quality (physical and chemical) almost the same as the control group. Treatment group C significantly reduced the physical and chemical quality of the meat. Administration of CP-CH at 12%-24% did not affect the blood profile of landrace crosses.

Assessing the causal relationship between blood metabolites and low back pain: a Mendelian randomization study.

Low back pain (LBP) is one of the most common health problems worldwide. This study aimed to determine whether blood metabolites were causally linked to the risk of LBP. Based on summary-level genome-wide association studies, we designed a Mendelian randomization (MR) study. Instrumental variables were selected for each blood metabolite with the following criteria: genome-wide significance levels of < 5e-8 and independent clumping (r2 < 0.001, distance < 10,000 kb). Inverse-variance weighting (IVW) was used as the primary statistical method. The weighted median (WM) method and MR-Egger regression were implemented to complement IVW. Subsequently, sensitivity analyses were conducted, including Cochran's Q test, MR-Egger intercept analysis, scatter plots, leave-one-out analysis, and funnel plots. IVW revealed that higher levels of lactate (odds ratio [OR] = 0.974, 95% confidence interval [CI] 0.953-0.995, P = 0.017), medium low-density lipoprotein triglycerides (OR = 0.990, 95% CI 0.983-0.997, P = 0.005) and albumin (OR = 0.985, 95% CI 0.973-0.998, P = 0.019) had a causal effect on decreased risk of LBP, whereas positive causality was detected between genetic predisposition to tyrosine and LBP (OR = 1.016, 95% CI 1.001-1.032, P = 0.043). Estimates from WM and MR-Egger were consistent with the direction of the IVW method. Additionally, there was no evidence of heterogeneity or pleiotropy in this study. This MR study demonstrated that four blood metabolites were causally related to LBP. It is possible to enhance the diagnosis of LBP, prognostic outcome predictions, and the personalization of therapy by analyzing novel signatures of metabolites.

Correlation between serum thyroid stimulating hormone level and glycolipid metabolism in patients with polycystic ovary syndrome

To investigate the correlation between serum thyroid-stimulating hormone (TSH) levels and glycolipid metabolism in patients with polycystic ovary syndrome (PCOS). From January 2021 to November 2022, 105 patients with PCOS were selected for this retrospective study. All patients were administered drug-induced ovulation treatment and were divided into 2 groups according to ovulation status. There were 67 and 38 patients in the ovulation and non-ovulation groups, respectively. Venous blood (5 mL) was collected on the day after admission from the non-ovulation group and on the day of physical examination from the ovulation group. Several indicators were measured, including TSH, fasting plasma glucose (FPG), glycosylated hemoglobin, total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride (TG), albumin (ALB), prealbumin (PA), and transferrin (TF). Weight, BMI, waistline, and hipline in the non-ovulation group were significantly higher than those in the ovulation group (P &lt; .05). There were no significant differences in glycosylated hemoglobin, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels between the non-ovulation and ovulation groups (P &gt; .05). Compared with the ovulation group, the levels of TSH, FPG, TC, and TG in the non-ovulation group were significantly higher (P &lt; .05). Serum ALB, PA, and TF the non-ovulation group were significantly higher than those in the ovulation group (P &lt; .05). Correlation analysis showed that TSH was negatively correlated with weight, BMI, waistline, hipline, waist-hip ratio, FPG, ALB, PA, and TF in the non-ovulation group (P &lt; .05) and had no significant correlation with TC and TG (P &gt; .05). Our findings demonstrate TSH levels may be associated with weight, BMI, waistline, hipline, waist-hip ratio, FPG, ALB, PA, and TF in patients with PCOS.

Blood lipids, lipid-regulatory medications, and risk of bladder cancer: a Mendelian randomization study.

The influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study. Genetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests. There was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625-0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05). This MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed.

The triglyceride glucose index trajectory is associated with hypertension: a retrospective longitudinal cohort study

BackgroundPrevious studies have found that the triglyceride glucose index (TyG index) trajectories are associated with cardiovascular diseases. However, the association between the patterns of TyG index trajectories and risk for hypertension has not been investigated. In a longitudinal general population, we aimed to identify distinct TyG index trajectories over 12 years and describe their association with incidence of hypertension.MethodOf the 15,056 adults retrospectively recruited from the Physical Examination Center of the Second Affiliated Hospital of Dalian Medical University in northeast of China from 2011 to 2022. TyG index was calculated as ln (fasting TG [mg/dL] × FPG [mg/dL]/2) and the TyG index trajectories were developed using group-based trajectory modelling. Cox regression analysis was accomplished to assess the association between TyG index and incidence of hypertension.ResultsThe median age of the population was 38 years, and 7352 (48.83%) of the participants were men. Three distinct TyG index trajectories were identified: “low increasing” (N = 7241), “moderate increasing” (N = 6448), and “high stable” (N = 1367). Using “low increasing” trajectory as a reference, “moderate increasing” and “high stable” trajectory were associated with increased risk of hypertension (HR = 2.45; 95% CI 2.25–2.67 and HR = 3.88; 95% CI 3.48–4.33). After adjusting for baseline sex, age, diabetes, smoking, systolic blood pressure, diastolic blood pressure, BMI, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood glucose, triglyceride, urea, uric acid, and glomerular filtration rate, the HR were slightly attenuate in “moderate increasing” and “high stable” trajectories to 1.38 (95% CI 1.23–1.54) and 1.69 (95% CI 1.40–2.02) respectively. Meanwhile, similar results were observed in multiple sensitivity analyses. The HR of the “moderate increasing” and “high stable” trajectory groups were 2.63 (95% CI 2.30–3.00) and 4.66 (95% CI 3.66–5.93) in female, and 1.66 (95% CI 1.48–1.86) and 2.33 (95% CI 2.04–2.66) in male.ConclusionsElevated TyG index at baseline and long-term TyG index trajectories were associated with the risk of hypertension. Early identification of increasing TyG index could provide insights for preventing hypertension later in life.

Serum lipoprotein subfractions are associated with the periodontal status: Results from the population-based cohort SHIP-TREND.

To investigate the medium-term associations of serum protein subfractions derived from proton nuclear magnetic resonance (1 H-NMR) spectroscopy with periodontitis and tooth loss. A total of 3031 participants of the cohort Study of Health in Pomerania (SHIP-TREND) were included. In addition to conventional serum testing, serum lipoprotein contents and subfractions were analysed by 1 H-NMR spectroscopy. Confounder-adjusted associations of lipoprotein variables with periodontitis and the number of missing teeth variables were analysed using mixed-effects models with random intercepts for time across individuals, accounting for multiple testing. While only spurious associations between lipoprotein levels from conventional blood tests were found-that is, triglycerides were associated with mean clinical attachment level (CAL) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with the number of missing teeth - several associations emerged from serum lipoprotein subfractions derived from 1 H-NMR analysis. Specifically, elevated LDL triglycerides were associated with higher levels of mean probing depth (PD), mean CALs, and increased odds of having <20 teeth. HDL-4 cholesterol levels were inversely associated with mean PD. Systemic inflammation (C-reactive protein) might mediate the effects of LDL and HDL triglyceride contents on periodontitis severity. Several associations between serum lipoprotein subfractions and periodontitis were observed. As the underlying biochemical mechanisms remain unclear, further research is needed.

Associations of Sedentary Time and Physical Activity From Childhood With Lipids: A 13-Year Mediation and Temporal Study.

Among children, evidence on long-term longitudinal associations of accelerometer-measured sedentary time, light physical activity (LPA), and moderate to vigorous PA (MVPA) with lipid indices are few. The mediating role of body composition and other metabolic indices in these associations remains unclear and whether poor movement behavior precedes altered lipid levels is unknown. This study examined the associations of sedentary time, LPA, and MVPA from childhood through young adulthood with increased lipids, the mediating role of body composition, and whether temporal interrelations exist. Data from 792 children (58% female; mean [SD] age at baseline, 11.7 [0.2] years), drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort, who had at least 2 time-point measures of accelerometer-based sedentary time, LPA, and MVPA during clinic visits at ages 11, 15, and 24 years and complete fasting plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and total cholesterol measured during follow-up visits at ages 15, 17, and 24 years were analyzed. Total fat mass partly mediated the inverse associations of LPA with low-density lipoprotein cholesterol by 13%, triglyceride by 28%, and total cholesterol by 6%. Total fat mass mediated the inverse associations of MVPA with low-density lipoprotein cholesterol by 37% and total cholesterol by 48%, attenuating the effect on total cholesterol to nonsignificance (P = .077). In the temporal path analyses, higher MVPA at age 15 years was associated with lower low-density lipoprotein cholesterol at 24 years (β = -0.08, SE, 0.01, P = .022) but not vice versa. Sedentary time worsens lipid indices, but increased LPA had a 5- to 8-fold total cholesterol-lowering effect and was more resistant to the attenuating effect of fat mass than MVPA.

Association Between Irritable Bowel Syndrome and Metabolic Syndrome

BackgroundStudies have shown an increased incidence of metabolic syndrome (MS) among irritable bowel syndrome (IBS) patients; we aimed to assess the eligibility of IBS as a risk factor for MS. MethodsPubMed, Scopus, Embase, and Web of Science were searched on the 1st of January 2023. Only observational controlled studies were included. Analysis was conducted by RevMan software version 5.4. ResultsIBS was associated with an increased incidence of MS (RR = 2.05, 95% CI = 1.50 to 2.79, p-value >0.00001). A significant association was seen between IBS, abdominal obesity (RR = 1.28, p-value = 0.0003), and increased waist circumference (MD = 5.01, 95% CI = 1.29 to 8.72, p-value = 0.008). IBS patients didn't have an increased risk of diabetes (RR= 1.29, 95% CI = 0.85 to 1.98, p-value = 0.23), however, they had increased HOMA- IR (MD = 0.21, 95% CI = 0.15 to 0.26, p-value < 0.00001). Analysis of blood pressure revealed an association between systolic not diastolic hypertension and IBS (MD = -0.50, 95% CI = -0.60 to -0.40, p-value >0.00001). Higher levels of LDL cholesterol (MD = 5.98, 95% CI = 0.91 to 11.05, p-value = 0.02), total cholesterol (MD = 12.21, 95% CI = 6.23 to 18.18, p-value >0.0001), and triglyceride (MD = 11.93, 95% CI = 11.55 to 12.31, p-value >0.00001) were detected among IBS patients. ConclusionIBS patients are at increased risk for MS and its components. Accordingly, patients should be screened for MS, and preventive programs should be implemented.

#213 : Causal Associations Between Different Plasma Lipid and Apolipoprotein Parameters with the Risk of Endometriosis: A Two-Sample Mendelian Randomization Study

Background and Aims: Endometriosis is a chronic gynecological disease with a high prevalence among reproductive-aged women. Several studies have investigated the causal effect of different plasma lipid and apolipoprotein parameters on the occurrence and progression of endometriosis. However, the results of these studies remained controversial. Herein, this study aims to analyze the causal associations of genetically predicted levels of different blood lipid and apolipoprotein traits with the risk of endometriosis using a two-sample Mendelian randomization (MR) approach. Methods: The single-nucleotide polymorphisms (SNPs) of exposures which indicate the genetic variants were used as instrumental variables (IVs). We assessed the correlation between each blood lipid and apolipoprotein parameter and the occurrence of endometriosis from various cohorts of European ancestry, and the SNPs of them were obtained from the genome-wide association study (GWAS) from the IEU GWAS database. The causal effects were estimated through the inverse-variance weighted method (IVW). The sensitivity examinations of each result after the MR analysis were performed to detect if any heterogeneity and pleiotropy existed. Besides, sub-analyses were performed to provide more detailed information about the actual associations. Results: Our results demonstrated that cholesterol in chylomicron (CM) and extremely large very low-density lipoprotein (VLDL) was causally linked to higher odds of endometriosis, while high-density lipoprotein (HDL) cholesterol showed the opposite correlation. No evidence was detected on the causal relations of low-density lipoprotein (LDL) cholesterol, VLDL cholesterol, triglyceride (TG), apolipoprotein A1 and apolipoprotein B with endometriosis. Neither pleiotropy nor heterogeneity was found in our study. In addition, subgroup analyses about subtypes of endometriosis suggested the causal association of several serum lipids with peritoneal endometriosis. Conclusion: Our results suggested that dysregulated lipid metabolism is causally associated with the occurrence of endometriosis, especially peritoneal endometriosis. Our findings provided genetic insights on potential novel strategies in the primary prevention and treatment of endometriosis.

Biochemical Blood Plasma Changes of Awassi Sheep Using Different Levels of Olive Pulp

16 male Awassi lambs were used, four months age weaning was diagnosed bythe teeth, it was placed in the animal field and left to acclimate for 14 days, then the actual experiment was introduced for a period of three months. The lambs were reared in four standard barns with a stage containing feeders and water troughs, it was divided from the inside by iron partitions into three sections. Four lambs, each treated under hygienic conditions, were placed in each section, underwent a treatment and vaccination program that supported to ensure her safety and that she was free from diseases. The animals were divided into four groups were T1: was fed on a diet devoid of olive pulp (control group). And fed on a diet containing 5, 10 and 15% olive pulp were T2, T3 and T4 respectively. fed on a diet containing 15% olive pulp. The results indicated that all olive pulp treatments led to a significant decrease in LDL cholesterol, triglycerides, glucose, uric acid, ALP and ALT, with a significant increase in HDL, total protein, albumin, globulin, phosphorus and calcium compared to the control treatment. The addition of 15% olive pulp in the diets of Awassi lambs gave the best results compared to a concentration of 5 and 10% olive pulp.

Association between urinary sodium and circulating lipid levels: a Mendelian randomization study.

Urinary sodium was indicated to be associated with dyslipidemia, but inconsistent conclusions for this association exist across the present observational studies. This study aimed to evaluate the causal association between urinary sodium and circulating lipid levels [low-density lipoprotein cholesterol (LDL-C), triglycerides, and high-density lipoprotein cholesterol (HDL-C)] through Mendelian randomization. Univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) with pleiotropy-resistant methods were performed. Data for urinary sodium were obtained from the genome-wide association study (GWAS) from 446,237 European individuals. Data for lipid profiles were extracted from GWAS based on the UK Biobank (for the discovery analysis) and the Global Lipids Genetics Consortium (for the replication analysis). In the discovery analysis, UVMR provided evidence that per 1-unit log-transformed genetically increased urinary sodium was associated with a lower level of HDL-C level (beta = -0.32; 95% CI: -0.43, -0.20; p = 7.25E-08), but not with LDL-C and triglycerides. This effect was still significant in the further MVMR when considering the effect of BMI or the other two lipid contents. In contrast, higher genetically predicted triglycerides could increase urinary sodium in both UVMR (beta = 0.030; 95% CI: 0.020, -0.039; p = 2.12E-10) and MVMR analyses (beta = 0.029; 95% CI: 0.019, 0.037; p = 8.13E-10). Similar results between triglycerides and urinary sodium were found in the replication analysis. Increased urinary sodium may have weak causal effects on decreased circulating HDL-C levels. Furthermore, genetically higher triglyceride levels may have independent causal effects on increased urinary sodium excretion.

Dyslipidemia Protective Effect of Resistant Starch-Based Dough Meals on Diabetes-Induced Rats

Aim: The adoption of functional foods as healthy diet therapy for the management of metabolic disorders such as diabetes is in vogue in the present world where many are no longer consuming carbohydrate or starchy foods. This study investigated the effect of resistant starch-based dough meals on dyslipidemia in rats with streptozotocin (STZ)-induced diabetes.&#x0D; Place and Duration: Functional Foods Laboratory and Animal House of Department of Biochemistry, Federal University of Technology, Akure, from July 2022 to February 2023.&#x0D; Methodology: Flour samples were prepared by dispersing the flour into boiling water and turning and being allowed to cook for 15 min to obtain dough meals: PLD – (100% Plantain flour), used as a control sample; PLPRD – plantain flour: pigeon pea flour: rice bran flour (73.08:15.15:11.76); PSPRD – native plantain starch: pigeon pea flour: rice bran flour (73.08:15.15:11.76); AP1SPRD – acetylated plantain starch: pigeon pea flour: rice bran flour (73.08:15.15:11.76); AP2SPRD – acetylated plantain starch: pigeon pea flour: rice bran flour (70.67:18.15:11.18). The weight gained, food intake, haematological parameters, fasting blood glucose and lipid profile of the resistant starch-based dough meal were compared with the commercial flour product, CRD (100% Cerolina flour: wheat and soybean) and the DM (untreated high-fat diet–STZ-induced diabetic rats) and NC (Normal control rats).&#x0D; Results: The weight gained and food intake ranged from 50.98±0.53 g to 180.12±1.07 g in NC and 33.98±1.64 g to 140.87±1.80 g in DM. The feed conversion ratio to the feed efficiency ratio was 0.28:0.25 and 4.15:3.53 in NC and DM respectively, which attributed to the food product to weight loss. The values of the haematological parameters (PCV, RBC, HB, MCV, MCH and MCHC) confirmed that the experimental rats had no trace of infection due to the generation of antibodies by WBC and differential counts (neutrophils, eosinophils, basophils, monocytes and lymphocytes). Rats fed with DM+AP1SPRD showed a decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglyceride, and an increase in high-density lipoprotein cholesterol (HLDL-C).&#x0D; Conclusion: A resistant starch-based dough meal was significant for the production of short-chain fatty acids with lots of benefits on health. The intervention of resistant starch-based dough meals, AP1SPRD and AP2SPRD used in this study, almost normalized metabolic profiles in the experimental rats, similar to the control group by reducing the total cholesterol, total triglycerides and LDL-C while increasing HDL-C.

1986. Switching to DOR/3TC/TDF Improves Renal Function and Decreases Lipid Levels in People Living With HIV: a Real-Life Multicentric Study

Abstract Background Pivotal studies on Doravirine (DOR) showed its high tolerability and effectiveness, even on resistant strains. Therefore, DOR and its single tablet combination treatment DOR/lamivudine (3TC)/tenofovir disoproxil fumarate (TDF) has been referred to as a cardiovascular-safe drug. However, data from real-life studies on safety and efficacy of DOR are lacking. Methods Retrospective multicenter cohort study, including 6 Italian HIV centers, evaluated adult treatment-experienced People Living With HIV (PLWH) who switched to DOR/3TC/TDF from June 2020 to June 2022. PLWH with known resistance mutations to DOR were excluded. Clinical and laboratory data were collected at the time of the switch and after 48 weeks. Results A total of 98 PLWH were switched to a DOR/3TC/TDF regimen, 75 (76.5%) male, with a median age of 52.41 years (IQR 42.95-58.79). The main reason for switching to DOR/FTC/TDF regimens was proactive switch (33.3%). No differences were found between the two timepoints on plasma viral load (pVL) (p = 0.345), lymphocytes T CD4+ (CD4+) percentage (p = 0.994) and count (p = 0.611), and CD4+/lymphocytes T CD8+ (CD8+) ratio (p = 0.899), confirming the effectiveness of the drug combination. We also found a significant reduction in total (p &amp;lt; 0.001) and LDL (p = 0.025) cholesterol and triglycerides (p = 0.002). Importantly, we found that the estimated glomerular filtration rate (eGFR) calculated with CKD-EPI formula significantly improved despite the presence of TDF (p = 0.028). Adverse events (AEs) were reported in 2 PLWHs and were characterized by the onset of a nodular rash in both arms and legs after 2 weeks of therapy in one PLWH, and by the onset of a progressive paresthesia in both extremities of arms after one week of treatment in the other PLWH. In both cases the treatment with DOR/3TC/TDF was interrupted. Conclusion The present real-life study showed that DOR/3TC/TDF significantly reduced lipid levels, surprisingly improving estimated renal function. The virological efficacy of DOR/3TC/TDF along with its immunological, metabolic and safety profile are key elements for a proactive management of the cardiovascular risk. Disclosures All Authors: No reported disclosures

A Study of Diabetes in Young Individuals with Special Reference to Type 2 Diabetes Mellitus

Background: Type 2 diabetes mellitus (T2DM) in young individuals is a serious concern for the society. Literature suggests that the incidence of T2DM is not only increasing, but also there is a shift of age of onset of T2DM toward younger age groups in India and worldwide. However, data about the frequency of T2DM among young subjects below 25 years of age are sparse in the Indian subcontinent. Hence, the current study was undertaken to find out the frequency and clinical profile of young individuals with T2DM in the departments of internal medicine and pediatrics in a tertiary care hospital. Aims and Objectives: The aim of the study was to study the frequency and clinical profile of T2DM among young individuals with diabetes mellitus. Materials and Methods: The study was a cross-sectional observational study conducted in the Departments of General Medicine and Pediatrics at JSS Hospital, Mysuru, Karnataka, India, over a 2-year period. The subjects with age of onset of diabetes mellitus below 25 years were included in the study. They were categorized according to the C-peptide values as type 1 diabetes mellitus (T1DM) and T2DM. Maturity-onset diabetes of the young (MODY) was diagnosed with the age of onset of diabetes below 25 years with a strong family history of diabetes for three generations and no insulin requirement for metabolic control for 5 years after diagnosis. The statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS version 25). Results: Of the 250 patients included in the study, 208 (83.2%) subjects were T1DM, 38 (15.2%) T2DM, and 4 (1.6%) with MODY. The mean age of onset of T1DM was 13.7 ± 6.201 years and T2DM was 23.28 ± 3.68 years. Body mass index (BMI) and waist circumference of young T2DM patients were more compared to T1DM, which were statistically significant P &lt; 0.0001, and family history showed strong positivity in patients with young T2DM compared to T1DM. Low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), and total cholesterol (TC) were more in young T2DM patients compared to T1DM which were statistically significant with P = 0.003 (LDL), P = 0.0015 (TG), and P = 0.03 (TC), respectively. Conclusions: T2DM, previously considered a middle-aged or elderly condition, is now commonly occurring in young adults and children, probably due to a growing epidemic of childhood obesity and lifestyle. Obesity and dyslipidemia were more in T2DM compared to T1DM among young diabetics.

Low Levels of Serum Total Vitamin B12 Are Associated with Worse Metabolic Phenotype in a Large Population of Children, Adolescents and Young Adults, from Underweight to Severe Obesity

Vitamin B12 (or cobalamin) is an essential vitamin for DNA synthesis, fatty acid and protein metabolism as well as other metabolic pathways fundamental to the integrity of cells and tissues in humans. It is derived from the diet and mostly stored in the liver. Its deficiency has been associated with metabolic derangements, i.e., obesity, glucose intolerance, increased lipogenesis and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). However, data with regard to body weight across the whole spectrum (from underweight to severe obesity) in children and young individuals are scarce. The present study aims to describe the association between serum total vitamin B12 and body mass index (BMI) ranging from underweight to severe obesity in a large population of children, adolescents and young adults. This study also investigates associations with visceral adiposity, glucose and lipid metabolism and liver dysfunction. A cross-sectional, single-centre study was conducted at the Paediatrics and Endocrinology units of the ”Bambino Gesù Children Hospital”, a tertiary referral institution for eating disorders. Clinical charts were reviewed and 601 patients aged from 5 to 25 years were enrolled in order to analyse anthropometric, auxological, clinical, biochemical and liver ultrasound data using robust statistical approaches. Analyses were adjusted for potential confounders. A reduction in serum total B12 levels was associated with a linear increase in body weight, as expressed by WHO BMI SDS (r = −0.31, p &lt; 0.001, BCa 95% −0.38, −0.24). Lower B12 levels were associated with higher waist circumference but only in pubertal girls (r = −0.33, p = 0.008, BCa 95% −0.53, −0.11). Hepatic insulin resistance was higher in males with lower B12 levels (B = −0.003 (−0.007, −0.0001), p = 0.039), but not in females, whereas whole-body insulin resistance was unaffected. Serum lipid profiles (total, HDL and LDL cholesterol and triglycerides) were not influenced by serum cobalamin levels. However, lower cobalamin levels were associated with higher grading of ultrasound-scored hepatic steatosis (ptrend = 0.035). Lastly, both AST and ALT showed a significant and direct correlation with total B12 levels in underweight (r = 0.22 and 0.24, p = 0.002 and &lt;0.001, respectively) and severely obese subjects (r = 0.24 and 0.32, p = 0.002 and &lt;0.001). In conclusion lower vitamin B12 levels are associated with higher body weight, adiposity and with worse metabolic health in a large population of children, adolescents and young adults.