Reduction In Total Cholesterol Research Articles

Leukemia inhibitory factor receptor inhibition reduces stenosis grade and total serum cholesterol levels in a mouse model for atherosclerosis

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation Atherosclerosis is characterized by the accumulation of lipids and immune cells in the arterial wall and it is the main underlying pathology causing cardiovascular diseases (CVD). Cytokines are involved in all stages of atherosclerosis and most cytokines contribute to disease progression. For instance, IL-6 cytokine family members, such as IL-6, oncostatin-M and cardiotrophin-1, are closely related to CVDs. However, the role of leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, and its receptor (LIFR) in atherosclerosis remains unknown. Therefore, the aim of this study is to assess the contribution of LIFR signaling to atherosclerosis development by systemically inhibiting LIFR in an atherosclerotic mouse model. First, the expression of LIF and LIFR was examined using single-cell RNA sequencing data of human carotid artery plaques. Mast cells highly and exclusively express LIF, whereas LIFR was specifically expressed by activated endothelial cells. To validate LIFR signaling in vivo, female western-type diet fed Ldlr-/- mice were treated with LIFR inhibitor EC359 (5 mg/kg s.c., n=15) or control solvent (n=15) three times per week for eight weeks. During the experiment, weights of the mice did not differ between groups, whereas total serum cholesterol levels were significantly reduced in EC359 treated mice (p=0.03). In particular, EC359 treatment reduced VLDL levels. Additionally, EC359 treatment significantly reduced Sr1, Abca1 and Lrp1 expression in the liver, suggesting an altered lipid metabolism in EC359 treated mice. Furthermore, LIFR inhibition affected innate immunity, both systemically and locally in the plaque. Neutrophil numbers were significantly increased in the circulation (ctrl 18.7±1.7%; EC359 28.0±2.0%; p=0.002) and aortic plaques (ctrl 3.9±0.8%; EC359 9.9±1.9%; p=0.003) of mice treated with EC359 compared to control mice. Moreover, LIFR inhibition affected circulating monocytes resulting in less inflammatory monocytes. The adaptive immune cells, such as T and B cells, remained largely unaffected. Collectively, the reduction of serum total cholesterol and increase in neutrophil numbers in EC359 treated mice resulted in a trend towards reduced atherosclerotic stenosis grade compared to control mice (39.8±1.4% versus 34.9±1.9%; p=0.054), but it did not affect plaque collagen and monocyte/macrophage content in the aortic root. Conclusively, LIFR signaling inhibition reduces atherosclerotic stenosis grade, lowers plasma total cholesterol levels and affects innate immunity.

Exploring the sex difference in cardiovascular risk during growth hormone therapy in adults.

Given the previously identified sex differences in cardiovascular (CV) morbidity and mortality in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT), our aim is to investigate sex-specific differences in the efficacy of (long-term) GHRT on CV risk profile and disease in subjects with GHD. Our hypothesis is that women will experience less beneficial effects than men. Retrospective nationwide cohort study. We compared all men (n = 1335) and women (n = 1251) with severe GHD registered in the Dutch National Registry of GH Treatment in Adults database with respect to CV risk profile and morbidity at baseline and during follow-up. Men had a more unfavourable CV risk profile at baseline. During the first years of GHRT, the reduction in waist circumference, waist-to-hip ratio, total cholesterol, and triglyceride levels was greater in men than in women (all P < .05). Between-sex differences in effects during later follow-up were less clear. No sex differences were found in the risk of developing non-fatal cardiovascular or cerebrovascular diseases during GHRT. Our results suggest that men with GHD did indeed experience more beneficial effects of GHRT on body composition and lipoprotein metabolism than women, at least in the early years of treatment. Also, the more unfavourable CV risk profile at baseline in men did not translate into a sex difference in the risk of developing CV and cerebrovascular morbidity during GHRT.

#1294 The impact of plant-based diet on renal function and metabolic profile in kidney transplant recipients

Abstract Background and Aims Controlling and reducing protein intake is the most used approach to preserve renal function in CKD patients. Compared to protein restriction alone, plant-based diets have received particular attention. However, data on the potential risks and benefits of a plant-based diet in kidney transplant patients remains sparse, and evidence in this population is indirect. The primary purpose of this study was to evaluate if a plant-based diet affects proteinuria and eGFR in renal transplant patients. Establishing whether it influences acid load, glycolipid profile, nutritional status, and performance status were secondary objectives. Method 26 renal transplant recipients with eGFR &amp;gt;20 ml/min/1.73 m², urinary protein excretion &amp;gt;0.5 g/day, and transplant age &amp;gt;1 year were considered eligible for the study. Enrolled subjects underwent dietary assessment and biochemical tests at baseline, three and six months after starting the plant-based diet. All subjects underwent performance tests: sit-to-stand and handgrip tests. Results Only 18 patients were included in the statistical analysis. After six months, no significant changes in levels of proteinuria, urinary anion gap, triglycerides, and grip strength were detected. However, there was a statistically significant reduction in total cholesterol (p=0.03), LDL (p=0.04), and fasting blood sugar levels (p=0.001). A statistically significant reduction in eGFR (p=0.033) was observed, likely the regression of the previous hyperfiltration caused by the animal protein diet. A significant improvement was found in sit-to-stand test performance (p=0.037). Finally, a direct relationship between azoturia and urinary anion gap was observed. Conclusions The work carried out has highlighted how some of the potential benefits of the plant-based diet may also be relevant among kidney transplant patients. The plant-based diet is also associated with improved performance tests.

Phytochemicals profiling of Cassia fistula fruit extract and its effect on serum lipids and hematological parameters in high‐fat diet‐induced hyperlipidemic female rats

AbstractCassia fistula (C. fistula) has shown strong anti‐inflammatory, hepatoprotective, antitussive, antibacterial, and antifungal properties and is being used for healing wounds and gastrointestinal illness. This study was planned to obtain fruit extract from C. fistula using ultrasonic‐assisted extraction (UAE) technique and evaluated for phytochemical contents, anti‐hyperlipidemia, and hematological parameters. The results showed that total phenolic (TPC), total flavonoids (TFC), condensed tannin (CT), and saponins were 13.07 mg GAE/g, 5.24 mg QE/g, 4.01 mg/g, and 27.55%, respectively, in the extract. Proximate composition of the extract showed 2.48%, moisture, 1.25% fat, 2.80% ash, 4.59% fiber, 11.93% protein, and 76.95% NFE. The 2, 2‐diphenyl‐1‐picrylhydrazyl (DPPH) and ferric reducing antioxidant power assay (FRAP) activity was 63.30 μg/mL and 15.02 nmol/g, respectively. High‐fat diet (HFD)‐induced hyperlipidemic rats were orally administrated with 0.5 and 1.0 g of extract/kg body weight (bw) daily. The reduction of total cholesterol (TC: 90.83 ± 8.86 mg/dL), triglycerides (TG; 74.16 ± 9.10 mg/dL), and low‐density lipoproteins (LDL; 74.83 ± 4.66 mg/dL) and increase of high‐density lipoproteins (HDL; 41.83 ± 8.4 mg/dL) was observed. Significant changes in red blood cells (RBCs; 8.03 ± 0.67106/μL), mean corpuscular hemoglobin concentration (MCHC; 35.02 ± 1.78 g/dL), mean corpuscular hemoglobin (MCH; 18.00 ± 0.26 pg), and mean corpuscular volume (MCV; 55.36 ± 4.01 fL) at 1.0 g extract intake was observed. Extract administration also improved significantly liver enzymes, body weight, and liver morphology. Therefore, C. fistula extract can be effectively used as a therapeutic agent to improve serum biochemistry and hematological values.

Antilipidemic and Hepatorenal Effects of Aqueous Extracts of Terminalia catappa on Streptozotocin-induced Diabetic Rats

Aims: Diabetes mellitus, a condition characterized by glucose receptor abnormalities affecting glucose uptake, affects approximately 600 million individuals globally as of 2021. This study aimed to assess the antilipidemic and renal effects of aqueous extracts from the root bark and flowers of Terminalia catappa on streptozotocin-induced diabetic rats. Methodology: Twenty-five Albino rats weighing 160 – 300g were divided into five groups: A - normal control, B - diabetic control, C - diabetic treated with root bark extract, D - diabetic treated with flower extract, E - diabetic rats treated with glibenclimide. Diabetes was induced using streptozotocin (55mg/kg). The extracts (200mg/kg) were orally administered for 14 days, after which lipid profiles, renal and liver function tests were conducted. Results: There was a significant (p&lt;0.05) increase in total cholesterol, serum liver enzymes, and kidney markers in the diabetic control group compared to the normal control group. Treatment with the Terminalia catappa extracts for 14 days resulted in more than 20% decrease in urea (from 18.58 Mmol/L to between 11.58 and 13.92 Mmol/L), creatinine (from 343.56 Mmol/L to between 223.94 and 266.30 Mmol/L) and uric acid (from 570.54 µmol/L to between 413.55 and 440.62 µmol/L) concentrations by more than 20%, with the root bark extract showing the most significant effect. Additionally, the Terminalia catappa extract-treated groups exhibited a substantial (around 40%) reduction in serum liver enzymes compared to the diabetic control group. The hepatoprotective capacity of the root bark extract was similar to the glibenclimide-treated group. Furthermore, the extracts led to a 3% reduction in total cholesterol, triglycerides, and low-density lipoproteins, along with a significant increase in high-density lipoproteins. Conclusion: The aqueous root bark and flower extracts of Terminalia catappa demonstrate potentials for managing diabetes mellitus at the specified dosage.

Comprehensive Cardiovascular Risk Factor Control With a Mobile Health Cardiovascular Risk Self-Management Program.

Mobile health technology's impact on cardiovascular risk factor control is not fully understood. This study evaluates the association between interaction with a mobile health application and change in cardiovascular risk factors. Participants with hypertension with or without dyslipidemia enrolled in a workplace-deployed mobile health application-based cardiovascular risk self-management program between January 2018 and December 2022. Retrospective evaluation explored the influence of application engagement on change in blood pressure (BP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and weight. Multiple regression analyses examined the influence of guideline-based, nonpharmacological lifestyle-based digital coaching on outcomes adjusting for confounders. Of 102 475 participants, 49.1% were women. Median age was 53 (interquartile range, 43-61) years, BP was 134 (interquartile range, 124-144)/84 (interquartile range, 78-91) mm Hg, TC was 183 (interquartile range, 155-212) mg/dL, LDL-C was 106 (82-131) mg/dL, and body mass index was 30 (26-35) kg/m2. At 2 years, participants with baseline systolic BP ≥140 mm Hg reduced systolic BP by 18.6 (SEM, 0.3) mm Hg. At follow up, participants with baseline TC ≥240 mg/dL reduced TC by 65.7 (SEM, 4.6) mg/dL, participants with baseline LDL-C≥160 mg/dL reduced LDL-C by 66.6 (SEM, 6.2) mg/dL, and participants with baseline body mass index ≥30 kg/m2 lost 12.0 (SEM, 0.3) pounds, or 5.1% of body weight. Interaction with digital coaching was associated with greater reduction in all outcomes. A mobile health application-based cardiovascular risk self-management program was associated with favorable reductions in BP, TC, LDL-C, and weight, highlighting the potential use of this technology in comprehensive cardiovascular risk factor control.

The Impact of Metabolic and Bariatric Surgery on Apo B100 Levels in Individuals with high BMI: A Multi-Centric Prospective Cohort Study.

Metabolic and Bariatric surgery (MBS) leads to significant weight loss and improvements in obesity-related comorbidities. However, the impact of MBS on Apolipoprotein B100 (Apo-B100) regulation is unclear. Apo-B100 is essential for the assembly and secretion of serum lipoprotein particles. Elevated levels of these factors can accelerate the development of atherosclerotic plaques in blood vessels. This study aimed to evaluate changes in Apo-B100 levels following MBS. 121 participants from the Iranian National Obesity and Metabolic Surgery Database (INOSD) underwent Laparoscopic Sleeve Gastrectomy (LSG) (n = 43), One-Anastomosis Gastric Bypass (OAGB) (n = 70) or Roux-en-Y Gastric Bypass (RYGB) (n = 8). Serum Apo-B100, lipid profiles, liver enzymes, and fasting glucose were measured preoperatively and six months postoperatively. Apo-B100 levels significantly decreased from 94.63 ± 14.35 mg/dL preoperatively to 62.97 ± 19.97 mg/dL after six months (p < 0.01), alongside reductions in total cholesterol, triglycerides, LDL, VLDL, AST, and ALT (p < 0.05). Greater Apo-B100 reductions occurred in non-diabetics versus people with diabetes (p = 0.012) and strongly correlated with baseline Apo-B100 (r = 0.455, p < 0.01) and LDL levels (r = 0.413, p < 0.01). However, surgery type did not impact Apo-B100 changes in multivariate analysis (p > 0.05). Bariatric surgery leads to a significant reduction in Apo-B100 levels and improvements in lipid profiles and liver enzymes, indicating a positive impact on dyslipidemia and cardiovascular risk in individuals with high BMI.

Anti-dyslipidemic and cardio-protective effects of dietary &lt;i&gt;Vernonia amygdalina&lt;/i&gt; leaves in monosodium glutamate intoxicated high fat diet fed Wistar rats

The study evaluated the proximate analysis, anti- dyslipidemic and cardioprotective effects of dietary incorporated Vernonia amygdalina (VA) leaves in Monosodium glutamate (MSG) intoxicated High fat diet (HFD) fed Wistar rats. The proximate analysis of the leaves revealed the highest ash and carbohydrate content in the control (basal) diet, highest protein, crude fibre and moisture content in the 10% VA incorporated HFD and the highest crude fat in the HFD only group. Dietary incorporation of VA in HFD reversed the trend of hypercholesterolemia and hypertriglyceridemia observed in experimental animals after chronic MSG, HFD and MSG + HFD administration. At the end of week 8, HFD only group produced a higher level of total cholesterol and triglyceride when compared to the basal control diet group and the MSG only group while the 10% VA HFD group produced the greatest reduction in total cholesterol and triglyceride from week 9 – week 12. Possible mechanisms include the presence of crude fibers which binds to bile acids reducing the absorption of cholesterol. Histopathology studies of the myocardial tissues at the end of the study revealed in the MSG + HFD group signs of a marked diffused edema of the myocardium which was absent in the MSG only and HFD only groups while 5% and 10% VA incorporated HFD and the standard drug Orlistat 10 mg/kg failed to reverse the observed toxicity. Conclusion: Dietary VA reversed lipid derangement observed but failed to reverse myocardial histopathologies after chronic MSG + HFD administration and could be used as an adjunct for the treatment of obesity.

The effect of increased fruit and vegetable consumption on blood pressure and lipids: a pooled analysis of six randomised controlled fruit and vegetable intervention trials.

Increasing fruit and vegetable (FV) consumption is associated with reduced cardiovascular disease risk in observational studies but with little evidence from randomised controlled trials (RCTs). The impact of concurrent pharmacological therapy is unknown. To pool data from six RCTs to examine the effect of increasing FV intake on blood pressure (BP) and lipid profile, also exploring whether effects differed by medication use. Across trials, dietary intake was assessed by diet diaries or histories, lipids by routine biochemical methods and BP by automated monitors. Linear regression provided an estimate of the change in lipid profile or BP associated with a one portion increase in self-reported daily FV intake, with interaction terms fitted for medication use. The pooled sample included a total of 554 participants (308 males and 246 females). Meta-analysis of regression coefficients revealed no significant change in either systolic or diastolic BP per portion FV increase, although there was significant heterogeneity across trials for systolic BP (I2= 73%). Neither adjusting for change in body mass index, nor analysis according to use of anti-hypertensive medication altered the relationship. There was no significant change in lipid profile per portion FV increase, although there was a significant reduction in total cholesterol among those not on lipid-lowering therapy (P < 0.05 after Bonferroni correction). Pooled analysis of six individual FV trials showed no impact of increasing intake on BP or lipids, but there was a total cholesterol-lowering effect in those not on lipid-lowering therapy.

Safety and Efficacy of the Consumption of the Nutraceutical "Red Yeast Rice Extract" for the Reduction of Hypercholesterolemia in Humans: A Systematic Review and Meta-Analysis.

Previous studies have shown encouraging results regarding the efficacy and safety of nutraceuticals, such as "red yeast rice (RYR) extract", on reducing hypercholesterolemia in humans. A systematic review and meta-analysis was conducted from January 2012 to May 2022. The search was strictly focused on clinical trials that examined the association between RYR extract consumption and parameters of the lipid profile in humans. Fourteen double-blinded clinical trials were identified. The interventions lasted 4-24 weeks. In most studies, there was one intervention group and one control group. RYR extract consumption statistically significantly reduced total cholesterol (mean absolute reduction: 37.43 mg/dL; 95% confidence interval [CI]: -47.08, -27.79) and low-density lipoprotein cholesterol (LDL-C; mean absolute reduction: 35.82 mg/dL; 95% CI: -43.36, -28.29), but not high-density lipoprotein cholesterol, triglycerides and apolipoproteins A-I and B. As regards the safety, RYR extract was considered a safe choice with neither threatening nor frequent side effects. The consumption of RYR extract by people with hypercholesterolemia was associated with statistically significant reduction in total cholesterol and LDL-C, whereas it was not associated with an increase in life-threatening side effects. Further research on specific subpopulations and outcomes could establish a consensus on determining the clinical benefits and potential risks, if any, of this nutraceutical.

Comprehensive meta-analysis of the effects of oral medroxyprogesterone acetate plus conjugated equine oestrogens on the lipid profile in women: Insights from randomized controlled trials.

Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.

Melatonin Modulates Lipid Metabolism and Reduces Cardiovascular Risk in Apolipoprotein E-Deficient Mice Fed a Western Diet

Melatonin (MLT), a natural compound found in the animal and vegetable kingdom, participates in several physiological processes. MLT exerts antioxidant and anti-inflammatory activities, among others, but information about its action on lipid metabolism is still scarce. For this reason, mice deficient in apolipoprotein E (ApoE−/−) fed a Western diet (WD) were intragastrically treated with different concentrations of MLT (2 and 9 mg/kg) for 12 weeks. The lipid parameters were quantified, and, since links between cardiovascular risk and immune function and oxidative stress have been established, we also analyzed the population of leukocytes and the oxidative stress status. Although there was no change in the weight of the mice, a significant reduction in low-density lipoprotein cholesterol (LDL-C) was observed in mice treated with the higher concentration of MLT tested in this study. Additionally, an improvement in cardiovascular risk indexes was observed. A reduction in the hepatic total cholesterol (TC) and LDL-C levels was also observed in the treated mice. Finally, a decrease in leukocytes and lymphocytes in particular, as well as an increase in the antioxidant status, were shown in MLT-treated mice. In conclusion, MLT is a promising candidate that could be considered as a possible functional ingredient capable of preventing cardiovascular risk.

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study

BackgroundRemnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited.MethodsThis prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment.ResultsAmong all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45–0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34–0.75; P < 0.001), without a significant increase of adverse reactions.ConclusionCurrent levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

Effect of &lt;i&gt;Vernonia amygdalina&lt;/i&gt; and fish oil-supplemented biscuits on lipid profile parameters and blood glucose concentration of diabetic rats

Biscuit, a popular snack, serve as an ideal vehicle for incorporating therapeutic agents for disease management. This study aimed to assess the effect of Vernonia amygdalina (VO) and fish oil (FO)-supplemented biscuits (VFSB) on the total lipid profile and blood glucose concentration of diabetic rats. Forty-nine Wistar rats were allocated into seven groups (A to G). Upon induction and confirmation of diabetes in experimental rats, fasting blood glucose (FBG) level were monitored weekly using glucometer. Twenty-four hours after the last day of treatment, rats were sacrificed and serum total cholesterol (TC), triglyceride (TG), High-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) concentrations were assayed using assay kits. Results showed a significant (p &lt; 0.05) reduction in FBG, TC, LDL-c, and TG concentrations in biscuit fed groups D, E, and F compared to group B fed VFSB. High-density lipoprotein cholesterol levels significantly increased (p &lt; 0.05) in groups D, E, and F compared to Group B. In conclusion, Vernonia amygdalina and fish oil-supplemented biscuits exhibited a glucose-lowering effect and mitigated dyslipidemia associated with diabetes mellitus.

A long-acting LEAP2 analog reduces hepatic steatosis and inflammation and causes marked weight loss in mice

ObjectiveThe number of individuals affected by metabolic dysfunction associated fatty liver disease [1] is on the rise, yet hormonal contributors to the condition remain incompletely described and only a single FDA-approved treatment is available. Some studies suggest that the hormones ghrelin and LEAP2, which act as agonist and antagonist/inverse agonist, respectively, for the G protein coupled receptor GHSR, may influence the development of MAFLD. For instance, ghrelin increases hepatic fat whereas synthetic GHSR antagonists do the opposite. Also, hepatic steatosis is less prominent in standard chow-fed ghrelin-KO mice but more prominent in 42% high-fat diet-fed female LEAP2-KO mice. MethodsHere, we sought to determine the therapeutic potential of a long-acting LEAP2 analog (LA-LEAP2) to treat MAFLD in mice. LEAP2-KO and wild-type littermate mice were fed a Gubra-Amylin-NASH (GAN) diet for 10 or 40 wks, with some randomized to an additional 28 or 10 days of GAN diet, respectively, while treated with LA-LEAP2 vs Vehicle. Various metabolic parameters were followed and biochemical and histological assessments of MAFLD were made. ResultsAmong the most notable metabolic effects, daily LA-LEAP2 administration to both LEAP2-KO and wild-type littermates during the final 4 wks of a 14 wk-long GAN diet challenge markedly reduced liver weight, hepatic triglycerides, plasma ALT, hepatic microvesicular steatosis, hepatic lobular inflammation, NASH activity scores, and prevalence of higher-grade fibrosis. These changes were accompanied by prominent reductions in body weight, without effects on food intake, and reduced plasma total cholesterol. Daily LA-LEAP2 administration during the final 10 d of a 41.5 wk-long GAN diet challenge also reduced body weight, plasma ALT, and plasma total cholesterol in LEAP2-KO and wild-type littermates and prevalence of higher grade fibrosis in LEAP2-KO mice. ConclusionsAdministration of LA-LEAP2 to mice fed a MAFLD-prone diet markedly improves several facets of MAFLD, including hepatic steatosis, hepatic lobular inflammation, higher-grade hepatic fibrosis, and transaminitis. These changes are accompanied by prominent reductions in body weight and lowered plasma total cholesterol. Taken together, these data suggest that LEAP2 analogs such as LA-LEAP2 hold promise for the treatment of MAFLD and obesity.

Continuous glucose monitoring for glycaemic control and cardiovascular risk reduction in patients with type 2 diabetes not on insulin therapy: A clinical trial.

To evaluate the impact of the Dexcom G6 continuous glucose monitoring (CGM) device on glycaemic control and cardiometabolic risk in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk who are not on insulin therapy. Adults with T2DM with glycated haemoglobin (HbA1c) >7% and body mass index (BMI) ≥30 kg/m2 not using insulin were enrolled in a two-phase cross-over study. In phase 1, CGM data were blinded, and participants performed standard glucose self-monitoring. In phase 2, the CGM data were unblinded, and CGM, demographic and cardiovascular risk factor data were collected through 90 days of follow-up and compared using paired tests. Forty-seven participants were included (44% women; 34% Black; mean age 63 years; BMI 37 kg/m2; HbA1c 8.4%; 10-year predicted atherosclerotic cardiovascular disease risk 24.0%). CGM use was associated with a reduction in average glucose (184.0 to 147.2 mg/dl, p < .001), an increase in time in range (57.8 to 82.8%, p < .001) and a trend towards lower glucose variability (26.2 to 23.8%). There were significant reductions in HbA1c, BMI, triglycerides, blood pressure, total cholesterol, diabetes distress and 10-year predicted risk for atherosclerotic cardiovascular disease (p < .05 for all) and an increase in prescriptions for sodium-glucose cotransporter 2 inhibitors (36.2 to 83.0%) and glucagon-like peptide-1 receptor agonists (42.5 to 87.2%, p < .001 for both). Dexcom G6 CGM was associated with improved glycaemic control and cardiometabolic risk in patients with T2DM who were not on insulin. CGM can be a safe and effective tool to improve diabetes management in patients at high risk for adverse cardiovascular outcomes.

Antidyslipidemic Effect of Diherbal mixture of Pteridium Aquilinum and Caesalpinia bonducella in Albino Rats

Pteridium aquilinum and Caesalpinia bonducella are plants commonly used in the management of various ailments in Nigerian folk medicine. Each of them have been found to possess antioxidant and anti-inflammatory properties that can help in maintaining cardiovascular health. In the present study, the effect of the herbal mixture on the lipid profile of albino rats was investigated. A total of twenty albino rats were used in the study. These rats were randomly distributed into 5 groups of 4 rats per group. The rats were allowed to acclimatize for ten days prior to treatment. Rats in group 1 (control) were kept on water and feed. While rats in groups 2, 3, 4 and 5 were treated with 200, 400, 600 and 800mg/kg bwt. of the di-herbal mixture respectively. The treatments lasted for 21 days. Twenty four hours after treatment, the rats were sacrificed. Blood samples collected and prepared for lipid profile. The following parameters: total cholesterol (TC), High-density Lipoprotein (HDL), Low-density lipoprotein (LDL) and triglycerides (TG) were evaluated by standard methods. Results showed that the di-herbal mixture exhibited a dose-dependent reduction in Total cholesterol, LDL cholesterol and Triglyceride. For instance, the control rats had a total cholesterol value of 91.28± 3.54mg/dl. When the herbal mixture was introduced at the dose of 200mgkg bwt, cholesterol value reduced to 90.28±3.77mg/dl. Dose-dependent increments in HDL Cholesterol levels were however, recorded. For instance, the control rats had a HDL Cholesterol value of 32.28 ± 1.81mg/dl. When the herbal sample was given at the initial dose of 200mg/kg bwt, HDL Cholesterol level increased to 34.21 ± 1.72mg/dl. When the extract dose was further increased to 400mg/kg bwt. HDL Cholesterol level was found to be 34.61± 2.10mg/dl. The conclusion was thus drawn that the sample has the potency of maintaining healthy levels of the cardiac function parameters investigated.

Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain.

We performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain. All non-diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were evaluated every 6 months during a 12-month follow-up. Overall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA-IR index was 3.18 and insulin resistance (HOMA-IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (-3.54 mcrUI/L [interquartile range -4.22 to -2.87]; p = 0.012), associated with a significant reduction in mean HOMA-IR index (-0.54 [interquartile range -0.91 to -0.18]; p = 0.021). A significant reduction in total and low-density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant. In our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight.

499 Physiological and Metabolomic Effects of a Community-Based Cardiorenal Protective Diet Intervention in African Americans with Chronic Kidney Disease and Hypertension

OBJECTIVES/GOALS: Chronic kidney disease (CKD) impacts 15% of US adults and African American (AA) persons are disproportionately affected with more than 3 times higher risk of kidney failure when compared to Caucasian persons. This study evaluated the physiological and metabolomic effects of increased fruits and vegetables (F&amp;V) on cardio-renal risk factors. METHODS/STUDY POPULATION: This pilot trial used a prospective, 2-group, randomized study design to evaluate a F&amp;V intervention (N=46), where participants received a prescribed amount of fresh, base-producing F&amp;V compared to a wait-list control (WL) condition (N=45). All participants were African American adults (≥18 years), had self-reported hypertension, and had CKD (Stage 1-3) on screening spot-urine microalbumin test. Participants were measured at baseline and 6 weeks post-intervention. Clinical data (i.e., systolic and diastolic blood pressure, lipid panel, hemoglobin A1C, BMI [body mass index], and albumin to creatinine ratio) were collected. Targeted metabolomic quantitative analysis was performed followed by LC-MS/MS and FIA-MS/MS. Linear mixed models evaluated analyte expression and clinical data. RESULTS/ANTICIPATED RESULTS: AA participants (N=91) were aged 58 ± 10.2 years, 66% female, and 54% had incomes ≤$50,000. T-tests compared change scores (baseline to 6-weeks) between groups. The F&amp;V group demonstrated a significant reduction in BMI of -4.7 ± 10.5 kg/m² compared to a 1.9 ± 8.3 kg/m² increase in the WL group, p&lt;.01. Further, the F&amp;V group demonstrated a reduction in total cholesterol of -15.4 ± 58.8 mg/dL compared to a 17.7 ± 68.8 mg/dL increase in the WL group, p&lt;.05. Non-significant reductions in hemoglobin A1c were found in the F&amp;V versus the WL group. Metabolomic analysis indicated significant variation with an increase of suggestive key biomarkers for worse CKD in the WL versus F&amp;V groups at 6-weeks. DISCUSSION/SIGNIFICANCE: Consumption of only 2 cups of F&amp;V via a community-based intervention reduced CVD risk factors in AA adults with CKD and HTN and resulted in molecular/biochemical changes which may improve long-term kidney health. Further investigation may lead to development of cost-effective dietary intervention models to improve CKD outcomes in AA persons.

The Lipid-Lowering Efficacy of a Nutraceutical Combination Including Leucoselect Phytosome, Red Yeast Rice, Policosanol and Folic Acid in Dyslipidaemia Patients: Real-World Insights.

Cardiovascular disease is a global health concern and reducing plasma LDL-C levels is a major goal in cardiovascular prevention. Our study aimed to evaluate the effectiveness of a nutraceutical formulation including leucoselect® phytosome®, red yeast rice, policosanol and folic acid on LDL-c levels in patients at low cardiovascular risk with dyslipidemia. We prospectively enrolled all consecutive patients with dyslipidemia at low cardiovascular risk who were unresponsive to diet and physical activity. Clinical assessments and laboratory analyses, encompassing lipid profile, hepatic function, and CPK levels, were performed at baseline prior to initiating treatment and repeated at the 12-week mark following administration of the study nutraceutical. Sixty (60) consecutive patients (mean age 48.02 ± 10.1 years; 60% male) were included. At the 12-week follow-up, a statistically significant reduction in Total Cholesterol (13.1%) and LDL-c serum level (20.4%) was observed. Hepatic and muscular function remain stable over the time. The adherence to therapy was 99% and the persistence was maximum. The nutraceutical formulation including leucoselect® phytosome® red yeast rice, policosanol and folic acid significantly reduced the LDL-c plasma levels, consistent with previous research showing that the bioactive component in red yeast rice-lovastatin-is effective in addressing problems with lipid metabolism. Importantly, it was safe and well-tolerated among patients with dyslipidemia in a real-world setting.