Improvements In Lipid Parameters Research Articles

A new phytopharmaceutical obtained from Polyalthia longifolia with Anti-dyslipidemic potential: Mechanistic pathway insights exploiting co-inverse miRNA-mRNA expression analysis.

Obesity and its associated metabolic disorders are significant global health challenges, necessitating novel therapeutic approaches. This study explores the anti-adipogenic and anti-dyslipidemic properties of 4655-EF, a novel phytopharmaceutical derived from Polyalthia longifolia, and explores the molecular pathways involved in its pharmacological activity. This phytopharmaceutical was prepared using a bioactivity-guided supercritical fluid extraction method suitable for large-scale production. The RP-UHPLC analysis of 4655-EF revealed that the percentage composition of its four biomarkers was 21.19 ± 1.21% (N-016-0014), 0.83 ± 0.02% (N-016-0015), 0.3 ± 0.02% (N-016-0016), and 35.09 ± 1.57% (N-016-0017).We examined the effects of 4655-EF on HFD-fed Syrian Golden Hamsters and HFD-fed C57BL/6 mice, models of dyslipidemia and obesity, respectively. In the hamsters, 4655-EF treatment reduced body weight and fat mass and improved lipid parameters. Similarly, in the mice, 4655-EF treatment resulted in reduced body weight and fat mass and improved dyslipidemia, glucose tolerance, and insulin sensitivity. Moreover, mechanistic study exploring the possible pathways responsible for its anti-adipogenic activity uncovered the downregulation of genes associated with adipogenesis, cholesterol metabolism, and PPAR (Peroxisome Proliferator-Activated Receptor) signaling pathways using next-generation sequencing. Additionally, miRNA expression analysis indicated the activation of the anti-adipogenic Wnt/β-catenin pathway. These findings signify a multifaceted mechanism by which 4655-EF exerts its beneficial effects and highlight its potential as a promising phytopharmaceutical for addressing obesity and dyslipidemia, along with its industry-friendly method for large-scale production.

Long-standing, Untreated Case of Autosomal Recessive Hypercholesterolemia in a Child

Abstract Background: Autosomal recessive hypercholesterolemia (ARH), a genetic disorder of the affecting lipid metabolism. We present a child with this disorder wo was long undiagnosed, for many years. Clinical Description: An 8-year-old girl presented with multiple soft, painless, progressively increasing since the age of 2 years. Although lipid profiles had been found to be abnormal, she was not evaluated nor treated till 8 years of age. On examination, the swellings were present over upper and lower limbs and buttocks. Management and Outcome: Low-density lipoprotein (LDL) levels were elevated. Histopathology of the lesions confirmed xanthoma with immunohistochemistry being positive for CD 68 and ki67 index - 15%–20%. Next-generation sequencing homozygous mutation involving intron 15 of chromosome variant c2312-1G > A, causing loss of function variant in gene LDL receptor. The child was treated with gradually increasing doses of atorvastatin, with periodic echocardiography. There was progressive lowering of LDL over 6 months. Conclusion: Ignorance among pediatricians regarding this rare entity of ARH may result in lack of initiation of treatment for years, which may lead to detrimental cardiovascular complications in later life. Genetic analysis and prompt treatment can help in improving lipid parameters.

The antihyperlipidemic effects of coenzyme Q10 and gemfibrozil on hyperlipidemic male rats: a comparative study

Dyslipidemia is considered as the most common risk factor for cardiovascular diseases, cerebrovascular diseases, and fatty liver disease. The available therapy aimed to decrease lipid profile and reduced long-term risk which do require lifelong therapy, hence adverse effects are suggestive. The goal of the present study is to compare the anti¬hyperlipidemic influence and hepatic side effects of CoQ10 and gemfibrozil in the hyperlipidemic male rats model. Twenty-five albino rats were divided into 5 groups: group 1(normal group), group 2 (olive oil group), group 3(hyperlipidemia-induced group) group 4 (CoQ10-treated group), and group 5 (gemfibrozil-treated group). Induction of hyperlipidemia lasts for 90 days and treatment lasts for 30 days. Serum liver enzyme analysis and liver histological study conducted to demonstrate the safety profile of the treatment agents. Analysis of the data revealed that the lipid profile parameters (except HDL) and liver enzymes were significantly (p< 0.001) higher in the hyperlipidemic group (Group 3) compared to either the control group (Group 1) or olive oil group. Using CoQ10 (Group 4) and gemfibrozil (Group 5) has revealed that the lipid parameters and liver enzymes were significantly (p<0.001) lower compared to the hyperlipidemic group (Group 3). Compared to control group, liver showed congestion of sinusoids, severe necrosis of hepatocytes, vacuolar degradation, and infiltration of inflammatory cells, these effects reversed in presence of CoQ10. Compared to gemfibrozil, CoQ10 provides safer and equally effective option for treatment of dyslipidemia represented by improved lipid parameters and liver enzymes alongside protected hepatic architecture.

A Comparison of Rosuvastatin Monotherapy and Rosuvastatin Plus Ezetimibe Combination Therapy in Patients With Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Type 2 diabetes mellitus is a metabolic condition where vascular inflammation and oxidative stress contribute to disease progression and associated complications. Although statins are recommended for managing dyslipidemia in diabetes, additional therapies are often required to achieve target lipid levels. This meta-analysis aimed to evaluate the efficacy of rosuvastatin monotherapy versus combination therapy with ezetimibe in patients with type 2 diabetes. A systematic literature search was conducted across multiple databases until April 2024, identifying six randomized controlled trials meeting the inclusion criteria. The meta-analysis revealed that the rosuvastatin plus ezetimibe combination resulted in significantly greater reductions in total cholesterol (mean difference, or MD: 19.49; 95% CI: 13.99 to 24.99), triglycerides (MD: 13.44; 95% CI: 2.04 to 24.85), and low-density lipoprotein cholesterol(MD: -17.68; 95% CI: 12.85 to 22.51) compared to rosuvastatin monotherapy. Conversely, rosuvastatin monotherapy achieved a greater reduction in HbA1c levels (MD: -0.11; 95% CI: -0.17 to -0.04). Subgroup analysis demonstrated that using the same dose of rosuvastatin in both groups led to more significant improvements in lipid parameters with lower heterogeneity. The findings suggest that the rosuvastatin-ezetimibe combination may be a more effective lipid-lowering strategy for patients with type 2 diabetes, though larger studies are needed to assess long-term safety and optimal dosing. Additionally, while rosuvastatin monotherapy provided modest HbA1c reductions, the clinical relevance remains uncertain, and potential risks with high-dose statins should be considered.

Benefits of Puerarin on Metabolic Syndrome and Its Associated Cardiovascular Diseases in Rats Fed a High-Fat/High-Sucrose Diet.

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases (CVDs) that has become a global public health problem. Puerarin (PUE), the principal active compound of Pueraria lobata, has the effects of regulating glucose and lipid metabolism and protecting against cardiovascular damage. This study aimed to investigate whether dietary supplementation with PUE could ameliorate MetS and its associated cardiovascular damage. Rats were randomly divided into three groups: the normal diet group (NC), the high-fat/high-sucrose diet group (HFHS), and the HFHS plus PUE diet group (HFHS-PUE). The results showed that PUE-supplemented rats exhibited enhanced glucose tolerance, improved lipid parameters, and reduced blood pressure compared to those on the HFHS diet alone. Additionally, PUE reversed the HFHS-induced elevations in the atherogenic index (AI) and the activities of serum lactate dehydrogenase (LDH) and creatine kinase (CK). Ultrasonic evaluations indicated that PUE significantly ameliorated cardiac dysfunction and arterial stiffness. Histopathological assessments further confirmed that PUE significantly mitigated cardiac remodeling, arterial remodeling, and neuronal damage in the brain. Moreover, PUE lowered systemic inflammatory indices including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII). In conclusion, dietary supplementation with PUE effectively moderated metabolic disorders, attenuated systemic inflammation, and minimized cardiovascular damage in rats with MetS induced by an HFHS diet. These results provide novel insights into the potential benefits of dietary PUE supplementation for the prevention and management of MetS and its related CVDs.

Comparison of Metformin and Myoinositol on Clinical, Hormonal and Metabolic Profile of Patients with Polycystic Ovarian Syndrome: An Open-label Randomised Clinical Trial

Introduction: The prevalence of Polycystic Ovarian Syndrome (PCOS), one of the common endocrine disorders among women of reproductive age, varies from 2.2% to 26% globally. The treatment for PCOS aims to reduce Body Mass Index (BMI), improve underlying hormonal disturbances, prevent future reproductive and metabolic complications, and enhance the quality of life. Aim: To evaluate the efficacy of metformin and Myoinositol (MI) on the metabolic, hormonal, and clinical profiles in PCOS. Materials and Methods: An open-label randomised clinical trial was conducted at the Department of Obstetrics and Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur, Chengelpet, Tamil Nadu, India, from January 2019 to May 2020. The study included 80 women with PCOS who were randomly assigned to two groups. One group received metformin 1500 mg/day (in three divided doses), while the other group received MI 1 gram/day for three months. At the end of the 12-week therapy, the participants were evaluated for changes in clinical, metabolic, and hormonal profiles. The data were analysed using Statistical Package for Social Sciences (SPSS) version 20.0. Descriptive statistics such as frequency, proportion, mean, and standard deviation were used for quantitative data. Results: Both the metformin and MI-treated groups showed a significant reduction in BMI, fasting blood glucose, and fasting insulin. Both drugs were equally effective in changing the hormonal profile. There was a significant improvement in lipid parameters in both groups, with High-density Lipoprotein (HDL) levels being more significantly raised in the metformin group. The post-treatment HDL values in the metformin group were 75.69±19.16 mg/dL compared to 41.43±6.18 mg/dL in the MI group (p<0.0001). Both groups demonstrated similar efficacy in improving menstrual regularity, with 60% of the patients in the metformin group and 65% in the MI group having regular cycles at the end of treatment. Among infertility patients, the conception rate was 40% in the metformin group and 25% in the MI group (p=0.70). Conclusion: Both drugs were equally efficient in improving the clinical, metabolic, and hormonal profiles in PCOS. Metformin was found to be superior to MI in improving fertility and increasing HDL levels.

Biological Selenium Nanoparticles in Quail Nutrition: Biosynthesis and its Impact on Performance, Carcass, Blood Chemistry, and Cecal Microbiota.

This study was conducted to examine the influence of dietary supplementation of biological nano-selenium (BNSe) on productive performance, hematology, blood chemistry, antioxidant status, immune response, cecal microbiota, and carcass traits of quails. In total, 180 Japanese quails (1week old) were randomly allocated into four groups, with five replicates of nine chicks each in a complete randomized design. The 1st group was fed a control diet without BNSe, and the 2nd, 3rd, and 4th treatments were fed diets supplemented with BNSe (0.2, 0.4, and 0.6g /kg feed, respectively). The best level of BNSe in body weight (BW) and body weight gain (BWG) parameters was 0.4g/kg diet. Feed conversion was improved (P < 0.01) by adding BNSe in quail feed compared with the basal diet without any supplementation. The inclusion of different BNSe levels (0.2, 0.4, 0.6g/kg) exhibited an insignificant influence on all carcass traits. The dietary addition of BNSe (0.4 and 0.6g/kg) significantly augmented aspartate aminotransferase (AST) activity (P = 0.0127), total protein and globulin (P < 0.05), white blood cells (WBCs) (P = 0.031), and red blood cells (RBCs) (P = 0.0414) compared with the control. The dietary BNSe supplementation significantly improved lipid parameters, antioxidant and immunological indices, and increased selenium level in the blood (P < 0.05). BNSe significantly increased (P = 0.0003) lactic acid bacteria population number and lowered the total number of yeasts, molds, total bacterial count, E. coli, Coliform, Salmonella, and Enterobacter (P < 0.0001). In conclusion, adding BNSe up to 0.4 and 0.6g/kg can boost the growth, lactic acid bacteria population number, hematology, immunological indices, antioxidant capacity, and lipid profile, as well as decline intestinal pathogens in growing quail.

Insulin resistance and iatrogenic hyperinsulinemia in type 1 diabetes - norm or complication? Role of metformin in type 1 diabetes mellitus

There is a rising trend of overweight and obesity among individuals with type 1 diabetes. This is often associated with decreased insulin sensitivity, increased insulin dose requirements and poor glycemic control. Insulin resistance is a state of diminished effect of insulin on target tissues, despite normal or elevated serum insulin levels. Metformin as an adjunct to insulin in treating overweight or also not specific image of insulin resistance (without overweight or hormonal disorders) adults with type 1 diabetes is increasingly used. The main goal of this off-label type 1 diabetes treatment method is to improve insulin signaling leading to a subsequent increase in glucose uptake by skeletal myocytes, inhibition of hepatic gluconeogenesis and, as a result, a reduction in the need for a daily dose of insulin. The use of metformin as an addition to insulin may increase the chance of achieving target glucose control and reduce the anabolic effect of this hormone. Metformin can improve insulin sensitivity, glycemia and modulate cardiovascular disease risk factors or nonalcoholic fatty liver disease. In the vast majority of clinical trials conducted with metformin in type 1 diabetes, the effect of the drug on daily insulin doses, improvement in lipid parameters, and decline in body fat was assessed without correlating pre-specified outcomes with drug plasma concentrations.

Black rice regulates lipid metabolism, liver injury, oxidative stress and adipose accumulation in high-fat/cholesterol diet mice based on gut microbiota and untargeted metabonomics

Black rice displays a series of properties including regulating lipid metabolism and attenuating liver injury. Our study aimed to investigate the effect of Zixiangnuo black rice (ZG), peeled rice (ZPG), rice bran (ZBG) on lipid metabolism, liver inflammation, gut microbiota and metabolite profiles in high-fat/cholesterol (HFCD) diet mice. A total of five treatment groups were fed a normal control diet or a HFCD with or without Highland barley (HB) supplementation for 10 weeks. The results showed that ZBG significantly improved lipid parameters, liver function and injury and blood glucose indexes related to hyperlipidemia compared with HFCD group. ZBG recovered the disorder of gut microbiota by increasing Bacteroidetes/Firmicutes ratio and Lactobacillus abundance, and decreasing Proteobacteria abundance. ZBG enhanced the levels of six short chain fatty acids. Fecal metabolomics analysis showed that the important differential metabolites between ZBG and HFCD group were Deoxycholic acid and Myclobutanil, and metabolic pathways were Arachidonic acid metabolism and ABC transporters. Results suggested that BR or bran were effective dietary candidates to ameliorate hyperlipidemia.

“Study of association of serum lipid profile, IL-6, &amp; ADMA levels with subclinical hypothyroidism”

Background &amp; Objectives: Subclinical hypothyroidism (SCH) represents the mildest form of thyroid hormone deficiency and may be associated with adverse consequences. SCH is defined as an elevated serum thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) level with normal levels of free thyroxine (FT4) that affects up to 10% of the adult population. The identification of patients with subclinical hypothyroidism having an increased cardiovascular risk is of great importance in the present era. The aim of the study was to evaluate cardiovascular risk factors in patients with subclinical hypothyroidism.&#x0D; Methods: 120 patients with subclinical hypothyroidism and 120 age and gender matched healthy euthyroid controls in the age group of 18-70 years were included in the study. Body mass index (BMI), lipid profile, and levels of serum biomarkers were estimated in both the groups and further compared using student t-test. Lipid profile was also correlated with the serum ADMA &amp; IL-6 and the results were analyzed using Pearson’s correlation coefficient.&#x0D; Results: Patients with subclinical hypothyroidism had significantly higher levels of serum TSH, IL-6 and ADMA. Similarly, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly increased and HDL-C was significantly decreased in SCH patients when compared to the same parameters of controls (p&lt;0.001). Significant positive correlations were found among lipid profile and serum IL-6 &amp; ADMA.&#x0D; Conclusions: The present study concluded that the SCH patients presented increased concentrations of cardiovascular disease (CVD) risk factors viz. IL-6, ADMA &amp; lipid profile. The potential benefits of diagnosis and treatment of subclinical hypothyroidism may have possible advantages firstly by preventing the progression to overt hypothyroidism and secondly decrease the risk of death from cardiovascular disease by starting appropriate therapy to improve lipid parameters.&#x0D;

OAGB with shortened excluded ileal loop as an effective treatment for type 2 diabetes mellitus in the cases of Caucasian men and women with obesity of the first degree (BMI 30–35 kg/m2)

IntroductionThe aim of the study is to assess the effect of shortening the excluded loop of the small intestine to 150 cm on the effectiveness of one anastomosis gastric bypass (OAGB) in remission of type 2 diabetes with Io obesity.Material and methodsThe study included 25 patients with a body mass index (BMI) 30–35 kg/m2, with a diagnosis of diabetes mellitus type 2 (T2DM), and undergoing OAGB with excluded 150 cm of the small intestine.ResultsThere were no deaths in the study group, bleeding during the postoperative period requiring reoperation, anastomotic leakage/leakage throught mechanical stitching. The mean a glycated haemoglobin (HbA1C) level 12 months after surgery was 6.16 ± 0.96%, corresponding to a 2.29 ± 3.3% decrease. In more than 85% of the patients taking insulin before surgery, the insulin was discontinued in the postoperative period. Additionally, the level of glycaemia was assessed in patients on the day of surgery (163 ± 58 mg/dl) and on the day of discharge from the hospital (4.7 ± 1.3 days)—it was lower by over 18% (133 ± 39.2 mg). Over the period of 12 months following OAGB, there was a reduction in the mean BMI value from 33.5 ± 2 to 25.5 ± 2.5 kg/m2 and improvement in lipid parameters and mean values of blood pressure.ConclusionOAGB with excluded 150 cm of the small intestine has beneficial effect on the remission of T2DM in patients with a BMI of 30–35kg/m2 and is associated with an acceptable level of complications. The achieved weight loss after surgery is satisfactory.

“Study of association of serum lipid profile, IL-6, &amp; ADMA levels with subclinical hypothyroidism”

Background &amp; Objectives: Subclinical hypothyroidism (SCH) represents the mildest form of thyroid hormone deficiency and may be associated with adverse consequences. SCH is defined as an elevated serum thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) level with normal levels of free thyroxine (FT4) that affects up to 10% of the adult population. The identification of patients with subclinical hypothyroidism having an increased cardiovascular risk is of great importance in the present era. The aim of the study was to evaluate cardiovascular risk factors in patients with subclinical hypothyroidism. Methods: 120 patients with subclinical hypothyroidism and 120 age and gender matched healthy euthyroid controls in the age group of 18-70 years were included in the study. Body mass index (BMI), lipid profile, and levels of serum biomarkers were estimated in both the groups and further compared using student t-test. Lipid profile was also correlated with the serum ADMA &amp; IL-6 and the results were analyzed using Pearson’s correlation coefficient. Results: Patients with subclinical hypothyroidism had significantly higher levels of serum TSH, IL-6 and ADMA. Similarly, serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly increased and HDL-C was significantly decreased in SCH patients when compared to the same parameters of controls (p&lt;0.001). Significant positive correlations were found among lipid profile and serum IL-6 &amp; ADMA. Conclusions: The present study concluded that the SCH patients presented increased concentrations of cardiovascular disease (CVD) risk factors viz. IL-6, ADMA &amp; lipid profile. The potential benefits of diagnosis and treatment of subclinical hypothyroidism may have possible advantages firstly by preventing the progression to overt hypothyroidism and secondly decrease the risk of death from cardiovascular disease by starting appropriate therapy to improve lipid parameters.

PS-C05-4: EFFECT OF EVOLOCUMAB ON CAROTID MAXIMUM INTIMA-MEDIA THICKNESS IN PATIENTS UNDERGOING STATIN THERAPY

Background: This study investigated the effect of evolocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, on carotid maximum intima media thickness (IMT), an established surrogate marker of atherosclerosis, in patients taking statins with and without renal impairment (estimated glomerular filtration rate (eGFR) &lt; 60 ml/min/1.73 m2). Methods: The annual change in carotid maximum IMT before and after administration of evolocumab was retrospectively analyzed in 229 statin treated patients (148 men and 81 women; mean age: 72.6 ± 8.6 years). The annual change in carotid maximum IMT was compared between patients with and without renal impairment (n = 73; mean eGFR 48.8 ± 8.3 ml/min/1.73 m2 vs. n = 156; mean eGFR 77.1 ± 11.9 ml/min/1.73 m2). The changes in lipid parameters were also evaluated. Results: Evolocumab significantly reduced the progression rate of carotid maximum IMT in whole patients (0.17 ± 0.38 mm/year to 0.08 ± 0.47 mm/year, p &lt; 0.005). Evolocumab significantly reduced the progression rate of carotid maximum IMT in patients without renal impairment (0.18 ± 0.39 mm/year to 0.08 ± 0.46 mm/year, p &lt; 0.05) but did not in patients with renal impairment (0.15 ± 0.36 mm/year to 0.06 ± 0.50 mm/year, p = 0.12). However, it significantly reduced total cholesterol, low density lipoprotein cholesterol, triglyceride, and lipoprotein (a), and increased high density lipoprotein cholesterol in both patients with and without renal impairment. Conclusion: Evolocumab attenuated the progression of carotid maximum IMT in patients undergoing statin therapy without renal impairment but not in patients with renal impairment. However, it improved lipid parameters in both patients with and without renal impairment. These results suggest that evolocumab protects against carotid atherosclerosis in only patients undergoing statin therapy without renal impairment.

Highland barley improves lipid metabolism, liver injury, antioxidant capacities and liver functions in high-fat/cholesterol diet mice based on gut microbiota and LC-MS metabonomics

Highland barley (HB) possesses a series of properties such as regulating lipid metabolism and attenuating liver injury. Our study aimed to investigate the effect of HB, highland barley bran (HBB), whole grain highland barley (WGHB) on lipid metabolism, liver inflammation, gut microbiota and metabolite profiles in high-fat/cholesterol (HFCD) diet mice. 5 treatment groups were fed a normal control diet or a HFCD with or without HB supplementation for 10 weeks. The results showed that HB especially HBB significantly improved lipid parameters, liver function and injury and blood glucose indexes related to hyperlipidemia compared with HFCD group. In addition, HBB recovered the disorder of gut microbiota by increasing Bacteroidetes/Firmicutes ratio and Lactobacillus and Allobaculum abundances, and decreasing Proteobacteria abundance related to lipid metabolism bacteria. HBB enhanced the levels of 6 short chain fatty acids induced by HFCD. Fecal metabolomics analysis showed that the important differential metabolites between HBB group and HFCD group were deoxycholic acid, myclobutanil and cis-4-Hydroxy-D-proline, and the important differential metabolic pathways were arachidonic acid metabolism, tyrosine metabolism and bile secretion. Results suggested that HBB was an effective dietary intervention candidate to ameliorate hyperlipidemia.

Paediatric patients with heterozygous familial hypercholesterolaemia treated with evolocumab for 80 weeks (HAUSER-OLE): a single-arm, multicentre, open-label extension of HAUSER-RCT

The HAUSER-RCT study showed that 24 weeks of evolocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in paediatric patients with heterozygous familial hypercholesterolaemia was safe and improved lipid parameters compared to placebo. Here, we aimed to evaluate the safety and efficacy of evolocumab in this population for an additional 80 weeks. HAUSER-OLE was an 80-week, single-arm, open-label extension of HAUSER-RCT, a randomised controlled trial, and was conducted at 46 centres in 23 countries. Paediatric patients aged 10-17 years with heterozygous familial hypercholesterolaemia who completed 24 weeks of monthly treatment with subcutaneously administered placebo or 420 mg evolocumab in HAUSER-RCT with no serious treatment-emergent adverse events were eligible to enrol in HAUSER-OLE. All patients received open-label subcutaneous evolocumab 420 mg monthly with background statins with or without ezetimibe for 80 additional weeks. The primary endpoint was treatment-emergent adverse events. Efficacy was evaluated by changes in lipids from the baseline of HAUSER-RCT to the end of HAUSER-OLE (104 weeks). This study is registered with ClinicalTrials.gov (NCT02624869) and is now completed. Between Sept 10, 2016, and Nov 25, 2019, 157 patients were enrolled in HAUSER-RCT and received randomised treatment; 150 continued to HAUSER-OLE, received evolocumab treatment, and were included in the full analysis set, presented here. 146 (97%) of 150 patients completed the open-label extension. The incidence of treatment-emergent adverse events in HAUSER-OLE was 70% (105 of 150). Overall, the most common treatment-emergent adverse events were nasopharyngitis (22 [15%] of 150), headache (14 [9%]), and influenza-like illness (13 [9%]). Serious treatment-emergent adverse events occurred in four (3%) of 150 patients (perforated appendicitis and peritonitis, wrist fracture, anorexia nervosa, and headache); none was considered related to evolocumab. No treatment-emergent adverse events led to treatment discontinuation. At week 80, the mean percentage change from baseline in LDL cholesterol was -35·3% (SD 28·0). After 80 weeks of treatment, evolocumab was safe, well tolerated, and led to sustained reductions in LDL cholesterol in paediatric patients with heterozygous familial hypercholesterolaemia. When lipid goals cannot be achieved with conventional treatments, evolocumab is an effective add-on therapy in paediatric patients. Amgen. For the French, Spanish, Spanish, Portuguese, Italian and Dutch translations of the abstract see Supplementary Materials section.

Rosuvastatin Slows Progression of Carotid Intima-Media Thickness: The METEOR-China Randomized Controlled Study.

Background:Atherosclerosis is the leading cause of cardiovascular disease worldwide, including in China. Primary prevention, through lipid-lowering, could avert development of atherosclerosis. Carotid intima-media thickness (CIMT) is a well-validated measure of atherosclerosis used in intervention studies as the primary outcome and alternative end point for cardiovascular disease events.Methods:This randomized, double-blind, placebo-controlled, multicenter, parallel-group study assessed the effects of rosuvastatin 20 mg/d compared with placebo on progression of CIMT over 104 weeks in Chinese people with subclinical atherosclerosis. The primary end point was the annualized rate of change in mean of the maximum CIMT measurements taken 7× over the study period from each of 12 carotid artery sites (near and far walls of the right and left common carotid artery, carotid bulb, and internal carotid artery). Secondary end points included CIMT changes at different artery sites and lipid-parameter changes. Safety was also assessed.Results:Participants were randomized (1:1) to receive rosuvastatin (n=272) or placebo (n=271). Baseline characteristics were well balanced between groups. The change in mean of the maximum CIMT of the 12 carotid sites was 0.0038 mm/y (95% CI, −0.0023–0.0100) for the rosuvastatin group versus 0.0142 mm/y (95% CI, 0.0080–0.0204) for the placebo group, with a difference of −0.0103 mm/y (95% CI, −0.0191 to −0.0016; P=0.020). For the CIMT secondary end points, the results were generally consistent with the primary end point. There were clinically relevant improvements in lipid parameters with rosuvastatin. We observed an adverse-event profile consistent with the known safety profile of rosuvastatin.Conclusions:Rosuvastatin 20 mg/d significantly reduced the progression of CIMT over 2 years in Chinese adults with subclinical atherosclerosis and was well tolerated.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02546323.

Changes of Peripheral Th17 Cells Subset in Overweight and Obese Children After Body Weight Reduction.

BackgroundObesity has been a growing problem in young patients leading to serious metabolic complications. There are many studies supporting the idea, that obesity should be considered as a chronic inflammation closely associated with immune system alterations. Th17 subpopulation is strongly involved in this process. The aim of our study was to evaluate circulating Th17 cells in overweight and obese children and explore the relationships between Th17 subset and metabolic parameters.MethodsWe evaluated peripheral Th17 cells in fresh peripheral blood samples from 27 overweight and obese and 15 normal-weight children. Th17 cells were identified by flow cytometry using monoclonal antibody and intracellular IL-17A staining. Th17 cells were defined as CD3+CD4+CD196+IL-17Aic+. The analysis involved anthropometric and metabolic parameters measured at baseline and three months after the change of lifestyle and diet. We evaluated the relationship between metabolic parameters and Th17 cells.ResultsIn overweight and obese children we found significantly higher Th17 cells percentage compared to normal weight controls (median 0.097% (0.044 - 0.289) vs 0.041% (0.023 - 0.099), p = 0.048). The percentage of Th17 cells decreased statistically significantly in children who reduced weight after the intervention (0.210% (0.143 - 0.315) vs 0.039% (0.028 - 0.106), p = 0.004). In this group we also noticed statistically significant reduction of TC and LDL-C concentration (p = 0.01, p = 0.04, respectively).ConclusionsObesity in children is associated with increased percentage of peripheral Th17 cells. Weight reduction leads to significant decrease of circulating Th17 cells and improvement of lipid parameters. This significant reduction of proinflammatory Th17 cells is a promising finding suggesting that obesity-induced inflammation in children could be relatively easily reversible.

Identification of different lipoprotein response types in people following a Mediterranean diet pattern with and without whole eggs

A Mediterranean (MED) diet decreases atherogenic lipoproteins and cardiovascular disease risk. We tested the hypothesis that daily consumption of whole eggs in a MED diet improves lipid metabolism compared with responses of both a control American diet and a MED diet without whole eggs. Thirty-nine overweight to obese participants were recruited into a randomized, crossover designed, controlled feeding trial evaluating 3 diets: a control, average American diet (AAD), a MED diet without whole eggs (MED-E), and a MED diet plus whole fresh eggs (1 whole egg/1000 kcal; MED+E). Treatments lasted 4 weeks followed by a >4-week washout period. Lipid concentrations, lipoprotein particle size, and number were determined at baseline and posttreatment. Intake of the AAD and MED-E decreased total cholesterol and low-density lipoprotein (LDL) concentrations (change from baseline, P < .05), without a treatment effect. Similarly, MED-E reduced (change from baseline, P < .05) triglyceride concentrations, without a treatment effect. Particle concentrations were reduced for intermediate-density lipoprotein (IDL; 26%, P < .05) and total LDL (8%, P < .05) by MED-E intake only. Very low-density lipoprotein size was reduced by MED-E intake (treatment effect, P = .04). Variability in responses, assessed by unsupervised machine learning, identified 3 main clusters of IDL- and LDL-type responses. Adoption of a MED diet meal plan without whole eggs improved lipid parameters associated with reduced cardiovascular disease risk. Significant treatment differences following inclusion of whole eggs were not observed. Individual differences in lipoprotein responses warrants further exploration.

Very Low-Calorie Ketogenic Diet: A Potential Application in the Treatment of Hypercortisolism Comorbidities.

A very low-calorie ketogenic diet (VLCKD) is characterized by low daily caloric intake (less than 800 kcal/day), low carbohydrate intake (<50 g/day) and normoproteic (1–1.5 g of protein/kg of ideal body weight) contents. It induces a significant weight loss and an improvement in lipid parameters, blood pressure, glycaemic indices and insulin sensitivity in patients with obesity and type 2 diabetes mellitus. Cushing’s syndrome (CS) is characterized by an endogenous or exogenous excess of glucocorticoids and shows many comorbidities including cardiovascular disease, obesity, type 2 diabetes mellitus and lipid disorders. The aim of this speculative review is to provide an overview on nutrition in hypercortisolism and analyse the potential use of a VLCKD for the treatment of CS comorbidities, analysing the molecular mechanisms of ketogenesis.

90-LB: Characterization of Tirzepatide-Treated patients achieving HbA1c &amp;lt;5.7% in the SURPASS 1-4 Trials

Tirzepatide, a novel dual GIP/GLP-1 receptor agonist, demonstrated clinically meaningful improvements in glycemic control with 23% to 62% of patients achieving a normal HbA1c (&amp;lt;5.7%) at the primary endpoints in addition to robust weight loss in adults with type 2 diabetes (T2D) in the SURPASS program. Herein we report results from exploratory analyses to better characterize subsets of tirzepatide-treated patients who achieved different HbA1c targets (&amp;lt;5.7%, 5.7-6.5%, or &amp;gt;6.5%) in the SURPASS 1-4 clinical trials. Baseline characteristics and change from baseline to Week 40 for several efficacy parameters were analyzed for compliant patients (≥75% doses received) , on treatment without rescue medication. Background medication at baseline included metformin only (63%) , combination of oral antidiabetic medication (OAM) (26%) , and no treatment (9%) . Those achieving HbA1c &amp;lt;5.7% were noted to be slightly younger, with shorter duration of T2D, and lower HbA1c at baseline. Furthermore, greater reductions in HbA1c, FSG, BW, BMI, waist circumference, BP, liver enzymes as well as greater improvement in lipid parameters were observed at Week 40 in the HbA1c &amp;lt;5.7% subset (Table) . In conclusion, patients who achieved HbA1c &amp;lt;5.7% showed greater improvements in several biomarkers which may be associated with a reduced risk of long-term cardiometabolic complications. Disclosure J. Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck &amp; Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. S. Del prato: Advisory Panel; Applied Therapeutics, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Consultant; Menarini Group, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker’s Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Sanofi, Stock/Shareholder; Novo Nordisk A/S. D. R. Franco: Advisory Panel; Abbott Diabetes, Medtronic, Novo Nordisk, Sanofi, Research Support; Eli Lilly and Company, Speaker’s Bureau; Abbott Diabetes, AstraZeneca, Medtronic, Roche Diabetes Care, Sanofi. L. A. Vázquez: Advisory Panel; Eli Lilly and Company, Research Support; Eli Lilly and Company, Novo Nordisk, Speaker’s Bureau; Eli Lilly and Company, Novo Nordisk, Stock/Shareholder; Eli Lilly and Company. B. Dai: None. G. J. Weerakkody: None. L. Fernandez lando: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Á. Rodríguez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. B. Bergman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company