Decreased HDL Cholesterol Research Articles

Current Perspectives of Diabetic Dyslipidemia and Treatment Modalities.

Diabetes mellitus is associated with an increased risk of atherosclerosis related to dyslipidemia. Although the terms hyperlipidemia and Diabetes Mellitus [DM] or diabetic dyslipidemia are interrelated to each other, these two conditions have some differences. This study aimed to highlight possible mechanisms of hyperlipidemia and/or dyslipidemia in diabetic patients, which can be treated with available and newer hypolipidemic drugs. We also re-checked current specific guidelines and their recommendations on the management of patients with diabetic dyslipidemia. Comprehensive search of peer-reviewed journals was performed based on a wide range of keywords, including diabetes mellitus, dyslipidemia, hyperlipidemia, insulin resistance, free-fatty acids, cardiovascular disease, SCORE-2 calculation, statins, PCSK-9 inhibitors, and fibrates. Diabetic patients with dyslipidemia, including decreased HDL cholesterol, a predominance of small dense LDL particles, and increased triglyceride levels, are more prone to suffering from micro and macrovascular complications regardless of plasma fasting glucose levels. Recent guidelines suggested using the validated scoring system called SCORE2-Diabetes. Moderate to high dosages of statins, aiming for LDL cholesterol reduction, is still the cornerstone in the management of diabetic patients with dyslipidemia. Nowadays, other recommended non-statin drugs, including proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors or other novel therapeutic agents [bempedoic acid, inclisiran], are particularly important and given place in recently published guidelines. The risk of developing atherosclerotic cardiovascular diseases in people with DM is relatively higher than in patients' without DM. Optimal management of lipid parameters and achieving desired target values in lipid parameters are still a challenging issue for clinicians.

Indole derivatives and their associated microbial genera are associated with the 1-year changes in cardiometabolic risk markers in Chinese adults

BackgroundAlthough emerging evidence suggests that indole derivatives, microbial metabolites of tryptophan, may improve cardiometabolic health, the effective metabolites remain unclear. Also, the gut microbiota that involved in producing indole derivatives are less studied. We identified microbial taxa that can predict serum concentrations of the key indole metabolite indole-3-propionic acid (IPA) at population level and investigated the associations of indole derivatives and IPA-predicting microbial genera with cardiometabolic risk markers.MethodsIn a cohort of 318 community-dwelling adults, serum indole metabolites and fecal microbiota (16S ribosomal RNA) were measured at baseline. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose were repeatedly measured at baseline and again after 1 year. Brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) were measured after 1 year. The association between indole derivatives and the 1-year changes in blood lipids and glucose, and association of indole derivatives with baPWV and ABI were investigated using linear regression models.ResultsEach 1 µmol/L increase in indole-3-acetic acid (IAA) levels was associated with 5.08% (P = 0.046) decrease in LDL-C. IPA levels were inversely associated with baPWV (percentage difference = -1.32%, P = 0.036). Per 1 µmol/L increase in Indole-3-aldehyde (IAld) levels was associated with 1.91% (P = 0.004) decrease in TC and 0.58% (P = 0.019) increase in ABI, but 1.79% decrease in HDL-C with borderline significance (P = 0.050). We identified 18 bacterial genera whose relative abundance was positively associated with serum IPA concentrations (PFDR < 0.05) and constructed a microbial score to reflect the overall IPA-producing potential. This score was inversely associated with baPWV (percentage difference = -0.48%, P = 0.007).ConclusionsOur results suggest that IAA, IPA, IAld, and IPA-predicting microbial score are favorably associated with several cardiometabolic risk markers, although IAld may decrease HDL-C levels.

Lipid disturbances induced by psychotropic drugs: clinical and genetic predictors for early worsening of lipid levels and new-onset dyslipidaemia in Swiss psychiatric samples.

Early worsening of plasma lipid levels (EWL; ≥5% change after 1 month) induced by at-risk psychotropic treatments predicts considerable exacerbation of plasma lipid levels and/or dyslipidaemia development in the longer term. We aimed to determine which clinical and genetic risk factors could predict EWL. Predictive values of baseline clinical characteristics and dyslipidaemia-associated single nucleotide polymorphisms (SNPs) on EWL were evaluated in a discovery sample (n = 177) and replicated in two samples from the same cohort (PsyMetab; n1 = 176; n2 = 86). Low baseline levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, and high baseline levels of high-density lipoprotein cholesterol (HDL-C), were risk factors for early increase in total cholesterol (P = 0.002), LDL-C (P = 0.02) and triglycerides (P = 0.0006), and early decrease in HDL-C (P = 0.04). Adding genetic parameters (n = 17, 18, 19 and 16 SNPs for total cholesterol, LDL-C, HDL-C and triglycerides, respectively) improved areas under the curve for early worsening of total cholesterol (from 0.66 to 0.91), LDL-C (from 0.62 to 0.87), triglycerides (from 0.73 to 0.92) and HDL-C (from 0.69 to 0.89) (P ≤ 0.00003 in discovery sample). The additive value of genetics to predict early worsening of LDL-C levels was confirmed in two replication samples (P ≤ 0.004). In the combined sample (n ≥ 203), adding genetics improved the prediction of new-onset dyslipidaemia for total cholesterol, LDL-C and HDL-C (P ≤ 0.04). Clinical and genetic factors contributed to the prediction of EWL and new-onset dyslipidaemia in three samples of patients who started at-risk psychotropic treatments. Future larger studies should be conducted to refine SNP estimates to be integrated into clinically applicable predictive models.

Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and its association with arterial stiffness in adolescents: Results from the EVA4YOU study.

To determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among Western Austrian adolescents and its association with arterial stiffness as a marker of early vascular ageing. In the cross-sectional Early Vascular Ageing in the YOUth study, liver fat content was assessed by controlled attenuation parameter (CAP) using signals acquired by FibroScan (Echosense, Paris, France) in 14- to 19-year-old Austrian adolescents. Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV) and cardiovascular risk factors by a face-to-face interview, physical examination, and fasting blood analyses. Linear regression models and one-way analysis of variance were performed to analyze the association between liver fat content, MASLD and cfPWV. A total of 1292 study participants (65.2% female) aged 17.2 ± 1.3 years were included. MASLD was detected in 62 (4.8%) adolescents. CAP value showed a significant association with cfPWV in the unadjusted model (p < 0.001) but lost its significant influence in the multivariable model after adjusting for sex, age and cardiovascular risk criteria (increased BMI or waist circumference, impaired glucose metabolism, elevated blood pressure, elevated plasma triglycerides, and decreased HDL cholesterol; p = 0.540). In the analysis of variance, a significant increase in cfPWV was observed in adolescents with any of the five cardiovascular risk criteria for MASLD (p < 0.001), but not with the additional presence of steatotic liver disease (p = 0.291). In our adolescent cohort, liver fat content and MASLD were not found to be independent predictors for early vascular ageing. Nevertheless, the determination of liver fat content can be a useful tool to identify adolescents at high risk for cardiovascular disease and metabolic syndrome.

Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes

Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be used as instruments. We included heel bone mineral density and hip fracture risk as positive control outcomes. Public GWAS and UK Biobank patient-level data were used for the study outcomes, which include cardiovascular events, risk factors, and biomarkers. Lower sclerostin levels were associated with higher bone mineral density and 85% reduction in hip fracture risk. However, genetically predicted lower sclerostin levels led to 25–85% excess coronary artery disease risk, 40% to 60% increased risk of type 2 diabetes, and worse cardiovascular biomarkers values, including higher triglycerides, and decreased HDL cholesterol levels. Results also suggest a potential (but borderline) association with increased risk of myocardial infarction. Our study provides genetic evidence of a causal relationship between reduced levels of sclerostin and improved bone health and fracture protection, but increased risk of cardiovascular events and risk factors.

Systematic review and meta-analysis assessing the status of carotid intima–media thickness and lipid profiles in type 2 diabetes mellitus

ObjectivesCarotid intima–media thickness (CIMT) is a measurement for subclinical atherosclerosis and has been associated with overall cardiovascular diseases, especially in type 2 diabetes mellitus (T2DM). We aimed to assess the...

Small hepatitis B virus surface antigen (SHBs) induces dyslipidemia by suppressing apolipoprotein-AII expression through ER stress-mediated modulation of HNF4α and C/EBPγ.

Persistent infection with hepatitis B virus (HBV) often leads to disruptions in lipid metabolism. Apolipoprotein AII (apoAII) plays a crucial role in lipid metabolism and is implicated in various metabolic disorders. However, whether HBV could regulate apoAII and contribute to HBV-related dyslipidemia and the underlying mechanism remain unclear. This study revealed significant reductions in apoAII expression in HBV-expressing cell lines, the serum, and liver tissues of HBV-transgenic mice. The impact of HBV on apoAII is related to small hepatitis B virus surface antigen (SHBs). Overexpression of SHBs decreased apoAII levels in SHBs-expressing hepatoma cells, transgenic mice, and the serum of HBV-infected patients, whereas suppression of SHBs increased apoAII expression. Mechanistic investigations demonstrated that SHBs repressed the apoAII promoter activity through a HNF4α- and C/EBPγ-dependent manner; SHBs simultaneously upregulated C/EBPγ and downregulated HNF4α by inhibiting the PI3K/AKT signaling pathway through activating endoplasmic reticulum (ER) stress. Serum lipid profile assessments revealed notable decreases in high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) in SHBs-transgenic mice compared to control mice. However, concurrent overexpression of apoAII in these mice effectively counteracted these reductions in lipid levels. In HBV patients, SHBs levels were negatively correlated with serum levels of HDL-C, LDL-C, TC, and TG, whereas apoAII levels positively correlated with lipid content. This study underscores that SHBs contributes to dyslipidemia by suppressing the PI3K/AKT pathway via inducing ER stress, leading to altered expression of HNF4α and C/EBPγ, and subsequently reducing apoAII expression.IMPORTANCEThe significance of this study lies in its comprehensive examination of how the hepatitis B virus (HBV), specifically through its small hepatitis B virus surface antigen (SHBs), impacts lipid metabolism-a key aspect often disrupted by chronic HBV infection. By elucidating the role of SHBs in regulating apolipoprotein AII (apoAII), a critical player in lipid processes and associated metabolic disorders, this research provides insights into the molecular pathways contributing to HBV-related dyslipidemia. Discovering that SHBs downregulates apoAII through mechanisms involving the repression of the apoAII promoter via HNF4α and C/EBPγ, and the modulation of the PI3K/AKT signaling pathway via endoplasmic reticulum (ER) stress, adds critical knowledge to HBV pathogenesis. The research also shows an inverse correlation between SHBs expression and key lipid markers in HBV-infected individuals, suggesting that apoAII overexpression could counteract the lipid-altering effects of SHBs, offering new avenues for understanding and managing the metabolic implications of HBV infection.

Dichlorvos evokes systemic lipid dysmetabolism in Wistar rats: rescindment influence of curcumin

Organophosphorus pesticides such as dichlorvos (DDVP) are often employed to eradicate pests, especially in low and medium-income countries. However, they have several negative impacts on the visceral organs. Astonishingly, curcumin protects organs from the detrimental effects of xenobiotics via the maintenance of redox homeostasis; unfortunately, its role in dichlorvos-provoked multi-organ impairment vis-à-vis lipid homeostasis has not been examined. Therefore, this undertaking probed the remedial efficacy of curcumin on DDVP-prompted combined systemic toxicity and major lipid distribution. Randomization was engaged to dedicate rats (40) into seven groups (6 rats/group): control, DDVP only (20 mg kg-1day-1), DDVP administered with either curcumin (50 and 100 mg kg-1day-1) or reference medication atropine (0.2 mg kg-1day-1), and curcumin only (50 and 100 mg kg-1day-1). DDVP was dispensed orally for one week, followed by two weeks of curcumin treatment. Twenty-four hours after the last administration, we sacrificed the rats and collected their blood and viscera (liver, kidney, heart, lung, and brain) for bioassays. Curcumin remarkably (p&lt;0.05) rescinded DDVP-mediated increases in plasma, LDL, and systemic cholesterol; markedly (p&lt;0.05) attenuated DDVP-elicited decreases in HDL-cholesterol and TAG contents in all the compartments except erythrocyte and liver; and significantly (p&lt;0.05) abated DDVP-induced plasma phospholipidaemia, multi-organ phospholipidosis, and up-regulation of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA-R) activity. This finding demonstrated that curcumin reverses DDVP-triggered anomalous lipid dynamics by abating cholesterogenesis and phospholipidosis and restoring HMG-CoA-R activity.

Molecular and serological diagnosis of the circulating Trypanosoma evansi in Egyptian livestock with risk factors assessment

This study aimed to characterize and determine the prevalence and the associated risk factors of trypanosomiasis in different Egyptian livestock from various governorates using molecular and serological techniques, adding to an assessment of some biochemical alterations in serum samples. A total 1019 blood samples were collected from nine governorates in the period from January 2020 to September 2021 from cattle (n = 752), buffaloes (n = 42), sheep (n = 65), goats (n = 60), donkeys (n = 54), and horses (n = 46). Molecular investigation followed by sequencing confirmed the presence of only Trypanosoma evansi (T. evansi) infection with a prevalence rate of 3.73 % (38/1019). Serologically, T. evansi was detected by indirect ELISA in 11 samples out of 519 negative PCR ones, with an overall prevalence 2.1 %. Furthermore, statistical difference was found between investigated governorates in both molecular and seroprevalence. Surprisingly, the risk of T. evansi infection was significantly (P < 0.05) higher in winter (9.83 %) than in autumn (1.4 %), while no infection was recorded in the spring and summer seasons. No significant difference regarding animal hosts, age, and sex as risk factors was recorded. Serum biochemical analysis showed a non-significant decrease of total proteins, albumin, A/G ratio, and HDL-cholesterol in cattle, equine, and goats with a non-significant increase in total globulins level. In sheep, a significant increase was determined in all tested parameters except a significant decrease in the level of albumin and A/G ratio. To the best of our knowledge, this is the first large-scale epidemiological study determining the endemicity of the neglected T. evansi infection in different animal species in multiple governorates of Egypt. It is recommended to use both molecular and serological techniques for efficient diagnosis of trypanosomiasis as a preliminary approach to control the disease.

The dyslipidemic effect of cytostatics in the treatment of early breast cancer as a serious risk factor of cardiovascular diseases.

The development of highly effective anti-cancer therapies over the past several decades has dramatically changed the situation of patients with malignant tumor disease, who currently achieve a high rate of cure in the early stages of the disease. Despite tremendous progress, chemotherapy remains the primary treatment modality for early breast cancer. However, chemotherapy-related complications have a major impact on cardiovascular morbidity and mortality in this group of patients. Almost 80% of women diagnosed with breast cancer are over 50 years of age and already have risk factors for cardiovascular disease, such as age, family history, hypertension, elevated cholesterol, smoking, diabetes, and elevated body mass index. Most breast cancer patients do not die and, in line with the general population, cardiovascular disease remains the most common cause of death. Clinical research, extensive retrospective analyzes and prospective works describe the dyslipidemic effect of cytostatics, which may predispose to the development of atherosclerotic cardiovascular diseases. The administration of neoadjuvant or adjuvant chemotherapy based on anthracyclines and taxanes can lead to an increase in total cholesterol, triacylglycerides, LDL cholesterol and a decrease in HDL cholesterol. Abnormally high concentrations of lipids in the blood represent one of the main risk factors for the development and progression of cardiovascular diseases. The works also indicate a correlation between serum lipid levels and the rate of achieving pathological complete remission after the administration of neoadjuvant chemotherapy. Dyslipidemia is associated with a worse prognosis in breast cancer patients treated with neoadjuvant chemotherapy. The aim of the thesis is to point out the dyslipidemic effects of cytostatics and the risks of atherosclerotic cardiovascular diseases in breast cancer patients who have undergone adjuvant or neoadjuvant chemotherapy for early breast cancer. The identification of cardiovascular risk factors at the beginning of oncological treatment, the monitoring of the lipid spectrum during the treatment and the timely intervention of dyslipidemia treatment escape attention at present.

Retrieval of Normal Sleep for Two Weeks Normalized Adiposity and Minimized Insulin Resistance Induced by 4-Week Insomnia in Aged Female Rats

Abstract Background Insomnia affects the energy metabolism components which may alter the body’s metabolic functions. Sleep disturbances, both quantitative and qualitative, may increase the risk of developing chronic conditions, such as obesity, metabolic disorders, diabetes, and cardiovascular disease. Aim This study was carried out to investigate the effect of insomnia on glucose homeostasis in aged female rats, and to elucidate the possible underlying mechanism(s), as well as the potential metabolic recovery after retrieval to the normal sleep pattern. Methods 60 Sprague Dawley aged female rats were randomly divided into two main groups: Control group (C) and Insomnia group (I). The latter was further subdivided into two subgroups, 10 rats each: Group Iins. which was subjected to insomnia four hours daily, five days /week for 4 weeks, and Group Іins, Rec. that was subjected to insomnia like Iins. group with retrieval to normal sleep for two weeks. Rats in all groups were subjected to estimation of Body weight (BW), Body mass index (BMI) and Waist circumference at the beginning of the study. The intraperitoneal glucose tolerance test (IPGTT) was measured at the beginning of the study and was monitored every two weeks. By the end of fourth week (for groups C and Iins.) &amp; By the end of the sixth week (for group Iins.rec). BW, BMI, Waist circumference, intraperitoneal glucose tolerance test (IPGTT), peak glycemia (PG) and area under the curve (AUC), Fasting blood glucose (FBG), Insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA- IR), Total cholesterol (TC), Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), High density lipoprotein cholesterol (HDL-C), Adiponectin, IL6 and Caspase 3 were estimated. Results After four weeks, Iins. rats exhibited a significantly higher change in BW, BMI, WC, FBG, blood glucose levels at 30 min., 60 min, 90 min., 120 min, PG and AUC of IPGGT, insulin level and HOMA-IR, serum (TGs), (TC), (LDL-C), serum IL6 &amp; caspase3 but showed significant decrease in serum level of (HDL-C) and adiponectin in comparison to C rats, After two week recovery from insomnia, Iins.rec. rats exhibited a significantly lower values of WC, FBG, insulin, HOMA-IR, (TGs), (TC), (LDL-C), serum IL6 &amp; caspase3 with insignificant change in BW, BMI, blood glucose levels at 30 min., 60 min, 90 min., 120 min, PG, AUC of IPGGT &amp; serum (HDL-C) with significantly higher values of adiponectin when compared to Iins.rats, and exhibited insignificant change in BW, BMI, WC, FBG, blood glucose levels at 60 min. and at 90 min, (TC), (LDL-C) and adiponectin with significantly higher values of blood glucose levels at 30 min., 120 min, PG and AUC of IPGGT insulin level, HOMA-IR, serum (TGs), serum IL6 &amp; caspase3 with significantly lower values serum (HDL-C) in comparison to the C rats. Conclusion Four-week insomnia in aged female rats resulted in increased blood glucose, insulin resistance, dyslipidemia and enhanced inflammatory and apoptotic states. Retrieval of normal sleep for two weeks normalized body adiposity, fasting blood glucose, total cholesterol and LDL-C and minimized the insulin resistance, hypertriglyceridemia and the decrease in HDL-C as well as inflammation and apoptosis.

Association Between Diet, Physical Activity, Smoking, and Ultra-Processed Food and Cardiovascular Health, Depression, and Sleep Quality.

This study evaluated cardiovascular health, dietary habits, physical activity, depression, and sleep quality in young university adults. A cross-sectional design was used to assess anthropometric, biochemical, and cardiovascular health behaviors. The study included 158 university students aged 18 to 30 years (65% women, 35% men, average age: 20.3 ± 2.4 years), selected through non-probabilistic sampling. Measurements included BMI, waist circumference, blood pressure, glucose, triglycerides, HDL and LDL cholesterol, and visceral fat using bioelectrical impedance. Health behaviors were evaluated via questionnaires on physical activity, fruit and vegetable consumption, smoking, ultra-processed food consumption, and sleep quality using the Pittsburgh Sleep Quality Index. The cardiovascular health index was assessed with the "Life's Essential 8" questionnaire and depression was assessed with Beck Depression Inventory. Statistical analyses included ANOVA, Fisher's F test, Student's t-test, and simple linear regression, conducted using SPSS Statistics version 25.0 (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp), with significance set at p<0.05. Women showed better adherence to healthy behaviors. Higher fruit and vegetable consumption and physical activity were associated with lower visceral fat. Higher visceral fat is correlated with increased blood pressure and decreased HDL cholesterol. Smoking and frequent ultra-processed food consumption were linked to higher depression scores, which were associated with poorer sleep quality. Healthy lifestyle habits are crucial for physical and mental health, providing a basis for public health interventions.

Diet and the Gut Microbiome as Determinants Modulating Metabolic Outcomes in Young Obese Adults.

Obesity, along with metabolic disorders such as dyslipidemia and insulin resistance, increases the risk of cardiovascular disease, diabetes, various cancers, and other non-communicable diseases, thereby contributing to higher mortality rates. The intestinal microbiome plays a crucial role in maintaining homeostasis and influencing human metabolism. This study enrolled 82 young obese individuals, who were stratified into groups with or without metabolic disturbances. No significant differences in the alpha or beta diversity of the microbiota were observed among the groups. Insulin resistance was characterized by an increase in the number of Adlercreutzia and Dialister as well as a decrease in Collinsella, Coprococcus and Clostridiales. The dyslipidemia and dyslipidemia+insulin resistance groups had no significant differences in the gut microbiota. Dietary patterns also influenced microbial composition, with high protein intake increasing Leuconostoc and Akkermansia, and high fiber intake boosting Lactobacillus and Streptococcus. The genus Erwinia was associated with increases in visceral fat and serum glucose as well as a decrease in high-density lipoprotein cholesterol. Our findings highlight a significant association between gut microbiota composition and metabolic disturbances in young obese individuals, and they suggest that dietary modifications may promote a healthy microbiome and reduce the risk of developing metabolic disorders.

Impact of CT-relevant skeletal muscle parameters on post-liver transplantation survival in patients with hepatocellular carcinoma.

The specific CT-related skeletal muscle parameters predictive of postoperative survival in liver transplant (LT) patients with hepatocellular carcinoma (HCC) remain unclear. There is increasing evidence supporting the role of fatty acids and their lipid intermediates in regulating skeletal muscle mass and function, the relationship between lipoprotein subfractions and body composition remains unclear. Adult patients with HCC who underwent LT between January 2015 and September 2022 were retrospectively analyzed. CT parameters, including skeletal muscle index (SMI), psoas muscle index (PMI), skeletal muscle density (SMD), visceral and subcutaneous adipose tissue (VAT and SAT), and the VAT/SAT ratio at the L3 level, and lipid profiles, were assessed prior to LT. Of the 284 LT patients with HCC, 224 underwent CT (L3 level) within 3months of LT, and 82 (37%) were diagnosed with myosteatosis. Patients with myosteatosis exhibited significantly lower 1- and 3-year survival rates (p = 0.002, p = 0.01), a trend persisting even beyond the Milan criteria (p = 0.004, p = 0.04). After adjusting for covariates, SMD demonstrated a significant negative correlation with post-transplant survival (HR: 0.90, [95% Confidence Interval(CI): 0.83-0.98], C-statistic: 0.78, p = 0.009). Pearson's correlation analysis revealed a positive correlation between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(ApoA1) levels and SMD. Multivariate stepwise regression analysis demonstrated that every 10 Hounsfield unit decrease in SMD was associated with a 0.16mmol/L decrease in HDL-C and a 0.18g/L decrease in ApoA1. Routine abdominal CT scans for assessing skeletal muscle density before LT were significantly associated with post-transplant mortality. Furthermore, abnormal HDL-C and ApoA1 levels before LT were associated with myosteatosis.

Investigation of setmelanotide, an MC4R agonist, for obesity in individuals with Smith-Magenis syndrome

BackgroundSmith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS. MethodsPeople with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included hunger, waist circumference, body composition, and safety. Results12 individuals, ages 11–39 y, enrolled and 10 completed the full-dose treatment phase. Mean percent change in body weight at end-treatment was − 0.28 % [(95 % CI, −2.1 % to 1.5 %; n = 12; P = 0.66]. Participants experienced a significant decrease in total cholesterol associated with a significant decrease in HDL-cholesterol and a trend for lower LDL-cholesterol. Self-reported hunger was reduced at end-treatment (p = 0.011). All participants reported adverse events (AEs), most commonly injection-site reactions and skin hyperpigmentation. No AEs led to withdrawal or death. ConclusionsIn this trial, setmelanotide did not significantly reduce body weight in participants with SMS. Participants reported significant differences in hunger, but such self-reports are difficult to interpret without a placebo-treated group. The changes in lipid profiles require further investigation. Results of this study do not suggest that dysfunction of the proximal MC4R pathway is the main etiology for obesity in people with SMS.

The Influence of a High-Cholesterol Diet and Forced Training on Lipid Metabolism and Intestinal Microbiota in Male Wistar Rats.

Adequate experimental animal models play an important role in an objective assessment of the effectiveness of medicines and functional foods enriched with biologically active substances. The aim of our study was a comparative assessment of the effect of consumption of 1 or 2% cholesterol with and without regular (two times a week), moderate running exercise on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. In experimental rats, a response of 39 indicators (body weight, food consumption, serum biomarkers, liver composition, and changes in intestinal microbiota) was revealed. Total serum cholesterol level increased 1.8 times in animals consuming cholesterol with a simultaneous increase in low-density lipoprotein cholesterol (2 times) and decrease in high-density lipoprotein cholesterol (1.3 times) levels compared to the control animals. These animals had 1.3 times increased liver weight, almost 5 times increased triglycerides level, and more than 6 times increased cholesterol content. There was a tendency towards a decrease in triglycerides levels against the background of running exercise. The consumption of cholesterol led to a predominance of the Bacteroides family, due to a decrease in F. prausnitzii (1.2 times) and bifidobacteria (1.3 times), as well as an increase in Escherichia family (1.2 times). The running exercise did not lead to the complete normalization of microbiota.

FEATURES OF LIPID METABOLISM DISORDERS IN INDIVIDUALS WITH GENETIC PREDISPOSITION TO ARTERIAL HYPERTENSION AND PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION

Objective: To determine the peculiarities of lipid metabolism indicators’ changes in healthy individuals with a genetic predisposition to arterial hypertension (AH) and patients with essential arterial hypertension (EAH). Design and method: 231 patients with second stage of EAH (105 men and 126 women; average age was 52.3±1.2 years) were examined. The duration of EAH was 9.7±0.45 years. 121 of them had a concomitant stable coronary artery disease (CAD). The control group included 30 healthy people of similar age and gender. A comparison group consisted of 23 healthy individuals with a AH family history. Additionally to lipid spectrum, levels of lipoprotein (a) (Lp(a)), apolipoprotein B100 (apoB100) and apolipoprotein A-1 (apoA-1) were determined. Statistical calculations were performed using Statistica for Windows 10.0. Results: Patients with genetic predisposition to AH had similar to indicators in patients with II EAH stage proatherogenic changes in lipid fractions. Their Lp(a) levels increased to 29.9 (24.5; 32.1) mg/dl, which is 67.0% higher than the levels in the control group (p=0.0005). Levels of apolipoproteins (apoB100 and apoA1) in the serum of healthy persons with AH predisposition did not differ from the control group. Patients with stage II EAH showed an increase in proatherogenic fractions of lipoproteins, apoB100, Lp(a), and a decrease in high-density lipoprotein cholesterol (HDL-C) and apoA-1 compared to control (p&lt;0.0001). Analysis of lipid indicators in patients with concomitant CAD compared to patients without CAD revealed no significant differences between these two groups, except of increasing in the Lp(a) level by 24.4% (p&lt;0.05). A significant positive correlations were found between the Lp(a) level with both the sum of scores on the SCORE scale and the CAD presence (r=0.25 and r=0.35, p=0.002), respectively. Conclusions: The lipid metabolism disorders in people with determinism for AH begin even before an increase in blood pressure and are genetically determined. The addition of hypertension contributes to the further progression of lipid metabolism disorders. The obtained data indicate the high prognostic significance of Lp(a) in patients with EAH in the development and establishment of both hypertension itself and CAD and increasing of patients’ cardiovascular risk.

AN AYURVEDIC METHODOLOGY FOR MANAGING DIABETIC DYSLIPIDEMIA - A CASE REPORT

Diabetic dyslipidemia is characterized by elevated plasma triglyceride levels, decreased HDL cholesterol levels, and an increase in small dense LDL-cholesterol particles. These lipid alterations in diabetes are linked to heightened free fatty acid flux due to insulin resistance. With the availability of various lipid-lowering medications and supplements, patients now have more options to reach target lipid levels. Lipid-lowering therapies in modern medicine, such as statins and fibrates, are generally well-tolerated with minimal side effects. However, these treatments often necessitate lifelong usage, which can impose significant financial strain, particularly in developing countries like India.In Ayurveda, dyslipidemia is understood as the manifestation of an imbalance in the Medovahasrotas.Dyslipidemia manifests as the consequent output of Medovahasrotodushti. A 31-year-old male patient presented with complaints of pain in calf muscles and weight gain. Upon investigation, his total cholesterol level was found to be elevated at 211 mg/dl, and triglycerides were elevated to 683.80 mg/dl. Giloykwath along with arjunkwath, Madhunashinivati extra power, Tablet lipidom, and Tablet Madhugrit were administered for the shaman therapy. Upon completion of the treatment, significant improvements were observed in the patients complaints. Additionally, a significant improvement was noted in the Lipid Profile.

Alterations in Alanine Transaminase, Aspartate Transaminase, Gamma-Glutamyl Transpeptidase, and Creatine Kinase in Acne Patients Undergoing Isotretinoin Treatment: A Retrospective Evaluation of Laboratory Tests.

Background Isotretinoin therapy is a commonly prescribed medication by dermatologists for the treatment of acne. Regular laboratory assessments are recommended throughout the treatment period to detect any potential complications. Objectives This study aims to present the alterations in laboratory parameters throughout the course of isotretinoin therapy and identify required diagnostic testing. Methods This study involved 136 patients undergoing isotretinoin treatment at doses of 0.3-0.5 mg/kg/day, with ages ranging from 18 to 41 years. A retrospective evaluation was conducted on biomarkers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), creatine kinase (CK), triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hemoglobin, white blood cells, and thrombocytes. Levels of these parameters were analyzed prior to treatment and at the third month of treatment from the records of patients and the data were compared statistically. Moreover, the parameters of ALT, AST, CK, and GGT were graded objectively, and any alterations were noted in the patients. Results The levels of ALT, AST and GGT, along with triglycerides, total cholesterol, LDL-C, and thrombocyte levels showed significant elevation (p=0.001, p<0.001, p<0.001, p=0.001, p<0.001, p<0.001, and p=0.003, respectively). A significant decrease in HDL-C with hemoglobin was also noted (p=0.022, p=0.006, respectively). One patient (0.73%) exhibited grade 1 elevations in ALT, AST, and CK. One patient (0.73%) displayed grade 1 elevations in ALT and AST. One patient (0.73%) exhibited grade 1 elevations in AST and CK, while another patient (0.73%) had grade 1 elevationin AST and grade 3 elevationin CK. Furthermore, one patient (0.73%) had a grade 1 elevation exclusively in ALT, two patients (1.47%) had a grade 1 elevation exclusively in AST, and six patients (4.41%) exhibited a grade 1 elevation in CK only. No grade changes were observed in the GGT levels in the patients. Conclusion During isotretinoin treatment, changes in ALT and AST levels were more frequently associated with the muscle enzyme CK, while GGT levels remained unaffected. Therefore, GGT can be considered a reliable parameter for evaluating liver function in patients undergoing isotretinoin treatment.

High Growth Differentiation Factor-15 (GDF-15) in Rheumatoid Arthritis Patients Potential Risk for Cardiovascular Disease

Rheumatoid arthritis (RA) is a chronic autoimmune disorder primarily affecting joints, leading to pain, stiffness, and functional disability. The inflammatory mechanisms underlying RA also impact various organ systems, with significant implications for morbidity and mortality. In this study, we analyzed the growth differentiation factor-15 (GDF-15), a cytokine implicated in inflammation and associated with RA and cardiovascular diseases. We conducted a case-control study involving 150 RA patients and 150 healthy individuals, assessing various biomarkers (ACPA, CRP, ESR, and RF) including GDF-15, lipid profile, and inflammatory markers. Our results demonstrated significantly elevated levels of GDF-15 in RA patients (309.44 pg/ml) compared to controls (64.40 pg/ml), indicating its potential role as a biomarker for RA and cardiovascular risk (p&lt;0.001). Furthermore, RA patients exhibited dyslipidemia characterized by elevated total cholesterol, triglycerides, LDL cholesterol, and atherogenic indices, along with decreased HDL cholesterol levels, predisposing them to a higher risk of atherosclerosis and cardiovascular complications (p&lt;0.001). Correlation analyses revealed associations between GDF-15 levels, lipid profile parameters, and disease severity markers, highlighting the intricate interplay between inflammation, lipid metabolism, and RA progression. These findings demonstrated the importance of early detection and management of dyslipidemia in RA patients to mitigate cardiovascular risk. Overall, our study contributes to understanding the pathophysiology of RA and identifies potential biomarkers for disease monitoring and risk stratification.