Changes In Lipid Levels Research Articles

Characterizing Lipid Changes and Use of Lipid-Lowering Medications in Patients With Alopecia Areata Treated With Baricitinib: Integrated Results From the BRAVE-AA1 and -AA2 Clinical Trials

Introduction. Elevations in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) can occur with baricitinib treatment, consistent with a class effect of JAK inhibitors. In this analysis, we characterized changes in lipid levels and use of lipid-lowering medication among patients with severe alopecia areata (AA) treated with baricitinib through 152-weeks of treatment. Methods. Two integrated datasets from the BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) trials were analyzed: 1. Extended BARI AA includes patients treated with continuous baricitinib 2 mg (N=383) and 4 mg (N=565) from baseline and censored at dose change: 2. ALL BARI AA (N=1303) includes data for patients who received ≥1 dose of baricitinib at any time. Outcomes included abnormal changes in lipid parameters, mean change from baseline in lipids, and concomitant use of lipid-lowering medications. Results. At time of enrollment, 43% of patients had hypercholesterolemia. Incidence rates for categorical increases in total cholesterol (TC; ≥240mg/dL), LDL-C (≥130 mg/dL), and HDL-C (>60 mg/dL) were 11.8, 13.3, and 12.9 per 100 patients-years of exposure, respectively in the ALL BARI AA dataset. In the Extended BARI AA the mean maximal increase in lipids (mg/dL) for baricitinib 4 mg was 20.9 for TC, 12.4 for LDL-C, and 8.5 for HDL-C. Changes occurred early and stabilized by one year for TC and LDL-C and by 12 weeks for HDL-C. 6.1% (n=79) of patients in the ALL BARI AA dataset used lipid-lowering medication at baseline; post-baseline, 3.9% (n=51) discontinued this medication and 4.7% (n=61) initiated lipid lowering medication. No patients discontinued baricitinib treatment due to treatment-emergent adverse events related to hyperlipidemia. Conclusions. Elevations in TC, LDL-C, and HDL-C, but not triglycerides were associated with baricitinib treatment in patients with AA, consistent with a class effect of JAK inhibitors. The relatively low use of lipid-lowering medications at baseline despite the prevalence of hypercholesterolemia may reflect undermanagement of this condition in the population. Notably, the mean maximal magnitude of increase in lipid levels on baricitinib was modest. Initiation of lipid-lowering medication was infrequent, and no patients discontinued due to lipid abnormalities.

Impact of fruits and vegetables consumption on metabolic health: a case–control study

Abstract Background According to the World Health Organization (WHO), it is recommended to consume more than 400 grams of (fruits + vegetables) per day to enhance healthful lifestyle and to lower the incidence of metabolic illnesses. Their low glycemic index helps prevent spikes in blood sugar, consequently controlling hunger. Our aim was to study the reflection of the intake of fruits and that of vegetables on metabolic risks in obese children. Results A case–control research enrolled 90 Egyptian children (44 obese and 46 normal weight control children) aged from 5 to 11 years. Thirty-three out of 46 controls (71.7%) consumed vegetables on a daily basis compared to only 27 (61.4%) among cases. As regards fruits, the daily consumption was frequented more among the obese group 25 (58.1%) and less frequented among the control group 20 (43.5%). No significant associations were found between vegetables/fruits’ consumption and the specified metabolic markers of dyslipidemia and hyperglycemia. Conclusion The role of fruits and vegetables is still debatable. In our study, the daily intake of fruits and vegetables was not significantly associated with changes in blood sugar or lipid levels.

Blood lipid profiles associated with metastatic sites in advanced gastric cancer

BackgroundThis study explored the correlation between peripheral blood lipid levels and clinicopathological parameters in patients with advanced gastric cancer (GC), focusing on changes in lipid levels during disease progression.MethodsPathological features and serum lipid profiles of 179 patients with stage III-IV gastric adenocarcinoma were analyzed. Lipid parameters examined included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein AI (Apo AI), apolipoprotein B (Apo B), lipoprotein(a) (Lp(a)), among others. The total cholesterol-lymphocyte score (TL score) and BMI were also calculated. The association between lipid parameters and clinicopathological characteristics such as age, gender, family history, and metastasis sites was assessed.ResultsIn GC patients, females had higher TG levels than males. Patients with peritoneal metastasis had significantly lower levels of TC, LDL-C, Apo B, and B/A ratio. Those with lung metastasis exhibited higher LDL-C levels and lower levels of VLDL-C. No significant associations were found between lipid levels and metastasis to distant lymph nodes, liver, or bone. Female patients with ovarian metastasis had significantly lower VLDL-C levels. Multivariate analysis revealed low TC as an independent risk factor for peritoneal metastasis, high LDL-C and low VLDL-C levels for lung metastasis, and younger age and low VLDL-C for ovarian metastasis.ConclusionSpecific blood lipid levels are significantly associated with metastatic sites in advanced gastric cancer. Lipid profiles could serve as potential biomarkers for predicting metastatic sites in GC patients.

A Graphene-Based Lipid Modulation Nanoplatform for Synergetic Lipid Starvation/Chemo/Photothermal Therapy of Oral Squamous Cell Carcinoma.

Chemotherapy is one of the most commonly used treatments for oral squamous cell carcinoma (OSCC), but its use is limited by drug resistance and severe systemic toxicity. To eliminate these side effects and improve anti-tumor efficacy, several therapeutic approaches have been developed for use with chemotherapy. In this study, we developed a graphene-based lipid modulation nanoplatform (NSD) that carries SB-204990, a small molecule inhibitor specific for ATP citrate lyase (ACLY), and doxorubicin (DOX), a chemotherapeutic agent, and the trio enables synergistic treatment of OSCC with lipid starvation, chemotherapy, and photothermal therapy. We first determined whether ACLY expression was upregulated in OSCC, and then assessed the growth inhibitory effects of SB-204990 on SCC-15 cells and changes in lipid (acetyl coenzyme A, free fatty acids, and cholesterol) levels. We characterized NSD and then evaluated the stability, photothermal properties, drug loading, and release ability of NSD. Finally, the therapeutic effects of NSD on OSCC were investigated by in vitro and in vivo experiments, and the changes in lipid levels in OSCC tissues after ACLY inhibition were further evaluated. The results showed that ACLY was highly expressed in OSCC, and ACLY inhibition produced reproductive suppression and decreased lipid levels in SCC-15 cells. The NSD nanoplatform possessed good stability, photothermal properties, high drug loading capacity and controlled release. In addition, the triple therapy achieved satisfactory anticancer effects in both in vivo and in vitro assays, and the inhibition rate of tumors was as high as 99.4% in the NSD+Laser treatment group. The changes in tumor cell lipid levels and cell proliferation arrest induced by ACLY inhibition suggest that ACLY may be a promising target for lipid starvation therapy and resistance to chemoresistance, and its inhibitors are expected to become new anticancer drugs. The NSD nanocarrier system enables synergistic treatment with lipid starvation, chemotherapy, and photothermal therapy, which represents an innovative approach to combating tumors.

Efficacy and acceptability of lurasidone for bipolar depression: a systematic review and dose–response meta-analysis

Question The optimal dose of lurasidone for bipolar depression is unclear. This study examined its dose–response relationship for efficacy, acceptability, and metabolic/endocrine profiles. Study selection and analysis Five databases and grey literature published until 1 August 2024, were systematically reviewed. The outcomes included efficacy (changes in depression, anxiety, clinical global impression, disability and quality of life), acceptability (dropout, manic switch, suicidality and side effects) and metabolic/endocrine profiles (changes in body weight, glucose, lipid and prolactin levels). Effect sizes were calculated using a one-step dose–response meta-analysis, expressed as standardised mean differences (SMDs), risk ratios (RRs) and mean differences (MDs) with 95% CIs. Findings Five randomised clinical trials (2032 patients, mean treatment duration 6 weeks) indicated that the optimal therapeutic dose of lurasidone (40–60 mg) improved depression (50 mg: SMD −0.60 (95% CI −0.30, –0.89)), anxiety (50 mg: −0.32 (95% CI −0.21, –0.42)), clinical global impression (50 mg: −0.67 (95% CI −0.30, –1.03)) and disability (50 mg: −0.38 (95% CI −0.08, –0.69)). Side effects increased with higher doses (50 mg: RR 1.15 (95% CI 1.05, 1.25); 100 mg: 1.18 (95% CI 1.02, 1.36)), but dropout, manic switch and suicidality did not show a dose–effect relationship. Weight increased at doses<60 mg (40 mg: MD 0.38 (95% CI 0.16, 0.60) kg), while blood glucose levels rose at doses>70 mg (100 mg: 3.16 (95% CI 0.76, 5.57) mg/dL). Prolactin levels increased in both males (50 mg: 3.21 (95% CI 1.59, 4.84) ng/mL; 100 mg: 5.61 (95% CI 2.42, 8.81)) and females (50 mg: 6.64 (95% CI 3.50, 9.78); 100 mg: 5.33 (95% CI 0.67, 10.00)). Conclusions A daily dose of 40–60 mg of lurasidone is a reasonable choice for bipolar depression treatment. Trial registration number INPLASY202430069.

Low-carbohydrate diet proved effective and safe for youths with type 1 diabetes: A randomised trial.

Low-carbohydrate (LC) diets have gained popularity. We compared glycaemic and metabolic parameters following an LC versus a Mediterranean (MED) diet in adolescents and youths with type 1 diabetes. In a six-month, open-label, randomised trial, 40 individuals were assigned to either diet. Glycaemic outcomes, based on continuous glucose monitoring, included per cent time of blood glucose in the range [3.9-10.0 mmol/L (70-180 mg/dL)] and haemoglobin A1c (HbA1c). Twenty-eight (70%) were females. The median age was 18 years. After 6 months, the median time in range increased from 47% to 58% in the LC and from 52% to 64% in the MED diet group (p = 0.98). The delta values for the time in range were 16% and 7% for the respective groups (p = 0.09). The percentage of time >13.9 mmol/L (>250 mg/dL) improved more in the LC diet than in the MED diet group: -10% vs. -2% (p = 0.005). The percentage of time <3.0 mmol/L (<54 mg/dL) was comparable. The delta HbA1c improved in both groups: -0.7% vs. -0.1% (p = 0.02). Changes in BMI Z-score and lipid levels were similar. Both diets improved glycaemic outcomes in adolescents and youths with type 1 diabetes, without increasing hypoglycaemia or cardiovascular risk factors, indicating comparable safety and efficacy.

Detection of serum alterations in polysubstance use patients by FT-Raman spectroscopy

Substance use disorders pose significant health risks and treatment challenges due to the diverse interactions between substances and their impact on physical and mental health. The chemical effects of multiple substance use on bodily fluids are not yet fully understood. Therefore, this study aimed to investigate the chemical changes induced by a combination of substances compared to a control group. Analysis of FT-Raman spectra revealed structural alterations in the amide III, I, and C = O functional groups of lipids in subjects treated with opioids, alcohol and cannabis (polysubstance group). These changes were evident in the form of peak shifts compared to the control group. Additionally, an imbalance in the amide-lipid ratio was observed, indicating perturbations in serum protein and lipid levels. Furthermore, a 2D plot of two-track two-dimensional correlation spectra (2T2D-COS) demonstrated a shift towards dominance of lipid vibrations in the polysubstance use groups, contrasting with the predominance of the amide fraction in the control group. This observation suggests distinct molecular changes induced by multiple substance use, potentially contributing to the pathophysiology of substance use disorders. Principal Component Analysis (PCA) was utilized to visualize the data structure and identify outliers. Subsequently, Partial Least Squares Discriminant Analysis (PLS-DA) was employed to classify the polysubstance use and control groups. The PLS-DA model demonstrated high classification accuracy, achieving 100.00 % in the training dataset and 94.74 % in the test dataset. Furthermore, receiver operating characteristic (ROC) analysis yielded perfect AUC values of 1.00 for both the training and test sets, underscoring the robustness of the classification model.This study highlights the quantitative and qualitative changes in serum protein and lipid levels induced by polysubstance use groups, as evidenced by FT-Raman spectroscopy. The findings underscore the importance of understanding the chemical effects of polysubstance use on bodily fluids for improved diagnosis and treatment of substance use disorders. Moreover, the successful classification of spectral data using machine learning techniques emphasizes the potential of these approaches in clinical applications for substance abuse monitoring and management.

Re-evaluating the necessity of routine laboratory monitoring during isotretinoin therapy for acne.

In this letter, we discuss the topic of necessity of routine laboratory monitoring during isotretinoin treatment for acne. According to Park and colleagues, it is advisable to monitor the levels of triglycerides, alanine aminotransferase, and aspartate aminotransferase every 5 to 6 months. Additionally, the levels of total cholesterol and low-density lipoprotein should be checked within the first two months of treatment. Isotretinoin is a commonly prescribed agent mainly used to treat acne. Despite its high effectiveness, it necessitates regular monitoring of laboratory parameters due to its side effect profile. Currently, there remains a lack of consensus on the appropriate frequency for monitoring these parameters during treatment with isotretinoin. This letter will provide insight into this complex and controversial topic. Based on existing literature, we concluded that the incidence of changes in lipid and liver aminotransferase levels during isotretinoin treatment for acne was low and likely clinically insignificant. For generally healthy people, we recommend testing lipid and liver profiles once at baseline and a second time at the peak dosage. However, frequent testing might still be beneficial in certain populations of patients.

6602 Classification of TSH Trajectories During Levothyroxine Treatment in the ELSA-Brasil Cohort

Abstract Disclosure: M.D. Ettleson: None. G.C. Penna: Consulting Fee; Self; Ipsen, Bayer, Inc.. W. Wan: None. I.M. Bensenor: None. N. Laiteerapong: None. A.C. Bianco: Consulting Fee; Self; Abbvie. Classification of TSH Trajectories During Levothyroxine Treatment in the ELSA-Brasil Cohort Introduction: Hypothyroidism is a common endocrine disorder for which levothyroxine (LT4) serves as the primary treatment. Periods during which thyroid stimulating hormone (TSH) levels are outside the normal range have been associated with adverse cardiovascular outcomes, including mortality. In practice, serial TSH levels are measured over time to ensure therapeutic LT4 treatment is maintained. However, there is no measure of the quality of treatment maintenance over time. TSH trajectory classification represents a novel approach to define the adequacy of LT4 treatment for hypothyroidism over time utilizing multiple observation points. Methods: With longitudinal clinical data, including thyroid function from a large prospective study, we aimed to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over a 9 year study period with three observation points. Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to measure within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. Results: From the 621 LT4-treated study participants, the best-fit GMM approach identified four TSH trajectory classes, as defined by their relationship to the normal TSH range: 1) High-high normal TSH, 2) Normal TSH, 3) Normal-to-low TSH, and 4) Low-to-normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 mcg, p &amp;lt;0.001). There were no significant differences in CV health markers between the classes at baseline. At least one significant difference in CV markers occurred in all classes, highlighted by the low-to-normal class, in which total and HDL cholesterol, triglycerides, and A1c all increased significantly (p = 0.049, p &amp;lt;0.001, p &amp;lt;0.001, and p = 0.001, respectively). Medication utilization increased in all classes over the study period. Conclusion: GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. In the future, more comprehensive datasets will allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes. Defining the adequacy of LT4 treatment using a longitudinal scope could allow clinicians to more accurately communicate treatment progress and identify patients at risk for adverse CV outcomes. Presentation: 6/3/2024

Role of the screening with coronary computed tomography angiography on lipid management and risk factors control in an asymptomatic Chinese population: a community-based, parallel-group, open-label, randomized clinical trial (RESPECT2).

Lipid management based on cardiovascular risk level is the cornerstone of primary prevention of coronary artery disease (CAD), while the accuracy and adherence of traditional cardiovascular risk stratification have been questioned. Prevention strategies based on imaging screening for atherosclerotic plaques are found to be more objective and adherent in recent studies. This trial aims to investigate the role of coronary computed tomography angiography (CCTA) in guiding the primary prevention of CAD in a randomized controlled design. Approximately 3400 middle-aged asymptomatic community participants will be recruited and randomized in a 1:1 ratio to a traditional cardiovascular risk score-guided (usual care group) or CCTA-guided (CCTA group) strategy. Participants with cardiovascular disease, prior lipid-lowering therapy, CCTA contraindication, or serious diseases that affect life span will be excluded. The intervention strategy includes blood pressure, blood glucose, and lipid management and lifestyle modifications. Blood pressure and glucose targets and lifestyle modification recommendations keep the same in both strategies, while lipid management is personalized based on traditional risk level or CCTA results, respectively. The primary outcome is the proportion of participants taking lipid-lowering medication regularly at both 6 and 12months. The secondary outcomes include the proportion of participants achieving low-density lipoprotein cholesterol lowering targets at 12months, mean changes in lipid levels from baseline to 12months, barriers to adherence, adverse reactions related to CCTA examination, and cardiovascular events. The study is the first randomized clinical trial to examine the effectiveness of a CCTA-guided versus a traditional risk score-guided primary prevention strategy in an asymptomatic community-based population. ClinicalTrials.gov NCT05725096. Registered on 2 February 2023.

Estimating the effect of inclisiran on hypercholesterolemia and primary prevention of cardiovascular disease: the NHANES 1999–2018 study

BackgroundHypercholesterolemia has been identified as an independent predictor of cardiovascular disease (CVD). Inclisiran, an innovative small interfering RNA agent, is anticipated to result in a notable reduction of approximately 50% in low-density lipoprotein cholesterol (LDL-C) levels. Given its transformative impact, this study scrutinized the eligibility of the US population for inclisiran treatment and evaluated its potential effects on hypercholesterolemia and the primary prevention of CVD.MethodsThis study applied the eligibility criteria from the ORION 10 and 11 trials to the 1999–2018 National Health and Nutrition Examination Survey (NHANES) dataset to estimate the size of the eligible population for atherosclerotic cardiovascular disease (ASCVD) and ASCVD-risk equivalents. Utilizing the reduction in LDL-C levels from ORION 10, this study predicted the impact of inclisiran on LDL-C levels among ASCVD patients. Similarly, leveraging the changes in lipid levels from ORION 11, this study predicted inclisiran’s effect on the 10-year change in CVD risk and preventable CVD events in the ASCVD-risk equivalents population, employing the Framingham CVD Risk Score.ResultsThe study identified 579 ASCVD patients (5 million) and 382 ASCVD-risk equivalents (2.66 million) who met the eligibility criteria from ORION 10 and 11. Among the ASCVD population, 3.5 million (70.2%) would achieve a ≥ 50% reduction in LDL-C levels after treatment. Furthermore, 4.6 million (91.3%) would achieve LDL-C levels < 70 mg/dL, and 3.8 million (75%) would achieve LDL-C levels < 55 mg/dL after treatment. For the ASCVD-risk equivalents population, the estimated 10-year CVD risk would decrease from 25.3 to 17.7%, an absolute reduction of 7.6% and a relative reduction of 30% following inclisiran treatment, potentially preventing 202,353 CVD events over a decade, including 138,084 coronary heart disease cases, 37,351 strokes, and 23,894 congestive heart failure cases.ConclusionsInclisiran has the potential to substantially reduce the prevalence of hypercholesterolemia and prevent nearly 200,000 CVD events in eligible US adults.

Evolution of metabolic disorders after resection of pheochromocytomas and paragangliomas: a single-center study

Background and aims. Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, responsible for inappropriate secretion of catecholamines, inducing metabolic disorders, increasing basal metabolic rate. Our study aimed to analyze the metabolic profile pre- and post-operatively in patients undergoing surgery for pheochromocytomas and paragangliomas and additionally to determine the predictive factors of metabolic remission. Methods. This was a retrospective, unicentric, descriptive, and analytical study with a duration of 9 years. It includes data from 35 patients followed up for pheochromocytoma or paraganglioma in the Endocrinology-Diabetology and Nutrition Department of a University Hospital Center. All patients underwent surgery for pheochromocytoma or paraganglioma. Results. Among the 35 patients, 51.4% of the patients with pheochromocytomas had diabetes mellitus, and 42.8% had dyslipidemia. We found that high levels of catecholamines were associated with the onset of diabetes. We also noted that patients with a long history of the disease were statistically at greater risk of developing dyslipidemia. After surgery, the body mass index of our patients had statistically increased, and 50% of patients experienced resolution or improvement of their diabetes. Improvement of dyslipidemia was observed in 53% of patients. We also found that the percentage of dyslipidemia was higher in patients who did not resolve their diabetes. Conclusion. Diabetes mellitus and dyslipidemia are metabolic complications that must be investigated in patients with pheochromocytoma. Post-operative monitoring of body mass index and changes in glycemic and lipid levels is essential to adapt therapeutic management.

Emodin repairs interstitial cells of Cajal damaged by cholelithiasis in the gallbladder.

Hypercholesterolemia induces cholelithiasis and dysfunction of gallbladder motility. Interstitial cells of Cajal (ICCs) contribute to gallbladder motility. Emodin modulates the contractility of the gallbladder muscle; however, the underlying mechanism is unknown. This study aimed to explore the effects of emodin on gallbladder ICCs with cholelithiasis in a guinea pig model. Animals were randomly divided into a healthy control group and three study groups. All study groups received a high-cholesterol diet (HCD) for 8 weeks. Subsequently, they were randomly assigned to either the HCD group or one of the emodin treatment groups lasting 4 or 8weeks. Total cholesterol (TC) and triglycerides (TG) were measured to determine changes in serum lipid levels. Immunohistochemistry was performed to detect the morphology and number of ICCs. TUNEL assays were performed to detect ICC apoptosis. Transmission electron microscopy was employed to observe ICC structure. Western blotting and real-time polymerase chain reaction were used to detect changes in stem cell factor (SCF)/c-kit pathway expression. Serum TC and TG were higher in all study groups. In cases of cholelithiasis, the SCF/c-kit pathway was downregulated, the number of gallbladder ICCs decreased, apoptosis increased, and the ICC network structure was damaged. After emodin treatment, the SCF/c-kit pathway was upregulated, the number of gallbladder ICCs increased, apoptosis decreased, and the ICC network structure recovered. Cholelithiasis downregulates the SCF/c-kit pathway and damages gallbladder ICCs. Emodin upregulates the SCF/c-kit pathway and increases gallbladder ICCs, contributing to recovery from gallbladder motility disorders.\.

The effect of family history of atherosclerosıs and other risk factors on changes in serum lipid levels in acne patients treated with isotretinoin.

Oral isotretinoin causes changes in serum lipid values. These changes are not seen in every patient, regardless of dose. It is unclear what causes these changes and how often serum lipid values should be followed up. We aimed to evaluate the relationship between the change in serum lipid values and personal and familial risk factors. Serum lipid values at baseline (0th), 1st, 3rd, and 6th months of isotretinoin treatment of acne patients aged 16 years and over using oral isotretinoin at a dose of 0.5-1mg/kg/day between January 2017 and December 2019 were recorded retrospectively. The relationship between personal and familial risk factors and changes in serum lipid values were evaluated statistically. In pairwise comparison, a significant difference was detected between the 0th and 1st month, 0th and 3rd month, 0th and 6th month, and 1st and 6th month in the average serum lipid (Low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), total cholesterol, triglyceride) levels. However, no significant difference was detected between 3rd and 6th month. The change in LDL levels between the 0th and the 3rd month was significantly higher in those with a family history of atherosclerosis than those without a family history of atherosclerosis (p = 0.034). The change in VLDL levels between the 0th and 6th month was significantly higher in those with a family history of atherosclerosis than those without a family history of atherosclerosis (p = 0.022). It was observed that the changes in total cholesterol and VLDL levels between the 0th and 3rd month increased as body mass index (BMI) increased (p = 0.03, p = 0.014, respectively). Similarly, the changes in triglyceride and VLDL levels between 0th and 6th month and between 1st and 6th month increased by an increase in BMI (respectively; p = 0.006, p = 0.019; p = 0.016, p = 0.022). The increase in the levels of VLDL between the 1st and the 6th month was found to be significantly higher in smokers than in non-smokers (p = 0,032). We recommend evaluation of serum lipids values in the 0th,1st, and 3rd month in all acne patients using oral isotretinoin and that these values have to be checked monthly in the following months for smokers, those with a history of atherosclerosis, and those with a BMI above normal.

The therapeutic effect of PCSK9 inhibitors on dyslipidemia: one-year follow up.

Despite the availability of statins and lifestyle modifications, many patients with Dyslipidemia struggle to achieve optimal low-density lipoprotein cholesterol (LDL-C) control. PCSK9 inhibitors offer a promising new therapeutic option with superior LDL-C lowering efficacy compared to statins. However, data on their real-world use, particularly in Iran, is limited. This study aims to address this gap by investigating the one-year effects of evolocumab on lipid profiles and potential cardiovascular outcomes in Iranian patients with Familial Hypercholesterolemia (FH).This single-center, prospective study evaluated evolocumab effectiveness in lowering LDL-C in 50 Iranian adults with FH. Participants with a documented LDL-C > 190 mg/dL on existing cholesterol medications (excluding PCSK9 inhibitors) and a clinical FH diagnosis was included. After baseline assessments (medical history, demographics, lipid profile), evolocumab was administered subcutaneously every two weeks for one year. Follow-up assessments at year one measured changes in LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. The study enrolled 50 participants with an average age of 55 years old (range 35-80 years).Treatment with evolocumab led to significant improvements in lipid profiles at all follow-up points compared to baseline. On average, LDL-C levels decreased by 105.24 mg/dL, triglycerides decreased by 59.20 mg/dL, and HDL-C levels increased by a modest but significant 4.5 mg/dL after one year(p<0.001). Subgroup analysis revealed no statistically significant interactions between baseline demographics (age, sex, BMI) or lifestyle habits (smoking, alcohol) and changes in lipid levels(p>0.05). However, a significant interaction emerged between baseline lipid levels and their corresponding reductions, suggesting greater improvement in patients with higher baseline values(p<0.05). It is noteworthy that no new cardiovascular events were reported during the study period. This study demonstrates the effectiveness of evolocumab in improving lipid profiles in Iranian patients with FH. The observed reductions in LDL-C and triglycerides, along with a modest increase in HDL-C, suggest potential benefits for cardiovascular risk reduction. The absence of new cardiovascular events during the study is encouraging, but further research with larger and longer-term follow-up is needed to confirm these findings and assess the long-term safety and impact on quality of life.

Comparative efficacy and safety of tenofovir amibufenamide vs tenofovir alafenamide in the initial 48-week treatment of high viral load chronic hepatitis B: A single-centre retrospective study.

Tenofovir amibufenamide (TMF) employs innovative ProTide technology and a methylation strategy to enhance the lipid solubility and plasma stability of the amide bond, providing advantages over tenofovir alafenamide (TAF). Despite promising Phase III clinical trial results demonstrating its antiviral efficacy, real-world data on TMF remains scarce. This study evaluates the antiviral efficacy and safety of TMF compared to TAF as the initial treatment in patients with high viral loads of chronic hepatitis B (CHB). We retrospectively collected clinical data from March 1 2022 to June 30 2022 for highly viremic CHB patients who received either TMF (n = 58) or TAF (n = 32) as their initial monotherapy at Beijing YouAn Hospital. To understand the efficacy and safety of TMF over 48 weeks, we compared the virological response rates and HBeAg/HBsAg serological clearance rates between TMF and TAF groups. Also, the changes in serum creatinine, eGFR and serum lipid levels were assessed. Baseline median HBV DNA levels were 7.85 (6.89, 8.36) IgIU/ml for TMF and 7.44 (6.89, 8.03) IgIU/ml for TAF. Median ALT levels were 102.0 (56.0, 210.0) U/L for TMF and 195.0 (73.5, 371.0) U/L for TAF, with HBeAg positivity rates of 70.7% and 75.0%, respectively. At 48 weeks, virological response rates (HBV DNA <10 IU/ml) were 43.5% (20/46) for TMF and 42.9% (12/28) for TAF (p = 1.000). ALT normalization rates were 87.9% for TMF and 90.6% for TAF (p = .969), and HBeAg serological clearance rates were 21.1% and 18.2%, respectively (p = 1.000). No patients achieved HBsAg clearance. Compared with the baseline, LDL-C levels increased, while eGFR decreased, with no significant differences in serum creatinine, triglycerides and total cholesterol levels noted at week 48 for both TMF and TAF groups. TMF demonstrates comparable antiviral efficacy to TAF when used as initial therapy in highly viremic CHB patients, with similar impacts on renal function and lipid profiles.

A Large-Scale Genome-Wide Gene-Sleep Interaction Study in 732,564 Participants Identifies Lipid Loci Explaining Sleep-Associated Lipid Disturbances.

We performed large-scale genome-wide gene-sleep interaction analyses of lipid levels to identify novel genetic variants underpinning the biomolecular pathways of sleep-associated lipid disturbances and to suggest possible druggable targets. We collected data from 55 cohorts with a combined sample size of 732,564 participants (87% European ancestry) with data on lipid traits (high-density lipoprotein [HDL-c] and low-density lipoprotein [LDL-c] cholesterol and triglycerides [TG]). Short (STST) and long (LTST) total sleep time were defined by the extreme 20% of the age- and sex-standardized values within each cohort. Based on cohort-level summary statistics data, we performed meta-analyses for the one-degree of freedom tests of interaction and two-degree of freedom joint tests of the main and interaction effect. In the cross-population meta-analyses, the one-degree of freedom variant-sleep interaction test identified 10 loci (P int <5.0e-9) not previously observed for lipids. Of interest, the ASPH locus (TG, LTST) is a target for aspartic and succinic acid metabolism previously shown to improve sleep and cardiovascular risk. The two-degree of freedom analyses identified an additional 7 loci that showed evidence for variant-sleep interaction (P joint <5.0e-9 in combination with P int <6.6e-6). Of these, the SLC8A1 locus (TG, STST) has been considered a potential treatment target for reduction of ischemic damage after acute myocardial infarction. Collectively, the 17 (9 with STST; 8 with LTST) loci identified in this large-scale initiative provides evidence into the biomolecular mechanisms underpinning sleep-duration-associated changes in lipid levels. The identified druggable targets may contribute to the development of novel therapies for dyslipidemia in people with sleep disturbances.

301P Changes in lipid-levels following aromatase inhibitor treatment in early postmenopausal breast cancer

301P Changes in lipid-levels following aromatase inhibitor treatment in early postmenopausal breast cancer

Integrated lipidomics and network pharmacology analysis to determine how Gu Fu Sheng Capsule improves lipid metabolism in rats with steroid-induced osteonecrosis of the femoral head

BackgroundSteroid-induced osteonecrosis of the femoral head (SONFH) is a prevalent refractory condition in orthopedics, often causing high disability rates. Gu Fu Sheng Capsule (GFSC) is commonly used to treat SONFH during the early and intermediate stages. However, the precise underlying mechanism of action of GFSC remains elusive. ObjectiveTo elucidate the mechanism through which GFSC improves lipid metabolism in rats with SONFH. MethodsA rat model of SONFH was established by administering methylprednisolone and lipopolysaccharide. Micro-computed tomography assessed femoral head effects, while hematoxylin–eosin staining examined femoral head tissues. Pathological changes were evaluated using an automated biochemical analyzer to measure changes in serum lipid levels. Besides, quantitative lipidomics and network pharmacology were used to determine how GFSC impacts SONFH. qRT-PCR and Western blotting were performed to assess mRNA and protein expression levels of key targets. ResultsGFSC can enhance bone density and prevents surface collapse of the femoral head, improve hollow bone lacuna density, reduce adipocyte infiltration, minimize osteocyte cavities, regulate the serum lipid levels and enhance lipid metabolism in SONFH rats. Moreover, integrated lipidomics and network pharmacology suggested that GFSC affects lipid metabolism-related genes by regulating nine targets, thereby influencing four metabolites and two metabolic pathways, which may mainly be due to components in GFSC such as quercetin, tanshinone iia, berberine. Western blotting and qRT-PCR data highlighted that GFSC improves lipid metabolism by regulating TP53, HSP90AA1, and ESR1. ConclusionGFSC effectively retards SONFH progression, potentially attributed to its ability to regulate lipid metabolism.

Lipidomics of sheep and goat Milk-based infant formulae during in vitro dynamic digestion

Lipid hydrolysis process during IF digestion, particularly the characterization of the lipidome and the resulting lipid breakdown products, has not been thoroughly investigated. This study aimed to compare the lipid hydrolysis profiles during the in vitro dynamic digestion of IFs made from whole sheep and goat milk. Using a lipidomics platform and multivariate statistical analysis, we observed changes in complex lipid levels during digestion. In the gastric compartment, we noted a progressive hydrolysis of triacylglycerols, phosphatidylcholines, and sphingomyelins. Conversely, lipolysis breakdown products like monoacylglycerols (e.g., MG(16:0), MG(18:0)), diacylglycerols, lysophosphatidylcholines (LPC 16:0, LPC 18:1, LPC 18:2), and free fatty acids increased in the intestinal compartment. The lipolysis trends were similar for both types of infant formulas, with long-chain fatty acid triglycerides (C > 46) exhibiting lower digestibility compared to medium-chain fatty acid triglycerides. Overall, these results indicate that sheep milk can be used as an ingredient in the manufacturing of IF.