Association of remnant cholesterol with nonalcoholic fatty liver disease: a general population-based study.

BACKGROUND: Remnant cholesterol (RC) mediates the progression of coronary artery disease, diabetic complications, hypertension, and chronic kidney disease. Limited information is available on the association of RC with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether RC can be used to independently evaluate the risk of NAFLD in the general population and to analyze the predictive value of RC for NAFLD. METHODS: The study included 14,251 subjects enrolled in a health screening program. NAFLD was diagnosed by ultrasound, and the association of RC with NAFLD was assessed using the receiver operating characteristic (ROC) curve and logistic regression equation. RESULTS: Subjects with elevated RC had a significantly higher risk of developing NAFLD after fully adjusting for potential confounding factors (OR 1.77 per SD increase, 95% CI 1.64-1.91, P trend< 0.001). There were significant differences in this association among sex, BMI and age stratification. Compared with men, women were facing a higher risk of RC-related NAFLD. Compared with people with normal BMI, overweight and obesity, the risk of RC-related NAFLD was higher in thin people. In different age stratifications, when RC increased, young people had a higher risk of developing NAFLD than other age groups. Additionally, ROC analysis results showed that among all lipid parameters, the AUC of RC was the largest (women: 0.81; men: 0.74), and the best threshold for predicting NAFLD was 0.54 in women and 0.63 in men. CONCLUSIONS: The results obtained from this study indicate that (1) in the general population, RC is independently associated with NAFLD but not with other risk factors. (2) Compared with traditional lipid parameters, RC has a better predictive ability for NAFLD in men.

Short-Term Intake of Yellowstripe Scad versus Salmon Did Not Induce Similar Effects on Lipid Profile and Inflammatory Markers among Healthy Overweight Adults despite Their Comparable EPA+DHA Content.

Yellowstripe scad (YSS) have comparable eicosapentaenoic acid and docosahexaenoic acid (EPA+DHA) content to salmon. We aimed to compare the effects of YSS and salmon on lipid profile and inflammatory markers. A randomized crossover trial with two diet periods was conducted among healthy overweight (with BMI 23.0-27.4 kg/m2) Malaysian adults aged 21-55 years. Steamed whole YSS fish (≈385 g whole fish/day) or salmon fillets (≈246 g fillet/day) were given for eight weeks (3 days per week), retaining approximately 1000 mg EPA+DHA per day. Diets were switched after an 8-week washout period. Fasting blood samples were collected before and after each diet period. A total of 49 subjects participated in the intervention (35% male and 65% female; mean age 29 (7) years). YSS did not induce any significant changes in outcome measures. However, the consumption of salmon as compared with YSS was associated with reduction in triglycerides (between-group difference: -0.09 mmol/1, p = 0.01), VLDL-cholesterol (between-group difference: -0.04 mmol/1, p = 0.01), atherogenic index of plasma (between-group difference: -0.05 mmol/1, p = 0.006), and IL-6 (between-group difference: -0.01 pg/mL, p = 0.03). Despite their comparable EPA+DHA content, short-term consumption of salmon but not YSS induced significant changes in lipid profile and inflammatory markers. Larger clinical trials are needed to confirm the findings.

Influence of hs-CRP, IL-6 and TNF-α and it's role in dyslipidemia and type 2 diabetes in population of Karachi, Pakistan.

The present study was conducted to estimate the prevalence of pro-inflammatory cytokine interleukin-6, highly sensitive C-reactive protein, and tumor necrotic factor alpha and evaluate the association and role of these inflammatory markers in the pathogenesis of type 2 diabetes mellitus. A retrospective case-control study was conducted in Karachi. 400 individuals participated in the study having 200 diabetic patients and 200 controls. The subjects' profile and anthropometric indices were recorded and the levels of FPG, fasting insulin, lipid profile, IL-6, and hs-CRP were determined. Insulin resistance, beta-cell function and sensitivity were calculated by HOMA analysis using the HOMA calculator. Using independent t-test BMI, percent body fats, HbA1c, FPG, and fasting insulin were found significant (p<0.05). HOMA-IR, percent beta cell, total cholesterol, triglyceride, and HDL showed significant (p<0.05) results among cases and controls. Similarly, TNF-α and hs-CRP were also found significant (p<0.05) in cases than controls. Multiple linear regression was performed to predict the values of FPG, fasting plasma insulin, and IL-6. All models were statistically significant (p<0.05). The current study reveals that inflammation is the fundamental mechanism in obesity-induced insulin resistance, and T2DM, expanded fat stores in the body, and sedentary lifestyle are involved in the alteration of metabolic processes.

Alternative Foods in Cardio-Healthy Dietary Models That Improve Postprandial Lipemia and Insulinemia in Obese People.

Obesity is one of the major health problems worldwide. Following healthy dietary patterns can be difficult in some countries due to the lack of availability of certain foods; thus, alternative foods are needed. Our aim was to evaluate the effect of a dietary pattern consisting of fruit, avocado, whole grains, and trout (FAWGT) on postprandial insulinemia and lipemia in obese Colombian subjects. A randomized controlled crossover study was conducted, in which 44 subjects with BMI ≥ 30 kg/m2 followed either a FAWGT diet or a diet high in saturated fat and rich in processed carbohydrates. Levels of lipids and carbohydrates were measured during the postprandial state. The FAWGT diet reduced fasting insulin, VLDL, and HOMA-IR after 8 weeks (p < 0.05), while there was a lower postprandial increase in TG, VLDL, and insulin levels after both acute and chronic intake of FAWGT diet (p < 0.05). The intake of FAWGT-diet was characterized by high consumption of foods rich in fiber, MUFAs, and vitamins C and E (p < 0.05). The consumption of a diet composed of fruit, avocado, whole grains, and trout has emerged as a valid alternative to the foods included in other heart-healthy diets since it improves postprandial lipemia and insulinemia in obese people and has similar beneficial effects to these healthy models.

Metabolomic signatures associated with depression and predictors of antidepressant response in humans: A CAN-BIND-1 report.

One of the biggest challenges in treating depression is the heterogeneous and qualitative nature of its clinical presentations. This highlights the need to find quantitative molecular markers to tailor existing treatment strategies to the individual's biological system. In this study, high-resolution metabolic phenotyping of urine and plasma samples from the CAN-BIND study collected before treatment with two common pharmacological strategies, escitalopram and aripiprazole, was performed. Here we show that a panel of LDL and HDL subfractions were negatively correlated with depression in males. For treatment response, lower baseline concentrations of apolipoprotein A1 and HDL were predictive of escitalopram response in males, while higher baseline concentrations of apolipoprotein A2, HDL and VLDL subfractions were predictive of aripiprazole response in females. These findings support the potential of metabolomics in precision medicine and the possibility of identifying personalized interventions for depression.

Triglyceride-Rich Lipoproteins, Apolipoproteins, and Atherosclerotic Cardiovascular Events Among Patients with Diabetes Mellitus and End-Stage Renal Disease on Hemodialysis.

Hypertriglyceridemia may be implicated in the high atherosclerotic cardiovascular disease (ASCVD) risk experienced by patients with end-stage renal disease (ESRD). In this post-hoc analysis of the "Die Deutsche Diabetes Dialyse Studie (4D)" clinical trial, we examined incident ASCVD events, defined as myocardial infarction, ischemic stroke, or a coronary revascularization procedure, among 1255 participants with type 2 diabetes and ESRD treated with hemodialysis. Cox-regression methods were used to evaluate the association of triglycerides, very-low density lipoprotein cholesterol (VLDL-C), and apolipoproteins B (Apo B) and C-III (Apo C-III) with ASCVD. During a median follow-up time of 2.3 years, 340 (27%) participants experienced an ASCVD event. Higher concentrations of triglycerides were not associated with ASCVD risk: Hazard ratio (HR) 0.95; 95% CI (0.83, 1.10) per doubling concentration. Similarly, VLDL-C HR 1.01; 95% CI (0.90, 1.13); Apo B HR 1.04; 95% CI (0.93, 1.16); and Apo C-III HR 0.97; 95% CI (0.86, 1.09) (per one standard deviation higher concentrations), were not associated with ASCVD events. These associations did not differ by allocation to treatment to atorvastatin or by concentrations of markers of inflammation or malnutrition. In conclusion, we found no evidence that triglycerides, triglyceride-rich lipoproteins, or apolipoproteins B or C-III were associated with risk of ASCVD events among patients with type 2 diabetes and ESRD on hemodialysis. These results suggest that lowering triglycerides may not decrease atherosclerotic cardiovascular risk in this population.

Comparative assessment of LDL-C and VLDL-C estimation in familial combined hyperlipidemia using Sampson's, Martin's and Friedewald's equations.

BACKGROUND: Sampson et al. developed a novel method to estimate very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) in the setting of hypertriglyceridemia. Familial Combined Hyperlipidemia (FCHL) is a common primary dyslipidemia in which lipoprotein composition interferes with LDL-C estimation. This study aimed to evaluate performance of LDL-C using this new method (LDL-S) compared with LDL-C estimated by Friedewald's and Martin eq. (LDL-F, LDL-M) in FCHL. METHODS: Data were collected from 340 subjects with confirmed FCHL. Concordance for VLDL-C measured by ultracentrifugation and LDL-C estimated using these measures compared to Sampson's, Martin's and Friedewald's equations was performed using correlation coefficients, root mean squared error (RMSE) and bias. Also, concordance of misclassified metrics according to LDL-C (< 70 and < 100 mg/dL) and Apo B (< 80 and < 65 mg/dL) thresholds were assessed. RESULTS: Sampson's equation was more accurate (RMSE 11.21 mg/dL; R2 = 0.88) compared to Martin's (RMSE 13.15 mg/dL; R2 = 0.875) and the Friedewald's equation (RMSE 13.7 mg/dL; R2 = 0.869). When assessing performance according to LDL-C, Sampson's had highest correlation and lowest RMSE compared to other equations (RMSE 19.99 mg/dL; R2 = 0.840). Comparing performance strength across triglyceride levels, Sampson's showed consistently improved correlations compared to Martin's and Friedewald's formulas for increasing triglycerides and for the FCHL phenotype of mixed dyslipidemia. Sampson's also had improved concordance with treatment goals. CONCLUSIONS: In FCHL, VLDL-C and LDL-C estimation using Sampson's formula showed higher concordance with lipid targets assessed using VLDL-C obtained by ultracentrifugation compared with Friedewald's and Martin's equations. Implementation of Sampson's formula could improve treatment monitoring in FCHL.

Saroglitazar, a PPAR-α/γ Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial.

BACKGROUND AND AIMS: NAFLD is characterized by insulin resistance and dysregulated lipid and glucose metabolism. Saroglitazar, a dual peroxisome proliferator activated receptor-α/γ agonist, improves insulin sensitivity, and lipid and glycemic parameters. Saroglitazar improved NASH histology in animal studies. In this randomized controlled clinical trial, we evaluated the efficacy and safety of saroglitazar in patients with NAFLD/NASH. APPROACH AND RESULTS: A total of 106 patients with NAFLD/NASH with alanine aminotransferase (ALT) ≥ 50 U/L at baseline and body mass index ≥25 kg/m2 were randomized in a 1:1:1:1 ratio to receive placebo or saroglitazar 1 mg, 2 mg, or 4 mg for 16 weeks. The primary efficacy endpoint was percentage change from baseline in ALT levels at week 16. Liver fat content (LFC) was assessed by MRI proton density fat fraction. The least-squares mean percent change from baseline in ALT at week 16 was -25.5% (5.8), -27.7% (5.9), and -45.8% (5.7), with saroglitazar 1 mg, 2 mg, and 4 mg, respectively, versus 3.4% (5.6) in placebo (P < 0.001 for all). Compared with placebo, saroglitazar 4 mg improved LFC (4.1% [5.9] vs. -19.7% [5.6]), adiponectin (-0.3 µg/mL [0.3] vs. 1.3 µg/mL [0.3]), homeostatic model assessment-insulin resistance (-1.3 [1.8] vs. -6.3 [1.7]), and triglycerides (-5.3 mg/dL [10.7] vs. -68.7 mg/dL [10.3]) (P < 0.05 for all). Saroglitazar 4 mg also improved lipoprotein particle composition and size and reduced lipotoxic lipid species. Saroglitazar was well-tolerated. A mean weight gain of 1.5 kg was observed with saroglitazar 4 mg versus 0.3 kg with placebo (P = 0.27). CONCLUSIONS: Saroglitazar 4 mg significantly improved ALT, LFC, insulin resistance, and atherogenic dyslipidemia in participants with NAFLD/NASH. (ClinicalTrials.gov identifier: NCT03061721.).

Low CETP activity and unique composition of large VLDL and small HDL in women giving birth to small-for-gestational age infants.

Cholesteryl ester transfer protein (CETP) regulates high density lipoproteins (HDL)-cholesterol (C) and HDL-C is essential for fetal development. We hypothesized that women giving birth to large-for-gestational-age (LGA) and small-for-gestational age (SGA) infants differed in longitudinal changes in lipoproteins, CETP activity and HDL-C and that placentas from women with higher or lower circulating HDL-C displayed differential expression of mRNAs involved in cholesterol/nutrient transport, insulin signaling, inflammation/ extracellular matrix (ECM) remodeling. Circulating lipids and CETP activity was measured during pregnancy, NMR lipidomics in late pregnancy, and associations with LGA and SGA infants investigated. RNA sequencing was performed in 28 placentas according to higher and lower maternal HDL-C levels. Lipidomics revealed high triglycerides in large VLDL and lipids/cholesterol/cholesteryl esters in small HDL in women giving birth to SGA infants. Placentas from women with higher HDL-C had decreased levels of CETP expression which was associated with mRNAs involved in cholesterol/nutrient transport, insulin signaling and inflammation/ECM remodeling. Both placental and circulating CETP levels were associated with growth of the fetus. Low circulating CETP activity at 36-38 weeks was associated with giving birth to SGA infants. Our findings suggest a link between increased maternal HDL-C levels, low CETP levels both in circulation and placenta, and SGA infants.

Prevalence of prediabetes, and diabetes in Chandigarh and Panchkula region based on glycated haemoglobin and Indian diabetes risk score.

There is a rapid increase in the prevalence of diabetes in India. We wanted to review the status of prediabetes and diabetes in the combined population of Chandigarh and Panchkula region based on both Indian Diabetes Risk Score (IDRS) and Glycated Haemoglobin (HbA1c). A total of 1215 subjects were recruited during the screening process, out of which 444 i subjects have been analysed for the current study on the basis of high risk for IDRS (≥60) and their known diabetes status. This study included 431 subjects having high risk for IDRS (≥60) and 13 known subjects with diabetes (IDRS < 60) which were further analysed for biochemical and anthropometric parameters. The prevalence of diabetes was found to be 12.67% and prediabetes 11.69% in the combined population of Chandigarh and Panchkula. There was an increased level of fasting blood glucose (183.12 ± 68.61), postprandial blood glucose (262.57 ± 96.92), triglyceride (193.84 ± 119.88), very low-density lipoprotein (VLDL) (34.87 ± 15.42) and High Density Lipoprotein(HDL) (4.61 ± 1.39) in the said diabetes population. Mean HDL was found to be decreased in subjects having diabetes. Glucose-induced lipid intolerance study revealed significant alteration in triglyceride, HDL and VLDL. The study has revealed that high prevalence of diabetes in the sampled population when compared with the national average of 8.8%.

Pemafibrate decreases triglycerides and small, dense LDL, but increases LDL-C depending on baseline triglycerides and LDL-C in type 2 diabetes patients with hypertriglyceridemia: an observational study.

BACKGROUND: Pemafibrate, a selective PPARα modulator, has the beneficial effects on serum triglycerides (TGs) and very low density lipoprotein (VLDL), especially in patients with diabetes mellitus or metabolic syndrome. However, its effect on the low density lipoprotein cholesterol (LDL-C) levels is still undefined. LDL-C increased in some cases together with a decrease in TGs, and the profile of lipids, especially LDL-C, during pemafibrate administration was evaluated. METHODS: Pemafibrate was administered to type 2 diabetes patients with hypertriglyceridemia. Fifty-one type 2 diabetes patients (mean age 62 ± 13 years) with a high rate of hypertension and no renal insufficiency were analyzed. Pemafibrate 0.2 mg (0.1 mg twice daily) was administered, and serum lipids were monitored every 4-8 weeks from 8 weeks before administration to 24 weeks after administration. LDL-C was measured by the direct method. Lipoprotein fractions were measured by electrophoresis (polyacrylamide gel, PAG), and LDL-migration index (LDL-MI) was calculated to estimate small, dense LDL. RESULTS: Pemafibrate reduced serum TGs, midband and VLDL fractions by PAG. Pemafibrate increased LDL-C levels from baseline by 5.3% (- 3.8-19.1, IQR). Patients were divided into 2 groups: LDL-C increase of > 5.3% (group I, n = 25) and < 5.3% (group NI, n = 26) after pemafibrate. Compared to group NI, group I had lower LDL-C (2.53 [1.96-3.26] vs. 3.36 [3.05-3.72] mmol/L, P = 0.0009), higher TGs (3.71 [2.62-6.69] vs. 3.25 [2.64-3.80] mmol/L), lower LDL by PAG (34.2 [14.5, SD] vs. 46.4% [6.5], P = 0.0011), higher VLDL by PAG (28.2 [10.8] vs. 22.0% [5.2], P = 0.0234), and higher LDL-MI (0.421 [0.391-0.450] vs. 0.354 [0.341-0.396], P < 0.0001) at baseline. Pemafibrate decreased LDL-MI in group I, and the differences between the groups disappeared. These results showed contradictory effects of pemafibrate on LDL-C levels, and these effects were dependent on the baseline levels of LDL-C and TGs. CONCLUSIONS: Pemafibrate significantly reduced TGs, VLDL, midband, and small, dense LDL, but increased LDL-C in diabetes patients with higher baseline TGs and lower baseline LDL-C. Even if pre-dose LDL-C remains in the normal range, pemafibrate improves LDL composition and may reduce cardiovascular disease risk.

The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis.

BACKGROUND: To our knowledge, data on the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis are limited. This study was conducted to determine the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 18-40 years old) with endometriosis. Participants were randomly allocated into two groups (30 participants each group) to receive either 50,000 IU vitamin D or placebo each 2 weeks for 12 weeks. RESULTS: Vitamin D supplementation significantly decreased pelvic pain (ß - 1.12; 95% CI, -2.1, -0.09; p=.03) and total-/HDL-cholesterol ratio (ß - 0.29; 95% CI, -0.57, -0.008; p=.04) compared with the placebo. Moreover, vitamin D intake led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (ß - 0.64 mg/L; 95% CI, -0.97, -0.30; p<.001) and a significant increase in total antioxidant capacity (TAC) (ß 47.54 mmol/L; 95% CI, 19.98, 75.11; p=.001) compared with the placebo. CONCLUSIONS: Overall, our study demonstrated that vitamin D intake in patients with endometriosis resulted in a significant improvement of pelvic pain, total-/HDL-cholesterol ratio, hs-CRP and TAC levels, but did not affect other clinical symptoms and metabolic profiles.

Very Low-Density Lipoprotein Cholesterol May Mediate a Substantial Component of the Effect of Obesity on Myocardial Infarction Risk: The Copenhagen General Population Study.

BACKGROUND: Individuals with obesity have higher concentrations of very low-density lipoprotein (VLDL) cholesterol and increased risk of myocardial infarction. We hypothesized that VLDL cholesterol explains a fraction of the excess myocardial infarction risk in individuals with obesity. METHODS: We included 29 010 individuals free of myocardial infarction at baseline, nested within 109 751 individuals from the Copenhagen General Population Study. During 10 years of follow-up, 2306 individuals developed myocardial infarction. Cholesterol content in large and small VLDLs, in intermediate-density lipoprotein (IDL), and in LDL was measured directly with nuclear magnetic resonance spectroscopy. RESULTS: Median concentrations of cholesterol in large and small VLDLs were 0.12 mmol/L (interquartile range [IQR], 0.07-0.20 mmol/L; 4.5 mg/dL [IQR, 2.6-6.9 mg/dL]) and 0.6 mmol/L (IQR, 0.5-0.8 mmol/L; 25 mg/dL [IQR, 20-30 mg/dL]) in individuals with obesity vs 0.06 mmol/L (IQR, 0.03-0.1 mmol/L; 2.2 mg/dL [IQR, 1.1-3.8 mg/dL]), and 0.5 mmol/L (IQR, 0.4-0.6 mmol/L; 20 mg/dL (IQR, 16-25 mg/dL]) in individuals with normal weight; in contrast, concentrations of IDL and LDL cholesterol were similar across body mass index (BMI) categories. Cholesterol in large and small VLDLs combined explained 40% (95% CI, 27%-53%) of the excess risk of myocardial infarction associated with higher BMI. In contrast, IDL and LDL cholesterol did not explain excess risk of myocardial infarction, whereas systolic blood pressure explained 17% (11%-23%) and diabetes mellitus explained 8.6% (3.2%-14%). CONCLUSIONS: VLDL cholesterol explains a large fraction of excess myocardial infarction risk in individuals with obesity. These novel findings support a focus on cholesterol in VLDL for prevention of myocardial infarction and atherosclerotic cardiovascular disease in individuals with obesity.

Probiotics for dementia: a systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Dementia is the fifth leading cause of death in the world. Animal studies indicate that in addition to the aging process, intestinal microbiota may play an important role in the neurodegeneration process through the modulation of the gut-brain axis. OBJECTIVE: A systematic review and meta-analysis was conducted to determine the effectiveness of probiotic and synbiotic supplementation on the cognitive function of individuals with dementia. DATA SOURCES: MEDLINE, BVS, SciELO, CENTRAL, Embase, and grey literature were searched from their inception to January 2019. STUDY SELECTION: We included data from randomized clinical trials (RCTs) that addressed dementias and assessed the following outcomes: cognitive function; inflammatory, oxidative stress, and metabolic markers; nutritional status; and intestinal microbiota composition. DATA EXTRACTION: Data searches, article selection, data extraction, and risk-of-bias assessments were performed according to the Cochrane guidelines. Data were pooled by inverse-variance random-effects meta-analyses. GRADE (Grading of Recommendations Assessment, Development, and Evaluations) was used to assess the quality of evidence. RESULTS: Data from 3 RCTs involving 161 individuals with Alzheimer's disease receiving Lactobacillus and Bifidobacterium strains showed no beneficial effect of probiotic supplementation on cognitive function (standardized mean difference, 0.56; 95%CI: -0.06 to 1.18), with very low certainty of evidence. However, probiotic supplementation improved plasma triglycerides, very-low-density lipoprotein cholesterol, insulin resistance, and plasma malondialdehyde. No RCTs included synbiotic supplementation or assessed microbiota composition. CONCLUSION: Current evidence regarding the use of probiotics and synbiotics for individuals with dementia is insufficient to support their clinical application. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no: CRD42018116148.

Sub-acute oral toxicity study of aqueous extract of tobacco leaves (Nicotiana tabacum L.) on lipid profile, the tissue, and serum of the liver and kidney of male Wistar rats.

CONTEXT: Tobacco consumption may pose a very serious threat to the physiological state of the body; yet, fewer records have been documented in that regard. OBJECTIVE: We investigated the impact of aqueous extract of tobacco leaves on the lipid profile, the tissue, and serum levels of the liver and kidney of male Wister rats. MATERIALS AND METHODS: Rats (n = 52; weight = 33 - 47 g; ∼ 2½ weeks old) were acclimatised for 7 days and administered aqueous extract of tobacco leaves at 100, 200, 400, 0 mg/kg of body weight (to group A, B, C, D) for 30 days. RESULTS: Compared with the control group, the kidney tissue and serum (i.e., urea and creatinine) were not influenced, in contrast, indices of the liver such as AST, ALT, and ALP, dose-dependently increased. Changes such as coagulative necrosis resulted in the infiltration of mononuclear inflammatory cells and the vacuolar degeneration of the liver. Beside the reduction in the high-density lipoprotein of the rats, there was an increase in the concentration of triglycerides, very low-density lipoprotein, low-density lipoprotein, and the total cholesterol. CONCLUSION: Thus, extract of tobacco leaves can greatly influence the body lipid profile, beside the serum and tissues of the liver.

Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes.

OBJECTIVE: Increased risk of atherosclerotic cardiovascular disease in subjects with type 2 diabetes is linked to elevated levels of triglyceride-rich lipoproteins and their remnants. The metabolic effects of PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors on this dyslipidemia were investigated using stable-isotope-labeled tracers. Approach and Results: Triglyceride transport and the metabolism of apos (apolipoproteins) B48, B100, C-III, and E after a fat-rich meal were investigated before and on evolocumab treatment in 13 subjects with type 2 diabetes. Kinetic parameters were determined for the following: apoB48 in chylomicrons; triglyceride in VLDL1 (very low-density lipoprotein) and VLDL2; and apoB100 in VLDL1, VLDL2, IDL (intermediate-density lipoprotein), and LDL (low-density lipoprotein). Evolocumab did not alter the kinetics of apoB48 in chylomicrons or apoB100 or triglyceride in VLDL1. In contrast, the fractional catabolic rates of VLDL2-apoB100 and VLDL2-triglyceride were both increased by about 45%, which led to a 28% fall in the VLDL2 plasma level. LDL-apoB100 was markedly reduced by evolocumab, which was linked to metabolic heterogeneity in this fraction. Evolocumab increased clearance of the more rapidly metabolized LDL by 61% and decreased production of the more slowly cleared LDL by 75%. ApoC-III kinetics were not altered by evolocumab, but the apoE fractional catabolic rates increased by 45% and the apoE plasma level fell by 33%. The apoE fractional catabolic rates was associated with the decrease in VLDL2- and IDL-apoB100 concentrations. CONCLUSIONS: Evolocumab had only minor effects on lipoproteins that are involved in triglyceride transport (chylomicrons and VLDL1) but, in contrast, had a profound impact on lipoproteins that carry cholesterol (VLDL2, IDL, LDL). Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02948777.

The nuclear magnetic resonance metabolic profile: Impact of fasting status.

INTRODUCTION: Measurement of lipoprotein subclass concentration (-c), particle number (-p), and size (-s) by nuclear magnetic resonance (NMR) has gained traction in the clinical laboratory due to associations between smaller lipid particle sizes and atherogenic risk, especially for LDL-p. The standard protocols for lipoprotein measurements by NMR require fasting blood samples; however, patients may not fast properly before sample collection. The study objective was to evaluate the impact of fasting status on the NMR-based lipid profile and to identify key parameters differentiating between fasting and post-meal specimens. METHODS: Forty-eight self-reported healthy male and female participants were recruited. Blood was collected after a 12 h fast and 4 h after a high fat meal. Samples were analyzed using the AXINON LipoFIT by NMR assay. The measurements included triglyceride, total cholesterol, IDL-c, and LDL, HDL, VLDL concentration, particle number, and size, as well as glucose, and four amino acids (alanine, valine, leucine and isoleucine). RESULTS: As expected, triglycerides increased after the meal (58%, p < 0.0001). Significant changes were also observed for VLDL, LDL, and HDL parameters, and the branched chain amino acids. The ratio of Valine*VLDL-c/LDL-c or Isoleucine*VLDL-c/LDL-c provided equally effective differentiation of fasting and post-meal samples. The ratio cutoffs (79.1 and 23.6 when calculated using valine and isoleucine, respectively) had sensitivities of 86% and specificities of 93-95%. CONCLUSIONS: The clinical impact on NMR results from post-meal samples warrants further evaluation. Algorithms to differentiate fasting and post-meal specimens may be useful in identifying suboptimal specimens.

Metabolic syndrome in rheumatoid arthritis patients: Relationship among its clinical components.

BACKGROUND: Metabolic syndrome (MetS) prevalence in rheumatoid arthritis (RA) patients is known to vary considerably across the world. This study aimed to determine the prevalence of MetS in RA patients from western Mexico and to analyze the interrelation of the MetS components with the clinical variables of RA. METHODS: This case-control study included 216 RA patients and 260 control subjects (CS). MetS prevalence was determined according to the NCEP/ATP III and the Latin American Consensus of the Latin American Diabetes Association (ALAD) criteria. RESULTS: MetS was observed in 30.6% RA patients and 33.3% of controls (p > 0.05) according to NCEP/ATP III and 28.7% in RA patients and 31.1% for controls using ALAD criteria. Total cholesterol, LDL-C, and Castelli's I-II indexes were lower in RA (p < 0.001) than in CS. The RA patients with MetS had more swollen joints than those without MetS (p = 0.018). In RA patients with MetS, DAS-28 score correlated with smoking index (rho = 0.4601, p = 0.0004) and VLDL-C (rho = 0.3108, p = 0.0056); similarly, rheumatoid factor (RF) correlated with age (rho = 0.2031, p = 0.0027), smoking index (rho = 0.3404, p < 0.0001), triglycerides (rho = 0.1958, p = 0.0039), and VLDL-C (rho = 0.1761, p = 0.0162). CONCLUSIONS: The MetS prevalence in RA patients from western Mexico is not higher than controls; however, in RA patients with MetS, some inflammatory markers are associated with MetS components; thus, the control of MetS in RA could be beneficial to regulate disease activity.

Maternal lipid profile and risk of pre-eclampsia in African pregnant women: A systematic review and meta-analysis.

INTRODUCTION: Some studies have reported the association between maternal serum lipid profile abnormalities and pre-eclampsia. However, many studies have reported controversial results. Hence, this systematic review and meta-analysis was planned to generate summarized evidence on the association between maternal serum lipid profiles and pre-eclampsia in African women. METHODS: Four electronic databases such as; PubMed, Hinari, Google Scholar, and African Journals Online were searched for studies published in English. Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument and Newcastle-Ottawa Scale were used for data extraction and quality assessment of the included studies. The meta- regression analysis was performed by Stata 14 software. The standardized mean difference (SMD) values of lipid profiles were computed to assess their association with pre-eclampsia at 95% CI. RESULTS: In this review a total of 15 observational studies were included. The mean values of triglyceride (TG), total cholesterol (TC), low density lipoprotein- cholesterol (LDL-c) and very low density lipoprotein- cholesterol (VLDL-c) were significantly higher in pre-eclamptic women as compared with normotensive pregnant women (TG = 229.61±88.27 and 147.00 ± 40.47, TC = 221.46 ± 45.90 and 189.67 ± 39.18, LDL = 133.92 ± 38.77 and 112.41 ± 36.08, VLDL = 41.44 ± 19.68 and 26.64 ± 7.87), respectively. The serum high density lipoprotein cholesterol (HDL-c) level was lower, but it is not statistically significant (HDL-c = 51.02 ± 16.01 and 61.80 ± 25.63) in pre-eclamptic women as compared with controls. The pooled standardized mean difference (SMD) of TG, TC, LDL-C and VLDL-C were significantly increased in pre-eclamptic women as compared with normotensive pregnant women with the SMD of (TG = 1.65 (1.10, 2.21), TC = 0.84 (0.40, 1.29), LDL-C = 0.95 (0.46, 1.45) and VLDL-C = 1.27 (0.72, 1.81)) at 95% CI, respectively, but the pooled SMD of HDL-cholesterol was decreased in pre-eclamptic women as compared with normotensive pregnant women (SMD = -0.91 (95% CI: -1.43, -0.39). CONCLUSIONS: In this review, the maternal serum levels of TG, TC, LDL-c and VLDL-c were significantly associated with the risk of preeclampsia. However, HDL- cholesterol was not significantly associated but it was lower in pre-eclamptic women. Further, large scale prospective studies should verify these outcomes and it is recommended that lipid profiles should be included as a routine diagnostic test for pre-eclamptic women.

Lipid profile: causal relationship on cognitive performance in multiple sclerosis?

Although cognitive impairment (CI) is classically associated with aging, it has been proposed that neurological pathologies may increase the risk to suffer CI. Despite the evidence of an elevated prevalence of CI in patients with multiple sclerosis (MS), it is not considered among standard clinical evaluations, due the lack of specialists and time required. The aim of this study was to evaluate if lipid profile is associated with cognitive performance in persons with MS. Twenty patients with MS were evaluated. Montreal Cognitive Assessment (MoCA) was employed to determine cognitive performance. CI was observed in 85% of patients, with memory recall and language as the most affected domains. Despite biomarkers were mostly found within reference values, several correlations were observed. MoCA total score was correlated with cholesterol (r = - 0.468, p = 0.037) and LDL (r = - 0.453, p = 0.045). Visuospatial domain was correlated with LDL (r = - 0.493, p = 0.027). Attention domain correlated with triglycerides (r = - 0.455, p = 0.044) and cholesterol (r = - 0.549, p = 0.012). When the person reaches borderline levels of triglycerides, LDL and cholesterol a decrease in cognitive performance can be observed. The mechanism underlying this association has not been established still, it has been proposed that it could be linked with neuroinflammation, alterations in synapses and in the metabolism of amyloid-ß protein. This study settles the potential importance that lipid profile could have on cognitive performance in MS. Further studies are needed to establish optimal levels and implication of lipid profile in the diagnosis and monitoring of cognitive performance in Mexican people with MS.