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To the best of our knowledge, no systematic review and meta-analysis has evaluated the cholesterol-lowering effects of intermittent fasting (IF) and energy-restricted diets (ERD) compared with control groups. The aim of this review and meta-analysis was to summarize the effects of controlled clinical trials examining the influence of IF and ERD on lipid profiles. A systematic review of four independent databases (PubMed/Medline, Scopus, Web of Science and Google Scholar) was performed to identify clinical trials reporting the effects of IF or ERD, relative to non-diet controls, on lipid profiles in humans. A random-effects model, employing the method of DerSimonian and Laird, was used to evaluate effect sizes, and results were expressed as weighted mean difference (WMD) and 95% confidence intervals (CIs). Heterogeneity between studies was calculated using Higgins I2, with values ≥50% considered to represent high heterogeneity. Subgroup analyses were performed to examine the influence of intervention type, baseline lipid concentrations, degree of energy deficit, sex, health status, and intervention duration. For the outcomes of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triacylglycerols (TG), there were 34, 33, 35, and 33 studies meeting all inclusion criteria, respectively. Overall, results from the random-effects model indicated that IF and ERD interventions resulted significant changes in TC (WMD, –6.93 mg/dL; 95% CI, –10.18 to –3.67; P < 0.001; I2 = 78.2%), LDL-C (WMD, –6.16 mg/dL; 95% CI, –8.42 to –3.90; P ˂ 0.001; I2 = 52%), and TG concentrations (WMD, –6.46 mg/dL; 95% CI, –10.64 to –2.27; P = 0.002; I2 = 61%). HDL-C concentrations did not change significantly after IF or ERD (WMD, 0.50 mg/dL; 95% CI, –0.69 to 1.70; P = 0.411; I2 = 80%). Subgroup analyses indicated potentially differential effects between subgroups for one or more lipid parameters in the majority of analyses. Relative to a non-diet control, IF and ERD are effective for the improvement of circulating TC, LDL-C, and TG concentrations, but have no meaningful effects on HDL-C concentration. These effects are influenced by several factors that may inform clinical practice and future research. The present results suggest that these dietary practices are a means of enhancing the lipid profile in humans. •Other than Ramadan intermittent fasting, specific intermittent fasting strategies may be adopted into clinical scenario.•Intermittent fasting and energy-restricted diets are effective in improving circulating total cholesterol, low-density lipoprotein cholesterol, and triacylglycerol levels.•However, intermittent fasting and energy-restricted diets have no meaningful effects on high-density lipoprotein cholesterol levels.

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a recently developed lipid parameter, but there is currently a lack of research exploring its relationship with periodontitis. This study aims to identify the potential association between NHHR and periodontitis. The association between NHHR and periodontitis were examined through univariate and multivariate weighted logistic regression utilizing the National Health and Nutrition Examination Survey data from 2009 to 2014. The participants were grouped based on the type of periodontitis. This study included a total of 9023 participants, with 1947 individuals having no periodontitis, and an additional 7076 individuals suffering from periodontitis. Patients in periodontitis group demonstrated a statistically significant elevation in NHHR values 2.82 (2.05–3.80) compared to those in no periodontitis group ( p  < 0.001). Logistic regression analysis of variables demonstrated a positive association between NHHR and periodontitis [1.07 (1.02, 1.12) p  = 0.0067]. The study revealed a positive association between NHHR and an elevated prevalence of periodontitis development. For each unit increase in NHHR, there is a 7% increase in the prevalence of periodontitis. Further investigations into NHHR may enhance our understanding of preventing and treating periodontitis. However, additional studies are required to validate these findings.

The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (NHHR) is a novel lipid parameter used to assess the risk of cardiovascular disease. Previous studies have demonstrated an association between the NHHR and risk of non-alcoholic fatty liver disease (NAFLD). Owing to the lack of research exploring this relationship in specific populations, this study aimed to determine the potential link between the NHHR and risk of NAFLD among American adults in the United States. Data were retrieved from the National Health and Nutrition Examination Survey (NHANES) spanning 2017–2020. After excluding individuals with other liver diseases, alcohol abuse, and missing lipid data, a total of 6809 eligible adults were included for analysis. The NHHR was calculated as the ratio of (non-HDL-C) to HDL-C, while NAFLD was identified by liver steatosis detected by transient elastography. Multivariable weighted logistic regression models and restricted cubic spline (RCS) models were employed to investigate the relationship between the NHHR and risk of NAFLD. Subgroup and sensitivity analyses were also conducted to test the robustness of the results. As the NHHR increased, the prevalence of NAFLD rose progressively (5.88% vs. 8.75% vs. 12.24% vs. 15.77%, p  < 0.001). In the overall population, after adjusting for confounding factors, each unit increase in the NHHR was associated with a 25% increase in NAFLD risk (OR = 1.25, 95% CI: 1.03–1.53, p  = 0.0372). When the NHHR was analyzed as a categorical variable (quartiles), participants in the highest quartile had a significantly higher risk of NAFLD than those in the lowest quartile (OR = 2.6, 95% CI: 1.75–3.85, p  = 0.009). RCS analysis further indicated a nonlinear dose–response relationship between the NHHR and risk of NAFLD ( p non-linearity < 0.0001). This association remained significant in both subgroup and sensitivity analyses. This study confirmed that the NHHR, particularly at higher levels, was an independent risk factor for NAFLD. As a comprehensive lipid indicator, the NHHR had the potential to predict NAFLD risk. These findings provided new insights for the prevention and clinical management of NAFLD.

Introduction Previous studies have shown that the serum uric acid‐to‐high‐density lipoprotein cholesterol ratio (UHR) is related to metabolic syndrome. However, no existing study has examined the relationship between UHR and insulin resistance (IR). Therefore, this study aims to explore the association between the UHR and IR in patients with type 2 diabetes mellitus (T2DM). Methods Patients with type 2 diabetes mellitus (1,532 males and 1,013 females) were enrolled. Insulin resistance was measured by homeostatic model assessment of insulin resistance (HOMA‐IR) and was defined as HOMI‐IR ≥ 2.69. Pearson correlation, multiple logistic regression, ROC analysis, and subgroup analysis were used to evaluate the association between UHR and IR. Results UHR was associated with HOMA‐IR in patients with type 2 diabetes mellitus (pearson's correlation coefficient = 0.274 in males and 0.337 in females, P < 0.001). Multiple logistic regression analysis showed that UHR was significantly correlated with insulin resistance (OR = 1.06, 95%CI = 1.03–1.08 in males and OR = 1.11, 95%CI = 1.08–1.15 in females). The area under the ROC curve (AUC) of UHR (AUC = 0.665 for males and 0.717 for females, all P < 0.01) was the largest compared with that of UA and HDL‐C in insulin resistance. Subgroup analysis showed that there was a more significantly positive correlation among subjects with BMI ≥ 24 kg/m2, age < 60 years old, HbA1c < 7%, non‐hypertension, or in female subjects. Conclusion Elevated UHR is significantly correlated with insulin resistance, which can be used as an indicator of insulin resistance in patients with type 2 diabetes mellitus. UHR is positively correlated with an increase in HOMA‐IR and the risk of insulin resistance (IR) in a mass of patients with type 2 diabetes mellitus. UHR is more effective in detecting IR compared with uric acid or HDL‐C alone.

Background Waist circumference, a metabolic syndrome (MetSy) criterion, is not routinely measured in clinical practice making early identification of individuals with MetSy challenging. It has been argued that ratios of commonly measured parameters such as lipids and lipoproteins may be an acceptable alternative for identifying individuals with MetSy. The objective of our study was to explore clinical utility of lipid ratios to identify men and women with MetSy; and to explore the association between lipid ratios and the number of MetSy components. Methods Men and women (N = 797) of Aboriginal, Chinese, European, and South Asian origin (35–60 years), recruited across ranges of body mass index (BMI), with no diagnosed cardiovascular disease (CVD) or on medications to treat CVD risk factors were assessed for anthropometrics, family history of CVD, MetSy components (waist circumference, blood pressure, glucose, triglycerides (TG), high-density-lipoprotein-cholesterol (HDL-C)), low-density-lipoprotein-cholesterol (LDL-C), nonHDL-C, and health-related behaviours. Results Mean levels of lipid ratios significantly increased with increasing number of MetSy components in men and women (p < 0.05). After adjustment for age, ethnicity, smoking, alcohol consumption, physical activity, family history of CVD and BMI, (and menopausal status in women), all lipid ratios were associated with the number of MetSy components in men and women (Poisson regression, p < 0.001). Compared to the rest of the lipid ratios (ROC curve analysis), TG/HDL-C was best able to discriminate between individuals with and without MetSy (AUC = 0.869 (95% CI: 0.830, 0.908) men; AUC = 0.872 (95% CI: 0.832, 0.912) women). The discriminatory power of TC/HDL-C and nonHDL-C/HDL-C to identify individuals with MetSY was the same (for both ratios, AUC = 0.793 (95% CI: 0.744, 0.842) men; 0.818 (95% CI: 0.772, 0.864) women). Additionally, LDL-C/HDL-C was a good marker for women (AUC = 0.759 (95% CI: 0.706, 0.812)), but not for men (AUC = 0.689 (95% CI: 0.631, 0.748)). Based on a multiethnic sample, we identified TG/HDL-C cut-off values of 1.62 in men and 1.18 in women that were best able to discriminate between men and women with and without MetSY. Conclusions Our results indicate that TG/HDL-C is a superior marker to identify men and women with MetSy compared to TC/HDL-C, LDL-C/HDL-C, and nonHDL-C/HDL-C.

Diabetes is one of the most prevalent chronic diseases in the world, and its prevalence is expected to rise further. To help understand the utility of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) in diabetes prevention, this large-scale longitudinal cohort study aims to explore the association of NHHR with diabetes risk and compare it as a risk predictor with conventional lipid parameters. This observational study extracted data from the NAGALA longitudinal cohort study conducted in Japan between 2004 and 2015. Multivariate Cox regression analysis was used to evaluate the association between NHHR and the risk of diabetes. The dose-response relationship was analyzed by restricted cubic spline (RCS) regression and the potential risk threshold was estimated. The receiver operator characteristic curve (ROC) was used to analyze and calculate the predictive value and optimal threshold of NHHR and other conventional lipids for new-onset diabetes. Of the 15,464 people aged 18-79, 373 (2.41%) were diagnosed with new-onset diabetes during the study period, with a median age of 46 years. The sensitivity analysis based on multivariate adjustment showed that the independent positive correlation between diabetes and NHHR was stable in different populations. RCS and ROC analysis indicated that the association between NHHR and diabetes was non-linear, and the NHHR was a better marker for predicting diabetes risk than other conventional lipid parameters; Additionally, it is worth noting that an NHHR of approximately 2.74 may be the optimal threshold for intervention in diabetes risk. In the general population, NHHR is a better marker for predicting diabetes risk than conventional lipid parameters, and an NHHR of about 2.74 may be the optimal threshold for assessing diabetes risk.

Neutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized low-density lipoprotein (oxLDL) promotes NET formation of neutrophils, and that the resulting NETs increase the inflammatory responses of endothelial cells. In this study, we investigated the effects of high-density lipoproteins (HDL) on NET formation. HL-60-derived neutrophils were treated with phorbol 12-myristate 13-acetate (PMA) and further incubated with oxLDL and various concentrations of HDL for 2 h. NET formation was evaluated by quantifying extracellular DNA and myeloperoxidase. We found that the addition of native HDL partially decreased NET formation of neutrophils induced by oxLDL. This effect of HDL was lost when HDL was oxidized. We showed that oxidized phosphatidylcholines and lysophosphatidylcholine, which are generated in oxLDL, promoted NET formation of PMA-primed neutrophils, and NET formation by these products was completely blocked by native HDL. Furthermore, we found that an electronegative subfraction of LDL, LDL(–), which is separated from human plasma and is thought to be an in vivo oxLDL, was capable of promoting NET formation. These results suggest that plasma lipoproteins and their oxidative modifications play multiple roles in promoting NET formation, and that HDL acts as a suppressor of this response.

Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower HDL cholesterol, raise LDL cholesterol, and increase the risk of coronary heart disease. The effects of conjugated linoleic acid and trans fatty acids from ruminant animals are less clear. We reviewed the literature, estimated the effects trans fatty acids from ruminant sources and of conjugated trans linoleic acid (CLA) on blood lipoproteins, and compared these with industrial trans fatty acids. We searched Medline and scanned reference lists for intervention trials that reported effects of industrial trans fatty acids, ruminant trans fatty acids or conjugated linoleic acid on LDL and HDL cholesterol in humans. The 39 studies that met our criteria provided results of 29 treatments with industrial trans fatty acids, 6 with ruminant trans fatty acids and 17 with CLA. Control treatments differed between studies; to enable comparison between studies we recalculated for each study what the effect of trans fatty acids on lipoprotein would be if they isocalorically replaced cis mono unsaturated fatty acids. In linear regression analysis the plasma LDL to HDL cholesterol ratio increased by 0.055 (95%CI 0.044-0.066) for each % of dietary energy from industrial trans fatty acids replacing cis monounsaturated fatty acids The increase in the LDL to HDL ratio for each % of energy was 0.038 (95%CI 0.012-0.065) for ruminant trans fatty acids, and 0.043 (95% CI 0.012-0.074) for conjugated linoleic acid (p = 0.99 for difference between CLA and industrial trans fatty acids; p = 0.37 for ruminant versus industrial trans fatty acids). Published data suggest that all fatty acids with a double bond in the trans configuration raise the ratio of plasma LDL to HDL cholesterol.

Decreased blood level of high-density lipoprotein (HDL) is one of the essential criteria in diagnosing metabolic syndrome associated with the development of atherosclerosis and coronary heart disease. Herein, we report the synthesis of a molecularly imprinted polymer (MIP) that selectively binds HDL, namely, HDL-MIP, and thus serves as an artificial, biomimetic sensor layer. The optimized polymer contains methacrylic acid and N-vinylpyrrolidone in the ratio of 2:3, cross-linked with ethylene glycol dimethacrylate. On 10 MHz dual electrode quartz crystal microbalances (QCM), such HDL-MIP revealed dynamic detection range toward HDL standards in the clinically relevant ranges of 2–250 mg/dL HDL cholesterol (HDL-C) in 10 mM phosphate-buffered saline (PBS, pH = 7.4) without significant interference: low-density lipoprotein (LDL) yields 5% of the HDL signal, and both very-low-density lipoprotein (VLDL) and human serum albumin (HSA) yield 0%. The sensor reveals recovery rates between 94 and 104% at 95% confidence interval with precision of 2.3–7.7% and shows appreciable correlation (R2 = 0.97) with enzymatic colorimetric assay, the standard in clinical tests. In contrast to the latter, it achieves rapid results (10 min) during one-step analysis without the need for sample preparation.

Aims/Introduction Dyslipidemia plays a critical role in the pathogenesis of metabolic syndrome and diabetes. Evidence has increasingly shown that the ratio of low‐ to high‐density lipoprotein cholesterol (LDL‐C/HDL‐C) is a novel marker for increased risk of insulin resistance and cardiovascular diseases. However, the correlation between the LDL‐C/HDL‐C ratio and diabetes risk is rarely reported. This is the first study to investigate the association between the LDL‐C/HDL‐C ratio and new‐onset diabetes in a large community‐based cohort. Materials and Methods In this retrospective cohort study, a total of 116,661 adults without baseline diabetes were enrolled. Participants were stratified into four groups based on LDL‐C/HDL‐C ratio quartiles. The outcome of interest was new‐onset diabetes. Results During a median follow‐up period of 2.98 years, 2,681 (2.3%) new diabetes cases were recorded. The total cumulative incidence of diabetes progressively increased alongside LDL‐C/HDL‐C ratio quartiles (0.31, 0.43, 0.68 and 0.88%, respectively, P‐value for trend <0.001). After adjusting for potential confounders, using the lowest quartile of the LDL‐C/HDL‐C ratio as the reference, the risk of diabetes increased with LDL‐C/HDL‐C ratio quartiles (P‐value for trend <0.001); in particular, from the second to fourth quartile, hazard ratios were 1.18 (95% confidence interval 0.87–1.59), 1.42 (95% confidence interval 1.07–1.90) and 1.92 (95% confidence interval 1.43–2.59), respectively. The results were also robust to challenges in multiple sensitivity analyses. Conclusions Among the Chinese population, elevated LDL‐C/HDL‐C ratio might be an independent risk factor for new‐onset diabetes. In the present study, we investigated a relationship between the low‐density lipoprotein cholesterol : high‐density lipoprotein cholesterol (LDL‐C/HDL‐C) ratio and the risk of new‐onset diabetes, and found that an elevated LDL‐C/HDL‐C ratio is independently and positively associated with the increased risks of diabetes in the general population. These findings suggested that the ratio of LDL‐C/HDL‐C is not only a surrogate indicator of insulin resistance and cardiovascular disease, but also plays a vital role in the pathogenesis of diabetes.