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1.
Lipids Health Dis ; 23(1): 163, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831433

ABSTRACT

OBJECTIVE: High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. METHODS: Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. RESULTS: Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004-1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002-1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995-0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994-0.999 and 0.986, 0.975-0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993-0.996). CONCLUSIONS: The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.


Subject(s)
Cholesterol, HDL , Cholesterol, LDL , Genome-Wide Association Study , Mendelian Randomization Analysis , Myocardial Infarction , Polymorphism, Single Nucleotide , Triglycerides , Humans , Myocardial Infarction/genetics , Myocardial Infarction/drug therapy , Cholesterol, LDL/blood , Triglycerides/blood , Male , Female , Cholesterol, HDL/blood , Middle Aged , Membrane Proteins/genetics , Membrane Transport Proteins/genetics , Proprotein Convertase 9/genetics , Hypolipidemic Agents/therapeutic use , Hydroxymethylglutaryl CoA Reductases/genetics , Aged
2.
Lipids Health Dis ; 23(1): 162, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831434

ABSTRACT

BACKGROUND: The Triglyceride glucose (TyG) index-related indicators improve risk stratification by identifying individuals prone to atherosclerosis early in life. This study aimed to examine the relation between TyG-waist circumference-to-height ratio (TyG-WHtR) and coronary heart disease. METHODS: Data from four National Health and Nutrition Examination Surveys (NHANES) cycles between 2011 and 2018 were used for a cross-sectional study. The association between TyG-WHtR and coronary heart disease risk was examined using a multifactorial logistic regression model, and corresponding subgroup analyses were performed. Nonlinear correlations were analyzed using smooth curve fitting and threshold effects analysis. When nonlinear connections were discovered, appropriate inflection points were investigated using recursive methods. RESULTS: TyG-WHtR and coronary heart disease were significantly positively correlated in the multifactorial logistic regression analysis. Subgroup analyses and interaction tests revealed that gender, age, smoking status, and cancer were not significantly associated with this correlation (P for interaction > 0.05). Furthermore, utilizing threshold effect analysis and smooth curve fitting, a nonlinear connection with an inflection point of 0.36 was observed between TyG-WHtR and coronary heart disease. CONCLUSIONS: According to this study, the American population is far more likely to have coronary heart disease if they have higher TyG-WHtR levels.


Subject(s)
Blood Glucose , Coronary Disease , Triglycerides , Humans , Male , Triglycerides/blood , Female , Middle Aged , Coronary Disease/blood , Coronary Disease/epidemiology , Cross-Sectional Studies , Blood Glucose/metabolism , Adult , Nutrition Surveys , Aged , Logistic Models , Waist-Height Ratio , Waist Circumference , Risk Factors
3.
Front Endocrinol (Lausanne) ; 15: 1343853, 2024.
Article in English | MEDLINE | ID: mdl-38828414

ABSTRACT

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT). Patients and methods: In total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed. Results: Serum FGF21 significantly increased in the fasting state (P < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD (P < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC (P < 0.05) and was an independent factor for MAFLD (P < 0.05, OR=1.403). Conclusion: Dyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.


Subject(s)
Fibroblast Growth Factors , Inflammation , Postprandial Period , Humans , Fibroblast Growth Factors/blood , Male , Female , Middle Aged , Adult , Inflammation/blood , Inflammation/metabolism , Lipids/blood , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/metabolism , Triglycerides/blood , Dietary Fats , Biomarkers/blood , Fatty Acids, Nonesterified/blood
4.
Turk Kardiyol Dern Ars ; 52(4): 253-259, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38829642

ABSTRACT

OBJECTIVE: This study aimed to explore the association between the triglyceride-glucose (TyG) index and major adverse cardiovascular events (MACE) over a ten-year period in non-diabetic patients with acute myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI). METHODS: We included 375 consecutive non-diabetic patients presenting with acute MI who underwent primary PCI. The TyG index was calculated and patients were divided based on a cut-off value of ≥ 8.84 into high and low TyG index groups. The incidence of MACE, including all-cause mortality, target vessel revascularization, reinfarction, and rehospitalization for heart failure, was assessed over 10 years. RESULTS: Over the next 10 years, patients who underwent PCI for acute MI experienced a significantly higher incidence of MACE in the group with a high TyG index (≥ 8.84) (P = 0.004). Multivariable analysis revealed that the TyG index independently predicted MACE in these patients [odds ratio = 1.64; 95% confidence interval (CI): 1.22-2.21; P = 0.002]. Analysis of the receiver operating characteristic curve indicated that the TyG index effectively predicted MACE in patients with acute MI following PCI, with an area under the curve of 0.562 (95% CI: 0.503-0.621; P = 0.038). CONCLUSION: This study established a correlation between high TyG index levels and an elevated risk of MACE in non-diabetic patients with acute MI. The findings suggest that the TyG index could be a reliable indicator of clinical outcomes for non-diabetic acute MI patients undergoing PCI.


Subject(s)
Blood Glucose , Myocardial Infarction , Percutaneous Coronary Intervention , Triglycerides , Humans , Male , Female , Myocardial Infarction/blood , Myocardial Infarction/mortality , Myocardial Infarction/epidemiology , Middle Aged , Triglycerides/blood , Blood Glucose/analysis , Prognosis , Aged , Predictive Value of Tests , Incidence , ROC Curve
5.
Cardiovasc Diabetol ; 23(1): 187, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822373

ABSTRACT

BACKGROUND: Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients. METHODS: INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE). RESULTS: Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045-3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253-4.364, P = 0.008). CONCLUSION: This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients.


Subject(s)
Biomarkers , Blood Glucose , Coronary Angiography , Myocardial Ischemia , Myocardial Perfusion Imaging , Predictive Value of Tests , Triglycerides , Humans , Male , Female , Middle Aged , Aged , Triglycerides/blood , Prognosis , Myocardial Ischemia/blood , Myocardial Ischemia/diagnosis , Myocardial Ischemia/mortality , Myocardial Ischemia/epidemiology , Biomarkers/blood , Blood Glucose/metabolism , Risk Factors , Risk Assessment , Retrospective Studies , Time Factors , Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/diagnosis , Coronary Artery Disease/mortality , Insulin Resistance
6.
Sci Rep ; 14(1): 12634, 2024 06 02.
Article in English | MEDLINE | ID: mdl-38824158

ABSTRACT

Acute ST-segment elevation myocardial infarction (STEMI) is a severe cardiovascular disease that poses a significant threat to the life and health of patients. This study aimed to investigate the predictive value of triglyceride glucose index (TyG) combined with neutrophil-to-lymphocyte ratio (NLR) for in-hospital cardiac adverse event (MACE) after PCI in STEMI patients. From October 2019 to June 2023, 398 STEMI patients underwent emergency PCI in the Second People's Hospital of Hefei. Stepwise regression backward method and multivariate logistic regression analysis were used to screen the independent risk factors of MACE in STEMI patients. To construct the prediction model of in-hospital MACE after PCI in STEMI patients: Grace score model is the old model (model A); TyG combined with NLR model (model B); Grace score combined with TyG and NLR model is the new model (model C). We assessed the clinical usefulness of the predictive model by comparing Integrated Discrimination Improvement (IDI), Net Reclassification Index (NRI), Receiver Operating Characteristic Curve (ROC), and Decision Curve Analysis (DCA). Stepwise regression and multivariate logistic regression analysis showed that TyG and NLR were independent risk factors for in-hospital MACE after PCI in STEMI patients. The constructed Model C was compared to Model A. Results showed NRI 0.5973; NRI + 0.3036, NRI - 0.2937, IDI 0.3583. These results show that the newly developed model C predicts the results better than model A, indicating that the model is more accurate. The ROC analysis results showed that the AUC of Model A for predicting MACE in STEMI was 0.749. Model B predicted MACE in STEMI with an AUC of 0.685. Model C predicted MACE in STEMI with an AUC of 0.839. For DCA, Model C has a better net return between threshold probability 0.1 and 0.78, which is better than Model A and Model B. In this study, by combining TyG, NLR, and Grace score, it was shown that TyG combined with NLR could reasonably predict the occurrence of MACE after PCI in STEMI patients and the clinical utility of the prediction model.


Subject(s)
Lymphocytes , Neutrophils , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Triglycerides , Humans , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/surgery , ST Elevation Myocardial Infarction/complications , Male , Female , Percutaneous Coronary Intervention/adverse effects , Middle Aged , Triglycerides/blood , Aged , Risk Factors , ROC Curve , Blood Glucose/analysis , Blood Glucose/metabolism , Predictive Value of Tests , Prognosis , Lymphocyte Count , Retrospective Studies
7.
Cardiovasc Diabetol ; 23(1): 188, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824550

ABSTRACT

BACKGROUNDS: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD. METHODS: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan-Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices. RESULTS: A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [TyGadjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05-1.50, P = 0.014; TyG-WCaHR for all-cause mortality = 1.28, 95% CI 1.07-1.52, P = 0.006; TyG-WHtRaHR for all-cause mortality = 1.50, 95% CI 1.25-1.80, P < 0.001; TyG-WCaHR for cardiovascular mortality = 1.81, 95% CI 1.28-2.55, P = 0.001; TyG-WHtRaHR for cardiovascular mortality = 2.22, 95% CI 1.55-3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD (P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD (P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices. CONCLUSION: Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD.


Subject(s)
Biomarkers , Blood Glucose , Cardiovascular Diseases , Cause of Death , Insulin Resistance , Nutrition Surveys , Triglycerides , Humans , Female , Male , Middle Aged , Triglycerides/blood , Prognosis , Risk Assessment , Biomarkers/blood , United States/epidemiology , Blood Glucose/metabolism , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Adult , Time Factors , Databases, Factual , Aged , Risk Factors , Non-alcoholic Fatty Liver Disease/mortality , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/diagnosis , Cross-Sectional Studies , Predictive Value of Tests , Retrospective Studies
9.
JCO Precis Oncol ; 8: e2300690, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38691814

ABSTRACT

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of cytotoxic cancer treatment, often necessitating dose reduction (DR) or chemotherapy discontinuation (CD). Studies on peripheral neuropathy related to chemotherapy, obesity, and diabetes have implicated lipid metabolism. This study examined the association between circulating lipids and CIPN. METHODS: Lipidomic analysis was performed on plasma samples from 137 patients receiving taxane-based treatment. CIPN was graded using Total Neuropathy Score-clinical version (TNSc) and patient-reported outcome measure European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN (EORTC-QLQ-CIPN20). RESULTS: A significant proportion of elevated baseline lipids were associated with high-grade CIPN defined by TNSc and EORTC-QLQ-CIPN20 including triacylglycerols (TGs). Multivariable Cox regression on lipid species, adjusting for BMI, age, and diabetes, showed several elevated baseline TG associated with shorter time to DR/CD. Latent class analysis identified two baseline lipid profiles with differences in risk of CIPN (hazard ratio, 2.80 [95% CI, 1.50 to 5.23]; P = .0013). The higher risk lipid profile had several elevated TG species and was independently associated with DR/CD when modeled with other clinical factors (diabetes, age, BMI, or prior numbness/tingling). CONCLUSION: Elevated baseline plasma TG is associated with an increased risk of CIPN development and warrants further validation in other cohorts. Ultimately, this may enable therapeutic intervention.


Subject(s)
Bridged-Ring Compounds , Lipidomics , Peripheral Nervous System Diseases , Triglycerides , Humans , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/blood , Female , Male , Middle Aged , Triglycerides/blood , Risk Factors , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Adult , Taxoids/adverse effects , Taxoids/therapeutic use
12.
J Oleo Sci ; 73(5): 751-760, 2024.
Article in English | MEDLINE | ID: mdl-38692897

ABSTRACT

A double-blind, placebo-controlled, crossover trial was performed to analyze the effects of a small amount of lysolecithin and canola oil on blood glucose levels after consuming japonica rice. Overall, 17 Japanese adult men were assigned to consume 150 g of normally cooked japonica rice (placebo group) and 150 g of japonica rice cooked with 18 mg of lysolecithin and 1.8 g of canola oil (treatment group); these lipids were added as emulsified formulation (EMF) for stability and uniformity. Subsequently, blood samples were collected before and 30, 45, 60, 90, and 120 min after consuming test foods. There was no significant difference in blood glucose, insulin, and triglyceride levels between the groups. However, a stratified analysis of 11 subjects with body mass index (BMI) ≥ 22 revealed that blood glucose levels were significantly lower after 30 min in the treatment group than in the placebo group (p = 0.041). Through in vitro digestibility test, the rice sample of the treatment group was observed to release significantly less glucose within 20 min than that in the placebo group rice. These results suggest that the combination of a small amount of lysolecithin and canola oil modulated the increase in postprandial blood glucose levels induced by the intake of cooked japonica rice in adult men with BMI ≥ 22. This clinical trial was registered with the University Hospital Medical Information Network (UMIN) Center, (UMIN000045744; registered on 15/10/2021).


Subject(s)
Blood Glucose , Cross-Over Studies , Oryza , Postprandial Period , Rapeseed Oil , Humans , Male , Rapeseed Oil/administration & dosage , Oryza/chemistry , Double-Blind Method , Blood Glucose/analysis , Adult , Triglycerides/blood , Middle Aged , Body Mass Index , Insulin/blood , Glycemic Index , Time Factors , East Asian People
14.
FASEB J ; 38(9): e23643, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38703030

ABSTRACT

Secreted phospholipase A2s are involved in the development of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease, which have become serious and growing health concerns worldwide. Integration of genome-wide association study and gene co-expression networks analysis showed that the secreted phospholipase A2 group XIIA (PLA2G12A) may participate in hepatic lipids metabolism. Nevertheless, the role of PLA2G12A in lipid metabolism and its potential mechanism remain elusive. Here, we used AAV9 vector carrying human PLA2G12A gene to exogenously express hPLA2G12A in the liver of mice. We demonstrated that the overexpression of hPLA2G12A resulted in a significant decrease in serum lipid levels in wild-type mice fed with chow diet or high-fat diet (HFD). Moreover, hPLA2G12A treatment protected against diet-induced obesity and insulin resistance in mice fed a HFD. Notably, we found that hPLA2G12A treatment confers protection against obesity and hyperlipidemia independent of its enzymatic activity, but rather by increasing physical activity and energy expenditure. Furthermore, we demonstrated that hPLA2G12A treatment induced upregulation of ApoC2 and Cd36 and downregulation of Angptl8, which contributed to the increase in clearance of circulating triglycerides and hepatic uptake of fatty acids without affecting hepatic de novo lipogenesis, very low-density lipoprotein secretion, or intestinal lipid absorption. Our study highlights the potential of PLA2G12A gene therapy as a promising approach for treating obesity, insulin resistance and T2DM.


Subject(s)
Diet, High-Fat , Energy Metabolism , Insulin Resistance , Mice, Inbred C57BL , Obesity , Triglycerides , Animals , Obesity/metabolism , Obesity/etiology , Mice , Triglycerides/metabolism , Triglycerides/blood , Male , Diet, High-Fat/adverse effects , Humans , Liver/metabolism , Lipid Metabolism
15.
Eur Rev Med Pharmacol Sci ; 28(8): 3016-3023, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38708458

ABSTRACT

OBJECTIVE: The triglyceride-glucose index (TyG) has been proposed as a marker of insulin resistance (IR) and has shown associations with cardiovascular diseases. This study aimed to investigate the relationship between the TyG and the coronary slow flow phenomenon (CSFP) and explore the index's potential as a predictor of this condition. PATIENTS AND METHODS: A total of 187 patients who underwent coronary angiography were included; of these, 91 patients were diagnosed with CSFP, and 96 patients with normal coronary flow served as a control group. The TyG was calculated using fasting triglyceride and glucose levels. RESULTS: The results showed that the TyG was significantly higher in the CSFP group compared with the control group (p < 0.001). Additionally, the TyG exhibited a moderate positive correlation with the thrombolysis-in-myocardial-infarction frame count in coronary arteries (p < 0.001). A multivariate logistic regression analysis revealed that the TyG, along with gender, ejection fraction, and uric acid, remained significant predictors of CSFP (p < 0.05). CONCLUSIONS: This study's findings suggest that the TyG may serve as a useful marker for identifying individuals at risk of CSFP and provide insights into the potential role of IR in its pathophysiology.


Subject(s)
Biomarkers , Blood Glucose , Coronary Angiography , No-Reflow Phenomenon , Triglycerides , Humans , Triglycerides/blood , Male , Female , Blood Glucose/analysis , Blood Glucose/metabolism , Middle Aged , Biomarkers/blood , No-Reflow Phenomenon/blood , No-Reflow Phenomenon/diagnosis , No-Reflow Phenomenon/diagnostic imaging , Insulin Resistance , Coronary Circulation , Aged
16.
Sci Rep ; 14(1): 10235, 2024 05 03.
Article in English | MEDLINE | ID: mdl-38702370

ABSTRACT

To reveal the sources of obesity and type 2 diabetes (T2D) in humans, animal models, mainly rodents, have been used. Here, we propose a pig model of T2D. Weaned piglets were fed high fat/high sugar diet suppling 150% of metabolizable energy. Measurements of weight gain, blood morphology, glucose plasma levels, cholesterol, and triglycerides, as well as glucose tolerance (oral glucose tolerance test, OGTT) were employed to observe T2D development. The histology and mass spectrometry analyses were made post mortem. Within 6 months, the high fat-high sugar (HFHS) fed pigs showed gradual and significant increase in plasma triglycerides and glucose levels in comparison to the controls. Using OGTT test, we found stable glucose intolerance in 10 out of 14 HFHS pigs. Mass spectrometry analysis indicated significant changes in 330 proteins in the intestine, liver, and pancreas of the HFHS pigs. These pigs showed also an increase in DNA base modifications and elevated level of the ALKBH proteins in the tissues. Six diabetic HFHS pigs underwent Scopinaro bariatric surgery restoring glycaemia one month after surgery. In conclusion, a high energy diet applied to piglets resulted in the development of hyperlipidaemia, hyperglycaemia, and type 2 diabetes being reversed by a bariatric procedure, excluding the proteomic profile utill one month after the surgery.


Subject(s)
Bariatric Surgery , Diabetes Mellitus, Type 2 , Proteomics , Animals , Diabetes Mellitus, Type 2/metabolism , Swine , Proteomics/methods , Diet, High-Fat/adverse effects , Glucose Tolerance Test , Disease Models, Animal , Blood Glucose/metabolism , Proteome/metabolism , Obesity/metabolism , Obesity/surgery , Triglycerides/blood , Triglycerides/metabolism
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 675-681, 2024 Apr 20.
Article in Chinese | MEDLINE | ID: mdl-38708500

ABSTRACT

OBJECTIVE: To investigate the role of irisin in exercise-induced improvement of renal function in type 2 diabetic rats. METHODS: Forty male SD rats aged 4-6 weeks were randomized into normal control group, type 2 diabetes mellitus model group, diabetic exercise (DE) group and diabetic irisin (DI) group (n=8). The rats in DE group were trained with treadmill running for 8 weeks, and those in DI group were given scheduled irisin injections for 8 weeks. After the treatments, blood biochemical parameters of the rats were examined, and renal histopathology was observed with HE, Masson and PAS staining. Western blotting was used to detect the protein expression levels in the rats'kidneys. RESULTS: The diabetic rats showed significantly increased levels of fasting insulin, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen with lowered serum irisin level (all P < 0.05). Compared with those in DM group, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen levels were decreased and serum irisin levels were increased in both DE and DI groups (all P < 0.05). The rats in DM group showed obvious structural disorders and collagen fiber deposition in the kidneys, which were significantly improved in DE group and DI group. Both regular exercises and irisin injections significantly ameliorated the reduction of FNDC5, LC3-II/I, Atg7, Beclin-1, p-AMPK, AMPK and SIRT1 protein expressions and lowered of p62 protein expression in the kidneys of the diabetic rats (all P < 0.05). CONCLUSION: Both exercise and exogenous irisin treatment improve nephropathy in type 2 diabetic rats possibly due to irisin-mediated activation of the AMPK/SIRT1 pathway in the kidneys to promote renal autophagy.


Subject(s)
Autophagy , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Fibronectins , Kidney , Physical Conditioning, Animal , Rats, Sprague-Dawley , Sirtuin 1 , Animals , Fibronectins/metabolism , Male , Rats , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Experimental/metabolism , Kidney/metabolism , Sirtuin 1/metabolism , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/therapy , Beclin-1/metabolism , Creatinine/blood , Blood Urea Nitrogen , Insulin , Triglycerides/metabolism , Triglycerides/blood , Cholesterol/blood , AMP-Activated Protein Kinases/metabolism
18.
BMC Pregnancy Childbirth ; 24(1): 347, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711000

ABSTRACT

BACKGROUND: This study investigates the causal relationship between lipid traits and GDM in an effort to better understand the aetiology of GDM. METHODS: Employing a two-sample Mendelian Randomization (MR) framework, we used Single Nucleotide Polymorphisms (SNPs) as instrumental variables to examine the impact of lipids and apolipoproteins on GDM. The research comprised univariable and multivariable MR analyses, with a prime focus on individual and combined effects of lipid-related traits. Statistical techniques included the fixed-effect inverse variance weighted (IVW) method and supplementary methods such as MR-Egger for comprehensive assessment. RESULTS: Our findings revealed the following significant associations: apoA-I and HDL cholesterol were inversely correlated with GDM risk, while triglycerides showed a positive correlation. In multivariable analysis, apoA-I consistently exhibited a strong causal link with GDM, even after adjusting for other lipids and Body Mass Index (BMI). CONCLUSION: The study demonstrates a significant causal relationship between apoA-I and GDM risk.


Subject(s)
Apolipoprotein A-I , Cholesterol, HDL , Diabetes, Gestational , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Triglycerides , Humans , Female , Pregnancy , Diabetes, Gestational/genetics , Diabetes, Gestational/blood , Triglycerides/blood , Apolipoprotein A-I/blood , Apolipoprotein A-I/genetics , Cholesterol, HDL/blood , Apolipoproteins/blood , Apolipoproteins/genetics , Body Mass Index , Lipids/blood , Risk Factors
19.
BMC Public Health ; 24(1): 1256, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714969

ABSTRACT

OBJECTIVES: Exposure to cigarette smoke introduces a large amount of nicotine into the bloodstream through the lungs. So, smoking can be a risk factor for many diseases. The present study was conducted to investigate the effect of active and passive cigarette smoke on the blood lipid profile and dyslipidemia. METHODS: This cross-sectional study was performed on 5052 individuals who participated in the recruitment phase of the Shahedieh cohort study. A logistic regression model was used to investigate the relationship between smoking exposure status and lipid profiles. RESULTS: The prevalence of abnormal low-density lipoprotein-cholesterol (LDL-C), abnormal HDL-C, abnormal total cholesterol (TC), abnormal triglyceride (TG), and dyslipidemia were 254 (5.00%), 562 (11.10%), 470 (9.30%), 1008 (20.00%), and 1527 (30.20%), respectively. Adjusting for confounders, it was observed that current smokers had higher odds of having abnormal HDL-C [OR (95% CI), 2.90 (2.28-3.69)], abnormal TG [OR (95% CI), 1.71 (1.38-2.13)] and dyslipidemia [OR (95% CI), 1.86 (1.53-2.25)]. Ex-smokers also had greater odds of abnormal HDL-C [OR (95% CI), 1.51 (1.06-2.16)] compared to non-smokers who were not exposed to cigarette smoke. CONCLUSIONS: The findings indicated that current smokers had higher TG and lower HDL. So, necessary measures should be taken to reduce smoking. The findings also showed that the prevalence of abnormal TG and HDL in ex-smokers was lower than in current smokers. Therefore, the existence of incentive policies to quit smoking seems necessary.


Subject(s)
Dyslipidemias , Lipids , Tobacco Smoke Pollution , Humans , Male , Female , Cross-Sectional Studies , Adult , Middle Aged , Tobacco Smoke Pollution/adverse effects , Tobacco Smoke Pollution/statistics & numerical data , Tobacco Smoke Pollution/analysis , Dyslipidemias/epidemiology , Lipids/blood , Iran/epidemiology , Cohort Studies , Risk Factors , Cigarette Smoking/epidemiology , Smoking/epidemiology , Triglycerides/blood , Cholesterol, HDL/blood , Prevalence
20.
Lipids Health Dis ; 23(1): 133, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38705980

ABSTRACT

BACKGROUND: Certain studies have indicated a link between obstructive sleep apnea and insulin resistance in specific populations. To gain more clarity, extensive research involving a broad sample of the overall population is essential. The primary objective of this study was to investigate this correlation by utilizing data from the National Health and Nutrition Examination Survey database. METHODS: The analysis incorporated data from the National Health and Nutrition Examination Survey database spanning the time periods from 2005 to 2008 and from 2015 to 2018, with a focus on American adults aged 18 years and older after applying weight adjustments. Key variables such as obstructive sleep apnea, triglyceride glucose index, and various confounding factors were considered. A generalized linear logistic regression model was used to investigate the association between obstructive sleep apnea and the triglyceride glucose index, with additional exploration of the consistency of the results through hierarchical analysis and other techniques. RESULTS: The study included participants aged between 18 and 90 years, with an average age of 46.75 years. Among the total sample, 50.76% were male. The triglyceride glucose index demonstrated a diagnostic capability for obstructive sleep apnea, with an AUC of 0.701 (95% CI: 0.6619-0.688). According to the fully adjusted model, individuals in the fourth quartile of the triglyceride glucose index showed an increased likelihood of having obstructive sleep apnea compared to those in the first quartile (OR: 1.45; 95% CI: 1.02-2.06; P < 0.05). Subgroup analysis indicated that male sex (OR: 2.09; 95% CI: 1.76-2.45; P < 0.05), younger age (OR: 2.83; 95% CI: 2.02-3.96; P < 0.05), white ethnicity (OR: 2.29; 95% CI: 1.93-2.73; P < 0.05), and obesity (OR: 1.54; 95% CI: 1.28-1.85; P < 0.05) were correlated with an elevated risk of OSA. CONCLUSIONS: This study demonstrated a strong association between an elevated TG index and OSA. Additionally, the triglyceride glucose index could serve as an independent predictor of obstructive sleep apnea.


Subject(s)
Blood Glucose , Nutrition Surveys , Sleep Apnea, Obstructive , Triglycerides , Humans , Sleep Apnea, Obstructive/blood , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiology , Male , Middle Aged , Triglycerides/blood , Female , Adult , Blood Glucose/metabolism , Aged , Adolescent , Young Adult , Aged, 80 and over , Insulin Resistance , Logistic Models
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