Liver steatosis and fibrosis increase the predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk, though the roles of chronic inflammation and metabolic dysregulation remain unclear. This cross-sectional study quantitatively assesses this association and evaluates the mediating effects of metabolic dysregulation and chronic inflammation.

In this study, we enrolled 6110 adults from ten communities in Canton, China. Hepatic steatosis and fibrosis were assessed using vibration-controlled transient elastography (VCTE) through controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), while predicted 10-year ASCVD risk was calculated using the China-PAR project model. Associations between CAP/LSM values and predicted 10-year ASCVD risk were analyzed. Mediation analysis quantified the effects of high-sensitivity C-reactive protein (hs-CRP), homeostasis model assessment of insulin resistance (HOMA-IR), remnant cholesterol (RC), and non-high-density lipoprotein cholesterol (non-HDL-C). The main statistical methods used included logistic regression, restricted cubic splines (RCS) analysis, interaction calculations, and mediation analysis to examine the relationships and mediators.

The study population had a mean age of 50.1 years (SD = 9.7), with 3927 females (64.3%) and 2183 males (35.7%). Additionally, 808 participants (13.2%) had type 2 diabetes, and 1911 participants (31.3%) had hypertension. Compared to the first CAP quartile (Q1), higher CAP quartiles showed increased odds ratios (OR) for predicted moderate to high 10-year ASCVD risk: 1.14 (0.89, 1.45), 1.37 (1.08, 1.73), and 2.44 (1.93, 3.10). Mediation analysis showed hs-CRP and HOMA-IR mediated CAP's link to ASCVD risk, with mediation proportions of 15.40% and 27.37%. RC and non-HDL-C mediated this association at 7.12% and 6.26%. Among patients with hepatic steatosis (CAP ≥ 248 dB/m), LSM Q4 participants had a significantly higher predicted 10-year ASCVD risk than those in LSM Q1 (OR 2.22, [1.52, 3.25]), with hs-CRP and HOMA-IR mediating 2.62% and 13.75%, respectively.

Liver steatosis and fibrosis were associated with the increased predicted ASCVD risk, with mediation effects from hs-CRP, HOMA-IR, RC, and non-HDL-C.

Many studies have demonstrated that multiple metabolic risk factors (MRFs) predict cardiovascular disease (CVD) in patients with diabetes, but changes in these markers before CVD onset are not well characterized. We aimed to explore the trajectories of various MRFs before the occurrence of CVD in patients with newly diagnosed diabetes.

Prospective cohort study.

We selected 21,798 patients with newly diagnosed diabetes from seven cycles in the Kailuan cohort. MRFs were measured at two-year intervals prior to CVD diagnosis. We used the mixed effects models to construct trajectories for 16 MRFs respectively.

During up to 15 years of follow-up, a total of 2,105 CVD events occurred. Participants who developed CVD had more adverse levels of most MRFs at baseline and during follow-up than those who did not develop CVD. Before CVD diagnosis, fasting plasma glucose, insulin resistance, pulse pressure, heart rate, liver function, and inflammatory biomarkers showed linear increases, while insulin sensitivity, lipids profiles, obesity indices, and diastolic blood pressure showed linear decreases. Systolic blood pressure, as one of the most important components in predicting CVD, showed a quadratic increase.

In patients with newly diagnosed diabetes, unfavorable levels of MRFs were present before CVD developed. Key MRFs, including the TyG index, VAI, SBP, and pulse pressure, progressively increased over time and remained higher compared to non-CVD populations. This highlights the need for early prevention to reduce the burden of cardiovascular complications in diabetes.

Patients with chronic kidney disease (CKD) experience high mortality rates from cardiovascular disease (CVD). Insulin resistance (IR) is a frequent complication of CKD and is associated with poorer cardiovascular outcomes. This study investigates the prevalence and associations of IR in hemodialysis (HD) patients.

A descriptive-analytic cross-sectional study was conducted on 103 HD patients. We used the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI) to measure IR. We examined potential associations between IR and the following factors: age, gender, etiology of kidney failure, BMI, waist circumference, blood lipids, hemoglobin concentration, uric acid, and duration of HD.

The prevalence of IR, as measured by HOMA-IR, was 61.2%, and by QUICKI, it was 48.5%. Age, gender, etiology of kidney failure and increased waist circumference did not significantly influence IR. A significant associations were observed between IR and higher BMI, anemia, dyslipidemia, and longer duration of HD therapy. Interestingly, the HOMA-IR and QUICKI indices correlated for most factors except total cholesterol, LDL-C, and uric acid.

This study found a high prevalence of IR in HD patients, with 61.2% identified by HOMA-IR and 48.5% by QUICKI. We confirmed significant associations between IR and BMI, anemia, dyslipidemia, and duration of HD therapy in this population.

This research investigates the relationships between the composite dietary antioxidant index (CDAI) and the likelihood of cardiovascular disease (CVD) and mortality in older adults with hypertension. Utilized data from the National Health and Nutrition Examination Survey (NHANES) to investigate the potential mediating role of the triglyceride-glucose (TyG) index in these relationships.

A cohort of 5,276 participants, aged 65 years or older and diagnosed with hypertension, was extracted from the NHANES database. The main outcomes examined were the odds of CVD and mortality, utilizing data from the National Center for Health Statistics (NCHS). Multivariate logistic regression models were utilized to evaluate the relationship between CDAI and CVD. Cox proportional hazards regression models and Kaplan-Meier survival curves were utilized to analyze the relationship between CDAI and mortality. Mediation analysis was conducted to assess the potential intermediary role of TyG-related indicators-specifically TyG, TyG-BMI, TyG-WC, and TyG-WHtR- in the connection between CDAI and mortality.

The mean CDAI for the study participants was 1.88 ± 3.90, and the average age was 74.15 ± 5.96 years. During an average follow-up duration of 109.51 months, 4,712 cases of CVD and 725 recorded deaths were observed. In the fully adjusted models, CDAI showed a negative association with both CVD (Odds Ratio [OR] = 0.94, 95% Confidence Interval [CI] = 0.92-0.97) and mortality (Hazard Ratio [HR] = 0.95, 95% CI = 0.93-0.97). Mediation analysis indicated that the TyG-BMI, TyG-WC, and TyG-WHtR indices accounted for 33.1%, 34.3%, and 19.1% of the relationship between CDAI and mortality, respectively.

A higher CDAI demonstrated an inverse association with both CVD and mortality in elderly hypertensive individuals. The relationship was partially mediated by TyG-related indices, indicating that increased antioxidant intake may lead to improved health outcomes and a decreased risk of poor prognosis in this population.

We aimed to investigate the associations of the triglyceride-glucose index, which measures insulin resistance, and the incidence of Parkinson's disease.

Our study used the Health Screening Cohort database of the National Health Insurance Service of South Korea (2002-2019). We included 310,021 participants who had no previous history of Parkinson's disease and for whom more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson's disease was determined via the International Classification of Diseases Tenth edition (G20) with a specific reimbursement code for rare intractable diseases and a history of prescriptions for anti-Parkinsonism drugs.

During a median of 9.64 years (interquartile range 8.72-10.53), 4,587 individuals (1.5%) had Parkinson's disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index score was associated with a significantly increased risk of Parkinson's disease (hazard ratio [HR]: 1.062; 95% confidence interval [CI] 1.007-1.119). In a sensitivity analysis, the triglyceride-glucose index was associated with the incidence of Parkinson's disease in a non-diabetes mellitus cohort (HR: 1.093; 95% CI 1.025-1.165), but not in the diabetes mellitus cohort (HR: 0.990; 95% CI 0.902-1.087). In a restricted cubic spline analysis, the association between the triglyceride-glucose index and the incidence risk of Parkinson's disease showed a nonlinear increasing (J-shaped) trend.

Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence of Parkinson's disease in the general population, particularly in a nondiabetic mellitus cohort.

Cardiovascular disease is the leading cause of death throughout most of the industrialized world. Metabolic syndrome (MetS) and its associated pathologies are underlying factors in the etiology of cardiovascular disease, as well as a plethora of other maladies which cause excess morbidity and mortality. Adipose tissue (AT) has come to be regarded as a bona fide endocrine organ which secretes specific molecular entities constituting part of a complex web of inter-organ crosstalk that functions as a key determinant of whole-body metabolic phenotype. Brown adipose tissue (BAT) has classically been regarded as a thermogenic tissue exerting its metabolic effects primarily through its capacity to oxidize substrates decoupled from ATP resynthesis, thereby resulting in increased energy expenditure (EE) and heat production. However, in recent years, BAT has begun to receive attention as a secretory organ in its own right. The molecules secreted specifically by BAT have been termed "batokines", and currently available evidence supports the notion that batokines exert favorable metabolic effects on multiple organ systems. While maintenance of healthy body composition by conferring resistance to excessive adiposity is a rather obvious mechanism by which BAT operates via increased EE, effects on critical organs such as the heart remain unclear. This narrative review focuses on four types of batokines (FGF21, neuregulin 4, 12,13-diHOME, and BAT-derived microRNAs) for which evidence of modulation of cardiovascular function exists in the context of pathological states such as hypertension, atherosclerosis, and ischemia/reperfusion injury. Given the overwhelming burden of cardiometabolic disease, further study of the functions of BAT and its secretome is warranted and will intensify in the future.

The development of insulin resistance (IR) is characterized by a series of metabolic disturbances, including, but not limited to, impaired glucose uptake, increased blood sugar levels, and disrupted lipid metabolism [...].

The study aimed to assess the association of five insulin resistance surrogates, namely HOMA-β (Homeostasis Model Assessment of Beta-cell Function), QUICKI (Quantitative Insulin Sensitivity Check Index), IGR (Insulin Glucose Ratio), e-IS (Estimated Insulin Sensitivity), and Bennett ISI(Bennett's insulin sensitivity index) with all-cause and cardiovascular mortality in respondents with metabolic syndrome(MetS). The prospective cohort of 6662 participants aged 18 years and older with metabolic syndrome was extracted from the National Health and Nutrition Examination Survey(NHANES 1999-2016). The multivariate Cox proportional hazards regression model, Kaplan-Meier survival curve, and log-rank tests were applied to determine the association between the five indices and all-cause mortality and cardiovascular mortality in the MetS population. Restricted cubic splines, a two-piece segmented Cox proportional hazards model, and threshold effect analyses were performed to evaluate the nonlinear relationship. Sensitivity analyses were then conducted by removing individuals with CKD, CHF, CAD, stroke, or cancer, respectively. All five insulin resistance (IR) surrogates displayed a negative association with all-cause and cardiovascular mortality in participants with metabolic syndrome. Restricted cubic spline curves showed QUICKI, IGR, and e-IS had a nonlinear relationship with statistical significance. MetS population at the highest quartile of HOMA-β or IGR exhibited lower all-cause and cardiovascular event probabilities compared with those at the lowest quartile, and e-IS had a similar correlation with cardiovascular events. Threshold effect analyses showed that there were inflection points of IGR for all-cause and cardiovascular mortality. As IGR gradually approached inflection points, the two types of mortality risks descended by 15%[HR 0.85(0.80,0.91)] and 19%[HR 0.81(0.71,0.92)], respectively. Sensitivity analysis indicated most results were robust, but Bennett ISI did not exhibit significant outcomes in participants without CKD. Our study provides evidence that HOMA-β, QUICKI, IGR, e-IS, and Bennett ISI displayed a reverse correlation with all-cause mortality and cardiovascular mortality in participants with metabolic syndrome. The five IR surrogates should be given more attention during the follow-up of MetS population.

Background/Objectives: The triglyceride/high-density lipoprotein (TG/HDL) ratio serves as a simple marker for insulin resistance. We investigated whether the TG/HDL ratio would be associated with the incidence risk of heart failure (HF). Methods: The study utilized data from the National Health Insurance Service-Health Screening Cohort database of South Korea from 2002 to 2019. The TG/HDL ratio was utilized as a time-dependent covariate or average value of at least three times throughout the follow-up period. The outcome of interest was incident heart failure (HF) corresponding with the International Classification of Disease, Tenth Revision code of I50. Results: A total of 293,968 individuals were included in this study. During the median 9.6 years (interquartile range 9.2-10.13), 27,852 individuals (9.47%) had a cumulative incidence of HF. Considering the multivariable time-dependent Cox proportional hazard model with the repeated measures of the TG/HDL ratio, per unit increase in the TG/HDL ratio significantly increased the risk of HF in the entire cohort (hazard ratio (HR): 1.007, 95% confidence interval (CI): 1.002-1.011), diabetes mellitus (DM) cohort (HR: 1.006. 95% CI: 1.002-1.010), and non-DM cohort (HR: 1.008, 95% CI: 1.003-1.013). Regarding average TG/HDL ratio quartiles, compared to the lowest quartiles (Q1), the highest quartiles (Q4) were positively associated with the incidence risk of HF accompanied by a significant p for trend (HR: 1.114, 95% CI: 1.075-1.155) in fully adjusted multivariable analysis. Conclusions: Our study demonstrated that the repeatedly measured TG/HDL ratio was associated with the incidence risk of HF regardless of the presence of DM history in the general population.

Cardiovascular diseases (CVDs) are gradually becoming the leading cause of morbidity and mortality among chronic non-communicable diseases. Previous studies have found that the TyG index is an effective alternative indicator for insulin resistance (IR) and is associated with cardiovascular events. Additionally, obesity directly or indirectly increases the risk of developing CVDs. Up to now, studies on the combined effects of these factors are insufficient, and the conclusions are not yet consistent. This study aims to analyze whether the baseline levels and fluctuations of triglyceride glucose-body mass index (TyG-BMI) are associated with the incidence of CVDs and their subtypes in a prospective cohort of middle-aged and elderly individuals.

The data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. After excluding participants with partially missing variables that could affect the study results, this study ultimately included 7,072 participants, with data records spanning from 2011 to 2020. The exposures were TyG-BMI and the change in TyG-BMI from 2011 to 2015. The TyG-BMI index was calculated as TyG index multiply BMI. The change of TyG-BMI was categorized using K-means clustering and baseline TyG-BMI was grouped based on quartiles. We used Cox proportional hazards models to evaluate the relationship between baseline quartiles of the TyG-BMI index and its variability with CVDs and their subtypes.

Among the 7,072 participants (mean age of 59.1 ± 9.3 years), 3330 (47%) were male. During an average follow-up of 7.1 years, 1,774 (25.1%) participants developed new-onset cardiovascular diseases. After stratification by baseline TyG-BMI quartiles, higher TyG-BMI levels were associated with an increased risk of CVDs, The hazard ratio (HR) and 95% confidence interval (95% CI) for the highest quartile group were 1.69 (1.44-2.00). After adjusting for potential confounding factors, compared to participants with consistently low TyG-BMI levels, those with moderate TyG-BMI levels and a slowly increasing trend had an HR of 1.27 (95% CI 1.10-1.47), while those with the highest TyG-BMI levels and a slowly decreasing trend had an HR of 1.52 (95% CI 1.26-1.83).

Material changes in the TyG-BMI are independently associated with the risk of CVDs in middle-aged and elderly individuals. Detecting long-term changes in the TyG-BMI may aid in the early identification of high-risk individuals and help prevent the occurrence of various cardiovascular diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is correlated with an increased cardiovascular risk, independent of other traditional risk factors. The mechanisms underlying this pathogenic link are complex yet remain incompletely elucidated. Among these, the most significant are visceral adiposity, low-grade inflammation and oxidative stress, endothelial dysfunction, prothrombotic status, insulin resistance, dyslipidemia and postprandial hyperlipemia, gut dysbiosis, and genetic mutations. Cardiovascular diseases are the leading cause of death in patients with MASLD. These patients have an increased incidence of coronary artery disease, carotid artery disease, structural and functional cardiac abnormalities, and valvulopathies, as well as arrhythmias and cardiac conduction disorders. In this review, we present the latest data on the association between MASLD and cardiovascular risk, focusing on the pathogenic mechanisms that explain the correlation between these two pathologies. Given the high rates of cardiovascular morbidity and mortality among patients with MASLD, we consider it imperative to raise awareness of the risks associated with this condition within the general population. Further research is essential to clarify the mechanisms underlying the increased cardiovascular risk linked to MASLD. This understanding may facilitate the identification of new diagnostic and prognostic biomarkers for these patients, as well as novel therapeutic targets.

The association between insulin resistance and increased risk of Parkinson's disease (PD) has rarely been investigated. Our study aimed to investigate the association between the triglyceride/high-density lipoprotein (TG/HDL) ratio (which represents insulin resistance), and the incidence risk of PD in the general population. This study was conducted using data from the National Health Insurance Service-Health Screening Cohort Database of South Korea (2002-2019). We enrolled 310,023 participants who had no previous PD history and who had undergone more than three repeated measurements for the TG/HDL cholesterol ratio. The diagnosis of PD was determined using the International Classification of Diseases, 10th Revision code G20, specific reimbursement codes for Rare Intractable Diseases of V124, and a history of anti-PD drug prescription. During a median of 9.64 years (interquartile range 8.72-10.53), 4,587 individuals (1.47%) had an incidence of PD. Considering the multivariable time-dependent Cox proportional hazard model with repeated measures of average TG/HDL cholesterol ratio, a per unit increase in TG/HDL cholesterol ratio significantly increased the risk of PD in the entire cohort (hazard ratio (HR), 1.010; 95% confidence interval (CI), 1.001-1.020). These repeated measures of the average TG/HDL cholesterol ratio were associated with the incidence risk of PD in a J-shaped pattern for the entire diabetes mellitus (DM) and non-DM cohorts in restricted cubic spline analysis. Compared to the lowest tertiles (T1), the highest tertiles (T3) were positively associated with the incidence risk of PD (HR: 1.149, 95% CI 1.065-1.239 in the entire cohort, p for trend < 0.001; HR: 1.175, 95% CI 1.075-1.285 in the non-DM cohort, p for trend < 0.001). In contrast, the lowest (T1) and highest tertiles (T3) were not associated with the incidence risk of PD in the DM cohort (HR: 1.128, 95% CI 0.909-1.348) in fully adjusted multivariable analysis. Our study provides information that TG/HDL ratio may be positively associated with PD incidence risk in a non-DM population in longitudinal setting of the general population.

Insulin resistance proxy indicators are significantly associated with cardiovascular disease (CVD) and diabetes. However, the correlations between the estimated glucose disposal rate (eGDR) index and CVD and its subtypes have yet to be thoroughly researched.

10,690 respondents with diabetes and prediabetes from the NHANES 1999-2016 were enrolled in the study. Three machine learning methods (SVM-RFE, XGBoost, and Boruta algorithms) were employed to select the most critical variables. Logistic regression models were established to evaluate the association between eGDR and CVD. We applied ROC curves, C-statistics, NRI, IDI, calibration curves, and DCA curves to assess model performance. Subgroup analyses were conducted to investigate the association among different subgroups.

Participants in the higher quartile showed a decreased prevalence of CVD. Multivariate logistic regression models and RCS curves demonstrated that eGDR had an independently negative linear correlation with the likelihood of CVD[Q4 vs. Q1: OR 0.24(0.18,0.32)], CAD[OR 0.81(0.78,0.85)], CHF[OR 0.81(0.76,0.86)], and stroke[0.85(0.80,0.90)]. Model evaluation showed better performance in fully adjusted models than basic models[C-statistics(Model 3 vs. Model 1): CVD(0.683 vs. 0.814), CAD(0.672 vs. 0.807), CHF(0.714 vs. 0.839) and stroke(0.660 vs. 0.790)]. The AUCs of eGDR were significantly higher than the values of other IR surrogates in the unadjusted models, and slightly higher in the fully adjusted models. Subgroup analyses indicated that the results were robust.

A lower eGDR was significantly associated with a heightened likelihood of CVD and its subtypes in diabetic and prediabetic populations. And eGDR exhibited better performance in evaluating the associations compared to other IR proxies encompassing TyG, HOMA-IR, QCUIKI, METS-IR, etc.

The global burden of gout, a severe and painful arthralgia, is of note and is expected to increase in the future. We aimed to investigate the association between the triglyceride/high-density lipoprotein (TG/HDL) ratio, a simple and validated biomarker for insulin resistance, and the incidence of gout in a longitudinal setting in the general population.

Our study was conducted using the National Health Insurance Service-Health Screening Cohort database of Republic of Korea (2002-2019). We included 300,107 participants who had no previous history of gout and had data for more than three repeated measurements of the triglyceride-glucose (TyG) index. The incidence of gout was determined using at least two or more claims of the ICD-10 code M10.

During a median 9.62 years (interquartile range 8.72-10.53), 14,116 individuals (4.72%) had a reported incidence of gout. In a fully adjusted multivariable time-dependent Cox proportional hazards model with repeated measures of the TyG index, a unit increase in the index significantly increased the risk of gout in the entire cohort (hazard ratio (HR) = 1.150, 95% confidence interval (CI) 1.116-1.184). In a multivariable Cox proportional model of average TyG index quartiles, comparison of the lowest (Q1) and highest quartiles (Q4) indicated a significant positive association with the incidence of gout (HR: 1.326, 95% CI: 1.260-1.397). This association was non-linear (J-shape) when assessing the entire cohort and the diabetes and non-diabetes cohorts.

Our study demonstrated that increased TyG index was associated with an incidence risk of gout in the general population. Additionally, this association was non-linear (J-shape) not only in the entire cohort, but also in diabetes mellitus and non-diabetes mellitus cohorts. The TyG index may be an important predictor of gout.

We intended to examine the relationship between estimated glucose disposal rate (eGDR) and risks of all-cause and cardiovascular deaths in non-diabetic adults.

38,175 participants from the National Health and Nutrition Examination Survey (1999-2018) were included, and deaths were identified through the National Death Index.

With a median follow-up of 9.8 years, we found that dose-response relationships between eGDR level and the risk of death differed between genders. In female participants, higher eGDR level was linearly correlated with lower risks of all-cause and cardiovascular deaths. In contrast, among male participants, there were L-shaped relationships between eGDR and risks of all-cause and cardiovascular deaths, with threshold points of 8.50 and 8.49 mg/kg/min, respectively. To the left of threshold points, eGDR was negatively linked with risks of all-cause (HR 0.91, 95 % CI 0.88-0.94, P < 0.001) and cardiovascular deaths (HR 0.87, 95 % CI 0.82-0.93, P < 0.001). After the inflection point, an increase in eGDR was not related to lower risks of all-cause and cardiovascular deaths (P > 0.05).

Higher eGDR level was associated with lower risks of all-cause and cardiovascular deaths in a linear dose-response manner among non-diabetic females, while L-shaped relationships were observed among non-diabetic males.

The evidence for the association between the triglyceride (TG) to high-density lipoprotein cholesterol (HDL-c) ratio and the risk of developing microalbuminuria is still limited in the Chinese population. Therefore, our research will endeavor to explore the relationship between the two. The cross-sectional survey enrolled 32,877 general population from eight regional centers in China. If the urinary albumin-creatinine ratio (UACR) ≥ 30 mg/g, it was considered microalbuminuria. The dependent variable in the study was microalbuminuria, while the independent variable was the TG/HDL-c ratio. A binary logistic regression model was utilized to examine the independent association between the likelihood of microalbuminuria and the TG/HDL-c ratio. A generalized additive model (GAM) and spline smoothing were employed to investigate non-linear relationships between these two variables. To confirm the findings and pinpoint important turning points, subgroup and threshold effect tests were performed. The average age of the study participants was 57.67 ± 9.29 years, with 22,052 (67%) females and 10,825 (33%) males. The ratio of TG/HDL-c had a median value of 1.06, while the UACR had a median value of 9.92 mg/g. The prevalence of microalbuminuria was 14.4%. Following covariate adjustment, the prevalence of microalbuminuria and the TG/HDL-c ratio showed a significant positive connection (OR = 1.17,95% CI 1.13-1.21). Interestingly, we discovered a non-linear relationship between the occurrence of microalbuminuria and the TG/HDL-c ratio. At a TG/HDL-c ratio of 0.911, we detected an inflection point, with ORs of 1.12 (95% CI: 1.08, 1.17) on the right side of the point and 1.89 (95% CI: 1.51, 2.36) on the left. Subgroup analyses further validated the results. Our research revealed a positive and non-linear connection between the TG/HDL-c ratio and the prevalence of microalbumin in Chinese individuals. The connection was especially robust when the TG/HDL-c ratio was below 0.911. Reducing TG or raising HDL-c levels in order to lower the TG/HDL-c ratio may significantly mitigate the risk of microalbuminuria.

The serum uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) is a novel biomarker that indicates inflammation and metabolic disorders. Also, it has been shown that UHR correlates with the risk of cardiovascular disease. Despite this, limited research exists on its prognostic significance. This study aimed to explore the association of UHR with all-cause and cardiovascular mortality in patients with diabetes or prediabetes.

This cohort study included 18,804 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 with diabetes or prediabetes aged 20 years or older, followed until December 31, 2019. Patients with diabetes or prediabetes were grouped according to quartiles of UHR, which was calculated as serum UA (mg/dL)/HDL-C (mg/dL). Kaplan-Meier survival analysis, multivariable Cox proportional hazards regression models, restricted cubic spline analysis, and threshold effects were performed to assess the association between baseline UHR and all-cause and cardiovascular mortality. Subgroup analysis and sensitivity analysis were also conducted.

During a median follow-up of 80 months, a total of 2,748 (14.61%) deaths occurred, including 869 (4.63%) cardiovascular deaths. Kaplan-Meier survival analysis revealed that the highest quartile of UHR had the highest mortality rates. Multivariable Cox regression analysis indicated that individuals in the highest quartile of UHR had a significantly higher risk of all-cause mortality (HR: 1.24, 95% CI: 1.07-1.45) and cardiovascular mortality (HR: 1.56, 95% CI: 1.19-2.04) compared to those in the second quartile. A J-shaped association between UHR and both all-cause and cardiovascular mortality was observed, with threshold points of 13.73% and 9.39%, respectively. Specifically, when UHR was above the respective thresholds, the HRs of a 10% increment of UHR for all-cause mortality and cardiovascular mortality were 1.45 (95% CI: 1.31-1.61) and 1.38 (95% CI: 1.20-1.60). However, UHR below the threshold did not significantly correlate with mortality. Furthermore, subgroup analyses showed that the correlation of UHR with all-cause mortality was significantly modified by sex and age, with a persistent positive correlation observed in women and those aged < 60.

Higher UHR was correlated with increased all-cause and cardiovascular mortality in patients with diabetes or prediabetes.

To investigate the association between low-density lipoprotein-cholesterol (LDL-C) levels and coronary artery disease (CAD) incidence based on combining high-density lipoprotein-cholesterol (HDL-C) levels and glucose status.

In this retrospective cohort study, we used data from a nationwide claims database (1,524,289 individuals without a history of CAD or familial hypercholesterolaemia; 2008-2019). Cox proportional hazards modelling identified the risk of incident CAD by a novel combination of four HDL-C levels, seven LDL-C levels and glucose status.

During the follow-up period (mean: 5.5 years), 8301 (0.99/1000 person-years) events occurred. The risk of CAD increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of the glucose status. Using the most favourable levels of HDL-C and LDL-C (i.e. 60-99 mg/dL and <80 mg/dL, respectively) as references, the hazard ratios (95% confidence interval) for the group with HDL-C levels <40 mg/dL and LDL-C levels <80 mg/dL were 2.74 (1.47-5.11), 2.52 (1.30-4.91) and 2.85 (1.68-4.84) for normoglycaemia, borderline glycaemia and diabetes, respectively. Comparison of the most favourable levels of HDL-C and LDL-C with their least favourable levels (i.e. <40 mg/dL and 180-199 mg/dL, respectively) revealed that the risk of new-onset CAD exhibited a 19-, nine- and seven-fold increase in individuals with normoglycaemia, borderline glycaemia and diabetes, respectively.

To prevent CAD, LDL-C levels should be strictly controlled in patients with low HDL-C levels regardless of glucose tolerance. Individualized treatment, which involves setting target LDL-C levels based on glucose tolerance and HDL-C values, is required.

Previous studies have compared single-port robotic cholecystectomy (SPRC) to single-incision laparoscopic (SILC). However, there is not a systematic review and meta-analysis in patient with BMI ≥ 25 kg/m2 even though higher BMI is a risk factor for gallstone disease, a common indication for cholecystectomy. PubMed, Scopus and Cochrane Library were searched for related literature. Studies and data were extracted by two independent reviewers. Inverse variances weighted mean differences (WMD) with random effects model were used for continues values and odds ratios (OR) with random effects model using the Mantel-Haenszel's formula were used for dichotomous value. Heterogeneity using Higgins I2 and p values were calculated. Sensitivity analysis was performed for operative duration and intraoperative complications. In this meta-analysis, six studies involving a total of 734 patients examined SPRC and SILC. The analysis revealed a statistically significant increase in operative duration for SPRC compared to SILC, with a weighted mean difference of 26.67 min (95% CI 14.99, 38.34; I2 = 93%; Pheterogeneity < 0.00001; Poverall < 0.00001). Regarding conversion to multi-port cholecystectomy (MC), no statistically significant difference was found, yielding an odds ratio of 0.94 (95% CI 0.36, 2.45; I2 = 0%; Pheterogeneity = 0.78; Poverall = 0.89). Intra-operative blood loss showed non-significant differences, with a weighted mean difference of - 16.76 ml (95% CI - 48.56, 15.03; I2 = 78%; Pheterogeneity = 0.03; Poverall = 0.30). Length of hospitalization was significantly reduced by approximately half a day for SPRC compared to SILC, with a weighted mean difference of - 0.52 days (95% CI - 0.89, - 0.14; I2 = 0%; Pheterogeneity = 0.52; Poverall = 0.007). Intra-operative complications did not differ significantly between the techniques, resulting in an odds ratio of 0.59 (95% CI 0.19, 1.81; I2 = 70%; Pheterogeneity = 0.04; Poverall = 0.36). Finally, two studies evaluated bile leak rates, concluding no significant difference with an odds ratio of 0.86 (95% CI 0.39, 1.88; I2 = 23%; Pheterogeneity = 0.25; Poverall = 0.70). Sensitivity analyses indicated that no single study unduly influenced the results for operative duration, while one study was identified as a source of heterogeneity in intra-operative complications. SPRC is associated with longer operative duration, but shorter length of hospitalization in patients with BMI ≥ 25 kg/m2, compared to laparoscopic. Future studies should aim to examine incisional hernias rates as well as determine the long-term outcomes. PROSPERO registration: CRD42024602514.

The strong association between gut microbiota (GM) and brain functions such as mood, behaviour, and cognition has been well documented. Gut-brain axis is a unique bidirectional communication system between the gut and brain, in which gut microbes play essential role in maintaining various molecular and cellular processes. GM interacts with the brain through various pathways and processes including, metabolites, vagus nerve, HPA axis, endocrine system, and immune system to maintain brain homeostasis. GM dysbiosis, or an imbalance in GM, is associated with several neurological disorders, including anxiety, depression, and Alzheimer's disease (AD). Conversely, AD is sustained by microglia-mediated neuroinflammation and neurodegeneration. Further, GM and their products also affect microglia-mediated neuroinflammation and neurodegeneration. Despite the evidence connecting GM dysbiosis and AD progression, the involvement of GM in modulating microglia-mediated neuroinflammation in AD remains elusive. Importantly, deciphering the mechanism/s by which GM regulates microglia-dependent neuroinflammation may be helpful in devising potential therapeutic strategies to mitigate AD. Herein, we review the current evidence regarding the involvement of GM dysbiosis in microglia activation and neuroinflammation in AD. We also discuss the possible mechanisms through which GM influences the functioning of microglia and its implications for therapeutic intervention. Further, we explore the potential of microbiota-targeted interventions, such as prebiotics, probiotics, faecal microbiota transplantation, etc., as a novel therapeutic strategy to mitigate neuroinflammation and AD progression. By understanding and exploring the gut-brain axis, we aspire to revolutionize the treatment of neurodegenerative disorders, many of which share a common theme of microglia-mediated neuroinflammation and neurodegeneration.

To explore the separate and joint association of estimated glucose disposal rate (eGDR) and high-sensitivity C-reactive protein (hsCRP) with cardiometabolic multimorbidity (CMM).

A total of 6900 participants aged 45 years or older with available data on eGDR and hsCRP and without cardiometabolic diseases at baseline from the China Health and Retirement Longitudinal Study were included. CMM was defined as the coexistence of two or more cardiometabolic diseases, including heart diseases, stroke, and diabetes.

During a median follow-up of 9.0 years, 464 (6.7 %) participants developed CMM. Low eGDR and high hsCRP separately and jointly increased the risk of CMM. The adjusted hazard ratio (HR) was 1.67 (95 % confidence interval [CI] 1.33-2.09) for low eGDR versus high eGDR, 1.43 (95 % CI 1.12-1.82) for high hsCRP versus low hsCRP) and 2.40 (95 % CI 1.77-3.27) for low eGDR plus high hsCRP versus high eGDR plus low hsCRP. The C-statistic, discriminatory power and risk reclassification significantly improved with the addition of combined eGDR and hsCRP for CMM (P < 0.001).

Low eGDR and high hsCRP were individually and jointly associated with increased risk of incident CMM. The findings highlighted the importance of joint evaluation of eGDR and hsCRP for primary prevention of CMM.

The impact of baseline triglyceride-glucose (TyG) index and abnormal low or high-density lipoprotein cholesterol (LDL-C or HDL-C) levels on all-cause and cardiovascular disease (CVD) mortality remains unclear. This study aimed to investigate the relationship between TyG index and LDL-C or HDL-C and all-cause and CVD mortality.

This retrospective cohort study analyzed data from health examinations of 69,068 older adults aged ≥60 in Xinzheng City, Henan Province, China, between January 2013 and January 2023. Cox proportional risk regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the TyG index and LDL-C or HDL-C about all-cause and CVD mortality. Restricted cubic spline was used to assess the dose-response relationship.

During 400,094 person-years of follow-up (median follow-up 5.8 years [interquartile range 3.0-9.12]), 13,664 deaths were recorded, of which 7,045 were due to CVD. Compared with participants in the second quartile of the TyG index, participants in the fourth quartile had a 16% increased risk of all-cause mortality (HR: 1.16, 95% CI: 1.12,1.22), and an 8% increased risk of CVD mortality (HR: 1.08, 95% CI: 1.01,1.16). Similar results were observed in LDL-C and HDL-C, with all-cause and CVD mortality risks for participants in the fourth quartile compared with participants in the third quartile for LDL-C of (HR: 1.07, 95% CI: 1.02,1.12) and (HR: 1.09, 95% CI: 1.01,1.17), respectively. The risk of all-cause and CVD mortality in participants in the fourth quartile group compared with those in the second HDL-C quartile group was (HR: 1.10, 95% CI: 1.05,1.16) and (HR: 1.11, 95% CI: 1.04,1.18), respectively. We found that the TyG index was nonlinearly associated with all-cause and CVD mortality (P non-linear <0.05), and LDL-C was nonlinearly associated with all-cause mortality (P non-linear <0.05) but linearly associated with CVD mortality (P non-linear >0.05). HDL-C, on the other hand, was in contrast to LDL-C, which showed a non-linear association with CVD mortality. We did not observe a significant interaction between TyG index and LDL-C or HDL-C (P >0.05).

TyG index and LDL-C or HDL-C increased the risk of all-cause and CVD mortality, especially a high TyG index combined with abnormal LDL-C.

To clarify whether Vitamin D prevent the occurrence of type 2 diabetes mellitus (T2DM) and improve glucose control in T2DM patients, we conducted this umbrella review, taking into account the inconsistent results of existing Meta-analyses. We aim to reveal the causal relationship between Vitamin D and T2DM through summarizing Meta-analyses of observational studies, and clarify the improvement on glucose control in T2DM patients through summarizing Meta-analyses of RCT studies between Vitamin D supplementation and T2DM patients, especially in T2DM patients with Vitamin D deficiency.

We collected the Meta-analyses of observational studies and RCTs in PubMed, Scopus, Embase, Web of Science, and Cochrane.

16 Meta-analyses (6 effect sizes for cohort studies and 10 effect sizes for RCTs) were included in the umbrella Meta-analyses. Random-effects model was carried out to calculate the pooled point estimates and their respective 95% confidence intervals (CI). The results revealed that lower 25(OH)D levels increased the risk of T2DM (Pooled ESRR = 1.34; 95%CI: 1.16, 1.53), Vitamin D supplementation ameliorated FBG (ES = -0.56; 95%CI: -1.00, -0.11), HbA1c (ES = -0.11; 95%CI: -0.20, -0.02), insulin (ES = -0.38; 95%CI: -0.59, -0.18) and HOMA-IR (ES = -0.37; 95%CI: -0.57, -0.16) in T2DM patients, especially in those with Vitamin D deficiency (FBG = -0.98; HbA1c = -0.27; HOMA-IR = -0.52).

The present umbrella Meta-analyses demonstrates the potential benefits of higher serum Vitamin D levels and Vitamin D supplementation in reducing the development and symptoms of T2DM.

To investigate the relationship between estimated glucose disposal rate (eGDR), a surrogate indicator of insulin resistance, and atherosclerotic cardiovascular diseases (ASCVD) incidence risk.

This prospective cohort study utilized data from the 6026 participants from the Multi-Ethnic Study of Atherosclerosis. The eGDR (mg/kg/min) was computed as 21.158 - (0.09 × waist circumference [cm]) - (3.407 × hypertension [yes/no]) - (0.551 × HbA1c [%]). The population was categorized into four subgroups according to the quartiles (Q) of eGDR. Cox proportional hazard models were applied to assess the associations between eGDR and ASCVD incidence, and restricted cubic spine (RCS) was employed to examine the dose-response relationship.

The mean age of participants was 63.6 ± 10.1 years, comprising 3163 (52.5%) women. Over a median follow-up duration of 14.1 years, 565 (9.4%) developed ASCVD, including 256 (4.2%) myocardial infarctions, 234 (3.9%) strokes, and 358 (5.9%) fatal coronary heart disease. Compared to the lowest quartile, the adjusted hazard ratios (95% confidence intervals) for incident ASCVD for Q2-Q4 were 0.87 (0.68-1.10), 0.63 (0.47-0.84), and 0.43 (0.30-0.64), respectively. Per 1 standard deviation increase in eGDR was associated with a 30% (HR: 0.70, 95% CI 0.60-0.80) risk reduction of ASCVD, with the subgroup analyses indicating that age and hypertension modified the association (P for interaction < 0.05). RCS analysis indicated a significant and linear relationship between eGDR and ASCVD incidence risk.

eGDR level was negatively associated with incident ASCVD risk in a linear fashion among the general population. Our findings may contribute to preventive measures by improving ASCVD risk assessment.

Evidence suggests that insulin resistance (IR) is an autonomous risk factor for cardiovascular disease (CVD). Nevertheless, the association between estimated glucose disposal rate (eGDR), a novel indicator of IR, and incident CVD and mortality in chronic kidney disease (CKD) patients without diabetes remains uncertain.

The study included 19,906 participants from the UK Biobank who had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and no history of CVD and diabetes. Individuals were divided into three categories based on tertiles of eGDR. The outcome was a composite CVD (coronary heart disease (CHD) and stroke) and mortality (all-cause, non-accidental, and cardiovascular mortality). Furthermore, a cohort of 1,600 individuals from the US National Health and Nutrition Examination Survey (NHANES) was applied to validate the association between eGDR and mortality. The Cox proportional hazards regression models were used to examine the association between eGDR and event outcomes.

During a follow-up of around 12 years, 2,860 CVD, 2,249 CHD, 783 stroke, 2,431 all-cause, 2,326 non-accidental and 492 cardiovascular deaths were recorded from UK Biobank. Higher eGDR level was not only associated with lower risk of CVD (hazard ratio [HR] 0.641, 95% confidence interval [CI] 0.559-0.734), CHD (HR 0.607, 95% CI 0.520-0.709), stroke (HR 0.748, 95% CI 0.579-0.966), but also related to reduced risk of all-cause (HR 0.803, 95% CI 0.698-0.923), non-accidental (HR 0.787, 95% CI 0.682-0.908), and cardiovascular mortality (HR 0.592, 95% CI 0.423-0.829). Validation analyses from NHANES yielded consistent relationship on mortality.

In these two large cohorts of CKD patients without DM, a higher eGDR level was associated with a decreased risk of CVD and mortality.

It remains unclear whether the association between dyslipidemia status and triglyceride-glucose (TyG) index with myocardial damage varies in the context of type 2 diabetes mellitus (T2DM). This study aimed to determine the differential effects of dyslipidemia status and TyG index on left ventricular (LV) global function and myocardial microcirculation in patients with T2DM using cardiac magnetic resonance (CMR) imaging.

A total of 226 T2DM patients and 72 controls who underwent CMR examination were included. The T2DM group was further categorized into subgroups based on the presence or absence of dyslipidemia (referred to as T2DM (DysL+) and T2DM (DysL-)) or whether the TyG index exceeded 9.06. CMR-derived LV perfusion parameters, remodeling index, and global function index (GFI) were assessed and compared among groups. A multivariable linear regression model was employed to evaluate the effects of various variables on LV myocardial microcirculation, remodeling index, and GFI.

The LV GFI sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (p < 0.001), and was lower (p = 0.003) in T2DM with higher TyG index group than in lower TyG index group. The LV remodeling index was higher in higher TyG index group than in lower TyG index group (p = 0.002), but there was no significant difference in whether the subgroup was accompanied by dyslipidemia. Multivariable analysis revealed that the TyG index, but not dyslipidemia status, was independently associated with LV remodeling index (β coefficient[95% confidence interval], 0.152[0.025, 0.268], p = 0.007) and LV GFI (- 0.159[- 0.281, - 0.032], p = 0.014). For LV myocardial microcirculation, perfusion index, upslope, and max signal intensity sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (all p < 0.001). Dyslipidemia status independently correlated with perfusion index (- 0.147[- 0.272, - 0.024], p = 0.02) and upslope (- 0.200[- 0.320, 0.083], p = 0.001), while TyG index was independently correlated with time to maximum signal intensity (0.141[0.019, 0.257], p = 0.023).

Both dyslipidemia status and higher TyG index were associated with further deterioration of LV global function and myocardial microvascular function in the context of T2DM. The effects of dyslipidemia and a higher TyG index appear to be differential, which indicates that not only the amount of blood lipids and glucose but also the quality of blood lipids are therapeutic targets for preventing further myocardial damage.

Prediabetes strongly increases the risk of type 2 diabetes and cardiovascular events. However, lifestyle intervention, the first-line treatment for prediabetes currently, was inconsistently beneficial for glucose metabolism, and the conventional medicines, such as metformin, is controversial for prediabetes due to the possible side effects.

This study was designed to evaluate the effects of Zhenyuan Capsule, a Chinese patented medicine consisting of ginseng berry saponins extracted from the mature berry of Panax Ginseng, on the glucose metabolism of prediabetic patients as a complementary therapy.

In this randomized, double-Blinded, placebo-controlled, crossover trial, 195 participants with prediabetes were randomized 1:1 to receive either placebo followed by Zhenyuan Capsule, or vice versa, alongside lifestyle interventions. Each treatment period lasted 4 weeks with a 4-week washout period in between. The primary outcomes were the changes in fasting plasma glucose (FPG) and 2-h postprandial plasma glucose (2-h PG) from baseline. Secondary outcomes includes the changes in fasting and 2-h postprandial insulin and C-peptide, the homeostatic model assessment-insulin resistance (HOMA-IR) index and quantitative insulin sensitivity check index (QUICKI) from baseline. Blood lipids and adverse events were also assessed.

Compared with placebo, Zhenyuan Capsule caused remarkable reduction in 2-h PG (-0.98 mmol/l) after adjusting treatment order. Zhenyuan Capsule also reduced the fasting and 2-h postprandial levels of insulin and C-peptide, lowered HOMA-IR index (-1.26), and raised QUICKI index (+0.012) when compared to placebo. Additionally, a significant increase in high density lipoprotein cholesterol (HDL-C; +0.25 mmol/l) was found in patients with Zhenyuan Capsule. No serious adverse event occurred during the study.

Among prediabetic patients, Zhenyuan Capsule further reduced 2-h PG level, alleviated insulin resistance and raised HDL-C level on the background of lifestyle interventions. The study protocol is registered with the Chinese Clinical Trial Registry (ChiCTR2000034000).

Dyslipidemia commonly complicates type 2 diabetes mellitus, yet the relationship between glycosylated hemoglobin and blood lipid levels remains uncertain.

This retrospective cross-sectional study included 27,158 participants from the People's Hospital of Yuxi. Statistical comparisons for continuous variables utilized analysis of variance (ANOVA), while chi-square analysis was employed for categorical variables. Boxplots assessed the concentration, dispersion, and deviation of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) distribution. A linear regression analysis examined the association between HbA1c and lipid profile, complemented by a fitting curve to visualize trends.

Participants who developed diabetes exhibited higher age and elevated Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, and FPG levels compared to those without diabetes (p < 0.001). Linear regression analysis demonstrated significant associations between HbA1c values and TC, TG, LDL-C, and HDL-C (p < 0.001). The plotted curve indicated that as TC, TG, and LDL levels increased, HbA1c levels rose, while HDL levels decreased.

HbA1c was positively correlated with TC, TG, LDL-C, and negatively correlated with HDL-C in the population in the central Yunnan Plateau.

Previous in vivo and in vitro studies have demonstrated that estrogen receptor agonist G-1 regulates glucose and lipid metabolism. This study focused on the effects of G-1 on cardiometabolic syndrome and anti-obesity under a high fat diet (HFD).

Bilateral ovariectomized female mice were fed an HFD for 6 weeks, and treated them with G-1. A cardiomyocyte insulin resistance model was used to simulate the in vivo environment. The main outcome measures were blood glucose, body weight, and serum insulin levels to assess insulin resistance, while cardiac function and degree of fibrosis were assessed by cardiac ultrasound and pathological observations. We also examined the expression of p-AMPK, p-AKT, and GLUT4 in mice hearts and in vitro models to explore the mechanism by which G-1 regulates insulin signaling.

G-1 reduced body weight in mice on an HFD, but simultaneously increased blood glucose and promoted insulin resistance, resulting in myocardial damage. This damage included disordered cardiomyocytes, massive accumulation of glycogen, extensive fibrosis of the heart, and thickening of the front and rear walls of the left ventricle. At the molecular level, G-1 enhances gluconeogenesis and promotes glucose production by increasing the activity of pyruvate carboxylase (PC) while inhibiting GLUT4 translocation via the AMPK/TBC1D1 pathway, thereby limiting glucose uptake.

Despite G-1's the potential efficacy in weight reduction, the concomitant induction of insulin resistance and cardiac impairment in conjunction with an HFD raises significant concerns. Therefore, comprehensive studies of its safety profile and effects under specific conditions are essential prior to clinical use.

Insulin resistance (IR) is closely linked to cardiometabolic diseases. Preventing and improving IR in nondiabetic populations is critically important. We aimed to investigate the relationship between Life's Essential 8 (LE8), the latest tool from the American Heart Association quantifying cardiovascular health, and IR among nondiabetic populations in the United States.

This cross-sectional study used data on 11 246 nondiabetic adults aged ≥20 years from the 2005 to 2018 the National Health and Nutrition Examination Survey. The LE8 score was classified into 2 subscale scores: health factor score and health behavior score. IR was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Weighted logistic and linear regression models analyzed associations among the LE8 score, health behavior score, health factor score, and IR. Restricted cubic spline models assessed dose-response relationships. Adjusted subgroup analyses and inverse probability of treatment weighting method also evaluated the LE8-IR relationship. Of the 11 246 participants, 4860 (43.2%) had IR. The mean LE8 score was 70.07 (95% CI, 69.57-70.58). In fully adjusted models, higher LE8 scores were associated with lower IR odds (odds ratio per 10-unit increase, 0.57 [95% CI, 0.54-0.61]). Nonlinear LE8-IR dose-response was observed. Similar patterns were seen for health behavior and health factor subscores, with stronger IR correlations for health factors. The inverse LE8-IR association was significantly more pronounced among White participants and those with higher education, higher income, and without hypertension, cardiovascular disease, or chronic kidney disease. Significant negative LE8-IR associations persisted after inverse probability of treatment weighting.

LE8 and subscale scores are negatively associated with IR in a nonlinear relationship. Promoting optimal cardiovascular health adherence may improve IR in nondiabetic populations.

Recent studies have suggested that insulin resistance (IR) contributes to the development of cardiovascular diseases (CVD), and the estimated glucose disposal rate (eGDR) is considered to be a reliable surrogate marker of IR. However, most existing evidence stems from studies involving diabetic patients, potentially overstating the effects of eGDR on CVD. Therefore, the primary objective of this study is to examine the relationship of eGDR with incidence of CVD in non-diabetic participants.

The current analysis included individuals from the China Health and Retirement Longitudinal Study (CHARLS) who were free of CVD and diabetes mellitus but had complete data on eGDR at baseline. The formula for calculating eGDR was as follows: eGDR (mg/kg/min) = 21.158 - (0.09 × WC) - (3.407 × hypertension) - (0.551 × HbA1c) [WC (cm), hypertension (yes = 1/no = 0), and HbA1c (%)]. The individuals were categorized into four subgroups according to the quartiles (Q) of eGDR. Crude incidence rate and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to investigate the association between eGDR and incident CVD, with the lowest quartile of eGDR (indicating the highest grade of insulin resistance) serving as the reference. Additionally, the multivariate adjusted restricted cubic spine (RCS) was employed to examine the dose-response relationship.

We included 5512 participants in this study, with a mean age of 58.2 ± 8.8 years, and 54.1% were female. Over a median follow-up duration of 79.4 months, 1213 incident CVD cases, including 927 heart disease and 391 stroke, were recorded. The RCS curves demonstrated a significant and linear relationship between eGDR and all outcomes (all P for non-linearity > 0.05). After multivariate adjustment, the lower eGDR levels were founded to be significantly associated with a higher risk of CVD. Compared with participants with Q1 of eGDR, the HRs (95% CIs) for those with Q2 - 4 were 0.88 (0.76 - 1.02), 0.69 (0.58 - 0.82), and 0.66 (0.56 - 0.79). When assessed as a continuous variable, per 1.0-SD increase in eGDR was associated a 17% (HR: 0.83, 95% CI: 0.78 - 0.89) lower risk of CVD, with the subgroup analyses indicating that smoking status modified the association (P for interaction = 0.012). Moreover, the mediation analysis revealed that obesity partly mediated the association. Additionally, incorporating eGDR into the basic model considerably improve the predictive ability for CVD.

A lower level of eGDR was found to be associated with increased risk of incident CVD among non-diabetic participants. This suggests that eGDR may serve as a promising and preferable predictor and intervention target for CVD.

Triglyceride and glucose (TyG) index, a surrogate marker of insulin resistance, has been validated as a predictor of cardiovascular disease. However, effects of TyG-related indices combined with obesity markers on cardiovascular diseases remained unknown. We aimed to investigate the associations between TyG index and modified TyG indices with new-onset cardiovascular disease and the time-dependent predictive capacity using a national representative cohort.

This study is a retrospective observational cohort study using data from China Health and Retirement Longitudinal Study (CHARLS) of 7 115 participants. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The modified TyG indices were developed combining TyG with body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). We used adjusted Cox proportional hazards regression to analyze the association and predictive capacity based on hazard ratio (HR) and Harrell's C-index.

Over a 7-year follow-up period, 2136 participants developed cardiovascular disease, including 1633 cases of coronary heart disease and 719 cases of stroke. Compared with the lowest tertile group, the adjusted HR (95% CI) for new-onset cardiovascular disease in the highest tertile for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.215 (1.088-1.356), 1.073 (0.967-1.191), 1.078 (0.970-1.198), and 1.112 (1.002-1.235), respectively. The C-indices of TyG index for cardiovascular disease onset were higher than other modified TyG indices. Similar results were observed for coronary heart disease and stroke.

TyG and TyG-WhtR were significantly associated with new-onset cardiovascular diseases, and TyG outperformed the modified TyG indices to identify individuals at risk of incident cardiovascular event.

The measurement of triceps skinfold (TSF) thickness serves as a noninvasive metric for evaluating subcutaneous fat distribution. Despite its clinical utility, the TSF thickness trajectories and their correlation with overall mortality have not been thoroughly investigated.

To explore TSF thickness trajectories of Chinese adults and to examine their associations with all-cause mortality.

This study encompassed a cohort of 14747 adults sourced from the China Health and Nutrition Survey. Latent class trajectory modeling was employed to identify distinct trajectories of TSF thickness. Subjects were classified into subgroups reflective of their respective TSF thickness trajectory. We utilized multivariate Cox regression analyses and mediation examinations to explore the link between TSF thickness trajectory and overall mortality, including contributory factors.

Upon adjustment for multiple confounding factors, we discerned that males in the 'Class 2: Thin-stable' and 'Class 3: Thin-moderate' TSF thickness trajectories exhibited a markedly reduced risk of mortality from all causes in comparison to the 'Class 1: Extremely thin' subgroup. In the mediation analyses, the Geriatric Nutritional Risk Index was found to be a partial intermediary in the relationship between TSF thickness trajectories and mortality. For females, a lower TSF thickness pattern was significantly predictive of elevated all-cause mortality risk exclusively within the non-elderly cohort.

In males and non-elderly females, lower TSF thickness trajectories are significantly predictive of heightened mortality risk, independent of single-point TSF thickness, body mass index, and waist circumference.

Type 2 diabetes (T2DM) is genetically heterogenous, driven by beta cell dysfunction and insulin resistance. Insulin resistance drives the development of cardiometabolic complications and is typically associated with obesity. A group of common variants at eleven loci are associated with insulin resistance and risk of both type 2 diabetes and coronary artery disease. These variants describe a polygenic correlate of lipodystrophy, with a high metabolic disease risk despite a low BMI.

In this cross-sectional study, we sought to investigate the association of a polygenic risk score composed of eleven lipodystrophy variants with anthropometric, glycaemic and metabolic traits in an island population characterised by a high prevalence of both obesity and type 2 diabetes.

814 unrelated adults (n = 477 controls and n = 337 T2DM cases) of Maltese-Caucasian ethnicity were genotyped and associations with phenotypes explored.

A higher polygenic lipodystrophy risk score was correlated with lower adiposity indices (lower waist circumference and body mass index measurements) and higher HOMA-IR, atherogenic dyslipidaemia and visceral fat dysfunction as assessed by the visceral adiposity index in the DM group. In crude and covariate-adjusted models, individuals in the top quartile of polygenic risk had a higher T2DM risk relative to individuals in the first quartile of the risk score distribution.

This study consolidates the association between polygenic lipodystrophy risk alleles, metabolic syndrome parameters and T2DM risk particularly in normal-weight individuals. Our findings demonstrate that polygenic lipodystrophy risk alleles drive insulin resistance and diabetes risk independent of an increased BMI.

Although the correlation between insulin resistance (IR) and cardiovascular disease (CVD) risk is well-established, the impact of changes in IR status over time has received little attention. This study aimed to investigate the effect of IR on CVD risk in a large prospective cohort of middle-aged Korean adults.

We assessed 3597 participants from the Korean Genome and Epidemiology Study (KoGES). Participants were categorized as having IR if their HOMA-IR was ≥2.5 at least once during the exposure period. Multivariate Cox proportional hazards regression analysis was performed to assess hazard ratios (HRs) with 95% CIs for incident CVD after adjusting for confounders.

Among a total of 3597 participants, 2259 did not have IR and 1138 had IR. The cumulative incidence rate of CVD in the IR group was significantly higher than that in the non-IR group (log-rank test, p = 0.015). Compared to the non-IR group, the HR and 95% CI for incident CVD in the IR group was 1.40 (1.07-1.83) in the unadjusted model. The presence of IR during the exposure period was significantly associated with a higher risk of incident CVD after adjusting for age, sex, body mass index, diabetes, hypertension, dyslipidemia, C-reactive protein, physical activity, alcohol intake, and smoking status (HR = 1.37; 95% CI: 1.01-1.84).

Individuals who have experienced IR have a consistently higher likelihood of developing CVD than those who have never had IR. More intensive efforts should be made to prevent IR in middle-aged and older adults.

The triglyceride and glucose-waist circumference (TyG-WC) index demonstrated a strong association with insulin resistance, especially in Asian population. However, evidence on the association between TyG-WC index and the occurrence of cardiovascular disease (CVD) is limited. This study aimed to verify association between the TyG-WC index and the occurrence of CVD by considering all-cause mortality as a competing risk.

The study included 7482 participants divided into four groups based on the TyG-WC index quartiles. Kaplan-Meier curves illustrated cumulative incidence rates of CVD and all-cause mortality during the follow-up period. Log-rank tests determined group differences. The Cox proportional hazard spline curve demonstrates the dose-dependent relationship between the TyG-WC index and incident CVD. Modified Cox regression (Fine and Gray) estimated hazard ratios (HRs) with 95% CIs for incident CVD, treating death as a competing risk. Death event after incident CVD was excluded from the death count.

During the median 15.94 year of follow-up period, a total of 691 (9.24%) new-onset CVD cases and 562 (7.51%) all-cause mortality cases were confirmed. Cox proportional hazard spline curves suggested that TyG-WC index exhibited a dose-dependent positive correlation with incident CVD. The cumulative incidence rate of CVD was significantly higher in the groups with higher TyG-WC index quartiles in Kaplan-Meier curves. The adjusted HR (95% CI) for incident CVD in Q2-Q4, compared with Q1, was 1.47 (1.12-1.93), 1.91 (1.44-2.54) and 2.24 (1.63-3.07), respectively. There was no significant association between TyG-WC index and all-cause mortality. Specifically, angina and stroke were significantly associated with the TyG-WC index, in contrast to myocardial infarction and peripheral artery disease.

The TyG-WC index was positively associated with incident CVD even considering all-cause mortality as a competing risk. Therefore, TyG-WC index may be a valuable marker for predicting the occurrence of CVD.

The relationship of fine particulate matter (PM2.5) exposure and insulin resistance remains inclusive. Our study aimed to investigate this association in the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). Specifically, we examined the associations between long-term PM2.5 exposure and three surrogate indicators of insulin resistance: the triglyceride-glucose index (TyG), TyG with waist circumference (TyG-WC) and metabolic score for insulin resistance (METS-IR). Additionally, we explored potential effect modification of dietary intake and components. Generalized estimating equations were used to evaluate the associations between PM2.5 and the indicators with an unbalanced repeated measurement design. Our analysis incorporated a total of 162,060 observations from 99,329 participants. Each 10 μg/m3 increment of PM2.5 was associated with an increase of 0.22 % [95 % confidence interval (CI): 0.20 %, 0.25 %], 1.60 % (95 % CI: 1.53 %, 1.67 %), and 2.05 % (95 % CI: 1.96 %, 2.14 %) in TyG, TyG-WC, and METS-IR, respectively. These associations were attenuated among participants with a healthy diet, particularly those with sufficient intake of fruit and vegetable, fish or tea (pinteraction < 0.0028). For instance, among participants with a healthy diet, TyG increased by 0.11 % (95 % CI: 0.08 %, 0.15 %) per 10 μg/m3 PM2.5 increment, significantly lower than the association observed in those with an unhealthy diet. The findings of this study emphasize the potential of a healthy diet to mitigate these associations, highlighting the urgency for improving air quality and implementing dietary interventions among susceptible populations in China.