The triglyceride-glucose index is associated with the severity of hepatic steatosis and the presence of liver fibrosis in non-alcoholic fatty liver disease: a cross-sectional study in Chinese adults.

BACKGROUND: The triglyceride-glucose index (TyG) is a reliable predictor of non-alcoholic fatty liver disease (NAFLD). Its association with the severity of hepatic steatosis and liver fibrosis in NAFLD is poorly understood. This study evaluated the relationship between these factors in NAFLD. METHODS: A total of 4784 participants who underwent ultrasonography were enrolled. Anthropometric and biochemical measurements were assessed. Participants with NAFLD were diagnosed by ultrasound. The degree of hepatic steatosis and liver stiffness was evaluated with transient elastography. RESULTS: The TyG index was significantly correlated with the severity of hepatic steatosis and the presence of liver fibrosis in patients with NAFLD. TyG quartile values correlated with increasing prevalence of NAFLD (Q1 30.9%, Q2 53.3%, Q3 71.7%, and Q4 86.4%, P < 0.001) and with the presence of liver fibrosis (Q1 13.5%, Q2 17.6%, Q3 18.8%, and Q4 26.1%, P < 0.001). The AUROC for the TyG index to predict NAFLD was 0.761, resulting in a cut-off value of 8.7. However, the AUC value of the TyG index was 0.589 for liver fibrosis, which was insufficient to predict this condition. The adjusted odds of having hepatic steatosis or liver fibrosis were more strongly associated with TyG values compared with HOMA-IR. CONCLUSION: The TyG index is positively related to the severity of hepatic steatosis and the presence of liver fibrosis in NAFLD. The index also performed better than HOMA-IR.

Association of serum proprotein convertase subtilisin/kexin type 9 with early atherosclerosis in newly diagnosed type 2 diabetes mellitus.

BACKGROUND AND AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is rapidly gaining attention as a potential risk of developing atherosclerosis due to its crucial role in the regulation of low-density lipoprotein cholesterol (LDL-C) metabolism. The present study investigated the relationship between serum PCSK9 levels and early atherosclerosis as assessed by carotid intimal-medial thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) in newly diagnosed type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: A total of 100 newly diagnosed T2DM were enrolled and further divided into the thickened CIMT group (n = 41) and the non-thickened CIMT group (n = 59) according to the results of color Doppler ultrasonography. Serum PCSK9 levels, CIMT, ba-PWV, and metabolic parameters were measured. Patients in the thickened CIMT group had higher serum PCSK9 levels than patients in the non-thickened CIMT group (all P < 0.05). CIMT and ba-PWV were both positively correlated to serum PCSK9 levels, while serum PCSK9 levels were positively correlated to white blood cell count, neutrophil, lymphocyte, and high-sensitivity C-reactive protein (P < 0.05). Multiple linear regression indicated that serum PCSK9 level was an independent predictor of CIMT (ß = 0.637, P < 0.001) and ba-PWV (ß = 0.600, P < 0.001). Binary logistic regression analysis showed that serum PCSK9 levels were independent risk factors of thickened CIMT [OR = 1.120, 95%CI (1.041-1.204), P = 0.002]. CONCLUSION: Serum PCSK9 levels are significantly correlated with CIMT and ba-PWV, independent of CAD risk factors. Therefore, serum PCSK9 level may have the potential to serve as a prescriptive biomarker for early arteriosclerosis in newly diagnosed T2DM.

Diagnostic values and appropriate cutoff points of lipid ratios in patients with abnormal glucose tolerance status: a cross-sectional study.

BACKGROUND: Lipid ratios, for example total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C), are associated with type 2 diabetes mellitus (T2DM). However, the predictive values of lipid ratios in prediabetes remain unclear. The aims of this study were: 1) to investigate the association between lipid ratios and abnormal glucose tolerance; 2) to compare the predictive significance of lipid ratios with commonly used indicators of lipid variables in clinical practice in a Chinese population. METHODS: The cross-sectional study enrolled 2680 participants from the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University. All participants received a 75 g oral glucose tolerance test. Blood samples were obtained at baseline and 120 min after glucose ingestion. Participants were classified as normal glucose tolerance (NGT), impaired glucose regulation (IGR), and T2DM. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression model. The receiver operating characteristic (ROC) curve was used to identify the cutoff points of lipid and lipid ratios. The area under the receiver operating characteristic curve (AUROC), sensitivity and specificity were calculated to estimate their diagnostic values. RESULTS: TC, TG, TC/HDL-C, TG/HDL-C and non-HDL-C were significantly correlated with both prediabetes and T2DM after adjustment for other risk factors such as blood glucose, whereas LDL-C was only positively correlated with prediabetes. TG and TG/HDL-C showed higher diagnostic values for prediabetes and T2DM than TC, LDL-C, HDL-C, TC/HDL-C and non-HDL-C, with the AUC values over 0.70. For predicting prediabetes, the optimal cutoff point was 1.36 mmol/l for TG and 1.13 for TG/HDL-C. For predicting T2DM, the optimal cutoff point was 1.46 mmol/l for TG and 1.22 for TG/HDL-C. CONCLUSIONS: Both TG and TG/HDL-C are promising biomarkers for distinguishing individuals with abnormal glucose tolerance, and can be used to predict prediabetes and T2DM in Chinese population.

Remnant cholesterol is associated with the progression and regression of metabolic dysfunction-associated steatotic liver disease in Chinese adults.

BACKGROUND: The aim of this study was to explore the associations of serum remnant cholesterol (RC) levels with the progression and regression of metabolic dysfunction-associated steatotic liver disease (MASLD) in Chinese adults. METHODS: We conducted a cross-sectional study in 13,903 individuals who underwent transient elastography tests (cohort 1) and a longitudinal study in 17,752 individuals who underwent at least two health check-up exams with abdominal ultrasound (cohort 2). Anthropometric and biochemical parameters were collected. Serum RC levels were calculated. Noninvasive fibrosis indices such as FIB-4 were evaluated in cohort 2. RESULTS: In cohort 1, serum RC levels were positively and independently associated with the severity of hepatic steatosis and liver fibrosis according to logistic regression analysis. In cohort 2, baseline serum RC levels were increased in participants with the incidence of MASLD and decreased in participants with the regression of MASLD during the follow-up period. Baseline serum RC levels were independently associated with an increased risk of development and a decreased likelihood of regression of MASLD: the fully adjusted hazard ratios (HR) were 2.785 (95 % CI 2.332-3.236, P < 0.001) and 2.925 (95 % CI 2.361-3.623, P < 0.001), respectively. In addition, when we used FIB-4 to evaluate liver fibrosis, baseline serum RC levels were positively correlated with the incidence of high-intermediate probability of advanced fibrosis. However, we did not find an association between serum RC levels and the regression of liver fibrosis. CONCLUSION: Serum RC levels are independently correlated with the progression and regression of MASLD in Chinese adults, suggesting that RC may participate in the pathophysiological process of MASLD.

Triglyceride to high-density lipoprotein cholesterol ratio and total cholesterol to high-density lipoprotein cholesterol ratio and risk of benign prostatic hyperplasia in Chinese male subjects.

Background: Lipid metabolism disorders contribute to the risk factor of prostatic hyperplasia. Lipid ratios have also attracted a lot of attention. Yet, research about the correlation of lipid ratios with prostatic hyperplasia is limited. Hence, the aim of this study was to investigate the association of lipid ratios with the risk of benign prostatic hyperplasia (BPH) in Chinese male subjects. Methods: Healthy men who underwent routine health check-ups from January 2017 to December 2019 were recruited. Twenty-four thousand nine hundred sixty-two individuals were finally enrolled in this research. Binary logistic regression analysis was performed to investigate the relationship between lipid ratios and BPH in Chinese adults. Results: After health examinations for more than 2 years, 18.46% of subjects were ascertained as incident BPH cases. Higher age, body mass index (BMI), prostate-specific antigen (PSA), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, and lower high-density lipoprotein cholesterol (HDL-C) were significantly associated with BPH risk, while total cholesterol (TC) was not significant. When quartiles of TG/HDL-C and TC/HDL-C were analyzed in multivariable model, higher TG/HDL-C and TC/HDL-C were associated with a risk of BPH (odds ratio [OR] = 2.11; 95% confidence interval [CI]: 1.89, 2.36; P-trend < 0.001; and OR = 1.67; 95% CI: 1.50, 1.85; P-trend < 0.001, respectively). In addition, stratified analyses based on the general population exhibited that with increasing age (≥35 years) the relationship of TG/HDL-C ratio with BPH risk was dominantly positive (all P-trend < 0.001, P-interaction = 0.001), and significant associations were also found in blood pressure strata and FBG strata (all P-trend < 0.001), except men with BMI ≥ 28 kg/m2 were slightly weakened (OR = 2.01, 95% CI: 1.41, 2.85; P-trend = 0.04). Moreover, there were significant associations between quartiles of TC/HDL-C and the risk of BPH was observed mainly in age 55-64 years, BMI 18.5-23.9 Kg/m2, blood pressure strata, and FBG strata. However, the P-value for a linear trend among those with BMI ≥ 28 Kg/m2 in which participants at the highest quartile of TC/HDL-C had an OR of 1.45 (95% CI: 1.09, 1.93) was 0.594. Additionally, higher TG/HDL-C ratio (≥0.65) may be a risk factor for BPH in China adults of different age decades (≥35 years) with normal TG and HDL-C. Conclusions: TG/HDL-C and TC/HDL-C were associated with BPH risk, TG/HDL-C was a powerful independent risk factor for BPH in Chinese adults, and higher TG/HDL-C ratio should be valued in male subjects with normal TG and HDL-C levels.

Association Between Skeletal Muscle Mass and Severity of Steatosis and Fibrosis in Non-alcoholic Fatty Liver Disease.

Background: Sarcopenia is known to be the risk factor of non-alcoholic fatty liver disease (NAFLD). However, studies evaluating the association of skeletal muscle mass (SMM) with liver fibrosis by transient elastography are limited. Here, we investigated the association of SMM with hepatic steatosis and fibrosis assessed in Chinese adults. Methods: Patients who underwent liver ultrasonography at the Health Promotion Center of the First Affiliated Hospital of Nanjing Medical University between January 2020 to June 2021 were enrolled. We used transient elastography to evaluate the degree of hepatic fat and liver stiffness. Appendicular skeletal muscle mass was determined by bioelectrical impedance and was adjusted for body weight to derive the skeletal muscle mass index (SMI). Results: Of 3,602 finally enrolled individuals, 1,830 had NAFLD and 1,772 did not have NAFLD. SMI gradually decreased as the severity of hepatic steatosis increased (40.47 ± 3.94% vs. 39.89 ± 3.57% vs. 39.22 ± 3.46% vs. 37.81 ± 2.84%, P < 0.001). Individuals with F3-F4 and F2 liver fibrosis groups had significantly lower SMI than individuals with F0-F1 stages (37.51 ± 3.19% vs. 38.06 ± 3.51% vs. 39.36 ± 3.38%, P < 0.001). As the SMI increased, the percentages of subjects with mild and severe NAFLD, and the percentages of subjects in F2 and F3-F4 stage were gradually decreased. SMI was independently associated with the severity of hepatic steatosis and fibrosis by logistic regression analysis. Moreover, decreased SMI was an independent risk factor for NAFLD and fibrosis. Conclusion: SMI is closely associated with liver fat content and liver fibrosis in Chinese adults with NAFLD.

Free Triiodothyronine Is Associated With Hepatic Steatosis and Liver Stiffness in Euthyroid Chinese Adults With Non-Alcoholic Fatty Liver Disease.

Objective: The association between non-alcoholic fatty liver disease (NAFLD) and thyroid hormones in euthyroid subjects is unclear. We investigated the relationship between thyroid function and the severity of hepatic steatosis and liver fibrosis in a large cohort of euthyroid Chinese adults. Methods: A total of 3496 participants were enrolled. Liver ultrasonography was used to define the presence of NAFLD (n=2172) or the absence of NAFLD (n=1324). Anthropometric and biochemical measurements were made and thyroid function parameters including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) were measured. The severity of hepatic steatosis and liver stiffness was assessed by transient elastography. Results: Levels of FT3 were significantly higher in the severe NAFLD group and moderate NAFLD group than in the mild NAFLD group (5.18 ± 0.58 vs 5.11 ± 0.57 vs 4.98 ± 0.60 pmol/L, P<0.001). Participants with F4 and F3 liver fibrosis had higher FT3 levels than those with F2 fibrosis (6.33 ± 0.39 vs 5.29 ± 0.48 vs 5.20 ± 0.50 pmol/L, P<0.001). However, FT4 and TSH levels did not correlate with hepatic steatosis or liver fibrosis severity. In addition, the proportions of participants with NAFLD (46.0% vs 63.1% vs 73.3%, P<0.001) and liver fibrosis (11.5% vs 18.6% vs 20.8%, P<0.001) increased as FT3 levels increased. Logistic regression analysis showed that FT3 levels were positively associated with the severity of hepatic steatosis and liver fibrosis presence, even after adjustment for metabolic risk factors including BMI. In non-obese participants, the FT3 level was an independently risk factor for the severity of hepatic steatosis. Conclusions: There are positive associations of FT3 levels with the severity of hepatic steatosis and the presence of liver fibrosis in NAFLD with euthyroidism.

Triglyceride Glucose Index Is Associated With Arterial Stiffness and 10-Year Cardiovascular Disease Risk in a Chinese Population.

Background: Insulin resistance (IR) is a significant risk factor for cardiovascular disease (CVD). In this study, the association of the triglyceride glucose (TyG) index, a simple surrogate marker of IR, with arterial stiffness and 10-year CVD risk was evaluated. Methods: A total of 13,706 participants were enrolled. Anthropometric and cardiovascular risk factors were determined in all participants, while serum insulin levels were only measured in 955 participants. Arterial stiffness was measured through brachial-ankle pulse wave velocity (baPWV), and 10-year CVD risk was evaluated using the Framingham risk score. Results: All participants were classified into four groups according to the quartile of the TyG index. BaPWV and the percentage of participants in the 10-year CVD risk categories significantly increased with increasing quartiles of the TyG index. Logistic regression analysis showed that the TyG index was independently associated with a high baPWV and 10-year CVD risk after adjusting for traditional CVD risk factors. The area under the receiver operating characteristics curve (AUROC) of the TyG index for predicting a high baPWV was 0.708 (95%CI 0.693-0.722, P < 0.001) in women, higher than that in men. However, the association of the homeostatic model assessment of IR (HOMA-IR) with a high baPWV and the 10-year CVD risk was absent when adjusting for multiple risk factors in 955 participants. Conclusions: The TyG index is independently associated with arterial stiffness and 10-year CVD risk.

Increased plasma miR-146a levels are associated with subclinical atherosclerosis in newly diagnosed type 2 diabetes mellitus.

AIMS: The association between circulating miR-146a and subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) remains poorly understood. This study aimed to investigate the correlation between plasma miR-146a levels and subclinical atherosclerosis as measured by the carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (baPWV) in patients with newly diagnosed T2DM. METHODS: We studied 100 patients with newly diagnosed T2DM. Subclinical atherosclerosis was defined as a thickened CIMT (≥1.0 mm) and high baPWV defined as a value greater than the 75th percentile. Plasma miR-146a levels and metabolic parameters were measured. RESULTS: Patients with thickened CIMT had higher plasma miR-146a levels than those without thickened CIMT (3.36 ±â€¯1.32 vs 1.38 ±â€¯1.11, P < 0.001). Patients in the high baPWV group had higher plasma miR-146a levels than those in the normal baPWV group (3.43 ±â€¯1.32 vs 1.98 ±â€¯1.48, P < 0.001). Both CIMT (ß = 0.569, P < 0.001) and baPWV (ß = 0.274, P = 0.001) positively correlated with plasma miR-146a levels after adjustment for confounding factors by multiple stepwise regression. On binary logistic regression, plasma miR-146a level was an independent risk factor for thickened CIMT (OR = 3.890, 95% CI 1.415-7.698, P = 0.008) and high baPWV (OR = 1.954, 95% CI 1.256-3.040, P = 0.002) after adjustment for established cardiovascular risk factors. The area under the receiver operating characteristics curve (AUROC) of plasma miR-146a level for predicting thickened CIMT was 0.795 (95%CI 0.708-0.883, P < 0.001) and for predicting high baPWV was 0.773 (95%CI 0.679-0.867, P < 0.001). CONCLUSION: Plasma miR-146a levels correlate with CIMT and baPWV and could act as a biomarker for early diagnosis and as a therapeutic target for atherosclerosis in T2DM.