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Background: Insulin resistance(IR) and inflammation have been regarded as common potential mechanisms in coronary heart disease (CHD) and nonalcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance, System immune-inflammation index(SII) and Systemic inflammation response index(SIRI) are novel biomarkers of inflammation, these biomarkers have not been studied in CHD with NAFLD patients. This study investigated the correlation between the TyG index, SII index, and SIRI index and CHD risk among NAFLD patients. Methods: This cross-sectional study included 407 patients with NAFLD in the Department of Cardiology, The Second Hospital of Shanxi Medical University. Of these, 250 patients with CHD were enrolled in the NAFLD+CHD group and 157 patients without CHD were enrolled as NAFLD control. To balance covariates between groups, 144 patients were selected from each group in a 1:1 ratio based on propensity score matching (PSM). Potential influences were screened using Lasso regression analysis. Univariate and multivariate logistic regression analyses and the Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent risk and protective factors for CHD. Construction of nomogram using independent risk factors screened by machine learning. The receiver operating characteristic(ROC) curve was used to assess the ability of these independent risk factors to predict coronary heart disease. The relationship between the Gensini score and independent risk factors was reflected using the Sankey diagram. Results: The LASSO logistic regression analysis and Logistic regression analyses suggest that TyG index (OR, 2.193; 95% CI, 1.242-3.873; P = 0.007), SII index (OR, 1.002; 95% CI, 1.001-29 1.003; P <0.001), and SIRI index (OR, 1.483;95%CI, 1.058-2.079, P=0.022) are independent risk factors for CHD. At the same time, Neutrophils, TG, and LDL-C were also found to be independent risk factors in patients, HDL-C was a protective factor for CHD in patients with NAFLD. Further analysis using three machine learning algorithms found these independent risk factors to have good predictive value for disease diagnosis, SII index shows the highest predictive value. ROC curve analysis demonstrated that combining the SII index, SIRI index, and TyG index can improve the diagnostic ability of nonalcoholic liver cirrhosis patients with CHD.ROC curve analysis showed that the combined analysis of these independent risk factors improved the predictive value of CHD(AUC: 0.751; 95% CI: 0.704-0.798; P <0.001). Conclusion: TyG index, SII index, and SIRI index are all independent risk factors for CHD in patients with NAFLD and are strongly associated with prediction and the severity of CHD. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is common chronic metabolic liver disorder which is associated with fat accumulation in the liver. It causes a wide range of pathological effects such as insulin resistance, obesity, hypertension, diabetes, non-alcoholic steatohepatitis (NASH) and cirrhosis, cardiovascular diseases. The molecular mechanisms that cause the initiation and progression of NAFLD remain fully unclear. Inflammation is regarded as a significant mechanism which could result in cell death and tissue injury. Accumulation of leukocytes and hepatic inflammation are important contributors in NAFLD. Excessive inflammatory response can deteriorate the tissue injury in NAFLD. Thus, inhibition of inflammation improves NAFLD by reducing intrahepatic fat content, increasing β-oxidation of fatty acids, inducing hepato-protective autophagy, overexpressing peroxisome proliferator-activated receptor-γ (PPAR-γ), as well as attenuating hepatocyte apoptosis and increasing insulin sensitivity. Therefore, understanding the molecules and signaling pathways suggests us valuable information about NAFLD progression. This review aimed to evaluate the inflammation in NAFLD and the molecular mechanism on NAFLD. [ABSTRACT FROM AUTHOR]

The liver is the central metabolic organ and plays a pivotal role in regulating homeostasis of glucose and lipid metabolism. Aberrant liver metabolism promotes insulin resistance, which is reported to be a common characteristic of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). There is a complex and bidirectional relationship between NAFLD and T2DM. NAFLD patients with hepatic insulin resistance generally share a high risk of impaired fasting glucose associated with early diabetes; most patients with T2DM experience non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and other more severe liver complications such as cirrhosis and hepatocellular carcinoma (HCC). Additionally, hepatic insulin resistance, which is caused by diacylglycerol-mediated activation of protein kinase C epsilon (PKC𝜀), may be the critical pathological link between NAFLD and T2DM. Therefore, this review aims to illuminate current insights regarding the complex and strong association between NAFLD and T2DM and summarize novel and emerging targets for the treatment of hepatic insulin resistance based on established mechanistic knowledge.

The liver is the central metabolic organ and plays a pivotal role in regulating homeostasis of glucose and lipid metabolism. Aberrant liver metabolism promotes insulin resistance, which is reported to be a common characteristic of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). There is a complex and bidirectional relationship between NAFLD and T2DM. NAFLD patients with hepatic insulin resistance generally share a high risk of impaired fasting glucose associated with early diabetes; most patients with T2DM experience non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and other more severe liver complications such as cirrhosis and hepatocellular carcinoma (HCC). Additionally, hepatic insulin resistance, which is caused by diacylglycerol-mediated activation of protein kinase C epsilon (PKC𝜀), may be the critical pathological link between NAFLD and T2DM. Therefore, this review aims to illuminate current insights regarding the complex and strong association between NAFLD and T2DM and summarize novel and emerging targets for the treatment of hepatic insulin resistance based on established mechanistic knowledge. [ABSTRACT FROM AUTHOR]

Obesity, characterized by chronic activation of inflammatory pathways, is a critical factor contributing to insulin resistance (IR) and type 2 diabetes (T2D). Free fatty acids (FFAs) are increased in obesity and are implicated as proximate causes of IR and induction of inflammatory signaling in adipose, liver, muscle, and pancreas. Cells of the innate immune system produce cytokines, and other factors that affect insulin signaling and result in the development of IR. In the lean state, adipose tissue is populated by adipose tissue macrophage of the anti-inflammatory M2 type (ATM2) and natural killer (NK) cells; this maintains the insulin-sensitive phenotype because ATM2 cells secrete IL10. In contrast, obesity induces lipolysis and release of pro-inflammatory FFAs and factors, such as chemokine (C-C motif) ligand 2 (CCL2) and tumor necrosis factor alpha (TNF-α), which recruit blood monocytes in adipose tissue, where they are converted to macrophages of the highly pro-inflammatory M1-type (ATM1). Activated ATM1 produce large amounts of pro-inflammatory mediators such as TNF-α, interleukin-1β, IL-6, leukotriene B4, nitric oxide (NO), and resistin that work in a paracrine fashion and cause IR in adipose tissue. In the liver, both pro-inflammatory Kupffer cells (M1-KCs) and recruited hepatic macrophages (Ly6Chigh) contribute to decreased hepatic insulin sensitivity. The present mini-review will update the bidirectional interaction between the immune system and obesity-induced changes in metabolism in adipose tissue and liver and the metabolic consequences thereof. [ABSTRACT FROM AUTHOR]