Background Triglyceride glucose-body mass index (TyG-BMI) is a recently developed alternative indicator to identify insulin resistance. However, few studies have investigated the association between the TyG-BMI and nonalcoholic fatty liver disease (NAFLD). Therefore, this study aimed to study the relationship between NAFLD and the TyG-BMI in the general population and its predictive value. Methods A cross-sectional study was conducted on 14,251 general subjects who took part in a comprehensive health examination. The anthropological characteristics and many risk factors for NAFLD were measured. Results After fully adjusting for confounding variables, a stable positive correlation was found between NAFLD and the TyG-BMI (OR: 3.90 per SD increase; 95% CI: 3.54 to 4.29; P-trend< 0.00001). This positive correlation was not simply linear but a stable non-linear correlation. Additionally, obvious threshold effects and saturation effects were found, in which a threshold effect occurred when the TyG-BMI was between 100 and 150; when the TyG-BMI was between 300 and 400, the corresponding NAFLD risk appeared saturated. Furthermore, receiver operating characteristic analysis showed that the TyG-BMI could better predict the risk of NAFLD than other traditional indicators [TyG-BMI (AUC): 0.886; 95% CI: 0.8797–0.8927; P < 0.0001], particularly among young and middle-aged and non-obese people. Conclusions This epidemiological study is the first on the association between the TyG-BMI and NAFLD risk in the general population. In this large data set from the general population, the TyG-BMI showed an independent positive correlation with NAFLD. The discovery of the threshold effect and saturation effect between them provides a new idea to prevent and treat NAFLD.
BackgroundCurrent checkpoint immunotherapy has shown potential to control cancer by restoring or activating the immune system. Nevertheless, multiple mechanisms are involved in immunotherapy resistance which limits the clinical benefit of checkpoint inhibitors. An immunosuppressive microenvironment is an important factor mediating the original resistance of tumors to immunotherapy. A previous report by our group has demonstrated that local angiotensin II (AngII) predominantly exists in a tumor hypoxic microenvironment where hypoxic tumour cells produced AngII by a hypoxia-lactate-chymase-dependent mechanism.ResultsHere, using 4T1 and CT26 syngeneic mouse tumor models, we found that local AngII in the tumor microenvironment was involved in immune escape of tumour cells and an AngII signaling blockage sensitized tumours to checkpoint immunotherapy. Furthermore, an AngII signaling blockage reversed the tumor immunosuppressive microenvironment, and inhibition of angiotensinogen (AGT, a precursor of AngII) expression strongly triggered an immune-activating cytokine profile in hypoxic mouse cancer cells. More importantly, AGT silencing combined with a checkpoint blockage generated an abscopal effect in resistant tumors.ConclusionOur study demonstrated an important role of local AngII in the formation of a tumor immunosuppressive microenvironment and its blockage may enhance tumor sensitivity to checkpoint immunotherapy. The combination of an AngII signaling blocker and an immune-checkpoint blockage could be a promising strategy to improve tumors responses to current checkpoint immunotherapy.Electronic supplementary materialThe online version of this article (10.1186/s40425-018-0401-3) contains supplementary material, which is available to authorized users.
Purpose Remnant cholesterol (RC) is the cholesterol of triglyceride-rich lipoproteins, which has a high degree of atherogenic effect. To date, epidemiological evidence supports that higher RC levels lead to a greater risk of adverse cardiovascular events in patients with diabetes, but the nature of the association between RC levels and diabetes risk remains unclear. This study was designed to assess the association of RC with the risk of new-onset diabetes and to investigate whether there is a causal relationship between the two. Patients and Methods The subjects included 15,464 individuals of the general population who participated in a health examination. Subjects were quartered according to the RC quartile, and the Cox proportional hazard model was used to assess the independent association between RC and new-onset diabetes. Results During an average observation period of 6.13 years, 2.41% of the subjects were diagnosed with new-onset diabetes. Kaplan–Meier analysis showed that the 13-year cumulative diabetes rates corresponding to the RC quartile were 8.62%, 2.49%, 12.78%, and 17.91%. Multivariate Cox regression analysis indicated that higher RC levels were independently associated with an increased risk of new-onset diabetes (HR: 2.44, 95% CI: 1.50–3.89). Additionally, according to the results of receiver operating characteristic curve analysis, RC had the largest area under the curve (0.7314) compared to traditional lipid parameters in predicting new-onset diabetes. Conclusion These results indicated that RC is an important independent predictor of new-onset diabetes in the general population.
Background Ectopic fat obesity and triglycerides are risk factors for diabetes and multiple cardiovascular diseases. However, there have been limited studies on the association between triglycerides and ectopic fat obesity. The purpose of this study was to explore the association between triglycerides and ectopic fat obesity. Methods and results In this cross-sectional study, we retrospectively analyzed 15464 adult participants recruited by Murakami Memorial Hospital (8430 men and 7034 women, average age of 43.71 ± 8.90). All patients were divided into two groups according to the threshold used to diagnose hypertriglyceridemia. The logistic regression model was used to analyze the association between triglycerides and the risk of ectopic fat obesity, and the generalized additive model was used to identify the nonlinear association. In this study population, the prevalence of ectopic fat obesity was 17.73%. After adjusting other covariables, triglycerides were positively correlated with the risk of ectopic fat obesity (OR: 1.54, 95% CI:1.41–1.69, P<0.0001). Through smooth curve fitting, we found that there was an inverted U-shaped curve association between triglycerides and ectopic fat obesity. This association remained unchanged even if the adjusted covariables were removed from the model, and the inflection point of the curve was 3.98. When triglyceride levels were ≤3.98, triglycerides were positively correlated with the risk of ectopic fat obesity (OR:1.784, 95% CI:1.611–1.975, P<0.0001). When triglyceride levels were >3.98 (right side of the inflection point), there was a negative correlation (OR:0.519, 95% CI:0.333–0.810, P = 0.0039). Conclusions Our research showed that there is a significant association between triglycerides and ectopic fat obesity. This relation is not a simple linear relationship but instead an inverted U-shaped curve association.
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