Shuang Zheng

BACKGROUND: Body mass index (BMI), waist circumference (WC), visceral adiposity index (VAI), triglyceride glucose index (TyG), TyG-BMI, and TyG-WC have been reported as markers of insulin resistance or type 2 diabetes mellitus (T2DM). However, little is known about the associations between the aforementioned markers and the risk of prediabetes and diabetes in first-degree relatives (FDRs) of T2DM patients. METHODS: 1544 FDRs of T2DM patients (635 men and 909 women) were enrolled in the initial cross-sectional study and all of them finished corresponding examinations. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to compare and identify the associations of the six parameters (BMI, WC, VAI, TyG, TyG-BMI and TyG-WC) with the prevalence of prediabetes and diabetes. Subsequently, 452 of them were followed-up for an average of 5 years. Cox proportional hazard regression model was applied to confirm the predictive value of the optimal marker. RESULTS: Among the indices, TyG-WC was more strongly associated with the prevalence of prediabetes and diabetes. Compared with participants in the lowest quartile of TyG-WC, the adjusted odds ratio and 95 % CIs for prediabetes and diabetes was 11.19 (7.62-16.42) for those in the top quartile of TyG-WC. Moreover, the largest AUC was also observed in TyG-WC (0.765, 95 % CIs 0.741-0.789, P < 0.001). The robust predictive value of TyG-WC was further confirmed in the follow-up study (HR: 7.13, 95 % CIs 3.41-14.90, P < 0.001). CONCLUSIONS: TyG-WC is a novel and clinically effective marker for early identifying the risks of prediabetes and diabetes in FDRs of T2DM patients.

OBJECTIVES: To explore the association between the triglyceride to HDL-C ratio (TG/HDL-C) and insulin resistance in Chinese patients with newly diagnosed type 2 diabetes mellitus. METHODS: Patients with newly diagnosed type 2 diabetes mellitus (272 men and 288 women) were enrolled and divided into three groups according to TG/HDL-C tertiles. Insulin resistance was defined by homeostatic model assessment of insulin resistance (HOMA-IR). Demographic information and clinical characteristics were obtained. Spearman's correlation was used to estimate the association between TG/HDL-C and other variables. Multiple logistic regression analyses were adopted to obtain probabilities of insulin resistance. A receiver operating characteristic analysis was conducted to evaluate the ability of TG/HDL-C to discriminate insulin resistance. RESULTS: TG/HDL-C was associated with insulin resistance in Chinese patients with newly diagnosed T2DM (Spearman's correlation coefficient = 0.21, P < 0.01). Patients in the higher tertiles of TG/HDL-C had significantly higher HOMA-IR values than patients in the lower tertiles [T1: 2.68(1.74-3.70); T2: 2.96(2.29-4.56); T3: 3.09(2.30-4.99)]. Multiple logistic regression analysis showed that TG/HDL-C was significantly associated with HOMA-IR, and patients in the higher TG/HDL-C tertile had a higher OR than those in the lower TG/HDL-C tertile, after adjusting for multiple covariates including indices for central obesity [T1: 1; T2: 4.02(1.86-8.71); T3: 4.30(1.99-9.29)]. Following stratification of waist circumference into quartiles, the effect of TG/HDL-C on insulin resistance remained significant irrespective of waist circumference. CONCLUSIONS: TG/HDL-C was associated with insulin resistance independent of waist circumference. Whether it could be a surrogate marker for insulin resistance in Chinese patients with newly diagnosed type 2 diabetes mellitus still needs to be confirmed by more researches.

Abstract Atherosclerosis is a maladaptive chronic inflammatory disease, which remains the leading cause of death worldwide. The NLRP3 inflammasome constitutes a major driver of atherosclerosis, yet the mechanism of action is poorly understood. Mitochondrial dysfunction is essential for NLRP3 inflammasome activation. However, whether activated NLRP3 inflammasome exacerbates mitochondrial dysfunction remains to be further elucidated. Herein, we sought to address these issues applying VX765, a well-established inhibitor of caspase 1. VX765 robustly restrains caspase 1-mediated interleukin-1β production and gasdermin D processing. Our study assigned VX765 a novel role in antagonizing NLRP3 inflammasome assembly and activation. VX765 mitigates mitochondrial damage induced by activated NLRP3 inflammasome, as evidenced by decreased mitochondrial ROS production and cytosolic release of mitochondrial DNA. VX765 blunts caspase 1-dependent cleavage and promotes mitochondrial recruitment and phosphorylation of Parkin, a key mitophagy regulator. Functionally, VX765 facilitates mitophagy, efferocytosis and M2 polarization of macrophages. It also impedes foam cell formation, migration and pyroptosis of macrophages. VX765 boosts autophagy, promotes efferocytosis, and alleviates vascular inflammation and atherosclerosis in both ApoE −/− and Ldlr −/− mice. However, these effects of VX765 were abrogated upon ablation of Nlrp3 in ApoE −/− mice. This work provides mechanistic insights into NLRP3 inflammasome assembly and this inflammasome in dictating atherosclerosis. This study highlights that manipulation of caspase 1 paves a new avenue to treatment of atherosclerotic cardiovascular disease.