To evaluate the associations between lipid-related metabolic indicators and incident type 2 diabetes mellitus (T2DM).
A diabetes family cohort study of 3,726 participants was conducted in Taizhou from May to October 2021 to track incident T2DM cases. Lipid metabolism indicators included triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride-glucose (TyG) and its related indices, Chinese Visceral Adiposity Index (CVAI), and homeostasis model assessment of insulin resistance (HOMA-IR). Mixed-effects Cox proportional hazards models, within-family Cox models, and quartile analyses were performed to examine the associations between these indicators and incident T2DM.
Among 1,257 participants without diabetes at baseline, 68 developed incident T2DM during the average follow-up of 3.92 years. Higher levels of TyG (HR = 1.758, 95% CI: 1.182–2.616), TyG-BMI (HR = 1.007, 95% CI: 1.002–1.013), TyG-WHtR (HR = 2.108, 95% CI: 1.468–3.027), TyG-WC (HR = 1.005, 95% CI: 1.003–1.007), CVAI (HR = 1.013, 95% CI: 1.006–1.020), and HOMA-IR (HR = 1.195, 95% CI: 1.038–1.376) were significantly associated with an increased risk of incident T2DM, whereas traditional lipid indicators showed no significant associations. These findings were consistent in within-family analyses. Furthermore, dose-response relationships were observed between TyG, TyG-WHtR, TyG-WC, CVAI and incident T2DM.
In conclusion, TyG-related indices, CVAI, and HOMA-IR were significantly associated with incident T2DM in this diabetes family-based cohort. These composite indicators may be useful for the early identification of high-risk individuals and for informing targeted prevention strategies.
Not applicable.
Haowei Li, Yilu Huang, Donghui Yang et al.· BMC Endocrine Disorders· 0 citations
Psoriasis is a chronic inflammatory skin disorder in which biologics targeting immune pathways have markedly improved clinical outcomes. Nevertheless, persistent oxidative stress and stromal abnormalities in lesional skin indicate that pathogenic mechanisms beyond canonical immune circuits remain active. Here, we integrated single‐cell RNA sequencing, an imiquimod (IMQ)‐induced psoriasiform murine model, LC–MS/MS‐based metabolomic profiling of fibroblast‐conditioned medium, and complementary in vitro studies to define ferroptosis‐related alterations in dermal fibroblasts under psoriasis‐like inflammatory conditions. Single‐cell analysis revealed a marked expansion of an inflammatory fibroblast subset (iFb1) in psoriasiform lesions, together with enrichment of ferroptosis‐related pathways. In vivo and in vitro analyses further showed that inflammatory stimulation induced ferroptosis‐related injury in dermal fibroblasts, as evidenced by increased lipid peroxidation, impaired antioxidant defenses, and characteristic ultrastructural alterations. Metabolomic profiling of conditioned medium further indicated secretory remodeling characterized by enrichment of lipid mediators and redox‐associated metabolites. Lipocalin‐2 (LCN2) was significantly upregulated in psoriasis‐associated fibroblasts and exacerbated lipid peroxidation and ferroptosis‐related injury. Conditioned medium from inflammation‐stimulated fibroblasts enhanced keratinocyte proliferation, whereas inhibition of fibroblast ferroptosis or LCN2 knockdown attenuated this effect. Further experiments suggested that 4‐hydroxy‐2‐nonenal (4‐HNE) may act as a potential mediator of fibroblast–keratinocyte crosstalk. Topical administration of carnosine, a potent 4‐HNE scavenger, alleviated IMQ‐induced psoriasiform skin lesions in vivo. Together, these findings support an LCN2‐driven fibroblast–keratinocyte crosstalk axis linked to ferroptosis‐related injury in psoriasis and highlight stromal lipid peroxidation as a potential therapeutic target.
Min Zhang, GuangDong Liu, Shu-Xin Wang et al.· The FASEB Journal· 0 citations
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