Mechanism elucidation of Polygonatum sibiricum-Prepared Cervus elaphus velvet antler in intervening non-alcoholic fatty liver disease based on network analysis combined with proteomics.

Temporomandibular disorder (TMD) refers to a group of conditions involving pain and impaired function of the temporomandibular joints (TMJs), the masticatory muscles, and related anatomical components. While traditionally viewed as a localized joint issue, increasing evidence suggests that TMD is influenced by systemic factors, including chronic low-grade inflammation and metabolic dysregulation [,]. A previous systematic review showed that TMD has a considerable effect on oral health–related quality of life, with pain being a particularly prominent factor []. Key symptoms of TMD often include localized pain in the facial and preauricular regions, restricted jaw mobility, and joint sounds such as clicking or popping during mandibular motion []. Among adults aged 20–49, the prevalence of painful TMD has been reported to be approximately 36% []. This condition may also be linked to broader health issues, including psychological conditions like depression, and can negatively impact a patient's overall quality of life []. Although the precise cause of TMD remains uncertain, current evidence suggests it results from an interplay of genetic predisposition, environmental exposures, and psychosocial influences [–]. Diabetes mellitus (DM) refers to a group of metabolic disorders primarily characterized by persistent hyperglycemia []. Chronic hyperglycemia in DM triggers systemic inflammatory cascades, elevating pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which can accelerate the degradation of joint [,]. Most DM cases are classified into two major etiological categories. Type 1 diabetes involves a complete lack of insulin production, whereas type 2 diabetes—the more common form—arises from a combination of insulin resistance and insufficient compensatory insulin secretion []. Additionally, DM has been linked to various musculoskeletal complications, such as restricted joint mobility, diabetic-related arthropathy, and neuropathic pain syndromes []. The biological plausibility of the DM–TMD relationship is further supported by the accumulation of advanced glycation end products (AGEs) in connective tissues, which increases tissue stiffness and impairs the reparative capacity of the TMJ []. Furthermore, diabetic neuropathy and metabolic-related obesity may lower pain thresholds and exacerbate musculoskeletal pain syndromes, potentially increasing the risk of TMD symptoms [,]. Some studies suggest an association between both types of DM and TMD []. The prevalence of TMD among patients with DM is higher [] and the incidence of limited joint mobility, a type of TMD, is higher in patients with type 2 DM []. However, most previous work has relied on cross-sectional data or smaller clinical samples, leaving the long-term temporal relationship unclear [,,]. Patient cohorts with an association between DM and TMD have not been extensively studied. As far as we are aware, this study is the first to explore the association between DM and the risk of TMD utilizing a large-scale, 15-year longitudinal cohort from Taiwan’s Longitudinal Generation Tracking Database (LGTD). We hypothesized that patients with DM are at an increased risk of developing TMD due to these systemic metabolic and inflammatory influences.