Abstract
BACKGROUND AND AIMS: Cardio-kidney-metabolic diseases are major causes of premature death worldwide, with type 2 diabetes mellitus (T2DM) playing a critical role. Inflammation and insulin resistance have been implicated in the pathogenesis of T2DM. This study aimed to investigate the sex-specific associations of metabolic inflammation and insulin resistance with incident T2DM to support personalized prevention and management strategies. METHODS: A retrospective cohort was used to analyse annual health examination data from the general practice department of a general hospital in Shanghai between 2021 and 2023. After excluding participants diagnosed with T2DM, cardiovascular disease or chronic kidney disease at baseline, 1214 adults were followed up for two years. Cox proportional hazards and logistic regression models were used to assess the associations of triglyceride-glucose body mass index (TyG-BMI), the lymphocyte/high-density lipoprotein cholesterol ratio (LHR), the monocyte/high-density lipoprotein cholesterol ratio (MHR), and the neutrophil/high-density lipoprotein cholesterol ratio (NHR) with incident T2DM. RESULTS: In the total population, TyG-BMI (all HR/OR > 1, P < 0.05), LHR, MHR and NHR were significantly and positively associated with incident T2DM. TyG-BMI was significantly associated with incident T2DM in men (both HR/OR > 1, P < 0.05), whereas LHR, MHR and NHR were strongly associated with incident T2DM in women (all HR/OR > 1, P < 0.05). The interaction effect between LHR and sex was statistically significant. CONCLUSION: Sex differences play an important role in incident T2DM. Men should be aware of weight control to avoid obesity-related insulin resistance, whereas women should monitor metabolic inflammation indicators such as LHR for early detection and intervention of their T2DM risk.