HDL-C and systemic inflammatory response index mediate the association between visceral adipose tissue and risk of cardiovascular disease among young and middle-aged adults with prediabetes or diabetes: a national cohort study

Visceral adipose tissue (VAT) is a harmful fat linked to cardiovasular disease (CVD). This study aims to investigate the relationship between VAT, as measured by dual-energy X-ray absorptiometry, and CVD risk in young and middle-aged adults with prediabetes or diabetes. This study analyzed data from 4,227 participants aged 18 to 59 years, collected through the National Health and Nutrition Examination Survey. To evaluate the association between VAT and CVD risk, multivariable logistic regression and restricted cubic spline (RCS) regression analyses were employed. Additionally, mediation, subgroup, and sensitivity analyses were performed to ensure the robustness of the results. Upon comprehensive adjustment for confounders, analysis of VAT index (VATI) as a continuous variable revealed that the odds ratio (OR) for CVD incidence was 2.11 (95% CI: 1.12–3.98; P = 0.022). Participants in the highest tertile of VATI demonstrated a 155% increased risk of CVD (OR 2.55, 95% CI: 1.37–4.72, P = 0.004) compared to those in the lowest tertile. RCS regression analysis suggested a nonlinear association between VATI and CVD incidence (P overall < 0.001, P non−linear = 0.027). Furthermore, mediation analysis indicated that high-density lipoprotein cholesterol (HDL-C) and the systemic inflammatory response index (SIRI) mediated 13.34% and 5.42% of association between VATI and CVD risk, respectively. VAT was positively associated with CVD risk among individuals with prediabetes or diabetes in a nonlinear manner. HDL-C and SIRI partially mediate the impact of VAT on CVD incidence, highlighting lipid metabolism and inflammation as potential underlying mechanisms. Nonlinear association: Visceral adipose tissue (VAT) exhibits a nonlinear positive relationship with cardiovascular disease (CVD) risk in adults under 60 with prediabetes or diabetes. Mediating mechanisms: HDL-C and systemic inflammatory response index partially mediate the impact of VAT on CVD incidence, highlighting lipid metabolism and inflammation as potential underlying mechanisms. Clinical implications: Underscoring the importance for clinicians managing patients with cardiometabolic disease to closely monitor the area of VAT and implement appropriate interventions.