Elevated ANGPTL8 (Angiopoietin‐Like Protein 8) Levels as a Novel Predictor of Atherosclerosis in Type 2 Diabetes: Beyond Lipid Metabolism

Background ANGPTL8 (angiopoietin‐like protein 8) regulates lipid metabolism, but its role in atherosclerosis among patients with type 2 diabetes, particularly through lipid‐independent mechanisms, remains unclear. Methods This matched case–control study included 202 patients with type 2 diabetes (101 with atherosclerosis, and 101 without) matched for age, body mass index, and sex. Atherosclerosis was assessed via carotid intima‐media thickness and plaque scores. Circulating ANGPTL8 levels were measured by ELISA. Associations were evaluated using multivariate logistic regression, restricted cubic splines, and mediation analyses. Results Patients with atherosclerosis had significantly higher circulating ANGPTL8 levels (529.96 [350.58–816.78] versus 470.62 [265.54–717.47] pg/mL; P =0.027). After adjusting for confounders, the highest ANGPTL8 quartile showed 3.71‐fold increased atherosclerosis risk (95% CI, 1.52–9.06; P =0.004) versus the lowest quartile. Each SD increase in ANGPTL8 was associated with 56% higher risk (odds ratio, 1.56 [95% CI, 1.18–2.05]). A significant linear dose–response relationship was observed ( P =0.036). Adding ANGPTL8 to traditional risk factors significantly improved discrimination (area under the curve, 0.62 [95% CI, 0.54–0.70]) and reclassification (net reclassification improvement, 0.40 [95% CI, 0.13–0.66]; P