Patients with the highest ANGPTL8 quartile had a 3.71-fold increased atherosclerosis risk compared to the lowest quartile, with each SD increase linked to a 56% higher risk.
Are elevated circulating ANGPTL8 levels associated with an increased risk of atherosclerosis in patients with type 2 diabetes?
Elevated ANGPTL8 levels are independently associated with increased atherosclerosis risk in type 2 diabetes, improving risk prediction beyond traditional lipid parameters.
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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 <0.001) for atherosclerosis prediction. Mediation analysis revealed that cystatin C partially mediated (8.22%) the effect of ANGPTL8 on atherosclerosis, whereas triglycerides showed negligible mediation. Conclusions Elevated ANGPTL8 levels are independently associated with increased atherosclerosis risk in patients with type 2 diabetes. This relationship is partially mediated through cystatin C but not lipid parameters. ANGPTL8 significantly improves cardiovascular risk prediction beyond traditional risk factors, suggesting its potential as a novel biomarker for cardiovascular risk stratification and a therapeutic target addressing residual cardiovascular risk through lipid‐independent inflammatory pathways in type 2 diabetes.
Ye et al. (Thu,) reported a other. Patients with the highest ANGPTL8 quartile had a 3.71-fold increased atherosclerosis risk compared to the lowest quartile, with each SD increase linked to a 56% higher risk.