Triglyceride-mediated influence of serum angiopoietin-like protein 8 on subclinical atherosclerosis in type 2 diabetic patients: results from the GDMD study in China

Background: Hypertriglyceridemia, insulin resistance and hyperglycemia are risk factors for atherosclerosis in type 2 diabetes. Angiopoietin-like protein 8 (ANGPTL8) is a newly identified liver-derived hormone related to these risk factors. Hence, we aimed to explore the correlations between serum levels of ANGPTL8 and subclinical atherosclerosis in type 2 diabetes. Methods: We measured serum ANGPTL8, blood lipids, blood glucose, common carotid artery Intima-Media Thickness (c-IMT) and calculated homeostasis model assessment of insulin resistance in (1) control subjects (n = 100), (2) type 2 diabetic patients without subclinical atherosclerosis (n = 100), and (3) type 2 diabetic patients with subclinical atherosclerosis (n = 100). Results: Serum levels of ANGPTL8 and triglyceride (TG) were significantly increased in type 2 diabetic patients with subclinical atherosclerosis as compared with type 2 diabetic patients without subclinical atherosclerosis and control subjects (P < 0.001). ANGPTL8 was positively associated with age, TG, diabetes duration, and c-IMT in type 2 diabetes. Logistic regression analysis revealed that ANGPTL8 had higher odds of having subclinical atherosclerosis [odds ratio (OR) 2.90, 95% confidence interval (CI) 1.48-5.70, P = 0.002] in type 2 diabetes. Mediation analysis indicated that TG acted as a partial mediator in the relationship between ANGPTL8 and c-IMT. Conclusions: TG partially mediates the positive relationship between ANGPTL8 and c-IMT. Our data provide the first evidence for a strong link between ANGPTL8 and subclinical atherosclerosis, suggesting ANGPTL8 to be a new biomarker for subclinical atherosclerosis in type 2 diabetes.