Circulating ANGPTL8 and ANGPTL4 Levels Are Increased in Patients with Hyperglycemia Combined Dyslipidemia

Context: Angiopoietin-like protein 8 (ANGPTL8) and Angiopoietin-like protein 4 (ANGPTL4) are regarded as protein regulating triglyceride (TG) metabolism in mice. However, whether ANGPTL8/4 are involved in glucose and/or lipid metabolism in human remain unclear.

Objective: To examine circulating ANGPTL8/4 levels in subjects with hyperglycemia and/or dyslipidemia and their correlation with glucose and lipid metabolism. Design, Setting and Participants: Serum ANGPTL8/4 levels were measured using ELISA in age-, sex-, and BMI- matched healthy control subjects (CON) (n=92), subjects with isolated hyperglycemia (IHG) (n=87), with isolated dyslipidemia (IDL)(n=86) and hyperglycemia combined dyslipidemia (HCD)(n=99) from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study.

Results: Serum ANGPTL8 and ANGPTL4 levels were both elevated in patients with HCD compared to CON subjects. After controlling for age, sex and blood lipid, ANGPTL8 levels positively correlated with fasting plasma glucose (FPG) (partial r = 0.154), HbA1c (partial r = 0.110) and triglycerides and glucose (TyG) index (age, sex adjusted)(partial r = 0.224). After controlling for age, sex and FPG, ANGPTL8 levels positively correlated with TG (r = 0.163), TG/HDL (r = 0.147) and non-HDL/HDL (r = 0.134). ANGPTL4 were positively correlated with FPG, 2h-glucose, HbA1c and TyG index. Among lipid-related variables, ANGPTL4 were positively correlated with TG, TG/HDL, non-HDL/HDL and negatively correlated with HDL-cholesterol. After controlling for related variables, the correlations were the same.

Conclusion: Circulating ANGPTL8 and ANGPTL4 levels were increased in patients with HCD and might play an important role in linking glucose and lipid metabolism.