Association between ANGPTL3, 4, and 8 and lipid and glucose metabolism markers in patients with diabetes
by Marina Harada, Tadashi Yamakawa, Rie Kashiwagi, Akeo Ohira, Mai Sugiyama, Yasuyuki Sugiura, Yoshinobu Kondo, Yasuo Terauchi
Lipid management, especially with respect to triglyceride (TG) metabolism, in patients with diabetes is not sufficient with current therapeutic agents, and new approaches for improvement are needed. Members of the angiopoietin-like protein (ANGPTL) family, specifically ANGPTL3, 4, and 8, have been reported as factors that inhibit lipoprotein lipase (LPL) activity and affect TGs. The present study investigated the association between lipid and glucose metabolism markers and the mechanism by which these proteins affect lipid metabolism. A total of 84 patients hospitalized for diabetes treatment were evaluated. Lipid and glucose metabolism markers in blood samples collected before breakfast, on the day after hospitalization, were analyzed. ANGPTL8 showed a significant positive correlation with TG values. HDL-C values displayed a significant positive correlation with ANGPTL3 but a negative correlation with ANGPTL4 and ANGPTL8. The results did not indicate a significant correlation among ANGPTL3, 4, and 8 levels. Thus, it is possible that the distribution of these proteins differs among patients. When patients were divided into groups according to the levels of ANGPTL3 and ANGPTL8, those with high levels of both ANGPTL3 and ANGPTL8 also had high levels of TG and small dense LDL-C/LDL-C (%). Multiple regression analysis indicated that low LPL, high ApoC2, high ApoC3, high ApoE, and high ANGPTL8 levels were the determinants of fasting hypertriglyceridemia. By contrast, no clear association was observed between any of the ANGPTLs and glucose metabolism markers, but ANGPTL8 levels were positively correlated with the levels of HOMA2-IR and BMI. Patients with high levels of both ANGPTL3 and ANGPTL8 had the worst lipid profiles. Among ANGPTL3, 4, and 8, ANGPTL8 is more important as a factor determining plasma TG levels. We anticipate that the results of this research will facilitate potential treatments targeting ANGPTL8 in patients with diabetes.