What is the clinical evidence from this study?

Study design: Observational. Population: Diabetes (n=84). Intervention: ANGPTL8. Primary outcome: Fasting plasma triglyceride levels (β 0.186, 95% CI 0.052-0.222, p=0.002).

July 22, 2021Open Access

Association between ANGPTL3, 4, and 8 and lipid and glucose metabolism markers in patients with diabetes

Resultado clave

In patients with diabetes, high circulating ANGPTL8 levels were significantly and independently associated with elevated fasting triglyceride levels (β 0.186, p=0.002).

Diseño del estudio

Tipo

Observational (n=84)

Multicéntrico

PICO estructurado

Población

84 patients hospitalized for uncontrolled diabetes (age >20 years) admitted for the purpose of controlling blood glucose levels, mean age 62.9, 57 male/27 female. Exclusion criteria: severe ketosis, diabetic coma, serious infection, serious trauma, and cancer.

Resultado

Association between lipid and glucose metabolism markers and ANGPTL3, 4, and 8 levelssurrogate

Resultado numérico

Estimación del efecto: β 0.186 (95% CI 0.052-0.222)

valor p: p=0.002

Limitaciones

LPL values measured were pre-heparin plasma LPL values
Fasting blood sample was used instead of postprandial blood
Did not investigate the dynamics between ANGPTLs and dietary load
Many patients were taking lipid-related and hypoglycemic drugs
Unclear whether measured ANGPTL is free or present in a complex
Small sample size

Resumen

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.

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