Key result
Elevated serum ANGPTL8 levels (highest vs lowest quartile) were associated with a significantly increased risk of all-cause mortality (RR 3.54) in patients with diabetes, and improved the predictive performance of the QFrailty score.
Why the study?
ANGPTL8 is increased in diabetes and linked to insulin resistance, but its role in clinical outcomes of diabetic patients remains unclear.
Do elevated serum ANGPTL8 levels predict all-cause mortality and adverse clinical outcomes in patients with diabetes?
Cohort (n=1,538)
Yes
Do elevated serum ANGPTL8 levels predict all-cause mortality and adverse clinical outcomes in patients with diabetes?
Relative Risk: 3.54 (95% CI 1.32–9.5)
Absolute Event Rate: 13% vs 3.1%
p-value: p=0.01
Elevated serum ANGPTL8 levels are independently associated with increased all-cause mortality and renal dysfunction in patients with diabetes, improving the predictive performance of the QFrailty score.
Elevated ANGPTL8 may flag higher mortality risk in diabetes; leaves open its added prognostic value beyond routine markers.
Background Angiopoietin-like protein 8 (ANGPTL8), an important regulator of lipid metabolism, is increased in diabetes and is associated with insulin resistance. However, the role of ANGPTL8 in the outcomes of diabetic patients remains unclear. This study aimed to investigate circulating levels of ANGPTL8 in participants with and without diabetes and its potential associations with clinical outcomes in a 5 year cohort study. Methods Propensity-matched cohorts of subjects with and without diabetes from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: A longitudinal (REACTION) study were generated on the basis of age, sex and body mass index at baseline. The primary outcome was all-cause mortality. The secondary outcomes were a composite of new-onset major adverse cardiovascular events, hospitalization for heart failure, and renal dysfunction (eGFR < 60/min/1.73 m 2 ). Results We identified 769 matched pairs of diabetic patients and control subjects. Serum ANGPTL8 levels were elevated in patients with diabetes compared to control subjects (618.82 ± ± 318.08 vs 581.20 ± ± 299.54 pg/mL, p = 0.03). Binary logistic regression analysis showed that elevated ANGPTL8 levels were associated with greater risk ratios (RRs) of death (RR in quartile 4 vs. quartile 1, 3.54; 95% CI 1.32–9.50) and renal dysfunction (RR in quartile 4 vs. quartile 1, 12.43; 95% CI 1.48–104.81) only in diabetic patients. Multivariable-adjusted restricted cubic spline analyses revealed a significant, linear relationship between ANGPTL8 and all-cause mortality in diabetic patients (p for nonlinear trend = 0.99, p for linear trend = 0.01) but not in control subjects (p for nonlinear trend = 0.26, p for linear trend = 0.80). According to ROC curve analysis, the inclusion of ANGPTL8 in QFrailty score significantly improved its predictive performance for mortality in patients with diabetes. Conclusion Serum ANGPTL8 levels were associated with an increased risk of all-cause mortality and could be used as a potential biomarker for the prediction of death in patients with diabetes.
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Zou et al. (2020) conducted a cohort in Diabetes (n=1,538). Elevated serum ANGPTL8 levels (Quartile 4) vs. Lower serum ANGPTL8 levels (Quartile 1) was evaluated on All-cause mortality (RR 3.54, 95% CI 1.32-9.50, p=0.01). Elevated serum ANGPTL8 levels (highest vs lowest quartile) were associated with a significantly increased risk of all-cause mortality (RR 3.54) in patients with diabetes, and improved the predictive performance of the QFrailty score.
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