Key result
High circulating ANGPTL8 levels were associated with a more than threefold higher risk of all-cause mortality (RR 3.23) compared to low levels in adults with newly diagnosed diabetes over 5 years.
Why the study?
ANGPTL8 is associated with diabetes, but its role in outcomes across novel subgroups of diabetes remains unclear.
Are high circulating ANGPTL8 levels associated with increased all-cause and cardiovascular mortality in adults with newly diagnosed diabetes?
Cohort (n=741)
Yes
Are high circulating ANGPTL8 levels associated with increased all-cause and cardiovascular mortality in adults with newly diagnosed diabetes?
Relative Risk: 3.23 (95% CI 1.13–9.22)
Elevated circulating ANGPTL8 levels are associated with a significantly increased risk of 5-year all-cause mortality in adults with newly diagnosed diabetes.
Does not yet support ANGPTL8-guided care in new diabetes; hypothesis-generating for mortality risk stratification.
ANGPTL8, an important regulator of glucose and lipid metabolism, is associated with diabetes, but the role of ANGPTL8 in the outcomes of novel subgroups of diabetes remains unclear. To assess the circulating ANGPTL8 levels in novel subgroups of diabetes and their association with health outcomes, we performed a data-driven cluster analysis (k-means) of patients with newly diagnosed diabetes (741 patients enrolled from 2011 through 2016) from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a longitudinal (REACTION) study. The primary outcomes were mortality from all causes and cardiovascular diseases (CVD), and the secondary outcome was any cardiovascular event. Comparisons among groups were performed using the Kruskal-Wallis test, and the correlations between variables were assessed using the Pearson correlation test. Logistic regression was used to detect associations between the risk of outcomes and the ANGPTL8 levels. We identified four replicable clusters of patients with diabetes that exhibited significantly different patient characteristics and risks of all-cause mortality. The serum ANGPTL8 levels in the cluster of mild age-related diabetes (MARD), severe insulin-resistant diabetes (SIRD), and severe insulin-deficient diabetes (SIDD) were significantly higher than those in the mild obesity-related diabetes (MOD) cluster (685.01 ± 24.50 vs. 533.5 ± 18.39, p < 0.001; 649.69 ± 55.83 vs. 533.5 ± 18.39, = 0.040; 643.29 ± 30.89 vs. 533.5 ± 18.39, p = 0.001). High circulating ANGPTL8 levels were more highly associated with a greater hazard of all-cause mortality (quartile 4 vs 1: risk ratio [RR] 3.23, 95% CI 1.13-9.22; per unit increase in the Z score: RR 1.53, 95% CI 1.17-2.01) than low circulating ANGPTL8 levels. In conclusion, this 5-year follow-up REACTION study revealed that the circulating ANGPTL8 levels show differences among novel subgroups of adult patients with diabetes and are associated with all-cause mortality in the subsequent 5 years.
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Zou et al. (2020) conducted a cohort in Newly diagnosed diabetes (n=741). High circulating ANGPTL8 levels (Quartile 4) vs. Low circulating ANGPTL8 levels (Quartile 1) was evaluated on All-cause mortality (RR 3.23, 95% CI 1.13-9.22). High circulating ANGPTL8 levels were associated with a more than threefold higher risk of all-cause mortality (RR 3.23) compared to low levels in adults with newly diagnosed diabetes over 5 years.
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