Abstract
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.
Highlights
Angiopoietin-like protein 8 (ANGPTL8), which is known as betatrophin, TD26, “refeeding induced in fat and liver” (RIFL) and lipasin, is a novel hormone and potentially a potent stimulator of β-cell proliferation[1,2,3,4,5]
Epidemiological studies have demonstrated that the ANGPTL8 levels are increased in patients with long-standing type 1 diabetes mellitus (T1DM)[14] and type 2 diabetes mellitus (T2DM)[15,16,17], but contradictory results have been obtained in other studies[18,19]
The present study aimed to evaluate the levels of circulating ANGPTL8, which serves as an important factor in glucose and lipid metabolism, in subjects belonging to different novel diabetes subgroups and its association with subsequent events or complications
Summary
Angiopoietin-like protein 8 (ANGPTL8), which is known as betatrophin, TD26, “refeeding induced in fat and liver” (RIFL) and lipasin, is a novel hormone and potentially a potent stimulator of β-cell proliferation[1,2,3,4,5]. The physiological basis of the features characterizing each cluster of novel diabetes subgroups provides a strong rationale for investigating the genetic and molecular mechanisms that lead to the observed heterogeneity in the presentation and progression of diabetes in a dults[26]. Based on these findings, the present study aimed to evaluate the levels of circulating ANGPTL8, which serves as an important factor in glucose and lipid metabolism, in subjects belonging to different novel diabetes subgroups and its association with subsequent events or complications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
