Abstract

Aims Betatrophin is a recently identified circulating adipokine that may affect lipid and glucose metabolism. However, the association between plasma betatrophin levels and carotid atherosclerosis has not been elucidated. Methods We investigated plasma betatrophin levels in 153 subjects undergoing carotid ultrasonography. The severity of plaque was evaluated as plaque score. Results Of the 153 subjects, plaque was found in 63 (41%). Plasma betatrophin levels were higher in 63 subjects with plaque than in 90 without plaque (median 906 vs. 729 pg/mL, P < 0.025). A stepwise increase in betatrophin levels was found depending on the plaque score: 729 pg/mL in score = 0 (n = 90), 802 pg/mL in score = 1 (n = 31), and 978 pg/mL in score ≥ 2 (n = 32) (P < 0.01). In particular, betatrophin levels in subjects with score ≥ 2 were higher than in those with score = 0 (P < 0.05). Moreover, betatrophin levels correlated with plaque score (r = 0.23, P < 0.01), but no significant correlation was found between betatrophin levels and triglyceride or HbA1c levels. The percentage of subjects with betatrophin > 800 pg/mL was higher in subjects with plaque than in those without plaque (65% vs. 44%) and was highest in score ≥ 2 (78%) (P < 0.005). In the multivariate analysis, betatrophin level was not a significant factor for the presence of plaque but was a significant factor for plaque score ≥ 2, independent of atherosclerotic risk factors. The odds ratio for score ≥ 2 was 4.9 (95% CI = 1.9-12.8) for betatrophin > 800 pg/mL. Conclusions Plasma betatrophin levels were found to be high in subjects with carotid plaque and to be associated with the severity of plaque. Betatrophin may play a role in the progression of carotid atherosclerosis.

Highlights

  • Betatrophin, called angiopoietin-like protein 8 (ANGPTL8), is a recently identified circulatory adipokine, mainly secreted from the liver and adipose tissues, which may affect both glucose and lipid metabolism [1]

  • Plasma high-sensitivity C-reactive protein (hsCRP) levels tended to be higher in subjects with plaque than in those without plaque, but this difference did not reach statistical significance

  • Betatrophin levels significantly correlated with the plaque score (r = 0:23) and the mean Intima-media thickness (IMT) (r = 0:22) (P < 0:01), but no significant correlation was found between betatrophin levels and TG, FPG, or HbA1c levels

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Summary

Introduction

Betatrophin, called angiopoietin-like protein 8 (ANGPTL8), is a recently identified circulatory adipokine, mainly secreted from the liver and adipose tissues, which may affect both glucose and lipid metabolism [1]. One study reported betatrophin to induce pancreatic beta cell proliferation [2], but another study showed betatrophin not to affect beta cell expansion nor glucose metabolism [3]. Most studies reported blood betatrophin levels to be high in patients with diabetes mellitus (DM) [4, 5], while some studies found no difference between DM and non-DM patients [6]. One low-frequency variant of the betatrophin gene (rs145464906) was reported to be associated with lower TG levels but not with lower glucose levels [8]. Some studies reported blood betatrophin levels to correlate with TG levels [5, 9], but others showed no correlation [4, 6]. The associations between blood betatrophin levels and DM or TG levels remain controversial

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