Association between proprotein convertase subtilisin/kexin 9 (PCSK9) and lipoprotein subclasses in children with type 1 diabetes mellitus: Effects of glycemic control
Association between proprotein convertase subtilisin/kexin 9 (PCSK9) and lipoprotein subclasses in children with type 1 diabetes mellitus: Effects of glycemic control
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DOI：
10.1016/j.atherosclerosis.2018.11.020
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发表时间：
2019-01-01
期刊：
影响因子：
5.3
通讯作者：
Spasojevic-Kalimanovska, Vesna
中科院分区：
文献类型：
--
作者：
Bojanin, Dragana;Vekic, Jelena;Spasojevic-Kalimanovska, Vesna
背景和目的：1型糖尿病(T1 DM)的血脂异常是以低密度脂蛋白(LDL)和高密度脂蛋白(HDL)亚类分布改变为特征的。最近的研究表明，原蛋白转换酶枯草杆菌/可信9(PCSK9)可能参与了T1 DM血脂异常的发生。方法：对2 0 7例接受胰岛素强化治疗的青年T1 DM患者(男10 6例，女10 1例)的血浆PCSK9和脂蛋白亚类进行检测。结果：随着血糖控制的恶化，血浆PCSK9水平显著升高(p<；0.001)。糖调节不良的T1糖尿病患者中，小而致密的低密度脂蛋白(SdLDL)比例最高，高密度脂蛋白颗粒也较小。PCSK9仅在糖调节不佳/差的患者中与血糖稳态标记物和血脂参数呈正相关。在控制良好的T1 DM中，血浆PCSK9水平与sdLDL颗粒的相对比例呈负相关(p<；0.01)，这种相关性在多变量分析中仍然显著。在血糖控制欠佳/差的T1 DM患者中，PCSK9与最小HDL3c颗粒的比例呈正相关(p<；0.001)，与高密度脂蛋白的大小呈负相关(p<；0.05)。结论：代谢控制的程度改变了T1 DM患者PCSk9与脂蛋白亚类的关系。需要进一步的研究来揭示观察到的血糖控制对PCSK9和sdLDL水平的影响是否对年轻T1 DM患者的心血管疾病风险有因果关系。
Background and aims: Dyslipidemia in type 1 diabetes mellitus (T1DM) is characterised by altered distributions of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses. Recent studies suggested that proprotein convertase subtilisin/kexin 9 (PCSK9) may contribute to the development of dyslipidemia in T1DM. In this cross-sectional study, we investigated the association between PCSK9 and lipoprotein subclasses in young T1DM patients, with respect to glycemic control.Methods: Plasma PCSK9 and lipoprotein subclasses were determined in 207 patients with T1DM (106 boys and 101 girls), aged 13.9 +/- 3.0 years and treated by intensive insulin therapy.Results: Plasma PCSK9 levels significantly increased with worsening of glycemic control (p < 0.001). T1DM patients with poor glucoregulation had the highest proportion of small, dense LDL (sdLDL) and smaller HDL particles, as well. PCSK9 was positively associated with markers of glucose homeostasis and serum lipid parameters only in patients with suboptimal/poor glucoregulation. In well-controlled T1DM, plasma PCSK9 level was inversely associated with a relative proportion of sdLDL particles (p < 0.01) and this association remained significant in multivariate analysis. In T1DM patients with suboptimal/poor glycemic control, PCSK9 was positively associated with the proportion of the smallest HDL3c particles (p < 0.001), but negatively with HDL size (p < 0.05).Conclusions: The extent of achieved metabolic control modifies the association between PCSK9 and lipoprotein subclasses in T1DM. Further investigations are needed to reveal whether the observed effects of glycemic control on PCSK9 and sdLDL levels have causal consequences on CVD risk in young patients with T1DM.