Abstract
BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9), which plays a crucial role in lipoprotein metabolism, has been also regarded as an important marker for atherosclerosis. Available evidence indicated that 2-h postchallenge plasma glucose (2-hPG) could be another biomarker for atherosclerosis. However, currently the association between circulating PCSK9 and 2-hPG remains unclear. Here, we explored this potential link in a Chinese Han population.MethodsTotally, 600 Chinese Han subjects from Nanjing district, China, were enrolled for the 75-g oral glucose tolerance test (OGTT), and they included normal glucose tolerance (NGT, n = 200), impaired glucose regulation (IGR, n = 200), and type 2 diabetes (T2DM, n = 200). Anthropometric and biochemical determinations such as serum lipid measurements were made. A sandwich ELISA assay was performed to measure serum PCSK9 levels in all subjects.ResultsSerum PCSK9 concentrations were higher in IGR group (77.63 ± 28.14 ng/ml) and T2DM group (90.62 ± 39.96 ng/ml) than in NGT group (65.33 ± 32.68 ng/ml), and it was significantly higher in T2DM group than in IGR group (p < 0.01). Serum PCSK9 levels positively correlated with 2-hPG and LDL-C in all subgroups, but presented a positive correlation with fasting blood glucose (FBG) only in T2DM group. Using multiple regression model analysis, we also found that PCSK9 levels closely correlated with 2-hPG in all tested groups. According to multinomial logistic regression analysis, PCSK9 levels positively correlated with T2DM (OR = 1.017[1.010–1.025], p < 0.001) even after adjustment for lipid levels. Moreover, in subjects with normal FBG level, 2-hPG gradually and significantly increased across PCSK9 tertiles (6.68 ± 2.01, 7.48 ± 2.10 and 8.27 ± 2.41 mmol/L, respectively, p < 0.01); however, in subjects with normal 2-hPG levels, no such difference was observed.ConclusionsPCSK9 levels increase as glucose metabolism deteriorated. Serum PCSK9 levels positively correlated with 2-hPG in patients with metabolic diseases.
Highlights
Proprotein convertase subtilisin/kexin type 9 (PCSK9), which plays a crucial role in lipoprotein metabolism, has been regarded as an important marker for atherosclerosis
Individuals with Impaired glucose regulation (IGR) or Type 2 diabetes (T2DM) were characterized by higher blood pressure (p < 0.01), Body mass index (BMI) (p < 0.01), heart rate (p < 0.01), TG (p < 0.01), fasting blood glucose (FBG) (p < 0.01), 2hPG (p < 0.01) and 2 h–INS (p < 0.01), increased waist circumference (p < 0.01), hip circumference (p < 0.05), Waist-to-Hip ratio (p < 0.01), Homeostasis model assessment-estimated insulin resistance index (HOMA-IR) (p < 0.01) than the Normal glucose tolerance (NGT) group
Those in T2DM group were characterized by higher Low-density lipoprotein cholesterol (LDL-C), fasting insulin (FINS) and lower high- density lipoprotein cholesterol (HDL-C) levels than in NGT, but there was no difference between participants with IGR and NGT
Summary
Proprotein convertase subtilisin/kexin type 9 (PCSK9), which plays a crucial role in lipoprotein metabolism, has been regarded as an important marker for atherosclerosis. Currently the association between circulating PCSK9 and 2-hPG remains unclear. We explored this potential link in a Chinese Han population. It has been proven that PCSK9 increases the degradation of LDLR on the surface of hepatocytes, decreases the uptake of LDL-C via LDLR, leading to the increase of plasma LDL-C levels [2]. Gain-of-function mutations in PCSK9 can cause hypercholesterolemia leading to premature coronary heart disease, whereas loss-offunction mutations are associated with reduced plasma levels of LDL-C and the risk of coronary heart disease [3]. PCSK9 directly correlates with other wellknown CVD risk factors, including TG levels, glucose metabolism, and insulin resistance [5]
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