| Objective:Studies have demonstrated that human PCSK9is a newly discovered protein which can not only regulate cholesterol metabolism by receptor-media ted endocytosis, but also be closely related to many risk factors which participate in the process of atherosclerosis. As we know, the incidence of atherosclerosis related macrovascular complications is very high in type2diabetes. However, there is no data available on the relationship between circulating PCSK9levels and varied risk factors of artherosclerosis in this population. This study was designed to measure the distribution of fasting serum concentrations of PCSK9in type2diabetic patients, to analysis the relationship between serum PCSK9and multiple risk factors of artherosclerosis, and to investigate whether the levels of PCSK9in this population was affected by statins therapy.Methods:Fasting blood samples were obtained from514type2diabetic patients who enrolled in the department of endocrinology and metabolism of Jiangsu Province Hospital between January2011to November2011.History-taking, physical and biochemical examinations, and the severity of carotid artery and artery of lower extremity atherosclerosis assessment were performed on these objects. Serum PCSK9was measured with a sensitive and specific sandwich ELISA. Besides, we also studied the variations of serum lipid metabolism-related parameters and circulating PCSK9levels in patients with type2diabetes which treated with statins therapy for several weeks by follow-up study.Results:1. The distribution of PCSK9value was skewed in this population with an average of83.501±42.604ng/ml (15.851-250.862ng/ml), and median of78.237ng/ml. There was no significant difference between the sexes in the levels of serum PCSK9.2. Serum PCSK9levels was positively correlated with multiple common risk factors of atherosclerosis including age, systolic blood pressure(SBP), total cholesterol(TC), Low density lipoprotein cholesterol (LDL-C), triglycerides (TG), atherogenic index of plasma (AIP) and fasting blood glucose (FBG) in this population (P<0.05). The result of multiple stepwise regression analysis showed that serum PCSK9levels was more closely with age, TC, AIP, LDL-C and TG.3. Circulating PCSK9levels was significantly positive associated with LCCA IMT, RCCA IMT and average IMT (p<0.01). Besides, there was also a positively correlation between serum PCSK9and varied carotid atherosclerosis related-index such as RCCA inside diameter, RCCA Vmax, RCCA PI, RICA PI, LCCA PI, LICA RI, RICA RI, LCCA RI (p<0.05). Furthermore, a negative association was between the serum PCSK9and RCCA Vmax, RCCA Vmin, RCCA Vmin, RCCA Tamx, LICA Tamx in this population (p<0.05).4. Compared with artherosclerosis patients, non-artherosclerosis subjects had significantly higher PCSK9levels (P＜0.0001). After adjustment for age, TC, LDL-C and systolic blood pressure, this difference still existed (P<0.05).5. Statins-treated individuals had higher serum PCSK9levels than controls (P<0.001). In addition, the levels of serum PCSK9was significantly enhanced after statin therapy (P<0.001). Conclusions:1. The distribution of PCSK9levels is in a wide range in type2diabetes patients. Circulating PCSK9levels is significantly positive associated with a variety of atherosclerosis related-index. In combination with traditional risk factors of atherosclerosis, serum PCSK9will provide more information for predicting the presence of atherosclerosis related cardiovascular diseases. Testing serum PCSK9routinely will not only have a great clinical significance but also bring certain economic benefits.2. Statins can enhance the levels of serum PCSK9, PCSK9inhibitors would be a newly promising lipid-lowering drugs in the future. PCSK9inhibitors combines with statins will be able to achieve a better Lipid lowering effect. It will be a newly lipid-regulating drugs which is the most suitable for type2diabetes patients to prevent and delay the progression of atherosclerosis related macro vascular complications. |
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