Association of circulating proprotein convertase subtilisin/kexin type 9 levels and the risk of incident type 2 diabetes in subjects with prediabetes: a population-based cohort study

循环前蛋白转化酶枯草溶菌素/kexin 9 型水平与糖尿病前期患者患 2 型糖尿病风险的关系:一项基于人群的队列研究

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作者:Jie Shi, Weiwei Zhang, Yixin Niu, Ning Lin, Xiaoyong Li, Hongmei Zhang, Renming Hu, Guang Ning, Jiangao Fan, Li Qin, Qing Su, Zhen Yang

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism by targeting the low-density lipoprotein receptor. Recent studies have shown that circulating PCSK9 is associated with glucose homeostasis and insulin resistance. The

Conclusion

Elevated circulating PCSK9 levels are associated with an increased incidence of type 2 diabetes in female subjects with prediabetes.

Methods

A population-based prospective study was conducted among 4205 Chinese subjects with prediabetes (average age 56.1 ± 7.5 years). Incident type 2 diabetes was diagnosed according to 2010 American Diabetes Association criteria. Circulating PCSK9 levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). The association of circulating PCSK9 levels with the risk of incident type 2 diabetes was assessed by Cox regression analysis.

Results

During a median follow-up period of 3.1 years, 568 subjects developed type 2 diabetes. Baseline circulating PCSK9 levels were significantly higher in female subjects developing incident type 2 diabetes than in those not developing incident type 2 diabetes (p < 0.001). In female subjects, the risk of incident type 2 diabetes was significantly higher in the highest PCSK9 quartile group (hazard ratio 2.16; 95% confidence interval 1.16-4.04) than in the lowest quartile group after adjustments for age, body mass index, waist circumference, C-reactive protein, γ-glutamyltransferase, triglycerides, low-density lipoprotein cholesterol, systolic blood pressure, and homeostatic model assessment of insulin resistance score. No significant association was observed between PCSK9 and incident type 2 diabetes in male subjects.

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