Association of circulating proprotein convertase subtilisin/kexin type 9 levels and the risk of incident type 2 diabetes
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Cardiovascular Diabetology
ORIGINAL INVESTIGATION
Open Access
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 Jie Shi1†, Weiwei Zhang1†, Yixin Niu1†, Ning Lin1, Xiaoyong Li1, Hongmei Zhang1, Renming Hu2, Guang Ning3, Jiangao Fan4, Li Qin1*, Qing Su1* and Zhen Yang1*
Abstract 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 aim of this study was to examine the association of circulating PCSK9 levels and risk for the development of type 2 diabetes in individuals 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 15%. The final study population consisted of 4,205 participants (mean ± SD age 56.1 ± 7.5 years), as depicted in Fig. 1. The study protocol was approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (No. LLWYH-201132). Written informed consent was obtained from all participants. Data collection
At baseline, a questionnaire, physical examination, anthropometric measurements, and laboratory
Shi et al. Cardiovasc Diabetol
(2020) 19:209
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Participants with prediabetes in the baseline survey n = 5,218 207 subjects were excluded due to tumor, severe liver and/or renal insufficiency, thyroid dysfunction, infectious or systematic inflammatory diseases, significant hemato -logic disorders, and the use of statins and fibrates 102 individuals were excluded due to the outlier value of circulating PCSK9 levels Eligible participants with prediabetes n = 4,909 578 were lost to follow up 126 subjects were excluded due to tumor, severe liver and/or renal insufficiency, thyroid dysfunction, infectious or systematic inflammatory diseases, significant hemato -logic disorders, and the use of statins and fibrates Participants available in the end of follow-up n = 4,205
Men n = 1,388 (33%)
Developed type 2 diabetes n = 207 (14.9%)
Did not develop type 2 diabetes n = 1,181
Women n = 2,817 (67%)
Developed type 2 diabetes n = 361 (12.8%)
Did not develop type 2 diabetes n = 2,456
Fig. 1 Overview of the s
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