title: Serum fibroblast growth factor 21 levels are related to subclinical atherosclerosis in patients with type 2 diabetes.
abstract: BACKGROUND
  Fibroblast growth factor 21 (FGF21), a glucose and lipid metabolic regulator, has recently been demonstrated to be associated with cardiovascular diseases (CVD) such as carotid atherosclerosis, coronary heart disease and carotid artery plaques. However, the relationship between circulating FGF21 and subclinical atherosclerosis or atherosclerosis of other arteries such as the femoral and iliac artery remains unclear. In this study, we evaluated the association of serum FGF21 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.
  
  
  METHODS
  Serum FGF21 levels were detected by enzyme-linked immunosorbent assay in 212 newly diagnosed type 2 diabetic patients without clinical symptoms of atherosclerosis or cardiovascular diseases. IMT of the carotid, femoral, and iliac arteries were measured by high-resolution B-mode ultrasound to determine the presence of subclinical atherosclerosis, which was defined as having an IMT > 1.0 mm and/or plaque on one or more of the three arteries without any clinical manifestations. The relationship between serum FGF21 levels and subclinical atherosclerosis was analyzed.
  
  
  RESULTS
  Serum FGF21 levels were significantly higher in patients with subclinical atherosclerosis compared to those without [261.3 (135.1-396.4) versus 144.9 (95.9-223.0) ng/L, P < 0.001]. These differences were also observed in both men and women with subclinical atherosclerosis compared to their respective groups without [men: 243.2 (107.6-337.0) versus 136.8 (83.6-212.8) ng/L, P = 0.048; women: 292.4 (174.2-419.9) versus 160.4 (115.3-258.5) ng/L, P = 0.001]. Moreover, serum FGF21 levels showed a significantly positive correlation with carotid IMT in women (r = 0.23, P = 0.018) and with iliac IMT in both genders (women: r = 0.27, P = 0.005; men: r = 0.22, P = 0.024). Multiple logistic regression analysis further showed that serum FGF21 was an independent impact factor for subclinical atherosclerosis in patients with type 2 diabetes.
  
  
  CONCLUSIONS
  Serum FGF21 is elevated in newly diagnosed type 2 diabetes, and positively correlates with carotid and iliac lesions in patients with subclinical atherosclerosis, especially in women. High levels of FGF21 may be a compensatory reaction to offset atherosclerosis.
authors.affiliation: Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Diabetes Center, Second Xiangya Hospital, and Institute of Metabolism and Endocrinology, Central South University, Changsha, Hunan, China. xiaoyang29@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Diabetes Center, Second Xiangya Hospital, and Institute of Metabolism and Endocrinology, Central South University, Changsha, Hunan, China. jorlin2008@163.com.
authors.forename: Lingjiao
authors.initials: L
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, the University of Hong Kong, Hong Kong, China. amxu@hku.hk.|Department of Medicine, the University of Hong Kong, Hong Kong, China. amxu@hku.hk.|Department of Pharmacology and Pharmacy, the University of Hong Kong, Hong Kong, China. amxu@hku.hk.|Research Center of Heart, Brain, Hormone, and Healthy Aging, the University of Hong Kong, Hong Kong, China. amxu@hku.hk.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, the University of Hong Kong, Hong Kong, China. zhoupc@hku.hk.|Department of Medicine, the University of Hong Kong, Hong Kong, China. zhoupc@hku.hk.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Geriatrics, Second Xiangya Hospital, Central South University, Changsha, Hunan, China. longzhaof@126.com.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Long
authors.affiliation: Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Diabetes Center, Second Xiangya Hospital, and Institute of Metabolism and Endocrinology, Central South University, Changsha, Hunan, China. xyzztyt@163.com.
authors.forename: Yiting
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Diabetes Center, Second Xiangya Hospital, and Institute of Metabolism and Endocrinology, Central South University, Changsha, Hunan, China. gzscxy@126.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Diabetes Center, Second Xiangya Hospital, and Institute of Metabolism and Endocrinology, Central South University, Changsha, Hunan, China. weilitang@hotmail.com.
authors.forename: Weili
authors.initials: W
authors.lastname: Tang
authors.affiliation: Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Diabetes Center, Second Xiangya Hospital, and Institute of Metabolism and Endocrinology, Central South University, Changsha, Hunan, China. huanggan007@163.com.
authors.forename: Gan
authors.initials: G
authors.lastname: Huang
authors.affiliation: Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Diabetes Center, Second Xiangya Hospital, and Institute of Metabolism and Endocrinology, Central South University, Changsha, Hunan, China. zhouzg@hotmail.com.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D058070:Asymptomatic Diseases; D050197:Atherosclerosis / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D059168:Carotid Intima-Media Thickness; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007083:Iliac Artery / Q000000981:diagnostic imaging; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017539:Tunica Intima / Q000000981:diagnostic imaging
chemical_list: C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors