Circulating lipocalin-2 and retinol-binding protein 4 are associated with intima-media thickness and subclinical atherosclerosis in patients with type 2 diabetes

PLoS One. 2013 Jun 17;8(6):e66607. doi: 10.1371/journal.pone.0066607. Print 2013.

Abstract

Background: The lipocalin family proteins, including lipocalin-2 and retinol-binding protein 4 (RBP4), are adipokines closely associated with obesity-related metabolic disorders. In this study, we evaluated the association of serum lipocalin-2 and RBP4 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.

Methods and results: Serum levels of lipocalin-2 and RBP4 were measured in 284 type 2 diabetic patients. Subclinical atherosclerosis was assessed by IMT at carotid, femoral and iliac arteries with ultrasound. Patients with subclinical atherosclerosis showed significantly higher circulating concentrations of lipocalin-2 and RBP4 when compared to those without [112.9 (86.4 to 202.1) µg/L versus 77.2(55.0-150.4) µg/L, 37.1(32.3-40.8) mg/L versus 23.2(20.1-29.2) mg/L, respectively; P = 0.002, P<0.001, respectively]. Moreover, positive correlations were observed between carotid IMT and lipocalin-2 (r = 0.170, P = 0.018) or RBP4 (r = 0.132, P = 0.040), femoral IMT and lipocalin-2 (r = 0.160, P = 0.027), as well as between iliac IMT and RBP4 (r = 0.241, P<0.001). Multiple logistic regression analysis further demonstrated that these two adipokines were independent risk factors for subclinical atherosclerosis in type 2 diabetes.

Conclusion: Circulating levels of lipocalin-2 and RBP4 are positively correlated with carotid IMT and subclinical atherosclerosis in type 2 diabetes, which suggests a potential role of these two lipid-binding chaperones in the pathogenesis of vascular complications of diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / pathology*
  • Female
  • Humans
  • Lipocalin-2
  • Lipocalins / blood*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / blood*
  • Retinol-Binding Proteins, Plasma / metabolism*
  • Tunica Intima / pathology*

Substances

  • Acute-Phase Proteins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • RBP4 protein, human
  • Retinol-Binding Proteins, Plasma

Grants and funding

This work is supported by the National key technology R&D program (2012BAI02B04), Program for Changjiang Scholars and Innovative Research Team in University (IRT1195), Hunan Provincial Natural Science Foundation of China (11JJ7005), the National Natural Science Foundation of China (Grant No. 81170725, to Z.Z.), Hong Kong Collaborative Research Fund (HKU/CRF/10, to A.X.), the National Natural Science Foundation of China (Grant No.81200600), the Research Fund for the Doctoral Program of Higher Education of China (20110162120014), and the Fundamental Research Funds for the Central University (2011QNZT176, to Y.X.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.