Angiopoietin-like 3 Is a Potential Biomarker for Retinopathy in Type 2 Diabetic Patients

Am J Ophthalmol. 2018 Jul:191:34-41. doi: 10.1016/j.ajo.2018.03.040. Epub 2018 Apr 3.

Abstract

Purpose: To investigate whether angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) are differentially associated with the severity of retinopathy in patients with type 2 diabetes mellitus (T2DM).

Design: Cross-sectional study.

Methods: Serum levels of ANGPTL3, ANGPTL4, high-sensitivity C-reactive protein (CRP), vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF) were quantified by ELISA. Retinal images were recorded to assess the grade of diabetic retinopathy (DR). Multivariable-adjusted logistic analysis was performed to estimate the association of each biomarker and DR stage.

Results: Among 1192 T2DM patients, 426 (35.7%) had nonproliferative diabetic retinopathy (NPDR) and 56 (4.5%) had proliferative diabetic retinopathy (PDR). After adjusting for covariables, the odds ratios expressing the risk of having DR vs no DR (n = 710 vs 482) were 1.23 (95% confidence interval [CI], 1.08-1.40, P = .002) for ANGPTL3; 0.90 (95% CI, 0.79-1.02; P = .095) for ANGPTL4; and 1.14 (95% CI, 1.00-1.29; P = .044) for VEGF. The risk of having no DR vs NPDR (n = 710 vs 426) was 1.16 (95% CI, 1.01-1.32; P = .036) for ANGPTL3; 0.90 (95% CI, 0.79-1.04; P = .15) for ANGPTL4; and 1.14 (95% CI, 1.00-1.31; P = .045) for VEGF. The odds ratios of having NPDR vs PDR (n = 426 vs 56) was 1.47 (95% CI, 1.03-2.10; P = .035) for serum ANGPTL3; 0.96 (95% CI, 0.69-1.35; P = .83) for ANGPTL4; and 1.05 (95% CI, 0.77-1.45; P = .74) for VEGF.

Conclusions: ANGPTL3 is independently and strongly associated with DR progression in all stages. Blockade of ANGPTL3 signal in retina might postpone the onset and development of DR in T2DM patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-Like Protein 3
  • Angiopoietin-Like Protein 4 / blood
  • Angiopoietin-like Proteins / blood*
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetic Retinopathy / blood*
  • Diabetic Retinopathy / diagnosis
  • Diabetic Retinopathy / etiology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Time Factors

Substances

  • ANGPTL3 protein, human
  • ANGPTL4 protein, human
  • Angiopoietin-Like Protein 3
  • Angiopoietin-Like Protein 4
  • Angiopoietin-like Proteins
  • Biomarkers