Association of the anti-angiogenic factor secreted protein and rich in cysteine (SPARC) with vascular complications among Chinese type 2 diabetic patients in Singapore

J Diabetes Complications. 2017 Jul;31(7):1222-1227. doi: 10.1016/j.jdiacomp.2016.03.029. Epub 2016 Mar 31.

Abstract

Aims: This study evaluated the association of the anti-angiogenic SPARC with known angiogenesis-associated factors and diabetes-related micro- and macro-vascular complications in a Singapore Chinese cohort with type 2 diabetes (T2DM).

Methods: Plasma SPARC was measured by immunoassay in 438 T2DM adults (mean age:58±11years).

Results: Higher SPARC levels in subjects stratified by SPARC tertiles displayed decreased pro-angiogenic adiponectin, osteopontin, vascular cell adhesion molecule (VCAM)-1 and matrix metalloproteinase (MMP)-2 concentrations (all p<0.05). The anti-angiogenic pigment epithelium-derived factor (PEDF) level was not statistically different among the SPARC tertiles. Age-adjusted partial correlation revealed significant associations of SPARC with adiponectin, osteopontin, VCAM-1, MMP-2, and PEDF (all p<0.05). Lower SPARC was accompanied by less favorable estimated glomerular filtration rate (eGFR) and carotid-femoral pulse wave velocity (PWV) readings (all p<0.05). Conversely, ankle-brachial index (ABI) reduced with increasing SPARC (p=0.048). The eGFR (B=0.834, p=0.019), PWV (B=-7.925, p=0.009), and ABI (B=-142.160, p=0.010) remained as determinants of SPARC after confounder adjustment. Moreover, individuals in the lowest SPARC tertile had increased odds of aortic stiffness (OR=1.900, 95% CI=1.103-3.274) but reduced odds of peripheral arterial disease (OR=0.400, 95% CI=0.175-0.919). However, SPARC was not independently associated with chronic kidney disease.

Conclusions: The anti-angiogenic SPARC may be associated with the pathophysiology of diabetes-related macrovascular complications.

Keywords: Angiogenesis; Aortic stiffness; Chronic kidney disease; Peripheral arterial disease; SPARC; Type 2 diabetes.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Ankle Brachial Index
  • Aortic Diseases / blood*
  • Aortic Diseases / complications
  • Aortic Diseases / ethnology
  • Asian People
  • Biomarkers / blood
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetic Angiopathies / blood*
  • Diabetic Angiopathies / ethnology
  • Down-Regulation*
  • Female
  • Humans
  • Immunoassay
  • Male
  • Middle Aged
  • Osteonectin / blood*
  • Peripheral Arterial Disease / blood
  • Peripheral Arterial Disease / complications
  • Peripheral Arterial Disease / ethnology
  • Primary Health Care
  • Pulse Wave Analysis
  • Reproducibility of Results
  • Singapore
  • Up-Regulation
  • Vascular Stiffness*

Substances

  • Biomarkers
  • Osteonectin
  • SPARC protein, human