title: Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy.
abstract: BACKGROUND
  To investigate possible associations between diabetic retinopathy (DR) and systemic vascular endothelial function and arterial stiffness measured using reactive hyperaemia peripheral arterial tonometry.
  
  
  METHODS
  This was a cross-sectional observational clinical study. Subjects with diabetes were recruited and DR was graded from retinal photographs. Systemic endothelial function was measured using reactive hyperaemia peripheral arterial tonometry (EndoPAT) and expressed as the reactive hyperaemia index (RHI). Peripheral arterial stiffness was measured using the same device and expressed as the augmentation index (AI).
  
  
  RESULTS
  In total, 164 eyes of 95 Chinese patients were evaluated. The mean age of the subject eyes was 60.1±8.2 years and 76.8% were men. The mean duration of diabetes was 15.5±9.8 years, and the mean HbA1c was 8.1±1.4%. In age-gender-adjusted models, increasing severity of DR was associated with increasing mean RHI (p=0.001) and increasing mean AI (p<0.001). In multivariate models, adjusting additionally for smoking, mean duration of diabetes, HbA1c and hypertension, the associations with RHI and AI persisted (p=0.011 and 0.001, respectively). In analyses of the dichotomous outcomes clinically significant macular oedema (CSME), moderate DR and vision-threatening DR, AI was a significant predictor of CSME and vision-threatening DR. In multivariate-adjusted models, for every SD increase in AI, the odds of having CSME was 1.78 times higher (95% CI 1.05 to 2.99; p=0.029). For every SD increase in AI, the odds of having vision-threatening DR was 1.73 times higher (95% CI 1.17 to 2.56; p=0.003).
  
  
  CONCLUSIONS
  Subjects with more severe DR have larger peripheral reactive hyperaemic responses and greater peripheral vascular stiffness. These findings support the link between the microvascular changes of diabetes and macrovascular disease.
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Gradate Medical School, Singapore, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Massachusetts Eye and Ear Infirmary, Harvard Medical School, MA, USA.
authors.forename: Laurence S
authors.initials: LS
authors.lastname: Lim
authors.affiliation: Cardiac Department, National University Heart Centre, Singapore, Singapore Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Lieng H
authors.initials: LH
authors.lastname: Ling
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Gradate Medical School, Singapore, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Chui Ming Gemmy
authors.initials: CM
authors.lastname: Cheung
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Gradate Medical School, Singapore, Singapore.
authors.forename: Peng Guan
authors.initials: PG
authors.lastname: Ong
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Lingli
authors.initials: L
authors.lastname: Gong
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Gradate Medical School, Singapore, Singapore.
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Gradate Medical School, Singapore, Singapore.
authors.forename: Ranjana
authors.initials: R
authors.lastname: Mathur
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Gradate Medical School, Singapore, Singapore.
authors.forename: Doric
authors.initials: D
authors.lastname: Wong
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Gradate Medical School, Singapore, Singapore.
authors.forename: Wallace
authors.initials: W
authors.lastname: Foulds
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Gradate Medical School, Singapore, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D003430:Cross-Sectional Studies; D003930:Diabetic Retinopathy / Q000097:blood / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008055:Lipids / Q000097:blood; D008269:Macular Edema / Q000097:blood / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000503:physiopathology*; D010991:Plethysmography; D059289:Vascular Stiffness / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008055:Lipids; C517652:hemoglobin A1c protein, human
keywords: Diagnostic tests/Investigation; Epidemiology; Retina