title: Retinal microvascular calibre and risk of diabetes mellitus: a systematic review and participant-level meta-analysis.
abstract: OBJECTIVE
  The calibre of the retinal vessels has been linked to diabetes mellitus but studies have not shown consistent results. We conducted a participant-level meta-analysis to evaluate the association between retinal arteriolar and venular calibre and diabetes.
  
  
  METHODS
  We performed a systematic review on MEDLINE and EMBASE for articles published up to December 2014. We identified five population-based prospective cohort studies that provided individual-level data on 18,771 diabetes-free participants. We used discrete time proportional hazards models to estimate pooled HRs of diabetes associated with 1 SD (20 μm) change in retinal vascular calibre.
  
  
  RESULTS
  We identified 2,581 incident cases of diabetes over a median follow-up period of 10 years (interquartile interval of 3.4-15.8 years). After adjustment for demographic, lifestyle and clinical factors, retinal venular calibre was significantly associated with incident diabetes (pooled HR 1.09 [95% CI 1.02, 1.15] per SD increase in venular calibre). This association persisted in analyses excluding individuals with <5 years of follow-up (1.07 [1.0, 1.12]) or those with impaired fasting glucose at baseline (1.10 [1.03, 1.17]); in subgroup analyses, the association was stronger in men than in women but was consistent across subgroups of race/ethnicity, smoking status, hypertension and BMI categories. Retinal arteriolar calibre was not associated with diabetes (0.95 [0.86, 1.06] per SD decrease in arteriolar calibre).
  
  
  CONCLUSIONS
  Wider retinal venules but not narrower retinal arterioles were associated with a modestly increased risk for diabetes. Knowledge of pathological mechanisms underlying wider retinal venule may provide further insights concerning microvascular alterations in diabetes.
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, 168751, Republic of Singapore.|Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore.|Department of Ophthalmology, National University of Singapore, Singapore, Republic of Singapore.
authors.forename: Charumathi
authors.initials: C
authors.lastname: Sabanayagam
authors.affiliation: Centre for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore.
authors.forename: Weng Kit
authors.initials: WK
authors.lastname: Lye
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA.
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: Cotch
authors.affiliation: Department of Ophthalmology and Westmead Millennium Institute, Centre for Vision Research, University of Sydney, Sydney, NSW, Australia.
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology and Westmead Millennium Institute, Centre for Vision Research, University of Sydney, Sydney, NSW, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.affiliation: Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Shaw
authors.affiliation: Department of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.affiliation: Department of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: A Richey
authors.initials: AR
authors.lastname: Sharrett
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, 168751, Republic of Singapore. ophwty@nus.edu.sg.|Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore. ophwty@nus.edu.sg.|Department of Ophthalmology, National University of Singapore, Singapore, Republic of Singapore. ophwty@nus.edu.sg.
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D012171:Retinal Vessels / Q000473:pathology*; D012306:Risk
keywords: Cohort studies; Diabetes; Meta-analysis; Retinal vessels; Systematic review