title: Sex differences in retinal microvasculature through puberty in type 1 diabetes: are girls at greater risk of diabetic microvascular complications?
abstract: OBJECTIVE
  Adolescent females with type 1 diabetes (T1D) are reported to have greater risk of early microvascular complications than males. We hypothesize sex differences in retinal vascular geometry (RVG) through puberty are associated with earlier-onset microvascular complications.
  
  
  METHODS
  Prepubertal patients (n = 64, 35 male) with T1D, complication-free at baseline, were followed through to sexual maturity with detailed Tanner-staging and repeated diabetes complications assessments. Retinal vascular geometry from digitized retinal photographs at each visit was assessed using a semiautomated computer program. Determinants of RVG measurements (pre-, during, and post puberty) were explored using generalized estimating equations (GEE). Factors associated with time to onset of retinopathy and albumin excretion rate (AER) were examined using multivariable Cox regression.
  
  
  RESULTS
  Median follow-up was 7.2 years. Retinopathy developed in 69% and elevated albumin excretion in 56%. In multivariable GEE, female sex was associated with wider venular caliber (prepuberty: lowest-quartile, odds ratio 0.40 [95% confidence interval: 0.17, 0.96]); P = 0.04) and lower arteriolar length-to-diameter-ratio (LDRa) (during puberty: lowest-quartile 2.87 [1.01, 8.13]; P = 0.047 and post puberty: 2.93 [0.96, 8.64]; P = 0.06). In Cox-regression, females developed retinopathy earlier than males (8.1 vs. 9.6 years; P = 0.002). Female sex (hazard ratio [HR] 3.8 [1.6-8.6]; P = 0.002) and growth velocity (1.3 [1.1-1.5]; P = 0.001) were associated with earlier retinopathy.
  
  
  CONCLUSIONS
  This is the first longitudinal study to repeatedly examine RVG through puberty in youth with T1D. Sex dimorphism was observed. Female sex was associated with lower LDRa, wider venules, and earlier onset of retinopathy. These RVG patterns have been associated with incident microvascular complications but did not reach statistical significance in this study. Larger studies are needed to investigate the RVG, microvascular complications, and sex associations early in the course of T1D.
authors.affiliation: The Children's Hospital at Westmead, New South Wales, Australia Discipline of Paediatrics and Child Health, New South Wales, University of Sydney.
authors.forename: Paul
authors.initials: P
authors.lastname: Benitez-Aguirre
authors.affiliation: The Children's Hospital at Westmead, New South Wales, Australia.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Craig
authors.affiliation: Department of Ophthalmology, Westmead Hospital, New South Wales, Australia.
authors.forename: Helene G
authors.initials: HG
authors.lastname: Cass
authors.affiliation: School of Women's and Children's Health, University of New South Wales, New South Wales, Australia.
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Sugden
authors.affiliation: Clinical Trials Centre, University of Sydney, New South Wales, Australia.
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Jenkins
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Australia Centre for Vision Research, University of Sydney, Sydney, Australia.
authors.forename: Jie Jin
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: The Children's Hospital at Westmead, New South Wales, Australia.
authors.forename: Janine
authors.initials: J
authors.lastname: Cusumano
authors.affiliation: Centre for Vision Research, University of Sydney, Sydney, Australia.
authors.forename: Lauren A B
authors.initials: LA
authors.lastname: Hodgson
authors.affiliation: Centre for Vision Research, University of Sydney, Sydney, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Lee
authors.affiliation: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Australia Singapore Eye Research Institute, National University of Singapore, Singapore.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: The Children's Hospital at Westmead, New South Wales, Australia Discipline of Paediatrics and Child Health, New South Wales, University of Sydney.
authors.forename: Kim C
authors.initials: KC
authors.lastname: Donaghue
mesh_terms: D000293:Adolescent; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008833:Microcirculation; D055806:Microvessels / Q000503:physiopathology; D009517:New South Wales / Q000453:epidemiology; D011446:Prospective Studies; D011627:Puberty; D012171:Retinal Vessels / Q000473:pathology / Q000503:physiopathology*; D012307:Risk Factors; D017678:Sex Distribution; D012737:Sex Factors; D013997:Time Factors
keywords: adolescents; diabetic retinopathy; microvascular complications; retinal vascular geometry; type 1 diabetes