title: The risk of proliferative retinopathy in siblings with Type 1 diabetes.
abstract: OBJECTIVE
  The siblings first affected by Type 1 diabetes (probands) within a sibship have been shown to have a lower age at onset of Type 1 diabetes compared with their later-affected siblings. The aim of the present study was to investigate whether this difference affects the long-term risk of proliferative diabetic retinopathy.
  
  
  METHODS
  A cohort of 396 siblings with Type 1 diabetes in 188 sibships was drawn from a larger Finnish Diabetic Nephropathy Study population (4800 patients). Ophthalmic records were obtained for 369/396 (93%) patients. Retinopathy was graded based on fundus photographs and/or repeated ophthalmoscopies.
  
  
  RESULTS
  The median age at onset of Type 1 diabetes was 8.4 (interquartile range 4.2-13.3) years in probands and 16.9 (interquartile range 10.2-27.8) years in later-affected siblings (P < 0.001). Proliferative retinopathy was diagnosed in 115/369 (31%) patients. The cumulative incidence estimates for proliferative retinopathy, accounting for the competing risk of death, were 21% (95% CI 15-27) in probands and 26% (95% CI 19-35) in later-affected siblings at 20 years of diabetes duration, and the respective 30 years' incidences were 37% (95% CI 29-45) and 53% (95% CI 40-64), (P = 0.05, Gray's test). The risk of proliferative retinopathy, adjusted for conventional risk factors, age at onset and sibship size, was higher in later-affected siblings [hazard ratio 1.75 (95% CI 1.13-2.75), P = 0.01] compared with their probands.
  
  
  CONCLUSIONS
  The siblings first affected by Type 1 diabetes had a better long-term prognosis with regards to development of proliferative retinopathy compared with their later-affected siblings.
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Centre, Biomedicum, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Hietala
authors.forename: C
authors.initials: C
authors.lastname: Forsblom
authors.forename: P
authors.initials: P
authors.lastname: Summanen
authors.forename: P-H
authors.initials: PH
authors.lastname: Groop
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000097:blood / Q000453:epidemiology / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005387:Finland / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D015994:Incidence; D008297:Male; D011379:Prognosis; D012307:Risk Factors; D035781:Siblings; D013997:Time Factors
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human