title: HbA1c variability is associated with an increased risk of retinopathy requiring laser treatment in type 1 diabetes.
abstract: OBJECTIVE
  This study aimed to investigate whether variation in long-term glycaemia in type 1 diabetes as measured by HbA1c variability is associated with the cumulative incidence and risk of retinopathy requiring laser treatment.
  
  
  METHODS
  The effect of HbA1c variability was assessed in 2,019 Finnish Diabetic Nephropathy (FinnDiane) study patients. The patients were studied in two partially overlapping subcohorts with either verified first laser treatment (n = 1,459) or retinopathy severity graded from ophthalmic records with the Early Treatment of Diabetic Retinopathy Study (ETDRS) scale (n = 1,346). The ratio of intrapersonal SD and mean of serially measured HbA1c was considered an estimate of HbA1c variability.
  
  
  RESULTS
  A subcohort of 1,459 patients did not have laser treatment prior to the first FinnDiane visit and 174 of these patients were treated during a mean follow-up period of 5.2 ± 2.2 years. The 5 year cumulative incidence of laser treatment was 19% (95% CI 15, 24) in the highest quartile of HbA1c variability and 10% (95% CI 7, 12) in the lowest quartile (p < 0.001, Gray's test) with a corresponding HR of 1.6 (95% CI 1.1, 2.5; p = 0.02) adjusted for renal status, diabetes duration, mean HbA1c, blood pressure, sex and number of HbA1c measurements. In a subcohort of 1,346 patients, 434 patients had proliferative diabetic retinopathy (PDR). Patients in the highest quartile of HbA1c variability had an increased risk of PDR compared with the lowest quartile (HR 1.7 [95% CI 1.3, 2.2]; p < 0.001]).
  
  
  CONCLUSIONS
  HbA1c variability was associated with an increased cumulative incidence and risk of retinopathy requiring laser treatment in type 1 diabetes.
authors: Folkhälsan Institute of Genetics, Folkhälsan Research Centre, Biomedicum Helsinki, University of Helsinki, PO Box 63, Haartmaninkatu 8, FIN-00014 Helsinki, Finland.
authors: K
authors: K
authors: Hietala
authors: J
authors: J
authors: Wadén
authors: C
authors: C
authors: Forsblom
authors: V
authors: V
authors: Harjutsalo
authors: J
authors: J
authors: Kytö
authors: P
authors: P
authors: Summanen
authors: P-H
authors: PH
authors: Groop
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000628:therapy*; D003930:Diabetic Retinopathy / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland; D014644:Genetic Variation; D006442:Glycated Hemoglobin / Q000235:genetics*; D006801:Humans; D053685:Laser Therapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human