title: Long-term glycemic control has a nonlinear association to the frequency of background retinopathy in adolescents with diabetes. Follow-up of the Berlin Retinopathy Study.
abstract: OBJECTIVE
  To assess the influence of long-term glycemic control on the development of background retinopathy in adolescents followed longitudinally from the onset of insulin-dependent diabetes mellitus (IDDM).
  
  
  METHODS
  Repeated retinal fluorescein angiographies, in intervals of 1-2 years, were evaluated prospectively in 346 patients (190 males, 156 females; 19.8 [8.8-35.4] years of age; diabetes duration of 10.4 [1.1-27.4] years at their latest eye examination, median [range]). The influences of long-term HbA1c (mean of 18 [1-95] determinations per person) and microalbuminuria (> or = 2 of > or = 3 measurements > or = 15 micrograms/min x 1.73 m2) were studied by multiple linear regression, life-table analysis, and trend analyses.
  
  
  RESULTS
  The rate of background retinopathy per 100 patient-years increased with poorer glycemic control from 0.7 (long-term HbA1c < 7% to 7.3 (HbA1c > 11%) following an exponential function. Life-table analysis after subdivision in HbA1c quartiles of equal sizes (HbA1c < 8, 8-9, 9-10, and > 10%) revealed an individual median expectation of background retinopathy after more than 25, 16.2, 12.7, or 12.0 years of diabetes, respectively. However, significant differences were found only between 8-9% and 9-10%, calculated either as prevalence, life-table analysis, or relative incidence, thus suggesting that a threshold model may also fit the data. After 12 years of diabetes, < 25% of those patients exhibiting microalbuminuria (n = 18) were expected to be free from retinopathy compared with 81% of those with normoalbuminuria (n = 86).
  
  
  CONCLUSIONS
  Two statistical models are appropriate to explain the relationship between glycemic control and risk for background retinopathy: 1) a continuous exponential relationship as described by the DCCT or 2) the presence of a threshold HbA1c level at 9%. Thus, diabetes treatment in children should aim at long-term HbA1c levels < 9.0%, but every progress closer to normal may further reduce the risk.
authors.affiliation: Children's Hospital, Kaiserin Auguste Victoria Haus, Klinikum Rudolf Virchow, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Danne
authors.forename: B
authors.initials: B
authors.lastname: Weber
authors.forename: R
authors.initials: R
authors.lastname: Hartmann
authors.forename: I
authors.initials: I
authors.lastname: Enders
authors.forename: W
authors.initials: W
authors.lastname: Burger
authors.forename: G
authors.initials: G
authors.lastname: Hovener
mesh_terms: D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000209:etiology; D001786:Blood Glucose / Q000032:analysis*; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy; D003930:Diabetic Retinopathy / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D011446:Prospective Studies; D012044:Regression Analysis; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin