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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

  1. Thomas Danne, MD,
  2. Bruno Weber, MD,
  3. Reinhard Hartmann, MD,
  4. Ingo Enders, BS,
  5. Walter Burger, MD and
  6. Gerd Hovener, MD
  1. Children's Hospital Kaiserin Auguste Victoria Haus, Klinikum Rudolf Virchow Free University Berlin Berlin, Germany
  2. Department of Ophthalmology, Klinikum Steglitz, Free University Berlin Berlin, Germany
  1. Address correspondence and reprint requests to Thomas Danne, MD, Universitäts-Kinderklinik (KAVH), Heubnerweg 6, 14059 Berlin, Germany.

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).

RESEARCH DESIGN AND 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 (≥2 of ≥3 measurements ≥ 15 μg/min × 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.

  • Received August 20, 1993.
  • Revision received July 11, 1994.
  • Accepted July 11, 1994.
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