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

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 HbA(1c) (mean of 18 [1-95] determinations per person) and microalbuminuria (greater than or equal to 2 of greater than or equal to 3 measurements greater than or equal to 15 mu g/min X 1.73 m(2)) 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 HbA(1c) <7%) to 7.3 (HbA(1c) >11%) following an exponential function. Life-table analysis after subdivision in HbA(1c) quartiles of equal sizes (HbA(1c) <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 HbA,, level al 9%. Thus, diabetes treatment in children should aim at long-term HbA,, levels <9.0%, but every progress closer to normal may further reduce the risk.