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 t he development of background retinopathy in adolescents followed longi tudinally from the onset of insulin-dependent diabetes mellitus (IDDM) . RESEARCH DESIGN AND METHODS - Repeated retinal fluorescein angiograp hies, in intervals of 1-2 years, were evaluated prospectively in 346 p atients (190 males, 156 females; 19.8 [8.8-35.4] years of age; diabete s duration of 10.4 [1.1-27.4] years at their latest eye examination, m edian [range]). The influences of long-term HbA(1c) (mean of 18 [1-95] determinations per person) and microalbuminuria (greater than or equa l to 2 of greater than or equal to 3 measurements greater than or equa l to 15 mu g/min X 1.73 m(2)) were studied by multiple linear regressi on, life-table analysis, and trend analyses. RESULTS - The rate of bac kground retinopathy per 100 patient-years increased with poorer glycem ic control from 0.7 (long-term HbA(1c) <7%) to 7.3 (HbA(1c) >11%) foll owing an exponential function. Life-table analysis after subdivision i n HbA(1c) quartiles of equal sizes (HbA(1c) <8, 8-9, 9-10, and >10%) r evealed an individual median expectation of background retinopathy aft er 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 i ncidence, thus suggesting that a threshold model may also fit the data . After 12 years of diabetes, <25% of those patients exhibiting microa lbuminuria (n = 18) were expected to be free from retinopathy compared with 81% of those with normoalbuminuria (n = 86). CONCLUSIONS - Two s tatistical 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 o f 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.