In the July issue of Diabetes Care, we read with interest the study by Zangh et al. (1). They revisited material from the Diabetes Control and Complications Trial database in order to search for potential prognostic factors of developing retinopathy in patients with extreme (either good or poor) metabolic control, but who were free of the complication at baseline. The development and progression of retinopathy was defined by a three-step change or more, according to the Early Treatment Retinopathy Study protocol, on stereoscopic color fundus photographs. Their conclusion was that other than duration of diabetes and metabolic control, BMI had a significant predictive value. We found a similar influence of BMI in our population of young diabetic subjects when we examined the risk factors of progression from background retinopathy to proliferative retinopathy.
In 1991, we published a longitudinal study (2), begun in the 1970s (3), in order to detect the initial retinal abnormalities at fluorescein angiography in 161 type 1 diabetic children and adolescents. Of these patients, 69 developed an early retinopathy. We showed, in several studies covering >20 years (summary in 4), that the development of microaneurysms, which are irreversible lesions, can be preceded by fluorescein leakage due to disruption of the blood-retinal barrier (5), and that risk factors for early retinopathy are diabetes duration, age at diagnosis (with younger children having longer times to retinopathy), puberty and sex (with onset 1 year earlier in girls than in boys), and glycated hemoglobin (GHb) measured over several years. Retinopathy was not found in children <12 years of age and was detected only after at least 3 years of diabetes. The mean age at which early abnormalities occurred was 16 years, after a mean duration of diabetes of 8 years (2).
In the year 2000, 32 subjects (15 women and 17 men), among the 69 patients who developed early retinopathy (2), were always treated by our team. Their mean age was 33 years, and mean diabetes duration was 26 years. Some potential risk factors (GHb, total cholesterol, blood pressure, BMI, insulin dose, frequency of home blood glucose monitoring and of clinic attendance, tobacco, and presence of other complications), measured during the whole follow-up, were analyzed in relation with the evolution of retinopathy to the proliferative stage using fluorescein angiography. In the statistical analysis, stepwise logistic regression was used to identify the most important parameters for the development of proliferative retinopathy. Proliferative retinopathy was diagnosed in six patients (19%), three men and three women. Its occurrence was significantly related to poor glycemic control during the preceding years (cumulated GHb was 143 vs. 120%; 100% is the upper normal limit, P = 0.049), cumulated cholesterol levels (>200 mg/dl, P = 0.014), higher BMI (27 vs. 22 kg/m2, P = 0.035), and the presence of other complications (P = 0.029). However, higher levels of LDL cholesterol are related to poor metabolic control (6).
In conclusion, our data suggest that the risk factors for developing proliferative retinopathy are poor long-term metabolic control, which is well known, and an elevated BMI, which is novel, as noticed by Zhang et al. (1). They confirm the importance of always maintaining a GHb level <120% of the upper normal limit, as we have shown in homozygous diabetic twins (7), which is possible in diabetic children and adolescents (8).
Address correspondence to Harry Dorchy, Clinique de Diabétologie, Hoêpital Universitaire des Enfants Reine Fabiola, Ave. JJ Crocq 15, B-1020 Bruxelles, Belgium. E-mail: firstname.lastname@example.org.