The significance of the prepubertal diabetes duration for the development of retinopathy and nephropathy in patients with type 1 diabetes

Abstract 

Objective: A Danish nationwide prospective cohort of children and adolescents with type 1 diabetes was followed for 8 years to study the effect of the prepubertal duration of diabetes on early retinopathy and elevated albumin excretion rate (AER) (>20 μg/min). Research Design and Methods: In 1989, blood glucose control (HbA_1c) and AER was investigated in approximately 80% of all Danish children and adolescents with type 1 diabetes. A cohort of 339 young patients were restudied in 1995 including physical examination, demographic data, HbA_1c, AER, and fundus photography with central reading. Among the patients, a number of 304 had a prepubertal onset of diabetes defined as an onset age less than 11.7 years in girls and 12.9 years in boys. Microalbuminuria was defined as an AER of 20–150 μg min⁻¹ and macroalbuminuria as AER >150 μg min⁻¹ in two out of three timed overnight urine samples. Results: At the follow-up in 1995–1996, no patients were younger than 12 years of age. The prevalence of any level of retinopathy was 17.7% in the age group 12–15 years, 45.4% from 16 to 20 years, and increased to 67.6% in patients more than 20 years of age. Diabetic retinopathy was significantly associated to poor long-term metabolic control (HbA_1c) (P<.0001) and to diabetes duration both in patients with a prepubertal onset of disease as well as patients with a pubertal (P<.001) onset of disease. However, the pubertal diabetes duration contributed two times more than the prepubertal diabetes duration. Mean postpubertal diabetes duration to any retinopathy was significantly shorter (9.4 years) in patients with prepubertal onset of the disease compared to patients with postpubertal onset (11.8 years) (P=.0004). In total, the prevalence of elevated AER (>20 μg/min) increased from 4% in 1989 to 13% in 1995. None of the patients younger than 15 years of age had elevated AER, while the prevalence of elevated AER was about 14% from 15 years of age and onwards. Elevated AER in 1995 was significantly related to long-term metabolic control (P<.001) and elevated AER in the preceding years (P<.001) but was not correlated to diabetes duration neither before nor after the age of 12 years. Conclusion: The prepubertal diabetes duration is significantly associated with the development of diabetic retinopathy. The period, however, contributes less compared to the years after puberty. In concert with other studies, we found no association between raised AER and diabetes duration. This may be explained by the fact that other factors are more significant and dilute the significance of diabetes duration. Nonetheless, it seems prudent to optimise blood glucose control irrespective of age.

Keywords:  Type 1 diabetes, Pre-pubertal diabetes duration, Glycosylated haemoglobin, Diabetic retinopathy, Diabetic nephropathy, Adolescents