Screening for subclinical complications in children and adolescents with type 1 diabetes mellitus: experience acquired in Brussels

Clinical studies conducted since the 1970s by the pediatric diabetology group of the Free University of Brussels have demonstrated that screening for subclinical retinopathy, neuropathy, and nephropathy should be started at puberty and three years after the diagnosis of diabetes with the goal of detecting early abnoramlities responsible for functional disorders that can be reversed by improved metabolic control, thus preventing the occurrence of irreversible potentially incapacitating lesions. A 1974 retinal fluorescein angiography study showed that the development of microaneurysms, which are irreversible lesions, can be preceded by fluorescein leakage due to disruption of the blood-retinal barrier. Risk factors for early retinopathy are diabetes duration, age at diagnosis (with younger children having longer times to retinopathy), puberty and gender (with onset one year earlier in girls than in boys), and glycated hemoglobin levels (GHb) measured over several years. Rapid improvement of glycated hemoglobin levels may worsen the retinopathy. Minimal electroencephalogram abnormalities were found in patients with a history of more than five episodes of hypoglycemic coma and with retinopathy (1979). Desynchronization of action potentials in distal sensory median nerve fibers preceded conduction velocity slowing (1981). A single high GHb value was associated with peroneal motor conduction velocity slowing (1985), which was not observed in the femoral nerve (1987). Early microproteinuria is mixed, i.e., both glomerular (microalbumin) and tubular (beta 2-microglobulin). Exercise testing to exhaustion did not provide additional information over microalbumin and beta 2-microglobulin assays at rest (1976). Microtransferrinuria may be the most sensitive marker for excess glomerular permeability (1984). Physical training reduced exercise-related proteinuria by half (1988). Poor metabolic control was associated with higher levels of triglycerides, LDL cholesterol, and apolipoprotein B (1990). High levels of lipoprotein (a) were not associated with the presence of subclinical complications (1996). Decreased glutathione peroxidase, glutathione reductase, and vitamin C levels denoting moderate oxidative stress were found (1996), although there was no evidence of increased LDL cholesterol peroxidation (1998). Erythrocytes exhibited increased glycolytic activity, and neutrophils decreased migration; both abnormalities were associated with the degree of metabolic control (1992). Patients with high GHb levels had decreased triiodothyronine levels (1985) and an increased risk for Helicobacter pylori infection 1997). Complement pathway activation was found to occur in patients given intermediate and long-acting insulin preparations without protamine sulfate (1992). Body mass index was higher in adolescents of either sex treated with four daily insulin injections (1988, 1997). Well-being was inversely related to the GHb level (1997).