Screening for subclinical complications in young type 1 diabetic patients: 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 at least 3 years after the diabetes diagnosis. The goal is to detect early abnormalities responsible for subclinical 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, could be preceded by fluorescein leakage due to disruption of the blood-retinal barrier. Risk factors for early retinopathy include: duration of diabetes, age at diagnosis (with younger children having longer times to retinopathy), puberty and sex (with onset one year earlier in girls than in boys), long-term bad metabolic control over several years, high cholesterol levels and excessive body mass index (BMI). On the other hand, rapid improvement of diabetic control may worsen diabetic retinopathy (1985). Minimal EEG abnormalities were found in relationship to frequent and severe hypoglycemic comas and/or convulsions and retinopathy (1979). Desynchronization of action potentials in distal nerve fibers preceded conduction velocity slowing (1981). A single high glycated hemoglobin value was associated with peroneal motor nerve conduction slowing (1985), which was not observed in the femoral nerve (1987). Sympathetic skin response (1996) and statistical analysis of heart rate variability (2001) could have some interest for the diagnosis of early diabetic autonomic neuropathy. Early microproteinuria is of mixed origin, being both glomerular (microalbumin) and tubular (Beta2-microglobulin). Exercise testing to exhaustion did not provide additional information than the basal excretion (1976). Microtransferrinuria (1984) and urinary acid glycosaminoglycans output (2001) could also be predictive markers of glomerular dysfunction. Physical training reduced exercise-related proteinuria by half (1988). High levels of serum lipoprotein (a) were not associated with the presence of subclinical complications (1996). On the other hand, ultra sensitive C-reactive protein could be an interesting indicator for the risk of developing early complications (2002). Poor metabolic control was associated with higher levels of triglycerides, total cholesterol, LDL cholesterol and apolipoprotein B (1990). Decreased gluthatione peroxidase, gluthatione reductase and of 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 in relationship with metabolic control (1992). The degree of metabolic control influenced serum triiodothyronine levels (1985), magnesium concentrations (1999) and infection by Helicobacter Pylori (1997). Insulin therapy could activate the complement pathway if intermediate and long-acting insulin preparations without protamine sulphate are used (1992) and provoke higher BMI in adolescents on 4 insulin injections (1988). Well-being was inversely related to glycated hemoglobin levels (1997).