Clinical analysis of aldose reductase for differential diagnosis of the pathogenesis of diabetic complication

A two-site immunoassay system for evaluating tissue levels of aldose reductase was developed using monoclonal and polyclonal antibodies to the recombinant human enzyme expressed in a baculovirus system. The calibration graph of this system was linear for concentrations of aldose reductase ranging from 0 to 16 ng ml−1. The detection limit was 0.034 ng ml−1. The coefficients of variation within and between assays were 3.7% and 4.8%, respectively. Analytical recovery was 101–106%. The amount of aldose reductase expressed in human tissues was measured by this system. Higher levels of aldose reductase were found in kidney medulla, sciatic nerve and lens indicating that the enzyme level was higher in the target organs of diabetic complications. The aldose reductase level of sciatic nerve was well correlated with that of erythrocytes (r=0.62, p<0.05). When erythrocyte aldose reductase was determined in 160 patients with a diabetic duration for less than 10 years, the enzyme level in patients with neuropathy was significantly higher than in those without any complications. The incidence of neuropathy in these patients was significantly increased in proportion to the enzyme levels (p<0.05). In this study, it has become apparent that the aldose reductase level in erythrocytes of patients with short diabetic duration (<10 years) is associated with the presence of neuropathy. It was also suggested that the immunoassay system will provide useful clinical information to optimize administration of aldose reductase inhibitors for effective prevention and treatment of diabetic complications.