Erythrocyte aldose reductase protein: a clue to elucidate risk factors for diabetic neuropathies independent of glycemic control.

Prolonged hyperglycemia has been thought to be the primary cause of diabetic complications, however, some diabetic patients develop severe complications early in duration of diabetes, while some patients have no or mild complications even after prolonged hyperglycemia. To investigate the risk factors for diabetic severe neuropathy independent of glycemic control and duration of diabetes, erythrocyte aldose reductase was determined in 43 non-insulin-dependent diabetic patients by a two-site ELISA using recombinant human aldose reductase. Among 20 patients with severe neuropathy which was developed within 5 years of diagnosis, the level of erythrocyte aldose reductase protein was significantly higher than that of 23 patients with no or mild neuropathy who had more than 8 years duration of diabetes and prolonged hyperglycemia (11.9+/-5.7 vs. 8.3+/-1.3 ng/mgHb, P < 0.0001). There was a significant stability of the erythrocyte aldose reductase (AR) in the 40 diabetic patients during 1-4 years. The logistic regression analysis revealed that the maximum body mass index (BMI) in the past minus present BMI and the level of erythrocyte aldose reductase protein were the independent risk factors for diabetic severe neuropathy. The measurement of erythrocyte AR level may be useful for predicting severe neuropathy in non-insulin-dependent diabetes mellitus (NIDDM) patients.