1156 POLYOL PATHWAY HYPERKINESIS IN CHILDREN WITH DIABETES

Abstract

Intracellular sorbitol accumulation has been implicated as an etiologic factor for many of the sequelae of diabetes mellitus. The human erythrocyte is a tissue that accumulates sorbitol in response to extracellular glucose concentration. Red cell sorbitol levels in children with diabetes were compared to those in red cells from non diabetics. Sorbitol was measured by a fluorometric assay utilizing sheep liver sorbitol dehydrogenase; glucose was measured by glucose oxidase. Red cell sorbitol in 140 children with diabetes (36.6±1.7nmols/gm Hb) was greater than in 50 non diabetics (10.3±.79) p<.0005. The influence of extracellular glucose was taken into account by expressing intracellular sorbitol in terms of plasma glucose concentration (S/G). The S/G ratio for red cells from diabetics was 20.6±.88 and non diabetics was 12.1±.95 p<.0005. When red cells from diabetics were exposed to non diabetic glucose concentrations for up to 14 hours the S/G ratio did not return to non diabetic levels. Non diabetic red cells exposed to elevated glucose concentrations (300 and 500 mg/dl) for 3 hours did not manifest elevated S/G ratios. Elevated S/G ratios were found in association with non diabetic hemoglobin Alc values suggesting long term exposure to near physiologic glucose levels. Increased sorbitol production was found in most, but not all individuals with diabetes and seems to be an acquired characteristic. This is the first evidence of altered polyol pathway activity not directly related to substrate availability in spontaneous human diabetes.