RELATIONSHIP BETWEEN GLUTATHIONE AND SORBITOL CONCENTRATIONS IN ERYTHROCYTES FROM DIABETIC-PATIENTS

Red blood cell (RBC) concentrations of sorbitol end reduced glutathion e (GSH) were evaluated in 29 type II diabetic subjects and eight norma l controls. In erythrocytes from diabetic subjects, sorbitol levels we re higher (18.7 +/- 1.33 v 11.2 +/- 0.7 nmol/g hemoglobin [Hb], P < .0 01) and GSH levels were lower (5.48 +/- 0.19 v 8.33 +/- 0.24 mu mol/g Hb, P < .01) than in nondiabetics. RBC sorbitol levels were positively correlated with fasting blood glucose (r =.57, P < .001) but not with HbA(1c) (r = .16, P = NS). RBC GSH levels showed a negative correlati on with fasting blood glucose (r = -.35, P < .05) and with HbA(1c) (r = -.34, P < .05) and a significant negative correlation with RBC sorbi tol levels (r = -.62, P < .001). Stepwise regression analysis highligh ted the fact that the hyperglycemia-dependent increase in RBC sorbitol was significantly influenced by GSH concentrations (partial F = 14.6, P < .001), These data suggest the hypothesis that the hyperglycemia-i nduced enhanced activity of the polyol pathway leads to GSH depletion and, in turn, GSH depletion, reducing the glycolytic flux to pyruvate, enhances the rate of glucose metabolism through the polyol pathway. T he overall effect is a progressive worsening of metabolic pseudohypoxi a and depletion of GSH, resulting in lower defense against oxidative s tress. (C) 1996 by W.B. Saunders Company.