Red blood cell (RBC) concentrations of
sorbitol and
reduced glutathione (GSH) were evaluated in 29 type 11 diabetic subjects and eight normal controls. In erythrocytes from diabetic subjects,
sorbitol levels were higher (18.7 +/- 1.33 v 11.2 +/- 0.7 nmol/g
hemoglobin [
Hb], P < .001) and GSH levels were lower (5.48 +/- 0.19 v8.33 +/- 0.24 micromol/g
Hb, P < .01) than in nondiabetics. RBC
sorbitol levels were positively correlated with fasting
blood glucose (r =.57, P < .001) but not with HbAlc (r =.16, P < .05). RBC GSH levels showed a negative correlation with fasting
blood glucose (r = -.35, P <.05) and with HbA1c (r = -.34, P < .05) and a significant negative correlation with RBC
sorbitol levels (r = -.62, P < .001). Stepwise regression analysis highlighted 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-induced 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. The overall effect is a progressive worsening of metabolic pseudohypoxia and depletion of GSH, resulting in lower defense against oxidative stress.