NEGATIVE ASSOCIATION BETWEEN ERYTHROCYTE REDUCED GLUTATHIONE CONCENTRATION AND DIABETIC COMPLICATIONS

1. Multiple logistic regression analysis of biochemical and clinical v ariables in diabetic patients was performed to identify those associat ed with the presence of diabetic complications (retinopathy, neuropath y and nephropathy). 2. The presence of diabetic complications correlat ed positively with duration of diabetes and patient age and negatively with the concentration of reduced glutathione in erythrocytes, Indivi dually, retinopathy, neuropathy and nephropathy correlated with durati on of diabetes, but retinopathy also correlated positively with haemog lobin Ale in diabetic patients, In insulin-dependent patients, the con centration of methylglyoxal was also in the logistic model for retinop athy and diabetic complications, but the logistic regression coefficie nt was not significant. 3. Multiple linear regression analysis indicat ed that erythrocyte reduced glutathione concentration correlated negat ively with D-lactate concentration and positively with duration of dia betes in insulin-dependent patients and correlated negatively with glu cose concentration in non-insulin-dependent diabetic patients. 4. In n on-diabetic subjects, erythrocyte glyoxalase I activity correlated pos itively with methylglyoxal concentration, There was no similar correla tion in diabetic patients, In insulin-dependent patients, methylglyoxa l concentration correlated positively with duration of diabetes. 5. Gl yoxal and methylglyoxal are detoxified by the glyoxalase system with r educed glutathione as co-factor, The concentration of reduced glutathi one may be decreased by oxidative stress and by decreased in situ glut athione reductase activity in diabetes mellitus, A reduced concentrati on of reduced glutathione may predispose diabetic patients to oxidativ e damage and to alpha-oxoaldehyde-mediated glycation by decreasing the in situ glyoxalase I activity, Recent studies of vascular endothelial cells in vitro have suggested that alpha-oxoaldehydes detoxified by g lyoxalase I are the major precursors of advanced glycation end product s implicated in the development of diabetic complications, The role of these factors in the development of diabetic complications and the pr ospective prevention of diabetic complications by supplementation of r educed glutathione and/or agents now deserve alpha-oxoaldehyde-scaveng ing investigation.