GOOD GLYCEMIC CONTROL REDUCES OXIDATION AND GLYCATION END-PRODUCTS INCOLLAGEN OF DIABETIC RATS

Blood glucose control plays a prominent role in the aetiology of diabe tic complications. Recent data support the hypothesis that non-enzymat ic pathways (glycation and oxidation) are involved in the pathogenesis of tissue damage in diabetes mellitus. In this study the level of pen tosidine, a marker of glycation, and the intensity of collagen-linked fluorescence glycation (370/440 and 335/385 nm) and oxidation-related (356/460 and 390/460 nm), have been examined in spontaneously diabetic rats with good and poor glycaemic control. Pentosidine increased dram atically in rats with poor control, and slightly in those with good co ntrol. At the end of the study, after 6 months of diabetes, pentosidin e levels were 13+/-5 and 2.1+/-0.5 pmol/mg collagen, respectively (con trol rats: 1.1+/-0.1 pmol/mg collagen). A similar pattern was observed for both glycation or oxidation-related fluorescence. The group of ra ts with poor control always showed elevated average values when compar ed to rats with good control, with a relative increase of over 200 %. The results emphasize the role of good glycaemic control in preventing the growth of glycation or oxidation end-products in collagen. On com parison between the general mean level of all glycated haemoglobin and the mean pentosidine level of the three groups, a very good exponenti al correlation was found (r = 0.993, p < 0.001). The fluorescence valu es presented a less strong relationship, but a correlation with glycae mic control was still present. If the post-translational modifications of proteins play a leading role in the pathogenesis of complications it is possible to conclude that strict glycaemic control, obtained by accurate insulin therapy can prevent them by inhibiting the non-enzyma tic modification of proteins and delaying their accumulation in collag en. The therapeutic implications are obvious.