Long term complications of diabetes mellitus are largely due to chemical, structural and mechanical changes of connective tissue proteins involving glucose mediated collagen cross links (GMCC). To date there are only experimental therapeutic approaches for preventing long term complications of diabetes mellitus using the toxic substance aminoguanidine.L-arginine, a nontoxic substance, has been shown to reduce GMCC in animal models of diabetes mellitus. We have now performed a blind placebo controlled study with crossing over of two treatment periods of three months each in 29 patients with diabetes mellitus in order to examine the effect of treatment withL-arginine (2 × 1g daily) on glucose mediated collagen cross links (GMCC). GMCC was evaluated by determining glycosyl lysine (hexosyl lysine) levels in skin punch biopsies. Patients treated byL-arginine showed significantly lower GMCC precursors of skin collagen compared with the placebo treated group (difference of hexosyl lysine as counts/mL/ug hydroxyproline between the first and second skin biopsy 0.11 ± 4.44 vs. 4.03 ± 5.27,t = 2.17,p < 0.05). The only side effects ofL-arginine were gastric pain occurring only in patients who did not follow the instructions to takeL-arginine at meals. We conclude thatL-arginine could be useful for treating long term complications of diabetes mellitus.
Collagen cross links Glucose mediated cross links Diabetes mellitus L-arginine Long term complications Hexosyl lysines Glycosylated lysines