Effects of aspirin or basic amino acids on collagen cross-links and complications in NIDDM

OBJECTIVE - To determine if long-term therapy with aspirin or basic amino acids for subjects with NIDDM reduces the severity of clinical complications and/or reduces tissue levels of markers of glycooxidative damage RESEARCH DESIGN AND METHODS - Subjects with NIDDM were administered either aspirin (100 mg/day) or a combination of basic amino acids consisting of L-arginine (2 g/day) plus L-lysine (0.5 g/day) for 1 year. The study was double-blind and placebo-controlled. The presence and severity of retinopathy, nephropathy, and neuropathy were assessed in all subjects at 4-month intervals, as were serum blood glucose, glycohemoglobin levels, and presence of albuminuria. Collagen cross-linking and collagen glycation were measured in skin collagen obtained by biopsy at the beginning and the end of the study. Skin biopsies were also obtained from age-matched control subjects. RESULTS - Skin samples obtained from NIDDM subjects at the beginning of the study had significantly increased levels of glucitolyllysine, pentosidine, and hydroxypyridinium, as compared with age-matched control subjects. Pentosidine levels were significantly correlated with severity of retinopathy and neuropathy, but not nephropathy Subjects receiving aspirin, but not amino acids or placebo, had significantly decreased levels of skin pentosidine after 1 year of therapy. CONCLUSIONS - It is concluded that 1) low-dose aspirin may reduce glycooxidative damage in people with NIDDM, and 2) treatment may need to continue for more than 1 year before clinical status improves.