Many of She debilities that characterize the aging syndrome can be explained by cross-linking of macromol-ecules such as collagen. And several of the characteristic complications of diabetes mellitus resemble age-like changes in collagen-rich tissues. In this laboratory, studies of human collagen that is not the site of lesions have revealed an age-related decrease in susceptibility to collagenase digestion and increased glucosylation of tendon collagen, both markedly increased in diabetes. An age-related decrease in solubility and an increase in glucosylation of skin collagen, both also markedly increased in diabetes, were also observed. Glucosylation of skin collagen was less than that of tendon, possibly because of the greater turnover of skin collagen. Collagen alterations in diabetes were most apparent in samples from younger adult subjects. Samples from older diabetics gave values within the range of nondiabetics, suggesting that the degree to which collagen can be cross-linked or glucosyiated is limited, and that limits may be attained at earlier ages in diabetes.

The association between glucosylation and cross-linking of collagen suggests that glucosylation may cause cross-linking, as has been shown to occur in albumin and eye lens protein.

Both the cross-linking of collagen occurring in maturation and glucosylation of protein involve the -amino group of lysine. If blood glucose is high during periods of collagen synthesis, namely during growth or fi-brosis, it is conceivable that lysine and hydroxylysine are glucosyiated rather than deaminated to form normal cross-links, and that an abnormal collagen forms that plays a role in the complications of diabetes. Control of diabetes during periods of collagen synthesis would then be a critical factor in preventing subsequent complications.

Epidemiologie studies of collagen properties, bearing on questions about the roles of genetic factors and control of diabetes in alterations in collagen and in complications of diabetes, would be feasible by the use Of skin biopsies.