Stiffening of connective tissue in elderly diabetic patients : relevance to diabetic nephropathy and oxidative stress

Limited joint mobility seen in diabetes mellitus is thought to be the result of stiffening of periarticular connective tissue, which is presumably derived from increased crosslinking of collagen related to advanced glycation end products. In this study the extent of the stiffening of connective tissue was measured by the passive extension angle of the metacarpophalangeal joints in 205 elderly diabetic patients. Association with diabetic nephropathy, with which advanced glycation end products have recently been demonstrated to increase, and metabolic abnormalities were also considered. The angle of the metacarpophalangeal joints was significantly correlated with age (r=−0.24, p<0.01), and was significantly smaller in men than in women (p<0.01). The angle demonstrated a decrease in association with diabetic retinopathy and nephropathy, and only the association with nephropathy was significant (p<0.05). The angle was weakly, but significantly, correlated with serum thiobarbituric acid reactants as a measure of lipid peroxides (r=−0.15, p<0.05), triglyceride (r=−0.20, p<0.01) and HDL cholesterol (r=0.19, p<0.01), but not with blood glucose (r=0.02), HbA1c (r=0.06) or duration of diabetes (r=−0.05). In addition, the angle in 14 non-diabetic patients on haemodialysis was significantly (p<0.05) smaller than that in age- and sexmatched normal subjects. Thus, it was indicated that the stiffening of connective tissue was associated with diabetic nephropathy, serum lipid peroxide and dyslipidaemia. Stiffening of connective tissue seems to be more affected by oxidative stress than non-enzymatic glycation per se. Factors contributing to the stiffening of connective tissue, such as male sex, ageing, serum lipid peroxide, high triglyceride and low HDL cholesterol resemble those associated with arteriosclerosis.