Relation between Complications of Type I Diabetes Mellitus and Collagen-Linked Fluorescence

Abstract

Nonenzymatically glycosylated proteins gradually form fluorescent cross-linked protein adducts — a process termed "browning." The rate of this reaction increases with the glucose concentration. Assaying for the presence of browning products in long-lived proteins should therefore provide information on long-term metabolic control.

We measured collagen-linked fluorescence typical for nonenzymatic browning in skin-biopsy specimens from 41 subjects with long-standing Type I diabetes and from 25 controls. Fluorescence correlated with age and (weakly) with the duration of diabetes. Mean age-adjusted fluorescence values were twice as high in diabetic subjects as in control subjects (P<0.0001) and increased with the severity of retinopathy, nephropathy, and arterial and joint stiffness. The correlation was significant for retinopathy (r = 0.42; P<0.01), arterial stiffness (r = 0.41; P<0.01), joint stiffness (r = 0.34; P<0.05), and the sum of all complications (r = 0.47; P<0.01). Fluorescence also correlated with systolic (r = 0.42; P<0.01) and diastolic (r = 0.36; P<0.05) blood pressures. If one can assume that the fluorescence results from a browning product of glucose, our data suggest that there is an overall correlation between the severity of diabetic complications and cumulative glycemia over many years. (N Engl J Med 1986; 314:403–8.)