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.), GLYCOHEMOGLOBIN is formed throughout the life span of the red cell through nonenzymatic condensation of glucose, primarily with the N-terminal valine of the beta chain. Its level reflects mean glycemia over the preceding five to six weeks — a property that makes glycohemoglobin an invaluable measure of metabolic control in diabetes.1 The nonenzymatic glycosylation reaction that leads to the formation of glycohemoglobin has been known for some time in food science as an intermediate step of the Maillard or nonenzymatic browning reaction.2 Food proteins that are stored or heated in the presence of reducing sugars eventually become insoluble and have. © 1986, Massachusetts Medical Society. All rights reserved.