OBJECTIVE Raised serum sialic acid concentration is a strong predictor of cardiovascular mortality in the general white population. A progressive increase in cardiovascular morbidity and mortality takes place in relation to increasing albuminuria in NIDDM patients. Therefore, we investigated the potential association between serum sialic acid and micro- and macroangiopathy in NIDDM patients. RESEARCH DESIGN AND METHODS We studied a prevalence cohort of all white NIDDM patients < 76 years of age attending a diabetic clinic during 1 year. Of the patients, 319 had normoalbuminuria, 148 had microalbuminuria, and 75 had macroalbuminuria (diabetic nephropathy was in 47 of 75 patients); 66 nondiabetic age- and sex-matched subjects acted as a control group. Blood samples were taken for measurements of sialic acid, lipids, creatinine, and HbA1c. Retinopathy was assessed by funduscopy. The prevalence of cardiovascular disease was based on Minnesota-coded electrocardiograms and the World Health Organization cardiovascular questionnaire. RESULTS A progressive raise in serum sialic acid was demonstrated with an increasing urinary albumin excretion rate: [median (range)] 2.02 (1.55–2.63); 2.42 (1.47–6.48); 2.67 (1.57–5.86), and 2.95 (1.52–7.86) mmol/l in nondiabetic subjects, NIDDM patients with normoalbuminuria, microalbuminuria, and diabetic nephropathy, respectively (P < 0.05 or less for differences between groups). Multiple linear regression analysis showed that serum cholesterol concentration, serum HDL cholesterol concentration, BMI, albuminuria, smoking, and cardiovascular disease correlate independently with logarithmic (10) serum sialic acid concentration. CONCLUSIONS Our study revealed a progressive raise in serum sialic acid with increasing urinary albumin excretion rate in NIDDM patients. Furthermore, several modifiable cardiovascular risk factors were associated with serum sialic acid.