Cohort study of predictive value of urinary albumin excretion for atherosclerotic vascular disease in patients with insulin dependent diabetes

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Abstract
Objective: To examine whether slightly elevated urinary albumin excretion precedes development of atherosclerotic vascular disease in patients with insulin dependent diabetes independently of conventional atherogenic risk factors and of diabetic nephropathy. Design: Cohort study with 11 year follow up. Setting: Diabetes centre in Denmark. Subjects: 259 patients aged 19-51 with insulin dependent diabetes of 6-34 years' duration and without atherosclerotic vascular disease or diabetic nephropathy at baseline. Main outcome measures: Baseline variables: urinary albumin excretion, blood pressure, smoking habits, and serum concentrations of total cholesterol, high density lipoprotein cholesterol, sialic acid, and von Willebrand factor. End point: atherosclerotic vascular disease assessed by death certificates, mailed questionnaires, and hospital records. Results: Thirty patients developed atherosclerotic vascular disease during follow up of 2457 person years. Elevated urinary albumin excretion was significantly predictive of atherosclerotic vascular disease (hazard ratio 1.06 (95% confidence interval 1.02 to 1.18) per 5 mg increase in 24 hour urinary albumin excretion, P=0.002). Predictive effect was independent of age; sex; blood pressure; smoking; serum concentrations of total cholesterol, high density lipoprotein cholesterol, sialic acid, and von Willebrand factor; level of haemoglobin A1c; insulin dose; duration of diabetes; and diabetic nephropathy (hazard ratio 1.04 (1.01 to 1.08) per 5 mg increase in 24 hour urinary albumin excretion, P=0.03). Conclusion: Slightly elevated urinary albumin excretion independently predicted atherosclerotic vascular disease in patients with insulin dependent diabetes. Key messages Preliminary studies suggested that this mortality might particularly occur among patients with elevated urinary albumin excretion We studied predictive effect of slightly elevated urinary albumin excretion in development of atherosclerotic vascular disease in 259 patients with insulin dependent diabetes Patients with urinary albumin excretion of 30-300 mg/24 h had 2.5 times higher risk of atherosclerotic vascular disease than those with lower excretion rates The predictive effect was independent of conventional atherogenic risk factors and of development of diabetic nephropathy, and duration and control of diabetes