A1C Variability Predicts Incident Cardiovascular Events, Microalbuminuria, and Overt Diabetic Nephropathy in Patients With Type 1 Diabetes

A1C Variability Predicts Incident Cardiovascular Events, Microalbuminuria, and Overt Diabetic Nephropathy in Patients With Type 1 Diabetes Johan Wadén 1 , 2 , Carol Forsblom 1 , 2 , Lena M. Thorn 1 , 2 , Daniel Gordin 1 , 2 , Markku Saraheimo 1 , 2 and Per-Henrik Groop 1 , 2 1 Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; 2 Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland. Corresponding author: Per-Henrik Groop, per-henrik.groop{at}helsinki.fi . Abstract OBJECTIVE Recent data from the Diabetes Control and Complications Trial (DCCT) indicated that A1C variability is associated with the risk of diabetes microvascular complications. However, these results might have been influenced by the interventional study design. Therefore, we investigated the longitudinal associations between A1C variability and diabetes complications in patients with type 1 diabetes in the observational Finnish Diabetic Nephropathy (FinnDiane) Study. RESEARCH DESIGN AND METHODS A total of 2,107 patients in the FinnDiane Study had complete data on renal status and serial measurements of A1C from baseline to follow-up (median 5.7 years), and 1,845 patients had similar data on cardiovascular disease (CVD) events. Intrapersonal SD of serially measured A1C was considered a measure of variability. RESULTS During follow-up, 10.2% progressed to a higher albuminuria level or to end-stage renal disease, whereas 8.6% had a CVD event. The SD of serial A1C was 1.01 versus 0.75 ( P < 0.001) for renal status and 0.87 versus 0.79 ( P = 0.023) for CVD in progressors versus nonprogressors, respectively. In a Cox regression model, SD of serial A1C was independently associated with progression of renal disease (hazard ratio 1.92 [95% CI 1.49–2.47]) and of a CVD event (1.98 [1.39–2.82]) even when adjusting for mean A1C and traditional risk factors. Interestingly for CVD, mean serial A1C itself was not predictive even though SD of A1C was. CONCLUSIONS In patients with type 1 diabetes, A1C variability was not only predictive of incident microalbuminuria and progression of renal disease but also of incident CVD events. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received May 8, 2009. Accepted July 14, 2009. © 2009 American Diabetes