A1C variability predicts incident cardiovascular events, microalbuminuria, and overt diabetic nephropathy in patients with type 1 diabetes.

  1. Johan Wadén1,2,
  2. Carol Forsblom1,2,
  3. Lena M Thorn1,2,
  4. Daniel Gordin1,2,
  5. Markku Saraheimo1,2,
  6. Per-Henrik Groop (per-henrik.groop{at},2 and
  7. on behalf of the FinnDiane Study group
  1. 1Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland
  2. 2Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland


    Objective. Recent data from the Diabetes Control and Complications Trial (DCCT) indicated that A1C variability is associated with the risk of diabetic microvascular complications. These results might, however, have been influenced by the interventional study design. Therefore, we investigated the longitudinal associations between A1C variability and diabetic complications in patients with type 1 diabetes in the observational Finnish Diabetic Nephropathy (FinnDiane) Study.

    Research design and methods. A total of 2107 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 1845 patients had similar data on cardiovascular events (CVD). Intra-personal standard deviation (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, while 8.6% had a CVD event. The SD of serial A1C was 1.01 vs. 0.75 (P<0.001) for renal status, and 0.87 vs. 0.79 (P=0.023) for CVD, in progressors vs. non-progressors, respectively. In a Cox regression model, SD of serial A1C was independently associated with progression of renal disease (HR, 95% CI: 1.92, 1.49-2.47) and of a CVD event (2.00, 1.41-2.82) 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.


      • Received May 8, 2009.
      • Accepted July 14, 2009.

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    1. Diabetes
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