A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes

Data from the Diabetes Control and Complications Trial

  1. Eric S. Kilpatrick, MD, FRCPATH1,
  2. Alan S. Rigby, MSC2 and
  3. Stephen L. Atkin, PHD, FRCP3
  1. 1Department of Clinical Biochemistry, Hull Royal Infirmary, Hull, U.K.
  2. 2Academic Department of Cardiology, University of Hull, Hull, U.K.
  3. 3Department of Diabetes, Hull York Medical School, Hull, U.K.
  1. Corresponding author: Eric S. Kilpatrick, eric.kilpatrick{at}hey.nhs.uk

Abstract

OBJECTIVE—Debate remains as to whether short- or long-term glycemic instability confers a risk of microvascular complications in addition to that predicted by mean glycemia alone. In this study, we analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of A1C variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS—A1C was collected quarterly during the DCCT in 1,441 individuals. The mean A1C and the SD of A1C variability after stabilization of glycemia (from 6 months onwards) were compared with the risk of retinopathy and nephropathy with adjustments for age, sex, disease duration, treatment group, and baseline A1C.

RESULTS—Multivariate Cox regression showed that the variability in A1C added to mean A1C in predicting the risk of development or progression of both retinopathy (hazard ratio 2.26 for every 1% increase in A1C SD [95% CI 1.63–3.14], P < 0.0001) and nephropathy (1.80 [1.37–2.42], P < 0.0001), with the relationship a feature in conventionally treated patients in particular.

CONCLUSIONS—This study has shown that variability in A1C adds to the mean value in predicting microvascular complications in type 1 diabetes. Thus, in contrast to analyses of DCCT data investigating the effect of short-term glucose instability on complication risk, longer-term fluctuations in glycemia seem to contribute to the development of retinopathy and nephropathy in type 1 diabetes.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 23 July 2008.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    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.

    • Accepted July 19, 2008.
    • Received May 7, 2008.
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  1. Published online before print July 23, 2008, doi: 10.2337/dc08-0864 Diabetes Care November 2008 vol. 31 no. 11 2198-2202
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