Additive Interaction of Hyperglycemia and Albuminuria on Risk of Ischemic Stroke in Type 2 Diabetes

Hong Kong Diabetes Registry

  1. Xilin Yang, PHD1,
  2. Gary T.C. Ko, MD12,
  3. Wing Yee So, MD1,
  4. Ronald C.W. Ma, MBCHB1,
  5. Alice P.S. Kong, MBCHB13,
  6. Christopher W.K. Lam, PHD4,
  7. Chung Shun Ho, PHD4,
  8. Chun-Chung Chow, MBBS1,
  9. Peter C.Y. Tong, PHD12 and
  10. Juliana C.N. Chan, MD123
  1. 1Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
  2. 2Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, China
  3. 3Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China
  4. 4Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
  1. Corresponding author: Xilin Yang, yang.xilin{at}cuhk.edu.hk

Abstract

OBJECTIVE—The study aims to test whether biological interaction between hyperglycemia and albuminuria can explain the inconsistent findings from epidemiological studies and clinical trials about effects of hyperglycemia on stroke in type 2 diabetes.

RESEARCH DESIGN AND METHODS—A total of 6,445 Hong Kong Chinese patients with type 2 diabetes and free of stroke at enrollment were followed up for a median of 5.37 years. Spline Cox proportional hazard regression was used to obtain hazard ratio curves, which were used to identify cutoff points of A1C and spot urinary albumin–to–creatinine ratio for increased ischemic stroke risk. The identified cutoff point of A1C was used to check biological interaction between A1C and albuminuria (micro- and macroalbuminuria). The biological interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index.

RESULTS—During the follow-up period, 4.45% (n = 287) of patients developed ischemic stroke. A1C was associated with increased hazard ratios of ischemic stroke in a near-linear manner except for two points—6.2 and 8.0%—where the slope between these two points accelerated. For A1C values <6.2%, the presence of micro/macroalbuminuria did not confer additional risk, while significant biological interaction between A1C and micro/macroalbuminuria for values ≥6.2% was observed (RERI 0.92, 95% CI 0.16–1.68, and AP 0.40, 0.01–0.78).

CONCLUSIONS—A1C ≥6.2% and micro/macroalbuminuria interact to markedly increase the ischemic stroke risk, which explains a large proportion of risk in patients with type 2 diabetes harboring both risk factors.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 22 September 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 August 30, 2008.
    • Received June 16, 2008.
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  1. Published online before print September 22, 2008, doi: 10.2337/dc08-1079 Diabetes Care December 2008 vol. 31 no. 12 2294-2300
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