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. 2013 Apr;56(4):724-36.
doi: 10.1007/s00125-012-2818-4. Epub 2013 Jan 17.

Plasma Total Bilirubin Levels Predict Amputation Events in Type 2 Diabetes Mellitus: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study

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Plasma Total Bilirubin Levels Predict Amputation Events in Type 2 Diabetes Mellitus: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study

K H Chan et al. Diabetologia. .

Abstract

Aims/hypothesis: Bilirubin has antioxidant and anti-inflammatory activities. Previous studies demonstrated that higher bilirubin levels were associated with reduced prevalence of peripheral arterial disease (PAD). However, the relationship between bilirubin and lower-limb amputation, a consequence of PAD, is currently unknown. We hypothesised that, in patients with type 2 diabetes, bilirubin concentrations may inversely associate with lower-limb amputation.

Methods: The relationship between baseline plasma total bilirubin levels and amputation events was analysed in 9,795 type 2 diabetic patients from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The analysis plan was pre-specified. Lower-limb amputation was adjudicated blinded to treatment allocation. Relevant clinical and biochemical data were available for analyses. Amputation was a pre-specified tertiary endpoint.

Results: Bilirubin concentrations were significantly inversely associated with lower-limb amputation, with a greater than threefold risk gradient across levels. Individuals with lower bilirubin concentrations had a higher risk for first amputation (HR 1.38 per 5 μmol/l decrease in bilirubin concentration, 95% CI 1.07, 1.79, p = 0.013). The same association persisted after adjustment for baseline variables, including age, height, smoking status, γ-glutamyltransferase level, HbA1c, trial treatment allocation (placebo vs fenofibrate), as well as previous PAD, non-PAD cardiovascular disease, amputation or diabetic skin ulcer, neuropathy, nephropathy and diabetic retinopathy (HR 1.38 per 5 μmol/l decrease in bilirubin concentration, 95% CI 1.05, 1.81, p = 0.019).

Conclusions/interpretation: Our results identify a significant inverse relationship between bilirubin levels and total lower-limb amputation, driven by major amputation. Our data raise the hypothesis that bilirubin may protect against amputation in type 2 diabetes.

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References

    1. Arterioscler Thromb Vasc Biol. 2005 Jan;25(1):155-60 - PubMed
    1. Atherosclerosis. 1997 May;131(1):107-13 - PubMed
    1. Circulation. 2004 Aug 10;110(6):738-43 - PubMed
    1. Angiology. 2012 May;63(4):248-53 - PubMed
    1. Circulation. 2008 Jul 1;118(1):9-16 - PubMed

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