Plasma total bilirubin levels predict amputation events in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Abstract

Aims/hypothesis Bilirubin has antioxidant and antiinflammatory 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 M. K. C. Ng and A. C. Keech are joint senior authors of this study Electronic supplementary material The online version of this article

Diabetes, bilirubin and amputations: is there a link?

“…In this issue of Diabetologia, Chan et al [1] report the results of a pre-specified subsidiary analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This trial included 9,795 patients with type 2 diabetes mellitus.…”

“…The hypothesis for this subsidiary analysis was that several actions attributed to bilirubin that may protect from atherosclerosis (e.g. antioxidant and anti-inflammatory effects) [1,2] might also extend to decreasing the risk of amputation in patients with type 2 diabetes. These findings are not only of interest in terms of explaining the pathogenesis leading to amputation but also in pointing towards future treatment options.…”

“…This would not only improve quality of life but also reduce the considerable cost associated with amputation, especially in patients at high risk of needing this procedure (e.g. those with type 2 diabetes) [1].…”

“…The authors discuss several limitations of their study [1]. There were only 190 amputations (115 patients) over the 5 year duration of the FIELD trial [1].…”

“…There were only 190 amputations (115 patients) over the 5 year duration of the FIELD trial [1]. This limits the power of multiple adjustments in specific patient subgroups.…”