Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
Diabetologia. 2013 Apr;56(4):724-36. doi: 10.1007/s00125-012-2818-4. Epub 2013 Jan 17.
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.
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.
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.
目的/假设：胆红素具有抗氧化和抗炎作用。先前的研究表明，胆红素水平较高与外周动脉疾病（PAD）的患病率降低有关。然而，胆红素与下肢截肢的关系（PAD 的后果）目前尚不清楚。我们假设，在 2 型糖尿病患者中，胆红素浓度可能与下肢截肢呈负相关。
对 Fenofibrate 干预和事件降低糖尿病（FIELD）研究中的 9795 例 2 型糖尿病患者的基线血浆总胆红素水平与截肢事件之间的关系进行了分析。分析计划是预先指定的。下肢截肢由盲于治疗分配的裁决。可用于分析的相关临床和生化数据。截肢是一个预先指定的三级终点。
胆红素浓度与下肢截肢显著负相关，随着胆红素水平的降低，风险梯度超过三倍。胆红素浓度较低的个体首次截肢的风险更高（胆红素浓度每降低 5 μmol/l，风险比为 1.38，95%置信区间为 1.07，1.79，p=0.013）。在调整基线变量后，包括年龄、身高、吸烟状况、γ-谷氨酰转移酶水平、HbA1c、试验治疗分配（安慰剂与非诺贝特）以及先前的 PAD、非 PAD 心血管疾病、截肢或糖尿病性皮肤溃疡、神经病变、肾病和糖尿病性视网膜病变后，这种关联仍然存在（胆红素浓度每降低 5 μmol/l，风险比为 1.38，95%置信区间为 1.05，1.81，p=0.019）。
结论/解释：我们的结果确定了胆红素水平与总下肢截肢之间存在显著的负相关关系，主要由主要截肢驱动。我们的数据提出了一个假设，即胆红素可能在 2 型糖尿病中预防截肢。
