The ACE insertion/deletion (I/D) polymorphism has been widely studied in people with diabetes, albeit not with regard to lower-limb amputation (LLA). We examined associations among this polymorphism, plasma ACE concentration, and LLA in people with type 1 diabetes.

ACE I/D genotype and plasma ACE were assessed in three prospective cohorts of participants with type 1 diabetes. LLA was defined as minor (below-the-ankle amputation consisting of at least one ray metatarsal resection) or major (transtibial or transfemoral) amputation. Linear, logistic, and Cox regression models were computed to evaluate the likelihood of prevalent and incident LLA by ACE genotype (XD [ID or ID] vs. II) and plasma ACE, after adjusting for confounders.

Among 1,301 participants (male 54%, age 41 ± 13 years), 90 (6.9%) had a baseline history of LLA. Baseline LLA was more prevalent in XD (7.4%) than in II genotype (4.5%, odds ratio [OR] 2.17 [95%CI 1.03–4.60]). Incident LLA occurred in 53 individuals during the 14-year follow-up and was higher in XD versus II carriers (hazard ratio 3.26 [95% CI 1.16–13.67]). This association was driven by excess risk of minor, but not major, LLA. The D allele was associated with increased prevalent LLA at the end of follow-up (OR 2.48 [1.33–4.65]). LLA was associated with higher mean (95% CI) ACE levels in II (449 [360, 539] vs. 354 [286, 423] ng/mL), but not XD (512 [454, 570] vs. 537 [488, 586]), carriers.

This report is the first of an independent association between ACE D allele and excess LLA risk, mainly minor amputations, in patients with type 1 diabetes.

ACE插入/缺失 (I/D) 多态性已在糖尿病患者中得到广泛研究，尽管与下肢截肢 (LLA) 无关。我们检查了 1 型糖尿病患者的这种多态性、血浆 ACE 浓度和 LLA 之间的关联。

ACE I/D 基因型和血浆 ACE 在三个前瞻性 1 型糖尿病参与者队列中进行了评估。LLA 被定义为小（踝下截肢，包括至少一次跖骨切除术）或大（经胫骨或经股骨）截肢。在调整混杂因素后，计算线性、逻辑和 Cox 回归模型，以通过ACE基因型（XD [ID 或 ID] 与 II）和血浆 ACE 评估流行和事件 LLA 的可能性。

在 1,301 名参与者（男性 54%，年龄 41 ± 13 岁）中，90 名（6.9%）有 LLA 基线病史。基线 LLA 在 XD (7.4%) 中比在 II 基因型中更普遍（4.5%，优势比 [OR] 2.17 [95% CI 1.03–4.60]）。在 14 年的随访期间，53 名个体发生了事件 LLA，XD 携带者高于 II 携带者（风险比 3.26 [95% CI 1.16–13.67]）。这种关联是由轻微但不是主要的 LLA 的过度风险驱动的。D 等位基因与随访结束时增加的流行 LLA 相关（OR 2.48 [1.33–4.65]）。LLA 与 II 中较高的平均 (95% CI) ACE 水平相关（449 [360, 539] vs. 354 [286, 423] ng/mL），但与 XD 无关（512 [454, 570] vs. 537 [488 , 586]), 载体。

该报告是 1 型糖尿病患者ACE D 等位基因与 LLA 风险（主要是轻微截肢）之间独立关联的第一份报告。