Snee Isabel, Kuo Keith T, Suresh Rachana, Chen Alec J, Lindley Abel, Chekfa Abdul Jabar, Tuffaha Sami H, Elhelali Ala
From the Department of Plastic and Reconstructive Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD.
University of Maryland School of Medicine, Baltimore, MD.
Ann Plast Surg. 2025 Aug 1;95(2):170-177. doi: 10.1097/SAP.0000000000004419. Epub 2025 Jun 4.
Painful neuromas are common cause of residual limb pain following lower extremity amputation, yet its incidence in diabetic populations remains unestablished. While diabetes is thought to reduce neuroma risk due to impaired nerve regeneration, the role of metformin on this process remains unclear. This study aims to explore the association of diabetes severity and metformin therapy on painful neuroma formation following lower extremity amputations.
This retrospective cohort study used TriNetX Research Network to identify adult patients (≥18 years) who underwent lower extremity amputation between January 2016 to February 2024. Patient cohorts were identified using International Classification of Disease-10 and Current Procedural Terminology codes. Patients were stratified by diabetic status, hemoglobin A1c levels, and metformin use. Propensity score matching was performed and adjusted for demographics, comorbidities, and medications. Risk differences, risk ratios, and odds ratios with corresponding 95% confidence intervals were calculated to quantify the association between the exposure and the outcome. Statistical significance was set at P < 0.05.
A total of 16,090 patients underwent lower extremity amputation, 9994 (62.1%) were diabetic, while 6096 (37.9%) were nondiabetic. The overall incidence of symptomatic neuromas was lower in diabetic patients (0.61%) compared to the nondiabetic group (1.67%). After propensity score matching, 5196 diabetic and 5104 nondiabetic amputees were identified. Diabetes was associated with a significant reduction in neuroma risk [risk difference of -0.893% (95% CI: -1.29% to -0.496%); P < 0.0001]. Patients using metformin at the time of surgery had a higher incidence of painful neuroma (0.718%) compared to nonusers (0.424%) ( P = 0.127, odds ratio = 1.69). There was no significant difference in neuroma rates between those with hemoglobin A1c levels 6.5%-8.0%, 8.1%-10%, and >10%.
Diabetes was associated with a lower painful neuroma risk after amputation, suggesting a possible protective role of hyperglycemia-induced nerve regeneration alterations. Metformin use had no significant impact on painful neuroma rates. These findings challenge assumptions about glycemic control and neuroma formation, highlighting the need for further research on metabolic influences in postamputation nerve healing and pain management.
疼痛性神经瘤是下肢截肢术后残肢疼痛的常见原因，但其在糖尿病患者中的发病率尚不清楚。虽然糖尿病被认为由于神经再生受损而降低了神经瘤风险，但二甲双胍在此过程中的作用仍不明确。本研究旨在探讨糖尿病严重程度和二甲双胍治疗与下肢截肢术后疼痛性神经瘤形成之间的关联。
这项回顾性队列研究使用TriNetX研究网络来识别2016年1月至2024年2月期间接受下肢截肢的成年患者（≥18岁）。使用国际疾病分类第10版和当前手术操作术语代码识别患者队列。患者按糖尿病状态、糖化血红蛋白水平和二甲双胍使用情况进行分层。进行倾向评分匹配，并对人口统计学、合并症和药物进行调整。计算风险差异、风险比和优势比以及相应的95%置信区间，以量化暴露与结局之间的关联。设定统计学显著性为P < 0.05。
共有16090例患者接受了下肢截肢，其中9994例（62.1%）为糖尿病患者，6096例（37.9%）为非糖尿病患者。糖尿病患者中症状性神经瘤的总体发病率（0.61%）低于非糖尿病组（1.67%）。经过倾向评分匹配后，识别出5196例糖尿病截肢患者和5104例非糖尿病截肢患者。糖尿病与神经瘤风险显著降低相关[风险差异为-0.893%（95%置信区间：-1.29%至-0.496%）；P < 0.0001]。手术时使用二甲双胍的患者疼痛性神经瘤的发病率（0.718%）高于未使用者（0.424%）（P = 0.127，优势比 = 1.69）。糖化血红蛋白水平在6.5%-8.0%、8.1%-10%和>10%的患者之间神经瘤发生率无显著差异。
糖尿病与截肢后疼痛性神经瘤风险较低相关，提示高血糖诱导的神经再生改变可能具有保护作用。使用二甲双胍对疼痛性神经瘤发生率无显著影响。这些发现挑战了关于血糖控制和神经瘤形成的假设，强调了对截肢后神经愈合和疼痛管理中代谢影响进行进一步研究的必要性。
