Evaluating the Impact of Diabetes and Metformin on Painful Neuromas After Lower Extremity Amputations.
| Title: | Evaluating the Impact of Diabetes and Metformin on Painful Neuromas After Lower Extremity Amputations. |
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| Authors: | Snee I; From the Department of Plastic and Reconstructive Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD.; Kuo KT; From the Department of Plastic and Reconstructive Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD.; Suresh R; From the Department of Plastic and Reconstructive Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD.; Chen AJ; From the Department of Plastic and Reconstructive Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD.; Lindley A; University of Maryland School of Medicine, Baltimore, MD.; Chekfa AJ; From the Department of Plastic and Reconstructive Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD.; Tuffaha SH; From the Department of Plastic and Reconstructive Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD.; Elhelali A; From the Department of Plastic and Reconstructive Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD. |
| Source: | Annals of plastic surgery [Ann Plast Surg] 2025 Aug 01; Vol. 95 (2), pp. 170-177. Date of Electronic Publication: 2025 Jun 04. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Little, Brown And Company Country of Publication: United States NLM ID: 7805336 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1536-3708 (Electronic) Linking ISSN: 01487043 NLM ISO Abbreviation: Ann Plast Surg Subsets: MEDLINE |
| Imprint Name(s): | Publication: Boston Ma : Little, Brown And Company; Original Publication: Boston, Little, Brown. |
| MeSH Terms: | Metformin*/therapeutic use ; Amputation, Surgical*/adverse effects ; Lower Extremity*/surgery ; Hypoglycemic Agents*/therapeutic use ; Neuroma*/epidemiology ; Neuroma*/etiology ; Neuroma*/prevention & control ; Diabetes Mellitus*/drug therapy ; Postoperative Pain*/etiology; Humans ; Male ; Retrospective Studies ; Female ; Middle Aged ; Aged ; Adult ; Propensity Score ; Incidence |
| Abstract: | Background: 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.; Methods: 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.; Results: 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%.; Conclusions: 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.; (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.) |
| Competing Interests: | Conflicts of interest and sources of funding: none declared. |
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| Contributed Indexing: | Keywords: diabetes; lower extremity amputation; metformin; neuroma |
| Substance Nomenclature: | 9100L32L2N (Metformin); 0 (Hypoglycemic Agents) |
| Entry Date(s): | Date Created: 20250618 Date Completed: 20250721 Latest Revision: 20260429 |
| Update Code: | 20260430 |
| DOI: | 10.1097/SAP.0000000000004419 |
| PMID: | 40532227 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't