Diabetic patients had lower skin levels of the antimicrobial peptide RNase 7 regardless of ulcer status, and metformin — the most common diabetes drug — further reduced its expression in lab tests.
Metformin suppresses RNase 7The most commonly used diabetes drug further reduced an already-depleted skin defense peptide in diabetic patients
What the researchers found
RNase 7 was significantly decreased in skin of diabetic patients with and without foot ulcers compared to healthy donors. Metformin reduced RNase 7 expression in keratinocytes in vitro, while calcitriol, phenyl butyrate, and L-isoleucine did not restore it.
Why it matters
Diabetic foot ulcers affect millions and can lead to amputation. If metformin — taken by most type 2 diabetics — further reduces skin antimicrobial defenses, this has major clinical implications for wound management.
The numbers in context
4 defense peptides measured; RNase 7 decreased in both diabetic groups; metformin reduced RNase 7 in vitro
How the study worked
Observational study with skin biopsies from three groups: DFU patients (Wagner grade 3), diabetic patients without ulcers, and healthy donors. qPCR and immunohistochemistry for RNase 7, cathelicidin, HBD-2, and psoriasin. In vitro keratinocyte stimulation with metformin, glyburide, insulin, calcitriol, phenyl butyrate, and L-isoleucine.
Who was studied
Type 2 diabetes patients with/without foot ulcers and healthy controls
What this study cannot tell us
Sample sizes not specified. In vitro metformin effect on keratinocytes may not reflect in vivo skin responses. Correlation between RNase 7 reduction and infection outcomes not established. Known inducers failed to restore expression.
How to read the evidence
Preliminary — observational biopsy data combined with in vitro drug testing. No clinical outcome data linking RNase 7 levels to infection risk.
When this study was published
Published in 2020; the impact of diabetes medications on innate immunity remains an important area of investigation.
The bigger picture
This study highlights an underappreciated connection between diabetes medication and innate immunity. It raises the broader question of how commonly prescribed drugs may inadvertently impair immune defenses in vulnerable patients.
Questions still open
- Do diabetic patients on metformin have higher rates of foot ulcer infections compared to those on other medications?
- What mechanisms cause diabetes itself to reduce RNase 7 expression?
- Are there alternative compounds that can restore RNase 7 in diabetic skin?
Common questions
What is RNase 7 and why does it matter for diabetic feet?
Should diabetic patients stop taking metformin because of this finding?
Read the original research
Host Defense Peptide RNase 7 Is Down-regulated in the Skin of Diabetic Patients with or without Chronic Ulcers, and its Expression is Altered with Metformin.
Archives of medical research, 51(4), 327-335
Citation
Rodríguez-Carlos, Adrian; Trujillo, Valentin; Gonzalez-Curiel, Irma; Marin-Luevano, Sara; Torres-Juarez, Flor; Santos-Mena, Alan; Rivas-Santiago, Cesar; Enciso-Moreno, Jose A; Zaga-Clavellina, Veronica; Rivas-Santiago, Bruno. (2020). Host Defense Peptide RNase 7 Is Down-regulated in the Skin of Diabetic Patients with or without Chronic Ulcers, and its Expression is Altered with Metformin.. Archives of medical research, 51(4), 327-335. https://doi.org/10.1016/j.arcmed.2020.03.006