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Systematic review and meta-analysis of mouse models of diabetes-associated ulcers
  1. Pacific Huynh1,
  2. James Phie1,
  3. Smriti Murali Krishna1,
  4. Jonathan Golledge1,2
  1. 1Queensland Research Centre for Peripheral Vascular Disease, James Cook University, Townsville, Queensland, Australia
  2. 2Department of Vascular and Endovascular Surgery, Townsville University Hospital, Townsville, Queensland, Australia
  1. Correspondence to Professor Jonathan Golledge; jonathan.golledge{at}jcu.edu.au

Abstract

Mouse models are frequently used to study diabetes-associated ulcers, however, whether these models accurately simulate impaired wound healing has not been thoroughly investigated. This systematic review aimed to determine whether wound healing is impaired in mouse models of diabetes and assess the quality of the past research. A systematic literature search was performed of publicly available databases to identify original articles examining wound healing in mouse models of diabetes. A meta-analysis was performed to examine the effect of diabetes on wound healing rate using random effect models. A meta-regression was performed to examine the effect of diabetes duration on wound healing impairment. The quality of the included studies was also assessed using two newly developed tools. 77 studies using eight different models of diabetes within 678 non-diabetic and 720 diabetic mice were included. Meta-analysis showed that wound healing was impaired in all eight models. Meta-regression suggested that longer duration of diabetes prior to wound induction was correlated with greater degree of wound healing impairment. Pairwise comparisons suggested that non-obese diabetic mice exhibited more severe wound healing impairment compared with db/db mice, streptozotocin-induced diabetic mice or high-fat fed mice at an intermediate stage of wound healing (p<0.01). Quality assessment suggested that the prior research frequently lacked incorporation of key clinically relevant characteristics. This systematic review suggested that impaired wound healing can be simulated in many different mouse models of diabetes but these require further refinement to become more clinically relevant.

  • transgenic and knockout mice
  • meta-analysis
  • ulcer(s)
  • laboratory research in diabetes
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Contributors PH, JP, SMK and JG were responsible for the conceptualization of the review, with data curation and analysis performed by PH and JP. The writing of this manuscript was performed by PH and JG.

  • Funding This work was supported by James Cook University’s Strategic Research Intent Fund. JG holds a National Health and Medical Research Council (NHMRC) Practitioner Fellowship (1117061) and Queensland Government Senior Clinical Research Fellowship (SCRF).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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