Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes.

Tao Y; Zhang D; Claire MacGilchrist; Ellen Kirwan; Liu YL; Caroline McIntosh

doi:10.12688/hrbopenres.13984.1

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Study Protocol

Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes.

[version 1; peer review: 1 approved with reservations, 1 not approved]

Tao Y¹, Zhang D², Claire MacGilchrist^1,3, Ellen Kirwan ¹, Liu YL⁴, Caroline McIntosh^1,3

Tao Y¹, Zhang D², [...] Claire MacGilchrist^1,3, Ellen Kirwan ¹, Liu YL⁴, Caroline McIntosh^1,3

PUBLISHED 07 Jan 2025

Author details Author details

¹ Discipline of Podiatric Medicine, School of Health Sciences, University of Galway, Galway, County Galway, Ireland
² School of Nursing and Midwifery, University of Galway, Galway, County Galway, Ireland
³ Alliance for Research and Innovation in Wounds, College of Medicine, Nursing & Health Sciences, University of Galway, Galway, County Galway, Ireland
⁴ Discipline of Occupational Therapy, School of Health Sciences, University of Galway, Galway, County Galway, Ireland

Tao Y
Roles: Conceptualization, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation

Zhang D
Roles: Investigation, Methodology, Writing – Original Draft Preparation

Claire MacGilchrist
Roles: Supervision, Writing – Review & Editing

Ellen Kirwan
Roles: Writing – Original Draft Preparation, Writing – Review & Editing

Liu YL
Roles: Methodology, Writing – Original Draft Preparation

Caroline McIntosh
Roles: Supervision, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Background

Diabetic foot ulcers (DFUs) are a serious complication of diabetes mellitus (DM), significantly contributing to mortality and morbidity in this population. Annually, approximately 18.6 million people with DM develop DFUs, with up to 34% experiencing a foot ulcer during their lifetime. DFUs are a leading cause of limb and life-threatening infections, lower limb amputations, and increased hospitalisations. Despite these public health challenges, there is a lack of research focusing on the primary prevention of DFUs, particularly the prevention of first-ever ulceration.

Objectives

To systematically review and synthesise research evidence and meta-analysis of previous research findings and derive conclusions regarding risk factors for the development of first-ever foot ulcers in patients with diabetes.

Methods and analysis

Four English and three Chinese databases will be utilised to identify eligible studies reporting risk factors for the first-ever foot ulcers in patients with diabetes. Two independent researchers will review the literature, extract relevant data, and assess the risk of bias of included studies using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and standardised mean differences (SMD) with 95% confidence intervals (CIs) for nominal and continuous data will be calculated employing either a fixed-effects or random-effects model based on heterogeneity (I² < 50% for fixed-effects and I² > 50% for random-effects models). All statistical analyses will be conducted using Stata Software Version 16.

Systematic review registration

PROSPERO (CRD42024508855)

Keywords

Diabetes, Risk Factors, First-ever Foot Ulceration, Systematic Review

Corresponding author: Ellen Kirwan

Competing interests: No competing interests were disclosed.

Grant information: Health Research Board: CDA-2019-007. Yan Tao is also a receipt of China Scholarship Council funding to support PhD Studies at the University of Galway, China Scholarship Council [202306370011].
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2025 Y T et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Y T, D Z, MacGilchrist C et al. Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes. [version 1; peer review: 1 approved with reservations, 1 not approved]. HRB Open Res 2025, 8:1 (https://doi.org/10.12688/hrbopenres.13984.1) First published: 07 Jan 2025, 8:1 (https://doi.org/10.12688/hrbopenres.13984.1) Latest published: 07 Jan 2025, 8:1 (https://doi.org/10.12688/hrbopenres.13984.1)

Introduction

Diabetic foot ulcers (DFUs) present a severe chronic complication of diabetes mellitus (DM). Due to the rising prevalence of DM, these complications are a major contributor to the burden on the global healthcare system. According to the International Diabetes Federation (IDF)¹, the number of adults living with DM reached 537 million in 2021 and is projected to reach 643 million by 2030 and 783 million by 2045. Worldwide, about 6.3% of people with DM experienced a DFU, with up to 34% developing one during their lifetime².

DFUs have a significant impact on individuals, family members and the healthcare system, as DFUs are associated with a high risk of hospitalisation, amputation, and mortality. Existing data indicates that approximately 20% of individuals living with a DFU required hospitalisation, with up to 20% of hospitalised patients undergoing amputation^3–5. The mortality rate following incident DFUs stands at 49.1% at five years and escalates to 76.9% at ten years⁴. Additionally, DFUs admissions also incur the highest average per-patients medical costs compared to admissions with non-DFU-related DM patients^6–8. A case-control study conducted in the U.S. revealed that the annual medical costs for each patient with DFUs range from $28,031 for Medicare to $26,881 for private insurance, making the cost for patients with DFU twice that of patients living with DM without DFUs⁶.

The first-ever foot ulcer is defined by the International Working Group on the Diabetic Foot (IWGDF) as “an ulcer occurring in a patient who has never before had a foot ulcer”⁹. Identifying the risk factors for the occurrence of DFUs and providing evidence for prevention strategies is an important topic. Guo et al.¹⁰ and Huang et al.¹¹ conducted systematic studies to pool risk factors for DFU recurrence. Another meta-analysis by Crawford investigated predictors for DFU occurrence, but this study did not differentiate between first-ever and recurrent cases¹². Recently, a prospective study characterised first-ever and recurrence DFUs, highlighting differences in patients’ characteristics between these two groups¹³. In addition, it is worth noting that a history of ulcers serves as the primary predictor for the recurrence of DFUs¹⁴. Consequently, there is a need to explore the risk factors specifically associated with the first-ever foot ulcers to prevent their onset.

However, factors specifically associated with the first-ever foot ulcers remain unclear. Several studies^15–17 have investigated the risk factors associated with the first-ever foot ulcers in patients with diabetes, and there is significant diversity among the findings of these studies. For example, a retrospective study identified the duration of DM as a significant risk factor for the first-ever foot ulcers¹⁸, which contrasted with the results of another 8-year prospective study conducted in the UK¹⁷, which found no significant association between the duration of diabetes and the first-ever foot ulcers. Similarly, disagreements on age as a risk factor for the first-ever foot ulcers were found in the study of Panagoulias et al.¹⁹ and Adem et al.¹⁸, with the former study suggesting that patients who developed DFUs were older, while the latter study did not show a significant difference. Therefore, there is a need to synthesise and analyse existing evidence, specifically focusing on the risk factors for the first-ever foot ulcers in patients with diabetes.

Thus, we outline a systematic review and meta-analysis study protocol to estimate the risk factors contributing to the first-ever foot ulcers in patients with diabetes and offering evidence-based strategies for DFUs prevention.

Study objectives

The aim of this systematic review and meta-analysis is to estimate risk factors for the first-ever foot ulcers in patients with diabetes.

Research questions

What are the risk factors for the first-ever foot ulcers in patients with diabetes?

Methods

Protocol design and registration

The study protocol for this systematic review will adhere to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guideline (PRISMA-P)^19,20 (see Supplementary File S1). Meta-analysis procedures will align with the Meta-Analyses and Systematic Reviews of Observational Studies guideline (MOOSE)²¹. Furthermore, the protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42024508855.

Data sourcing and search strategies

A comprehensive search strategy was devised to identify potential articles across seven databases: PubMed/Medline, Embase, Web of Science, the Cochrane Library, China Knowledge Resource Integrated Database (CNKI), Weipu Database (VIP), and Wanfang Database. The reference lists of the included studies will be examined for additional relevant studies, and citation tracking will be employed to identify further pertinent research. A research librarian was involved in formulating this search strategy. Our approach incorporated relevant keywords representing three core concepts: "diabetes mellitus", "diabetic foot ulcers", and "risk factors". Medical Subject Heading (MeSH) terms were employed in PubMed/Medline and the Cochrane Library to further refine the search for articles relevant to our topic. Boolean operators (OR, AND) and truncation (*) to capture variations in word endings and quotation marks (" ") for exact phrases were consistently utilised throughout the search strategy (see Supplementary data, File S2 for the search strategy).

Inclusion and exclusion criteria

Studies will be eligible if they report risk factors potentially contributing to the first-ever foot ulcers in patients diagnosed with either Type 1 or Type 2 DM. In this study, “first-ever foot ulcer” will be defined as “a foot ulcer occurring in a patient who has never before had a foot ulcer”⁹. To be included, studies had to be retrospective or prospective cohorts, cross-sectional or case-control studies published in English or Chinese.

Due to limitations in translation capabilities, non-English/Chinese articles will be excluded. Additionally, intervention studies, review articles, case reports, letters, comments, meeting abstracts, studies not published in peer-reviewed journals, and incomplete or non-full text articles will be excluded due to duplication or limited quality of evidence (see Table 1).

Table 1. Inclusion and exclusion criteria.

Inclusion criteria	Exclusion criteria
Patients diagnosed with either Type 1 or Type 2 diabetes mellitus	Foot ulcers due to causes other than diabetes mellitus
Articles reported factors contributing to the first-ever foot ulcers in patients with diabetes.	Incomplete or non-full text articles
Articles in English or Chinese	Non-English/Chinese language articles
Retrospective or prospective cohorts, cross-sectional and case-control studies	Intervention studies, review articles, case reports, letters, comments, meeting abstracts, or studies not published in peer-reviewed journals.

Study selection procedure

The search results will be exported to Covidence data-management software for screening, and duplicates will be eliminated using the software's functionality. Two reviewers (Tao Y and Zhang D) will independently assess the titles and abstracts of all retrieved studies to exclude studies following the inclusion and exclusion criteria. Full texts of the remaining studies will be evaluated by two reviewers (Tao Y and Zhang D) for inclusion in the meta-analysis. Any discrepancies between the reviewers during the study selection process will be resolved through discussion until a consensus is reached. If necessary, a third reviewer (Liu YL) will be consulted to make the final decision.

Data extraction

Data will be extracted into a predefined Excel spreadsheet. Two reviewers (Tao Y and Zhang D) will independently extract and cross-check the extracted information. The following data will be extracted:

i. Study characteristics: last name of the first author, publication year, enrolment year, country, setting, study design and follow-up period (if applicable).
ii. Participants' characteristics include population, population size (DFUs/total), age, gender, type of DM, and duration of diabetes.
iii. Outcome: Estimated effects (e.g., relative risks (RRs), odds ratio (ORs), or hazard ratio (HRs)) for all risk factors for first-ever foot ulcers in patients with diabetes mentioned in included studies. For studies without reported risk estimates, raw data (e.g., means, standard deviations (SDs), median, inter-quartile range (IQR), and frequency data) will be extracted to calculate effect sizes.

Study quality and risk of bias

The methodological quality of the included studies will be assessed using the Newcastle-Ottawa Scale (NOS)²². This scale encompasses three main domains: selection of study groups, comparability of the groups, and assessment of outcome (for cohort studies) or exposure (for case-control studies). Total scores on the NOS range from 0 to 9 stars, with 6–9 stars indicating a low risk of bias, 4–5 stars indicating a medium risk of bias, and 1–3 stars indicating a high risk of bias. The quality of evidence for each risk factor and the incidence of first-ever foot ulcers will be evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach²³.

Statistical analysis and meta-analysis

Statistical analyses will be performed using Stata Software Version 16²⁴. When more than one studies report the same risk factor with consistent definitions, pooled ORs for nominal data and standard mean differences (SMD) for continuous variables will be computed. For the purpose of this study, RRs and HRs reported in the included studies will be treated as estimates of ORs. For studies that do not provide reported risk estimates, calculations will be carried out for both nominal data (ORs) and continuous variables (SMD) using the original data. Corresponding 95% confidence intervals (CIs) will be computed for all parameters. Descriptive presentation will be employed for lack of sufficient data within the literature or risk factors identified in only one study.

Heterogeneity among included studies will be assessed using the Cochran Q-test and the I² test. A significance level of P < 0.10 for the Q-test will indicate potential study variance, recognising its limited power. Meta-analysis will be conducted using either a fixed-effects or random-effects model based on the absence (I² < 50%) or presence (I²> 50%) of statistically significant heterogeneity. A separate subgroup analysis based on study type and study quality will be conducted to explore the source of heterogeneity if at least ten studies reported a certain factor for first-ever foot ulcers. Sensitivity analyses by removing a single study at the time will be performed to examine the robustness of the pooled results. For meta-analyses that contain at least five studies, publication bias will be evaluated using a funnel plot, where asymmetry may indicate potential bias. Egger’s test will be employed to quantify the bias. To address potential bias, the trim-and-fill method will be used. A two-tailed P < 0.05 will be considered statistically significant.

Discussion

The aim of this systematic review and meta-analysis is to collect and statistically analyse all accessible data to identify potential risk factors for the first-ever foot ulcers in patients with diabetes. The outcomes of this study will enhance the current understanding of DFUs and equip healthcare professionals with information that could facilitate earlier identification of individuals at heightened risk of DFUs. Consequently, this could lead to the implementation of improved management strategies for diabetic patients predisposed to DFUs, potentially resulting in reduced mortality and alleviating the economic burden associated with DFUs.

Ethics and consent

Ethical approval and consent were not required.

Data availability statement

Underlying data

No underlying data are associated with this article.

Extended data

Zenodo: A systematic review and meta analysis risk study protocol

https://doi.org/10.5281/zenodo.14282490²⁵

This project contains following data:

- S2 Search strategy (1).docx

Reporting guidelines

PRISMA-P Checklist for ‘Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes.’ https://doi.org/10.5281/zenodo.14282490²⁵

Data are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication) (http://creativecommons.org/publicdomain/zero/1.0/).

Author contributions

Tao Y and Zhang D designed the work and developed the search strategy for this study. Tao Y, Zhang D and Liu YL will review the literature, extract the data and assess the quality of studies. Tao Y drafted the present protocol. Tao Y will perform the statistical analysis and write up of manuscript. MacGilchrist C, Kirwan E and McIntosh C contributed to the proposal's writing and review.

Faculty Opinions recommended

References

1. IDF: IDF Diabetes Atlas 2021. Reference Source
2. Zhang P, Lu J, Jing Y, et al.: Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis. Ann Med. 2017; 49(2): 106–16. PubMed Abstract | Publisher Full Text
3. Skrepnek GH, Mills JL Sr, Armstrong DG: A diabetic emergency one million feet long: disparities and burdens of illness among Diabetic Foot Ulcer cases within Emergency Departments in the United States, 2006–2010. PLoS One. 2015; 10(8): e0134914. PubMed Abstract | Publisher Full Text | Free Full Text
4. McDermott K, Fang M, Boulton AJM, et al.: Etiology, epidemiology, and disparities in the burden of Diabetic Foot Ulcers. Diabetes Care. 2023; 46(1): 209–21. PubMed Abstract | Publisher Full Text | Free Full Text
5. Cortes-Penfield NW, Armstrong DG, Brennan MB, et al.: Evaluation and management of diabetes-related foot infections. Clin Infect Dis. 2023; 77(3): e1–e13. PubMed Abstract | Publisher Full Text | Free Full Text
6. Rice JB, Desai U, Cummings AKG, et al.: Burden of Diabetic Foot Ulcers for medicare and private insurers. Diabetes Care. 2014; 37(3): 651–8. PubMed Abstract | Publisher Full Text
7. Syed MH, Salata K, Hussain MA, et al.: The economic burden of inpatient Diabetic Foot Ulcers in Toronto, Canada. Vascular. 2020; 28(5): 520–9. PubMed Abstract | Publisher Full Text
8. Hicks CW, Selvarajah S, Mathioudakis N, et al.: Trends and determinants of costs associated with the inpatient care of Diabetic Foot Ulcers. J Vasc Surg. 2014; 60(5): 1247–54.e2. PubMed Abstract | Publisher Full Text | Free Full Text
9. Boulton AJM, Armstrong DG, Kirsner RS, et al.: Diagnosis and management of diabetic foot complications. Arlington (VA): American Diabetes Association, 2018. PubMed Abstract | Publisher Full Text
10. Guo Q, Ying G, Jing O, et al.: Influencing factors for the recurrence of Diabetic Foot Ulcers: a meta-analysis. Int Wound J. 2023; 20(5): 1762–75. PubMed Abstract | Publisher Full Text | Free Full Text
11. Huang ZH, Li SQ, Kou Y, et al.: Risk factors for the recurrence of Diabetic Foot Ulcers among diabetic patients: a meta-analysis. Int Wound J. 2019; 16(6): 1373–1382. PubMed Abstract | Publisher Full Text | Free Full Text
12. Crawford F, Inkster M, Kleijnen J, et al.: Predicting foot ulcers in patients with diabetes: a systematic review and meta-analysis. QJM. 2007; 100(2): 65–86. PubMed Abstract | Publisher Full Text
13. Yin K, Qiao T, Zhang Y, et al.: Unraveling shared risk factors for Diabetic Foot Ulcer: a comprehensive Mendelian randomization analysis. BMJ Open Diabetes Res Care. 2023; 11(6): e003523. PubMed Abstract | Publisher Full Text | Free Full Text
14. Ahmed MU, Tannous WK, Agho KE, et al.: Prevalence and burden of Diabetes-Related Foot Disease in New South Wales, Australia: evidence from the 45 and up study survey data linked with health services data. Int J Environ Res Public Health. 2021; 18(21): 11528. PubMed Abstract | Publisher Full Text | Free Full Text
15. Yin K, Qiao T, Zhang Y, et al.: Unraveling shared risk factors for Diabetic Foot Ulcer: a comprehensive Mendelian randomization analysis. BMJ Open Diabetes Res Care. 2023; 11(6): e003523. PubMed Abstract | Publisher Full Text | Free Full Text
16. Adebabay AA, Worede AG, Sume BW, et al.: Prevalence and associated factors of foot deformity among adult diabetic patients on follow-up at Debre Markos comprehensive specialized hospital, Northwest Ethiopia, 2022, cross-sectional study. BMC Endocr Disord. 2023; 23(1): 265. PubMed Abstract | Publisher Full Text | Free Full Text
17. Orlando G, Reeves ND, Boulton AJM, et al.: Sedentary behaviour is an independent predictor of Diabetic Foot Ulcer development: an 8–year prospective study. Diabetes Res Clin Pract. 2021; 177: 108877. PubMed Abstract | Publisher Full Text
18. Adem AM, Andargie AA, Teshale AB, et al.: Incidence of Diabetic Foot Ulcer and its predictors among Diabetes Mellitus patients at Felege Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia: a retrospective follow-up study. Diabetes Metab Syndr Obes. 2020; 13: 3703–3711. PubMed Abstract | Publisher Full Text | Free Full Text
19. Page MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372: n71. PubMed Abstract | Publisher Full Text | Free Full Text
20. Shamseer L, Moher D, Clarke M, et al.: Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 350: g7647. PubMed Abstract | Publisher Full Text
21. Stroup DF, Berlin JA, Morton SC, et al.: Meta-analysis Of Observational Studies in Epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000; 283(15): 2008–12. PubMed Abstract | Publisher Full Text
22. Wells G, Shea B, O'Connell J: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute Web site, 2014; 7. Reference Source
23. Schünemann HJ, Cuello C, Akl EA, et al.: GRADE guidelines: 18. How ROBINS-I and other tools to assess risk of bias in nonrandomized studies should be used to rate the certainty of a body of evidence. J Clin Epidemiol. 2019; 111: 105–114. PubMed Abstract | Publisher Full Text | Free Full Text
24. Daly C, Soobiah C: Software to conduct a Meta-Analysis and Network Meta-Analysis. Methods Mol Biol. 2022; 2345: 223–244. PubMed Abstract | Publisher Full Text
25. Kirwan E: A systematic review and meta analysis risk study protocol. [Data set]. Zenodo. 2024. http://www.doi.org/10.5281/zenodo.14282490

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Author details Author details

¹ Discipline of Podiatric Medicine, School of Health Sciences, University of Galway, Galway, County Galway, Ireland
² School of Nursing and Midwifery, University of Galway, Galway, County Galway, Ireland
³ Alliance for Research and Innovation in Wounds, College of Medicine, Nursing & Health Sciences, University of Galway, Galway, County Galway, Ireland
⁴ Discipline of Occupational Therapy, School of Health Sciences, University of Galway, Galway, County Galway, Ireland

Tao Y
Roles: Conceptualization, Investigation, Methodology, Project Administration, Writing – Original Draft Preparation

Zhang D
Roles: Investigation, Methodology, Writing – Original Draft Preparation

Claire MacGilchrist
Roles: Supervision, Writing – Review & Editing

Ellen Kirwan
Roles: Writing – Original Draft Preparation, Writing – Review & Editing

Liu YL
Roles: Methodology, Writing – Original Draft Preparation

Caroline McIntosh
Roles: Supervision, Writing – Review & Editing

Competing interests

No competing interests were disclosed.

Grant information

Health Research Board: CDA-2019-007. Yan Tao is also a receipt of China Scholarship Council funding to support PhD Studies at the University of Galway, China Scholarship Council [202306370011].
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Article Versions (1)

version 1

Published: 07 Jan 2025, 8:1

https://doi.org/10.12688/hrbopenres.13984.1

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© 2025 Y T et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Y T, D Z, MacGilchrist C et al. Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes. [version 1; peer review: 1 approved with reservations, 1 not approved]. HRB Open Res 2025, 8:1 (https://doi.org/10.12688/hrbopenres.13984.1)

NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.

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Reviewer Report 26 Feb 2025

Bootan Hasan Ahmed, Case Western Reserve University, Cleveland, USA; Nursing, Case Western Reserve University Frances Payne Bolton School of Nursing (Ringgold ID: 15735), Cleveland, Ohio, USA

Not Approved

https://doi.org/10.21956/hrbopenres.15349.r45374

Abstract

In background, DFUs are a leading cause of limb and life-threatening infections, lower limb amputations, and increased hospitalizations should come after the first sentence as it the significance to the problem.
The study will be ... Continue reading

Abstract

In background, DFUs are a leading cause of limb and life-threatening infections, lower limb amputations, and increased hospitalizations should come after the first sentence as it the significance to the problem.
The study will be about first DFUs, but authors states that there is a lack of research focusing on the primary prevention of DFUs, particularly the prevention of first-ever ulceration, meaning that the review will be about the prevention of DFUs and it is inconsistent with the Objectives of the studies. Authors can write there is lack of a review about the risk factor that are associated with first DFUs among people living with diabetes, instead.

Introduction

Authors need to clarify where did they take from ‘Existing data indicates that approximately 20%....... to 76.9% at ten years’, meaning that is it from an original study (e.g., study design, sample size and where) or a review paper?
Inconsistent findings among the prior research studies (e.g., association between age and developing DFUs) is expected and it may be using different study designs or sample sizes etc. However, authors need to clarify what does this study add to the literature as several studies have addressed the risk factors for DFUs and they are most likely could addressed first DFUs. For example, this study [Ref 1]
Further, objective of this study is almost the same as the aforementioned study in the link except that the authors used first DFUs concept in the protocol.

Method
Authors mentioned that they will include articles who addressed first DFUs, but they need clarify that how they will identify articles that addressed first DFUs. This should be clearly stated. Otherwise, the article would be a repeated review.
Further, authors did not use first in the searching strategy and how first DFUs can be identified.
It is not necessary to write ‘Non-English/Chinese language articles since authors mentioned that they included articles written and published English and Chinese.

Authors should clarify that why will they exclude intervention studies, review articles, case report and letters?

Ethical and consent

Authors need to add that the present review included studies that are already published and publicly available. Further, data were not collected from any subjects for the purpose of the present review. Therefore, ethical and consent were not required.

Notes

There is another review about risk factors that are associated with DFUs among people living with diabetes, and authors need to clarify that why are they going to repeat the same review? What is the contribution of this paper to the risk factors of DFUs among people living with diabetes?

Is the rationale for, and objectives of, the study clearly described?

No
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

Yes
Are the datasets clearly presented in a useable and accessible format?

Yes

References

1. Tang WH, Zhao YN, Cheng ZX, Xu JX, et al.: Risk factors for diabetic foot ulcers: A systematic review and meta-analysis.Vascular. 2024; 32 (3): 661-669 PubMed Abstract | Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: I am expertise in diabetes and risk factors for first and recurrent diabetic foot ulcers. I have also expertise in social determents of diabetes.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

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Reviewer Report 07 Feb 2025

Ketan Dhatariya, University of East Anglia, Norwich, UK; Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, England, UK

Approved with Reservations

https://doi.org/10.21956/hrbopenres.15349.r45141

This is my review of the paper by Tao et al Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes

In the introduction the authors say that ... Continue reading

This is my review of the paper by Tao et al Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes

In the introduction the authors say that there are 537,000,000 adults living with diabetes. I would suggest the update this reference to that found in The Lancet in 2024 [Ref-1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02317-1/fulltext

In the introduction to the authors mean that the 6.3% of people is an annual incidence?

One of my main concerns with current methodology is that their search findings will also depend on the health care system one is dealing with, so a socialized healthcare system (e.g. the UK NHS) may provide and offer a significantly different degree of preventative measure and access to health care that sub-Saharan African may get - e.g. annual primary care screening for neuropathy or PVD. Will this work take such factors into account?

It will be very difficult to tease out 'health' or 'disease' related factors from the social determinants of health related factors. This being defined as the broad conditions in which people are born, live, learn, work, play, worship, and age, affecting the wide variety of health functioning and quality of life outcomes and risks throughout the life course (Lancet. 2008;372(9650):1661-9). [Ref-2]

I assume when the authors say ‘Chinese’, this will cover Mandarin and Cantonese and other 'Chinese' languages?

How will the authors deal with different papers maybe using the same datasets?

In the data extraction, the authors do not mention measures of glycaemic control? Or the presence or absence of 'traditional' risk factors - e.g. presence of other microvascular disease urine ACR or eGFR /retinopathy/neuropathy (and how that was diagnosed) macrovascular disease? And all of the measures reported in the English National Diabetic Foot Audit. I assume this is what they will be looking for when they say ‘risk factors’, but why not proactively look for the things already strongly associated with DFU development?

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Partly
Are sufficient details of the methods provided to allow replication by others?

Partly
Are the datasets clearly presented in a useable and accessible format?

Yes

References

1. NCD Risk Factor Collaboration NCD-RisC: Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants.Lancet. 2024; 404 (10467): 2077-2093 PubMed Abstract | Publisher Full Text
2. Marmot M, Friel S, Bell R, Houweling TA, et al.: Closing the gap in a generation: health equity through action on the social determinants of health.Lancet. 2008; 372 (9650): 1661-9 PubMed Abstract | Publisher Full Text

Competing Interests: No competing interests were disclosed.

Reviewer Expertise: Diabetic foot, inpatient diabetes, perioperative diabetes care

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Ketan Dhatariya, University of East Anglia, Norwich, UK; Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK
Bootan Hasan Ahmed, Case Western Reserve University, Cleveland, USA; Case Western Reserve University Frances Payne Bolton School of Nursing (Ringgold ID: 15735), Cleveland, USA

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Reviewer Report

9 Views

26 Feb 2025 | for Version 1

Bootan Hasan Ahmed, Case Western Reserve University, Cleveland, USA; Nursing, Case Western Reserve University Frances Payne Bolton School of Nursing (Ringgold ID: 15735), Cleveland, Ohio, USA

9 Views Cite this report Responses(0)

Not Approved

Abstract

In background, DFUs are a leading cause of limb and life-threatening infections, lower limb amputations, and increased hospitalizations should come after the first sentence as it the significance to the problem.
The study will be about first DFUs, but authors states that there is a lack of research focusing on the primary prevention of DFUs, particularly the prevention of first-ever ulceration, meaning that the review will be about the prevention of DFUs and it is inconsistent with the Objectives of the studies. Authors can write there is lack of a review about the risk factor that are associated with first DFUs among people living with diabetes, instead.

Introduction

Authors need to clarify where did they take from ‘Existing data indicates that approximately 20%....... to 76.9% at ten years’, meaning that is it from an original study (e.g., study design, sample size and where) or a review paper?
Inconsistent findings among the prior research studies (e.g., association between age and developing DFUs) is expected and it may be using different study designs or sample sizes etc. However, authors need to clarify what does this study add to the literature as several studies have addressed the risk factors for DFUs and they are most likely could addressed first DFUs. For example, this study [Ref 1]
Further, objective of this study is almost the same as the aforementioned study in the link except that the authors used first DFUs concept in the protocol.

Method
Authors mentioned that they will include articles who addressed first DFUs, but they need clarify that how they will identify articles that addressed first DFUs. This should be clearly stated. Otherwise, the article would be a repeated review.
Further, authors did not use first in the searching strategy and how first DFUs can be identified.
It is not necessary to write ‘Non-English/Chinese language articles since authors mentioned that they included articles written and published English and Chinese.

Authors should clarify that why will they exclude intervention studies, review articles, case report and letters?

Ethical and consent

Authors need to add that the present review included studies that are already published and publicly available. Further, data were not collected from any subjects for the purpose of the present review. Therefore, ethical and consent were not required.

Notes

There is another review about risk factors that are associated with DFUs among people living with diabetes, and authors need to clarify that why are they going to repeat the same review? What is the contribution of this paper to the risk factors of DFUs among people living with diabetes?

Is the rationale for, and objectives of, the study clearly described?

No
Is the study design appropriate for the research question?

Yes
Are sufficient details of the methods provided to allow replication by others?

Yes
Are the datasets clearly presented in a useable and accessible format?

Yes

References

1. Tang WH, Zhao YN, Cheng ZX, Xu JX, et al.: Risk factors for diabetic foot ulcers: A systematic review and meta-analysis.Vascular. 2024; 32 (3): 661-669 PubMed Abstract | Publisher Full Text

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

I am expertise in diabetes and risk factors for first and recurrent diabetic foot ulcers. I have also expertise in social determents of diabetes.

I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.

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Reviewer Report

15 Views

07 Feb 2025 | for Version 1

Ketan Dhatariya, University of East Anglia, Norwich, UK; Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, England, UK

15 Views Cite this report Responses(0)

Approved With Reservations

This is my review of the paper by Tao et al Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes

In the introduction the authors say that there are 537,000,000 adults living with diabetes. I would suggest the update this reference to that found in The Lancet in 2024 [Ref-1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02317-1/fulltext

In the introduction to the authors mean that the 6.3% of people is an annual incidence?

One of my main concerns with current methodology is that their search findings will also depend on the health care system one is dealing with, so a socialized healthcare system (e.g. the UK NHS) may provide and offer a significantly different degree of preventative measure and access to health care that sub-Saharan African may get - e.g. annual primary care screening for neuropathy or PVD. Will this work take such factors into account?

It will be very difficult to tease out 'health' or 'disease' related factors from the social determinants of health related factors. This being defined as the broad conditions in which people are born, live, learn, work, play, worship, and age, affecting the wide variety of health functioning and quality of life outcomes and risks throughout the life course (Lancet. 2008;372(9650):1661-9). [Ref-2]

I assume when the authors say ‘Chinese’, this will cover Mandarin and Cantonese and other 'Chinese' languages?

How will the authors deal with different papers maybe using the same datasets?

In the data extraction, the authors do not mention measures of glycaemic control? Or the presence or absence of 'traditional' risk factors - e.g. presence of other microvascular disease urine ACR or eGFR /retinopathy/neuropathy (and how that was diagnosed) macrovascular disease? And all of the measures reported in the English National Diabetic Foot Audit. I assume this is what they will be looking for when they say ‘risk factors’, but why not proactively look for the things already strongly associated with DFU development?

Is the rationale for, and objectives of, the study clearly described?

Yes
Is the study design appropriate for the research question?

Partly
Are sufficient details of the methods provided to allow replication by others?

Partly
Are the datasets clearly presented in a useable and accessible format?

Yes

References

1. NCD Risk Factor Collaboration NCD-RisC: Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants.Lancet. 2024; 404 (10467): 2077-2093 PubMed Abstract | Publisher Full Text
2. Marmot M, Friel S, Bell R, Houweling TA, et al.: Closing the gap in a generation: health equity through action on the social determinants of health.Lancet. 2008; 372 (9650): 1661-9 PubMed Abstract | Publisher Full Text

Competing Interests

No competing interests were disclosed.

Reviewer Expertise

Diabetic foot, inpatient diabetes, perioperative diabetes care

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

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Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes.

Abstract

Background

Objectives

Methods and analysis

Systematic review registration

Keywords

Introduction

Study objectives

Research questions

Methods

Protocol design and registration

Data sourcing and search strategies

Inclusion and exclusion criteria

Table 1. Inclusion and exclusion criteria.

Study selection procedure

Data extraction

Study quality and risk of bias

Statistical analysis and meta-analysis

Discussion

Ethics and consent

Data availability statement

Underlying data

Extended data

Reporting guidelines

Author contributions

References

Comments on this article Comments (0)

Open Peer Review

Comments on this article Comments (0)

Open Peer Review

Reviewer Status

Reviewer Reports

Comments on this article

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Study protocol: A systematic review and meta-analysis of risk factors for the first-ever foot ulcers in patients with diabetes.

Abstract

Background

Objectives

Methods and analysis

Systematic review registration

Keywords

Introduction

Study objectives

Research questions

Methods

Protocol design and registration

Data sourcing and search strategies

Inclusion and exclusion criteria

Table 1. Inclusion and exclusion criteria.

Study selection procedure

Data extraction

Study quality and risk of bias

Statistical analysis and meta-analysis

Discussion

Ethics and consent

Data availability statement

Underlying data

Extended data

Reporting guidelines

Author contributions

References

Comments on this article Comments (0)

Open Peer Review

Comments on this article Comments (0)

Open Peer Review

Reviewer Status

Reviewer Reports

Comments on this article

Competing Interests Policy

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Are you a HRB-funded researcher?

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