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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Aging</journal-id>
<journal-title>Frontiers in Aging</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Aging</abbrev-journal-title>
<issn pub-type="epub">2673-6217</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">1507232</article-id>
<article-id pub-id-type="doi">10.3389/fragi.2025.1507232</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Aging</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Exploring the exercise for enhancing postural control, gait, and muscle strength in older adults with diabetic peripheral neuropathy: a systematic review and meta-analysis</article-title>
<alt-title alt-title-type="left-running-head">Pang et al.</alt-title>
<alt-title alt-title-type="right-running-head">
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fragi.2025.1507232">10.3389/fragi.2025.1507232</ext-link>
</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Pang</surname>
<given-names>Xiangsheng</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>&#x2020;</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2425161/overview"/>
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<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Wang</surname>
<given-names>Dongmei</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>&#x2020;</sup>
</xref>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhang</surname>
<given-names>Fei</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/Writing - review &#x26; editing/"/>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Guo</surname>
<given-names>Bin</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>4</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Liu</surname>
<given-names>Wenming</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
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<aff id="aff1">
<sup>1</sup>
<institution>Department of Sports Science</institution>, <institution>Zhejiang University, Hangzhou</institution>, <addr-line>Zhejiang</addr-line>, <country>China</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Sport Science School</institution>, <institution>Beijing Sport University</institution>, <addr-line>Beijing</addr-line>, <country>China</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>College of Physical Education</institution>, <institution>Hangzhou Normal University, Hangzhou</institution>, <addr-line>Zhejiang</addr-line>, <country>China</country>
</aff>
<aff id="aff4">
<sup>4</sup>
<institution>School of Physical Education</institution>, <institution>Da Lian University, Dalian</institution>, <addr-line>Liaoning</addr-line>, <country>China</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>
<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1887700/overview">Wiktoria Sta&#x15b;kiewicz-Bartecka</ext-link>, Medical University of Silesia, Poland</p>
</fn>
<fn fn-type="edited-by">
<p>
<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2583948/overview">Agata Kiciak</ext-link>, Faculty of Public Health in Bytom Medical University of Silesia in Katowice, Poland</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2907302/overview">Ivan Julian-Rochina</ext-link>, University of Valencia, Spain</p>
</fn>
<corresp id="c001">&#x2a;Correspondence: Bin Guo, <email>guobin@dlu.edu.cn</email>; Wenming Liu, <email>liuwenming@zju.edu.cn</email>
</corresp>
<fn fn-type="equal" id="fn001">
<label>
<sup>&#x2020;</sup>
</label>
<p>These authors share first authorship</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>29</day>
<month>04</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>6</volume>
<elocation-id>1507232</elocation-id>
<history>
<date date-type="received">
<day>07</day>
<month>10</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>16</day>
<month>04</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2025 Pang, Wang, Zhang, Guo and Liu.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Pang, Wang, Zhang, Guo and Liu</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec>
<title>Objective</title>
<p>The purpose of this study was to conduct a systematic review and meta-analysis to evaluate the effects of exercise on postural control, gait, and muscle strength in older adults with diabetic peripheral neuropathy (DPN).</p>
</sec>
<sec>
<title>Research Design</title>
<p>Systematic review and meta-analysis.</p>
</sec>
<sec>
<title>Methods</title>
<p>An extensive literature search was performed in PubMed, EBSCO, Web of Science and Cochrane Library from database inception to 30 September 2023. The inclusion criteria were exercise intervention on postural control, gait characteristics, and muscle strength in older adults with DPN. Two reviewers independently extracted data and assessed the quality of studies by Cochrane Risk of Bias.</p>
</sec>
<sec>
<title>Results</title>
<p>The literature search elicited a total of 523 references, 23 articles were included in this systematic review and meta-analyses. Exercise could effectively decrease the Centre of Pressure (COP) path (SMD &#x3d; &#x2212;0.38, 95%CI &#x3d; &#x2212;0.77 <inline-formula id="inf1">
<mml:math id="m1">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> 0.01), increase gait speed (MD &#x3d; 0.08, 95%CI &#x3d; 0.05 <inline-formula id="inf2">
<mml:math id="m2">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> 0.11), but did not change stride length (MD &#x3d; 0.04, 95%CI &#x3d; &#x2212;0.01 <inline-formula id="inf3">
<mml:math id="m3">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> 0.09), and enhance muscle strength (SMD &#x3d; 0.76, 95%CI &#x3d; 0.19 <inline-formula id="inf4">
<mml:math id="m4">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> 1.33).</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Exercise improves postural control, gait speed, and muscle strength in older adults with DPN, reducing fall risk and enhancing lower limb strength, though evidence on stride length improvement is limited.</p>
</sec>
<sec>
<title>Systematic Review Registration</title>
<p>identifier CRD42023436799.</p>
</sec>
</abstract>
<kwd-group>
<kwd>diabetic peripheral neuropathy</kwd>
<kwd>gait characteristics</kwd>
<kwd>muscle strength</kwd>
<kwd>postural control</kwd>
<kwd>fall prevention</kwd>
</kwd-group>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Interventions in Aging</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1">
<title>1 Introduction</title>
<p>Diabetic Peripheral Neuropathy (DPN), a prevalent chronic complication of diabetes, significantly impacts the quality of life in approximately 50% of diabetic patients (<xref ref-type="bibr" rid="B44">Sloan et al., 2021</xref>). The pathogenesis of DPN is multifaceted, primarily attributed to prolonged hyperglycemia and metabolic dysregulation, leading to sensory and motor nerve damage (<xref ref-type="bibr" rid="B44">Sloan et al., 2021</xref>). Notably, individuals with DPN exhibit a 2.3-fold higher risk of falls compared to diabetic patients without DPN (<xref ref-type="bibr" rid="B37">Reeves et al., 2021</xref>; <xref ref-type="bibr" rid="B20">Kruse et al., 2010</xref>), and a staggering 15-fold increase relative to their healthy counterparts (<xref ref-type="bibr" rid="B17">Khan et al., 2021a</xref>; <xref ref-type="bibr" rid="B30">Mustapa et al., 2016</xref>). Clinical manifestations of DPN include distal sensory abnormalities, neuropathic pain, muscle weakness, and motor dysfunction, collectively contributing to gait disturbances and impaired postural control (<xref ref-type="bibr" rid="B44">Sloan et al., 2021</xref>). These impairments substantially elevate fall risk, with potentially severe consequences such as fractures and intracranial hemorrhages, which not only impose significant economic burdens but are also associated with increased mortality rates (<xref ref-type="bibr" rid="B13">Gupta et al., 2023</xref>).</p>
<p>A complex interaction of factors affects the increased risk of falls among older adults with DPN. This is attributed to the glycation of skeletal muscle proteins as well as axonal degeneration and segmental demyelination of the peripheral motor nerve (<xref ref-type="bibr" rid="B37">Reeves et al., 2021</xref>), leading to lower extremity motor impairments and a loss of sensory feedback in the feet (<xref ref-type="bibr" rid="B37">Reeves et al., 2021</xref>). DPN causes pain, diminished muscle quality, diminished peripheral sensation, unstable gait, impaired balance, and motor dysfunction, ultimately resulting in increased fall risk (<xref ref-type="bibr" rid="B19">Khan et al., 2021b</xref>). In particular, postural instability and gait imbalance in DPN mainly contribute to high fall incidence (<xref ref-type="bibr" rid="B50">Wang et al., 2022</xref>). People with DPN usually exhibit a conservative gait strategy with worse gait speed and step length (<xref ref-type="bibr" rid="B37">Reeves et al., 2021</xref>). Reeves et al. reported the strongest correlations with individuals&#x2019; self-perceived unsteadiness were with gait velocity, stride length and severity of DPN (<xref ref-type="bibr" rid="B36">Reeves et al., 2017</xref>). Otherwise, it is possibly due to the part absence of peripheral sensation and the delaying of neuromuscular control this could result in balance impairment and a high risk of falls in the medial-lateral (ML) dynamic sway (<xref ref-type="bibr" rid="B7">Brown et al., 2015</xref>), as a key indicator to distinguish among people with and without DPN (<xref ref-type="bibr" rid="B36">Reeves et al., 2017</xref>).</p>
<p>Exercise intervention, as a first-line non-pharmacological treatment strategy for diabetic peripheral neuropathy (DPN), holds significant potential in enhancing patients&#x2019; postural control, gait function, and muscle strength (<xref ref-type="bibr" rid="B16">Johnson and Takemoto, 2019</xref>). These interventions include balance training (<xref ref-type="bibr" rid="B45">Song et al., 2011</xref>; <xref ref-type="bibr" rid="B21">Lee et al., 2013</xref>; <xref ref-type="bibr" rid="B12">Grewal et al., 2015</xref>), resistance training (<xref ref-type="bibr" rid="B26">Melai et al., 2014</xref>; <xref ref-type="bibr" rid="B40">Sartor et al., 2014</xref>), aerobic training (<xref ref-type="bibr" rid="B1">Abdelaal and El-Shamy, 2022</xref>; <xref ref-type="bibr" rid="B52">Zhao et al., 2021</xref>), multicomponent exercise (<xref ref-type="bibr" rid="B34">Perrin et al., 2021</xref>; <xref ref-type="bibr" rid="B49">Waheed et al., 2021</xref>), and Tai Chi, which can effectively control blood glucose levels and thereby reverse motor dysfunction caused by neuropathy (<xref ref-type="bibr" rid="B44">Sloan et al., 2021</xref>). Improving balance ability in older adults is often a primary goal of fall prevention interventions (<xref ref-type="bibr" rid="B6">Blodgett et al., 2022</xref>). Research by Ahmad and colleagues further confirmed that an eight-week sensorimotor training intervention significantly improved patients&#x2019; balance and proprioception (<xref ref-type="bibr" rid="B3">Ahmad et al., 2019</xref>). Aerobic training not only enhances neural structure and function but also alleviates neuropathic signs and symptoms (<xref ref-type="bibr" rid="B34">Perrin et al., 2021</xref>; <xref ref-type="bibr" rid="B10">Dixit et al., 2016</xref>). Additionally, physical exercise can reduce pain and/or numbness caused by neuropathy, ultimately improving instability and mobility (<xref ref-type="bibr" rid="B22">Li and Hondzinski, 2012</xref>). A review noted that exercise combined with dietary interventions can induce systemic and cellular changes, thereby ameliorating complications associated with DPN (<xref ref-type="bibr" rid="B11">Enders et al., 2023</xref>). Although exercise can improve balance, reduce fear of falling, and enhance the quality of life (<xref ref-type="bibr" rid="B23">Lima et al., 2021</xref>), there is currently no consensus on the extent to which exercise improves postural control, gait characteristics, and muscle strength in older adults with DPN. Furthermore, it remains unclear whether these improvements contribute to reducing the risk of falls in this population.</p>
<p>This study conducted a systematic review and meta-analysis of randomized controlled trials to assess the outcomes of exercise interventions on fall risk factors including postural control, gait and muscle strength in older adults with DPN.</p>
</sec>
<sec sec-type="methods" id="s2">
<title>2 Methods</title>
<sec id="s2-1">
<title>2.1 Protocol and registration</title>
<p>The review study followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 statement (<xref ref-type="bibr" rid="B32">Page et al., 2021</xref>). A protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) ID: CRD42023436799.</p>
</sec>
<sec id="s2-2">
<title>2.2 Eligibility criteria</title>
<p>The PICOS (populations, interventions, comparator interventions, outcomes and study design) framework guided the eligibility criteria selection (<xref ref-type="bibr" rid="B9">Cochrane Collaboration, 2024</xref>).</p>
<sec id="s2-2-1">
<title>2.2.1 Populations</title>
<p>The diagnosis of DSPN follows an exclusion-based approach, with diagnostic criteria encompassing the following key points: (1) a confirmed history of diabetes; (2) onset of neuropathy at or after the diagnosis of diabetes; (3) presence of clinical symptoms of neuropathy (e.g., pain, numbness, paresthesia) accompanied by at least one abnormal finding in five neurological examinations (ankle reflex, vibration sensation, pressure sensation, temperature sensation, and pinprick sensation); in the absence of clinical symptoms, at least two abnormal findings are required; (4) exclusion of other potential causes of neuropathy, including neurotoxic medications (e.g., chemotherapeutic agents), vitamin B12 deficiency, cervical or lumbar spine disorders (e.g., compression, stenosis, degenerative changes), cerebral infarction, chronic inflammatory demyelinating polyneuropathy, hereditary neuropathies, vasculitis, infections (e.g., acquired immunodeficiency syndrome), and metabolic neurotoxicity secondary to renal insufficiency.</p>
</sec>
<sec id="s2-2-2">
<title>2.2.2 Interventions</title>
<p>The included interventions in this study primarily encompass aerobic exercise, anaerobic training, resistance exercise, whole-body vibration training, balance exercise, sensorimotor training, foot-ankle functional exercise, Tai Chi, yoga, dance training, as well as combinations of two or more of the aforementioned exercise modalities. Exercise combined with other non-exercise interventions, such as co-administration of medication, acupuncture, electrical stimulation, heat application, or physical therapy, or lifestyle modifications, have been excluded. Moreover, studies with fully supervised exercise programs or those involving short-term exercise interventions (&#x3c;1&#xa0;week) have also been excluded.</p>
</sec>
<sec id="s2-2-3">
<title>2.2.3 Comparator interventions</title>
<p>The control group interventions may include no exercise, routine foot care, health education, or regular physical activity interventions.</p>
</sec>
<sec id="s2-2-4">
<title>2.2.4 Outcomes</title>
<p>The outcome of the study was one or more of the following: (1) postural control: COP sway path; (2) gait parameters: speed, stride length, step cycle time, cadence, etc.; (3) muscle strength.</p>
</sec>
<sec id="s2-2-5">
<title>2.2.5 Studies design</title>
<p>This study included RCTs on exercise interventions for older adults with DPN in all settings (community, hospitals and institutions). It is acceptable that this literature only considered exercise as the exposure or intervention factor.</p>
</sec>
</sec>
<sec id="s2-3">
<title>2.3 Information sources and search strategy</title>
<p>Three-step search for relevant randomized controlled trials (RCTs) as recommended by the Cochrane Handbook for Systematic Reviews of Interventions was conducted (<xref ref-type="bibr" rid="B9">Cochrane Collaboration, 2024</xref>). Four electronic databases (PubMed, Web of Science, EBSCO, Cochrane Library) were searched for articles published up to 9 September 2023. Then, searching was also done in published trial articles. Medical Subject Headings (MeSH) terms and keywords were chosen based on study design (&#x201c;Randomized Controlled Trials&#x201d;), exposure (&#x201c;Exercise&#x201d; OR &#x201c;Training&#x201d; OR &#x201c;Physical activity&#x201d;), outcomes (&#x201c;Postural Control&#x201d; OR &#x201c;Gait Performance&#x201d; OR &#x201c;Biomechanics&#x201d;) and participants (&#x201c;Diabetic Peripheral Neuropathy&#x201d;). The full search strategy for PubMed can be found in the online <xref ref-type="sec" rid="s12">Supplementary Appendix B</xref>. Reference lists of included studies were also searched for relevant articles.</p>
</sec>
<sec id="s2-4">
<title>2.4 Study selection</title>
<p>All returned titles were screened by the first author (DW) to exclude duplicate or non-relevant studies. The abstract of each remaining study was then independently reviewed by DW and XP during the literature search. Then the full texts of the remaining studies were independently reviewed by the two authors against the inclusion and exclusion criteria. Disagreements were discussed and consensus was reached among the authors in all cases. All studies in the systematic review were eligible for inclusion in the meta-analyses.</p>
</sec>
<sec id="s2-5">
<title>2.5 Data collection process and data items</title>
<p>We collected data on authors, year of publication, number of participants allocated to the intervention and control groups, participant-based information (age, gender, BMI, duration of diabetes, HbA1c), type and duration of exercise intervention for the experimental and control groups (time, frequency), outcome measures, and study duration. This study gathered the outcomes including RCTs in exercise intervention, encompassing statistical metrics of continuous variables such as sample size, mean, standard deviation, and others for each study.</p>
</sec>
<sec id="s2-6">
<title>2.6 Study risk of bias assessment</title>
<p>Two authors (DW and XP) independently assessed the risk of bias at the study level of included RCTs following the Cochrane Risk of Bias Tool (RoB 2) (<xref ref-type="bibr" rid="B46">Sterne et al., 2019</xref>). The seven items considered for the risk of bias included: the randomization process, bias arising from period and carryover effects, deviations from intended interventions, missing outcome data, measurement of the outcome, selection of the reported result and overall bias. Open and apply the macro using the Excel tool (website of Cochrane Methods Bias: <ext-link ext-link-type="uri" xlink:href="https://www.riskofbias.info/">https://www.riskofbias.info/</ext-link>) to assess the risk of bias for each article (<xref ref-type="bibr" rid="B24">Liu et al., 2021</xref>).</p>
</sec>
<sec id="s2-7">
<title>2.7 Synthesis methods</title>
<p>This study employed RevMan 5.3 (The Cochrane Collaboration, Copenhagen, Denmark) software to perform meta-analysis, subgroup analysis, and generate forest plots. The extracted data were all continuous variables, expressed as mean difference (MD) and their 95% confidence intervals (CI). If the units were inconsistent, standardized mean difference (SMD) was used. Heterogeneity of outcome measures was assessed using the I<sup>2</sup> statistic and p-values. If heterogeneity was low (I<sup>2</sup> &#x2264; 50%, p &#x2264; 0.01), a fixed-effects model was applied; if heterogeneity was high (I<sup>2</sup> &#x3e; 50%, p &#x3e; 0.01), a random-effects model was used (<xref ref-type="bibr" rid="B14">Higgins et al., 2003</xref>). Subgroup analyses focused on three key factors: postural control, gait, and muscle strength. Each factor was further subdivided based on different variables to minimize heterogeneity in the study. If significant heterogeneity persisted, sensitivity analysis was conducted to identify its sources. If the sources of heterogeneity could not be determined, descriptive analysis was performed. The significance level <italic>&#x251;</italic> for the pooled effect size was set at 0.05.</p>
</sec>
</sec>
<sec sec-type="results" id="s3">
<title>3 Results</title>
<sec id="s3-1">
<title>3.1 Study selection</title>
<p>After the initial search, a total of 532 articles were included. After removing 128 duplicate articles, 280 articles were excluded based on title and abstract screening. Further full-text retrieval, reading, and quality assessment led to the exclusion of 98 articles that did not meet the inclusion criteria. Ultimately, 23 articles were included in the study. The process of article inclusion and exclusion is illustrated in <xref ref-type="fig" rid="F1">Figure 1</xref>. The characteristics of the study participants, intervention, control, and outcome measures were shown in the review (<xref ref-type="table" rid="T1">Table 1</xref>).</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>Study selection based on PRISMA 2020 flow diagram.</p>
</caption>
<graphic xlink:href="fragi-06-1507232-g001.tif"/>
</fig>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Characteristics of the included studies, including type and duration of exercise, control intervention, and outcome measure.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Reference (year)</th>
<th align="left">Exercise</th>
<th align="left">Control</th>
<th align="left">Type and duration of exercise</th>
<th align="left">Control intervention</th>
<th align="left">Outcome measures</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left">
<xref ref-type="bibr" rid="B5">Allet et al. (2010)</xref>
</td>
<td align="left">N &#x3d; 35</td>
<td align="left">N &#x3d; 36</td>
<td align="left">Balance exercise (12&#xa0;weeks, 2&#xa0;days/week)</td>
<td align="left">None</td>
<td align="left">Gait velocity, Cadence, Gait cycle time, Stride length, Stance time percentage</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B20">Kruse et al. (2010)</xref>
</td>
<td align="left">N &#x3d; 41</td>
<td align="left">N &#x3d; 38</td>
<td align="left">Strength and balance exercise (12&#xa0;weeks, 8 sessions)</td>
<td align="left">Medical care</td>
<td align="left">Ankle dorsiflexion strength</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B45">Song et al. (2011)</xref>
</td>
<td align="left">N &#x3d; 19</td>
<td align="left">N &#x3d; 19</td>
<td align="left">Balance exercise (8&#xa0;weeks, 2&#xa0;days/week)</td>
<td align="left">Health education (8&#xa0;weeks, 1&#xa0;day/week)</td>
<td align="left">COP sway path, 10-m walk time</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B21">Lee et al. (2013)</xref>
</td>
<td align="left">N &#x3d; 37</td>
<td align="left">N &#x3d; 18</td>
<td align="left">1: Whole-body vibration training (6&#xa0;weeks, 3&#xa0;days/week) and balance exercise (6&#xa0;weeks, 2&#xa0;days/week); 2: Balance exercise (6&#xa0;weeks, 2&#xa0;days/week)</td>
<td align="left">None</td>
<td align="left">COP sway velocity, FTSTS</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B29">Mueller et al. (2013)</xref>
</td>
<td align="left">N &#x3d; 15</td>
<td align="left">N &#x3d; 14</td>
<td align="left">Strength and aerobic exercise (12&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">Aerobic Exercise (12&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">Six-minute Walking Test</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B26">Melai et al. (2014)</xref>
</td>
<td align="left">N &#x3d; 48</td>
<td align="left">N &#x3d; 46</td>
<td align="left">Strength training (24&#xa0;weeks, 2&#xa0;days/week)</td>
<td align="left">None</td>
<td align="left">Gait velocity, Stride length, Stance phase duration, Stride time</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B40">Sartor et al. (2014)</xref>
</td>
<td align="left">N &#x3d; 26</td>
<td align="left">N &#x3d; 29</td>
<td align="left">Strength training (12&#xa0;weeks, 2&#xa0;days/week)</td>
<td align="left">None</td>
<td align="left">COP sway velocity, Muscle function</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B51">Yoosefinejad et al. (2015)</xref>
</td>
<td align="left">N &#x3d; 10</td>
<td align="left">N &#x3d; 10</td>
<td align="left">Whole-body vibration training (6&#xa0;weeks, 2&#xa0;days/week)</td>
<td align="left">None</td>
<td align="left">COP sway velocity, Quadriceps strength, Tibialis Anterior strength, General strength</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B10">Dixit et al. (2016)</xref>
</td>
<td align="left">N &#x3d; 36</td>
<td align="left">N &#x3d; 46</td>
<td align="left">Aerobic exercise (8&#xa0;weeks, 3&#x2013;6&#xa0;days/week)</td>
<td align="left">Health education</td>
<td align="left">COP sway velocity, COP sway displacement</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B3">Ahmad et al. (2019)</xref>
</td>
<td align="left">N &#x3d; 20</td>
<td align="left">N &#x3d; 17</td>
<td align="left">Sensorimotor training (8&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">Health education</td>
<td align="left">COP range, COP sway path, FRT</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B48">Venkataraman et al. (2019)</xref>
</td>
<td align="left">N &#x3d; 70</td>
<td align="left">N &#x3d; 73</td>
<td align="left">Strength and balance exercise (8&#xa0;weeks, 1&#xa0;day/week)</td>
<td align="left">Routine clinical care</td>
<td align="left">COP sway velocity, Ankle muscle strength, FTSTS</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B2">Abdelbasset et al. (2020)</xref>
</td>
<td align="left">N &#x3d; 14</td>
<td align="left">N &#x3d; 14</td>
<td align="left">Proprioceptive training (8&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">None</td>
<td align="left">Six-minute Walking Test</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B28">Monteiro et al. (2020)</xref>
</td>
<td align="left">N &#x3d; 15</td>
<td align="left">N &#x3d; 15</td>
<td align="left">Foot-ankle exercise (12&#xa0;weeks, 2&#xa0;days/week)</td>
<td align="left">Usual Care</td>
<td align="left">Gait velocity, Hallux maximum force, Toe maximum force</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B4">Ahmad et al. (2021)</xref>
</td>
<td align="left">N &#x3d; 32</td>
<td align="left">N &#x3d; 26</td>
<td align="left">Sensorimotor training (8&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">Health education</td>
<td align="left">Gait velocity, Cadence, Stride length, Single stance support, Double limb support</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B34">Perrin et al. (2021)</xref>
</td>
<td align="left">N &#x3d; 12</td>
<td align="left">N &#x3d; 12</td>
<td align="left">Balance and proprioceptive exercise (8&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">Usual Care</td>
<td align="left">FTSTS</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B52">Zhao et al. (2021)</xref>
</td>
<td align="left">N &#x3d; 20</td>
<td align="left">N &#x3d; 20</td>
<td align="left">Tap dance training (16 weeks, 3&#xa0;days/week)</td>
<td align="left">Educational workshops (1 session/month)</td>
<td align="left">COP trajectory, COP elliptical area, FTSTS</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B1">Abdelaal and El-Shamy (2022)</xref>
</td>
<td align="left">N &#x3d; 23</td>
<td align="left">N &#x3d; 22</td>
<td align="left">Antigravity treadmill training and traditional physical therapy (12&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">Traditional physical therapy (12&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">Step length, Step time, Double support time, Gait velocity, Cadence</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B18">Khan et al. (2022)</xref>
</td>
<td align="left">N &#x3d; 15</td>
<td align="left">N &#x3d; 15</td>
<td align="left">Strength exercise (12&#xa0;weeks, 2&#x2013;3&#xa0;days/week)</td>
<td align="left">None</td>
<td align="left">Gait speed</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B27">Monteiro et al. (2022)</xref>
</td>
<td align="left">N &#x3d; 39</td>
<td align="left">N &#x3d; 39</td>
<td align="left">Foot-ankle exercise (12&#xa0;weeks, 4&#xa0;days/week)</td>
<td align="left">Usual Care</td>
<td align="left">Gait velocity, Hallux strength, Toes strength</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B39">Rodr&#xed;guez-reyes et al. (2022)</xref>
</td>
<td align="left">N &#x3d; 20</td>
<td align="left">N &#x3d; 21</td>
<td align="left">Whole-body vibration training (12&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">Usual care</td>
<td align="left">Gait speed</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B49">Waheed et al. (2021)</xref>
</td>
<td align="left">N &#x3d; 19</td>
<td align="left">N &#x3d; 19</td>
<td align="left">Whole-body vibration and balance exercise (3&#xa0;weeks, 5&#xa0;days/week) and dietary advice (1&#xa0;day/week)</td>
<td align="left">Balance exercise (3&#xa0;weeks, 5&#xa0;days/week) and dietary advice (1&#xa0;day/week)</td>
<td align="left">Quadriceps strength, Tibialis anterior strength</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B15">Hizomi arani et al. (2023)</xref>; <xref ref-type="bibr" rid="B42">Silva et al. (2021)</xref>
</td>
<td align="left">N &#x3d; 22</td>
<td align="left">N &#x3d; 22</td>
<td align="left">Foot-ankle exercise (8&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">None</td>
<td align="left">Gait velocity</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B43">Silva et al. (2023)</xref>
</td>
<td align="left">N &#x3d; 25</td>
<td align="left">N &#x3d; 25</td>
<td align="left">Foot-related exercise (8&#xa0;weeks, 3&#xa0;days/week)</td>
<td align="left">Usual care</td>
<td align="left">Hallux strength, Toes strength</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s3-2">
<title>3.2 Risk of bias in the included studies</title>
<p>The 10 studies included in this research all exhibited a low risk in the randomization process (<xref ref-type="bibr" rid="B20">Kruse et al., 2010</xref>; <xref ref-type="bibr" rid="B45">Song et al., 2011</xref>; <xref ref-type="bibr" rid="B21">Lee et al., 2013</xref>; <xref ref-type="bibr" rid="B40">Sartor et al., 2014</xref>; <xref ref-type="bibr" rid="B49">Waheed et al., 2021</xref>; <xref ref-type="bibr" rid="B10">Dixit et al., 2016</xref>; <xref ref-type="bibr" rid="B18">Khan et al., 2022</xref>; <xref ref-type="bibr" rid="B27">Monteiro et al., 2022</xref>; <xref ref-type="bibr" rid="B15">Hizomi arani et al., 2023</xref>; <xref ref-type="bibr" rid="B43">Silva et al., 2023</xref>), with no instances of missing data. Among these, one study was an open-label randomized controlled trial (<xref ref-type="bibr" rid="B38">Rodrigues et al., 2022</xref>), resulting in a high risk in intervention allocation; two studies did not implement allocation concealment for participants or assessors (<xref ref-type="bibr" rid="B26">Melai et al., 2014</xref>; <xref ref-type="bibr" rid="B48">Venkataraman et al., 2019</xref>), leading to some risk in intervention allocation; and two studies failed to conceal allocation from treatment providers, leading to a high risk of bias in intervention compliance (<xref ref-type="bibr" rid="B38">Rodrigues et al., 2022</xref>; <xref ref-type="bibr" rid="B51">Yoosefinejad et al., 2015</xref>). The ten studies have not clearly described the concealment of the allocation of treatment and testing personnel, introducing some risk to intervention adherence (<xref ref-type="bibr" rid="B26">Melai et al., 2014</xref>; <xref ref-type="bibr" rid="B1">Abdelaal and El-Shamy, 2022</xref>; <xref ref-type="bibr" rid="B52">Zhao et al., 2021</xref>; <xref ref-type="bibr" rid="B34">Perrin et al., 2021</xref>; <xref ref-type="bibr" rid="B49">Waheed et al., 2021</xref>; <xref ref-type="bibr" rid="B3">Ahmad et al., 2019</xref>; <xref ref-type="bibr" rid="B48">Venkataraman et al., 2019</xref>; <xref ref-type="bibr" rid="B5">Allet et al., 2010</xref>; <xref ref-type="bibr" rid="B29">Mueller et al., 2013</xref>; <xref ref-type="bibr" rid="B2">Abdelbasset et al., 2020</xref>). The risk of bias assessment results for the included studies are presented in <xref ref-type="table" rid="T2">Table 2</xref>.</p>
<table-wrap id="T2" position="float">
<label>TABLE 2</label>
<caption>
<p>Risk of bias summary.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Reference (year)</th>
<th align="left">Randomization process</th>
<th align="left">Bias arising from period and carryover effects</th>
<th align="left">Deviations from intended interventions</th>
<th align="left">Missing outcome data</th>
<th align="left">Measurement of the outcome</th>
<th align="left">Selection of the reported result</th>
<th align="left">Overall bias</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left">
<xref ref-type="bibr" rid="B5">Allet et al. (2010)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B20">Kruse et al. (2010)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B45">Song et al. (2011)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B21">Lee et al. (2013)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B29">Mueller et al. (2013)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B26">Melai et al. (2014)</xref>
</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B40">Sartor et al. (2014)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B51">Yoosefinejad et al. (2015)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">H</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">H</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B10">Dixit et al. (2016)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B3">Ahmad et al. (2019)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B48">Venkataraman et al. (2019)</xref>
</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B2">Abdelbasset et al. (2020)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B28">Monteiro et al. (2020)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B4">Ahmad et al. (2021)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B34">Perrin et al. (2021)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B52">Zhao et al. (2021)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B1">Abdelaal and El-Shamy (2022)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">S</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B18">Khan et al. (2022)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B27">Monteiro et al. (2022)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B39">Rodr&#xed;guez-reyes et al. (2022)</xref>
</td>
<td align="left">S</td>
<td align="left">L</td>
<td align="left">H</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">H</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B49">Waheed et al. (2021)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B15">Hizomi arani et al. (2023)</xref>; <xref ref-type="bibr" rid="B42">Silva et al. (2021)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
<tr>
<td align="left">
<xref ref-type="bibr" rid="B43">Silva et al. (2023)</xref>
</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
<td align="left">L</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>L: low risk of bias; S: some concerns bias; H: high risk of bias.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3-3">
<title>3.3 Outcome measures</title>
<sec id="s3-3-1">
<title>3.3.1 COP sway path</title>
<p>There were three studies regarding the COP sway path after exercise in the AP and ML directions (<xref ref-type="fig" rid="F2">Figure 2</xref>). Overall, it was shown that exercise could effectively decrease the sway path of postural control (SMD &#x3d; &#x2212;0.38, 95%CI &#x3d; &#x2212;0.77 <inline-formula id="inf5">
<mml:math id="m5">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> 0.01). In particular, the pooled results showed significant differences with EO (SMD &#x3d; &#x2212;0.55, 95%CI &#x3d; &#x2212;0.108 <inline-formula id="inf6">
<mml:math id="m6">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> &#x2212;0.03), but no difference with EC (SMD &#x3d; &#x2212;0.21, 95%CI &#x3d; &#x2212;0.82 <inline-formula id="inf7">
<mml:math id="m7">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> 0.39). The total heterogeneity was low to moderate (I<sup>2</sup> &#x3d; 28%, <inline-formula id="inf8">
<mml:math id="m8">
<mml:mrow>
<mml:msup>
<mml:mi>&#x3c7;</mml:mi>
<mml:mn>2</mml:mn>
</mml:msup>
</mml:mrow>
</mml:math>
</inline-formula> &#x3d; 12.55).</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>Forest plot of meta-analyses showing the effect of centre of pressure (COP) sway path with open eye (EO) and closed eye (EC).</p>
</caption>
<graphic xlink:href="fragi-06-1507232-g002.tif"/>
</fig>
</sec>
<sec id="s3-3-2">
<title>3.3.2 Gait characteristics</title>
<p>There were ten studies on gait speed involving 412 participants and three studies on stride length involving 145 participants in <xref ref-type="fig" rid="F3">Figure 3</xref>-1.2.1. Gait performance was measured with the gait velocity and stride length. Gait velocity had significant differences between the interventional and control groups (MD &#x3d; 0.08, 95%CI &#x3d; 0.05 <inline-formula id="inf9">
<mml:math id="m9">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> 0.11), with moderate heterogeneity (I<sup>2</sup> &#x3d; 63%, <inline-formula id="inf10">
<mml:math id="m10">
<mml:mrow>
<mml:msup>
<mml:mi>&#x3c7;</mml:mi>
<mml:mn>2</mml:mn>
</mml:msup>
</mml:mrow>
</mml:math>
</inline-formula> &#x3d; 24.55). There were two studies on stride length involving 145 participants in <xref ref-type="fig" rid="F3">Figure 3</xref>-1.2.2. Stride length was not increased after exercise (MD &#x3d; 0.04, 95%CI &#x3d; &#x2212;0.01 <inline-formula id="inf11">
<mml:math id="m11">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> 0.09), with related low heterogeneity on the whole (I<sup>2</sup> &#x3d; 0%, <inline-formula id="inf12">
<mml:math id="m12">
<mml:mrow>
<mml:msup>
<mml:mi>&#x3c7;</mml:mi>
<mml:mn>2</mml:mn>
</mml:msup>
</mml:mrow>
</mml:math>
</inline-formula> &#x3d; 0.10).</p>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption>
<p>Forest plot of meta-analyses showing the effect of gait speed and stride length.</p>
</caption>
<graphic xlink:href="fragi-06-1507232-g003.tif"/>
</fig>
</sec>
<sec id="s3-3-3">
<title>3.3.3 Muscle strength</title>
<p>As shown in <xref ref-type="fig" rid="F4">Figure 4</xref>, six studies involving 262 participants presented the muscle strength of lower limbs. The muscle strength of the lower extremity was significantly reduced after exercise (SMD &#x3d; 0.76, 95%CI &#x3d; 0.19 <inline-formula id="inf13">
<mml:math id="m13">
<mml:mrow>
<mml:mo>&#x223c;</mml:mo>
</mml:mrow>
</mml:math>
</inline-formula> 1.33).</p>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption>
<p>Forest plot of meta-analyses showing the effect of muscle strength.</p>
</caption>
<graphic xlink:href="fragi-06-1507232-g004.tif"/>
</fig>
</sec>
</sec>
</sec>
<sec sec-type="discussion" id="s4">
<title>4 Discussion</title>
<p>Exercise, as a clinical rehabilitation tool, can partially restore sensorimotor impairments accompanied by neuropathic symptoms and promote physical function. This review aims to evaluate the effectiveness of exercise interventions on postural control, gait characteristics, and muscle strength in older adults with DPN, and to provide evidence-based exercise recommendations.</p>
<sec id="s4-1">
<title>4.1 Effect of exercise on postural control</title>
<p>Impaired Balance is a strong risk factor for falls with a medium to large effect size (<xref ref-type="bibr" rid="B8">Chantanachai et al., 2021</xref>). In previous studies, these methods of balance testing had a high heterogeneity within or across settings (<xref ref-type="bibr" rid="B33">Perell et al., 2001</xref>), such as COP, TUG, BBS, OLS, and so on (<xref ref-type="bibr" rid="B6">Blodgett et al., 2022</xref>; <xref ref-type="bibr" rid="B33">Perell et al., 2001</xref>). Objective evaluation of postural control is usually based on the analysis COP using a force platform (<xref ref-type="bibr" rid="B6">Blodgett et al., 2022</xref>; <xref ref-type="bibr" rid="B35">Quijoux et al., 2020</xref>), as the gold standard for evaluation of balance. The velocity and sway area of COP were the best features for discriminating between fallers and non-fallers (<xref ref-type="bibr" rid="B33">Perell et al., 2001</xref>), and had a high correlation with the severity of neuropathy (<xref ref-type="bibr" rid="B7">Brown et al., 2015</xref>; <xref ref-type="bibr" rid="B33">Perell et al., 2001</xref>). In this review, three studies (<xref ref-type="bibr" rid="B26">Melai et al., 2014</xref>; <xref ref-type="bibr" rid="B11">Enders et al., 2023</xref>) included meta-analysis to estimate postural control between experimental and control groups and observed that could significantly decrease AP sway amplitude with EO and EC after balance training. Although studies presented stability in the ML direction as a key factor to differentiate high fall risk among older population (<xref ref-type="bibr" rid="B7">Brown et al., 2015</xref>), <xref ref-type="fig" rid="F2">Figure 2</xref> showed only COP sway path with EC had improved compared with EO.</p>
<p>Otherwise, five studies with other exercises were not included in the meta-analysis (<xref ref-type="bibr" rid="B40">Sartor et al., 2014</xref>; <xref ref-type="bibr" rid="B52">Zhao et al., 2021</xref>; <xref ref-type="bibr" rid="B10">Dixit et al., 2016</xref>; <xref ref-type="bibr" rid="B48">Venkataraman et al., 2019</xref>; <xref ref-type="bibr" rid="B51">Yoosefinejad et al., 2015</xref>). Dixit and coworkers only found that eight-week aerobic exercise could reduce COP sway velocity along the x-axis and increase ML displacement on foam with EC (<xref ref-type="bibr" rid="B10">Dixit et al., 2016</xref>). Zhao et al. also validated the effect of aerobic exercise significantly affected COP trajectory and elliptical area (<xref ref-type="bibr" rid="B52">Zhao et al., 2021</xref>). A study described a relatedly lower COP velocity measured by plantar pressure system after 12-week strength training (<xref ref-type="bibr" rid="B41">Sartor et al., 2012</xref>), but the number and quality of each study were relatively less. However, a meta-analysis reported that balance exercise intervention changed the COP parameters in either eyes or closed condition among older adults (age &#x3e; 60), while resistance and multi-component exercise did not (<xref ref-type="bibr" rid="B25">Low et al., 2017</xref>). What are the possible explanations for the relatively fewer changes observed in COP sway indicators of ML direction? A study showed that ML sway path length/velocity did not change in older adults after balance exercises (<xref ref-type="bibr" rid="B25">Low et al., 2017</xref>), similar to this review. Moreover, another review showed that ML data were found to be more discriminatory than AP features (<xref ref-type="bibr" rid="B35">Quijoux et al., 2020</xref>). The possible reasons were the small sample size and inconsistencies in the data collection protocols, leading to high heterogeneity (69%) of the ML sway path.</p>
<p>In conclusion, exercise interventions revealed a moderate to high effect on balance performance parameters compared to the control group, and balance training significantly improved postural control to a greater extent compared to other exercises. Balance exercise, in this review, included regular stability training, sensorimotor training, proprioception training, and combined training above. A review presented that sensorimotor training also plays a crucial role in targeting balance control and existing sensory and motor signs and symptoms of DPN (<xref ref-type="bibr" rid="B47">Streckmann et al., 2022</xref>).</p>
</sec>
<sec id="s4-2">
<title>4.2 Effect of exercise on gait performance</title>
<p>It is well known that gait performance, a natural daily activity heavily reliant on the synergy between the nervous and musculoskeletal systems, can be easily affected by the pathological process in older adults with DPN (<xref ref-type="bibr" rid="B50">Wang et al., 2022</xref>). Adults with DPN usually adopt a conservation gait with lower gait velocity, shorter stride length, longer stride time and stance time, compared with non-neuropathy diabetes (<xref ref-type="bibr" rid="B50">Wang et al., 2022</xref>). A study showed that exercise could significantly improve gait velocity compared to a control group, especially balance exercise (<xref ref-type="bibr" rid="B5">Allet et al., 2010</xref>). Some described that velocity and stride length effectively increased after 8-week sensorimotor exercise in older adults with DPN regardless of age (<xref ref-type="bibr" rid="B37">Reeves et al., 2021</xref>), similar to this review. In general, studies reported that lower walking speeds accompanied by increased falling risk in older adults, significantly discriminate between fallers and non-fallers (<xref ref-type="bibr" rid="B36">Reeves et al., 2017</xref>). Based on meta-analysis, balance exercise could more greatly increase gait velocity under both self-gait speed and fast-gait speed conditions than resistance training. Otherwise, this review reported that stride length only had an increase trend after exercise interventions. There was a potential factor that the sample size was small only 75 in the interventional group and 70 in the control group. Another reason was that cadence contributed 80% whereas stride length only contributed 20% to this change of gait velocity, resulting in difficulty regulating stride length (<xref ref-type="bibr" rid="B5">Allet et al., 2010</xref>).</p>
</sec>
<sec id="s4-3">
<title>4.3 Effect of exercise on muscle strength</title>
<p>Diabetes is responsible for the deterioration of muscle strength and becomes more severe as DPN progresses, leading to altered gait biomechanics, impaired stability and increased fall risks (<xref ref-type="bibr" rid="B31">Orlando et al., 2022</xref>). Some suggested that reduced strength of the knee and ankle may cause a disturbance in perturbation response in balance, potentially increasing the risk of falling. Although these results had a low level of quality and evidence, in this review, exercise could increase muscle strength and joint mobility in people with DPN, especially after foot-ankle functional training. Regarding the foot-ankle exercise, the exercise protocol is designed to consist of the same set: warm-up exercise, strengthening of the intrinsic foot muscles, strengthening of the extrinsic foot muscles, and functional exercise (e.g., balance and gait training), to manage the musculoskeletal complications related to diabetes (<xref ref-type="bibr" rid="B43">Silva et al., 2023</xref>; <xref ref-type="bibr" rid="B28">Monteiro et al., 2020</xref>). The observed phenomenon of reducing foot-ankle joint mobility and intrinsic muscle strength may be attributed to symptoms of distal peripheral neuropathy (<xref ref-type="bibr" rid="B30">Mustapa et al., 2016</xref>; <xref ref-type="bibr" rid="B50">Wang et al., 2022</xref>). Strength combined with functional training provided a better effect on increasing muscle strength of the lower extremity, compared to resistance training alone. Although resistance exercise was an effective intervention to combat muscle loss and delay some neurological symptoms (<xref ref-type="bibr" rid="B26">Melai et al., 2014</xref>; <xref ref-type="bibr" rid="B48">Venkataraman et al., 2019</xref>), people with neuropathy should be wary of weight-bearing exercise because of plantar loading links to potential foot ulcer development (<xref ref-type="bibr" rid="B22">Li and Hondzinski, 2012</xref>). Combinational exercises could more greatly improve metabolic control of the organism than aerobic and resistance training, similar to the previous study (<xref ref-type="bibr" rid="B31">Orlando et al., 2022</xref>). Improving foot functionality has a positive impact on people&#x2019;s overall physical activity levels and quality of life (<xref ref-type="bibr" rid="B47">Streckmann et al., 2022</xref>). Foot-ankle functional training significantly increased ankle joint ranges of motion including dorsiflexion and plantarflexion in older adults with DPN. That is the foot-ankle exercise program focused mainly on the foot joints of muscle strength and mobility in gait or dynamic activities.</p>
</sec>
<sec id="s4-4">
<title>4.4 Limitations of the study</title>
<p>This review has some limitations. The primary limitation is the focus on short-term outcomes, without accounting for the potential long-term benefits or risks associated with the interventions. Moreover, this study did not conduct subgroup analyses based on exercise types or exercise prescriptions (such as intensity, duration, frequency, etc.), and failed to provide detailed guidance for the implementation of specific exercise programs in the daily rehabilitation of DPN patients. Furthermore, although 23 studies were included in this review, the exercise modalities assessed were not evenly distributed. Most studies focused on balance training, followed by multi-component and foot-ankle functional exercises. In contrast, strength training and whole-body vibration training were represented by fewer studies. This uneven distribution may contribute to increased heterogeneity across the meta-analysis and limit the precision of the confidence intervals. Therefore, clinicians should interpret the results with caution when considering them for decision-making.</p>
</sec>
</sec>
<sec sec-type="conclusion" id="s5">
<title>5 Conclusion</title>
<p>Exercise is a fundamental intervention for older adults with DPN and significantly improves physical activity, measured by postural control, gait characteristics and muscle strength. Exercise could enhance postural control under the open eye and closed eye to prevent or reduce the risk of falls. Gait is a component of ability and skill for daily life. Exercise could effectively decrease the gait speed in walking, but did not improve the stride length with low-quality evidence. This study found that the muscle strength in the lower limbs was significantly enhanced after exercise among older adults with DPN.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="s6">
<title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec sec-type="author-contributions" id="s7">
<title>Author contributions</title>
<p>XP: Data curation, Investigation, Validation, Visualization, Writing &#x2013; original draft. DW: Data curation, Investigation, Software, Validation, Writing &#x2013; original draft. FZ: Visualization, Writing &#x2013; review and editing, Data curation, Validation. WL: Writing &#x2013; review and editing, Conceptualization, Methodology, Supervision. BG: Methodology, Supervision, Writing &#x2013; review and editing, Funding acquisition.</p>
</sec>
<sec sec-type="funding-information" id="s8">
<title>Funding</title>
<p>The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by the Key Research and Development Program of Zhejiang Province, 2022C03148.</p>
</sec>
<sec sec-type="COI-statement" id="s9">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="s10">
<title>Generative AI statement</title>
<p>The author(s) declare that no Generative AI was used in the creation of this manuscript.</p>
</sec>
<sec sec-type="disclaimer" id="s11">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec id="s12">
<title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fragi.2025.1507232/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fragi.2025.1507232/full&#x23;supplementary-material</ext-link>
</p>
<supplementary-material xlink:href="Table1.csv" id="SM1" mimetype="application/csv" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
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