{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T17:03:50Z","timestamp":1792343030544,"version":"4.4.0"},"reference-count":37,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Diabetes mellitus is defined as a group of metabolic diseases characterized by chronically elevated blood glucose levels. This condition influences the course of orthodontic treatment, as it affects various clinical aspects of the patient that must be taken into consideration prior to initiation. Therefore, achieving adequate control and management of diabetic patients undergoing orthodontic therapy is essential. This article presents a qualitative synthesis of studies addressing how diabetes affects orthodontic treatments, emphasizing the importance of understanding the necessary considerations prior to initiating treatment and how to manage potential complications. Methods: This systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A database search was performed on 5 May 2025, in PubMed, Scopus, Scielo, and The Cochrane Library, using terms related to \u201cdiabetes mellitus\u201d and \u201corthodontic treatments\u201d. Studies meeting the search criteria were included, particularly those that were published in the past ten years and reported on the influence of diabetes on orthodontic treatment. The quality of the case\u2013control studies was assessed using the Newcastle\u2013Ottawa Scale (NOS); for cross-sectional studies, the Joanna Briggs Institute (JBI) critical appraisal checklist was used; and for experimental studies, the SYRCLE\u2019s Risk of Bias Tool was applied. Results: Fourteen studies ultimately met the inclusion criteria. The evidence showed that diabetes increases gingival bleeding due to elevated levels of advanced glycation end-products (AGEs) and pro-inflammatory cytokines; reduces the efficiency of tooth movement; increases root resorption and affects bone remodeling; and compromises both periodontal and pulpal responses, thereby hindering tissue regeneration. It was also observed that the use of insulin or antidiabetic agents such as metformin may partially mitigate these adverse effects. Conclusions: This systematic review reveals a clear relationship between diabetes and various clinical aspects that influence the progression of orthodontic treatments. Nonetheless, further studies are needed to better understand the impact of this systemic condition on dental treatment outcomes.<\/jats:p>","DOI":"10.3390\/jcm14144879","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T11:26:37Z","timestamp":1752233197000},"page":"4879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Influence of Diabetes on Orthodontic Treatment: A Systematic Review of the Clinical Considerations and Challenges in Response"],"prefix":"10.3390","volume":"14","author":[{"given":"Paula","family":"Garc\u00eda-Rios","sequence":"first","affiliation":[{"name":"Gerodontolog\u00fd and Special Care Dentistry Unit, Morales Meseguer Hospital, Faculty of Medicine, University of Murcia, 30008 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0623-740X","authenticated-orcid":false,"given":"Francisco Javier","family":"Rodr\u00edguez-Lozano","sequence":"additional","affiliation":[{"name":"Gerodontolog\u00fd and Special Care Dentistry Unit, Morales Meseguer Hospital, Faculty of Medicine, University of Murcia, 30008 Murcia, Spain"},{"name":"Biomedical Research Institute of Murcia Pascual Parrilla\u2013IMIB, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Guerrero-Giron\u00e9s","sequence":"additional","affiliation":[{"name":"Gerodontolog\u00fd and Special Care Dentistry Unit, Morales Meseguer Hospital, Faculty of Medicine, University of Murcia, 30008 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel R.","family":"Pecci-Lloret","sequence":"additional","affiliation":[{"name":"Gerodontolog\u00fd and Special Care Dentistry Unit, Morales Meseguer Hospital, Faculty of Medicine, University of Murcia, 30008 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4490-3282","authenticated-orcid":false,"given":"Ricardo E.","family":"O\u00f1ate-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Gerodontolog\u00fd and Special Care Dentistry Unit, Morales Meseguer Hospital, Faculty of Medicine, University of Murcia, 30008 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"P\u00e9rez-Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Gerodontolog\u00fd and Special Care Dentistry Unit, Morales Meseguer Hospital, Faculty of Medicine, University of Murcia, 30008 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00508-022-02122-y","article-title":"Diabetes mellitus: Definition, classification, diagnosis, screening and prevention (Update 2023)","volume":"135","author":"Harreiter","year":"2023","journal-title":"Wien Klin. Wochenschr"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/ggi.14414","article-title":"Insulin-dependent diabetes mellitus in older adults: Current status and future prospects","volume":"22","author":"Ikegami","year":"2022","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1055\/a-1624-2897","article-title":"Definition, Classification and Diagnosis of Diabetes Mellitus","volume":"130","author":"Schleicher","year":"2022","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2025). 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. . Diabetes Care, 48, S27\u2013S49.","DOI":"10.2337\/dc25-S002"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12933-021-01289-4","article-title":"Variability of risk factors and diabetes complications","volume":"20","author":"Ceriello","year":"2021","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"278","DOI":"10.32641\/andespediatr.v94i3.4477","article-title":"[New Insulins for Type 1 Diabetes treatment]","volume":"94","author":"Araya","year":"2023","journal-title":"Andes Pediatr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.rce.2020.06.005","article-title":"Medical treatment of type 2 diabetes mellitus: Recommendations of the Diabetes, Obesity and Nutrition Group of the Spanish Society of Internal Medicine","volume":"221","author":"Ena","year":"2021","journal-title":"Rev. Clin. Esp."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Scribante, A., Butera, A., and Alovisi, M. (2022). Customized Minimally Invasive Protocols for the Clinical and Microbiological Management of the Oral Microbiota. Microorganisms, 10.","DOI":"10.3390\/microorganisms10040675"},{"key":"ref_10","first-page":"e46741","article-title":"Probiotics and Their Role in the Management of Type 2 Diabetes Mellitus (Short-Term Versus Long-Term Effect): A Systematic Review and Meta-Analysis","volume":"15","author":"Ayesha","year":"2023","journal-title":"Cureus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","article-title":"Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses","volume":"25","author":"Stang","year":"2010","journal-title":"Eur. J. Epidemiol."},{"key":"ref_13","first-page":"2127","article-title":"Methodological quality of case series studies: An introduction to the JBI critical appraisal tool","volume":"18","author":"Munn","year":"2020","journal-title":"JBI Evid. Synth."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hooijmans, C.R., Rovers, M.M., de Vries, R.B., Leenaars, M., Ritskes-Hoitinga, M., and Langendam, M.W. (2014). SYRCLE\u2019s risk of bias tool for animal studies. BMC Med. Res. Methodol, 14.","DOI":"10.1186\/1471-2288-14-43"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1186\/s13287-024-04058-8","article-title":"AGEs impair osteogenesis in orthodontic force-induced periodontal ligament stem cells through the KDM6B\/Wnt self-reinforcing loop","volume":"15","author":"Ying","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_16","first-page":"8351","article-title":"Effect of type 2 diabetes mellitus in adults undergoing fixed orthodontic treatment on proinflammatory chemokine profile and levels of advanced glycation in gingival crevicular fluid","volume":"26","author":"Alshahrani","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2319\/051120-420.1","article-title":"Levels of proinflammatory chemokines and advanced glycation end products in patients with type-2 diabetes mellitus undergoing fixed orthodontic treatment","volume":"91","author":"Alqerban","year":"2021","journal-title":"Angle Orthod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"233","DOI":"10.2319\/052823-382.1","article-title":"Salivary and crevicular fluid proinflammatory cytokines and advanced glycation end products in patients with different glycemic levels undergoing fixed orthodontic treatment","volume":"94","author":"Kamran","year":"2024","journal-title":"Angle Orthod."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.ajodo.2015.05.031","article-title":"Bone remodeling during orthodontic tooth movement in rats with type 2 diabetes","volume":"148","author":"Plut","year":"2015","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"349","DOI":"10.17219\/acem\/153956","article-title":"The impact of IGF-1 on alveolar bone remodeling and BMP-2 expression in orthodontic tooth movement in diabetic rats","volume":"32","author":"Wang","year":"2023","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/ocr.12117","article-title":"Effects of diabetes on tooth movement and root resorption after orthodontic force application in rats","volume":"19","author":"Arita","year":"2016","journal-title":"Orthod. Craniofacial Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/ocr.12340","article-title":"Diabetes mellitus and periodontitis: Inflammatory response in orthodontic tooth movement","volume":"23","author":"Santamaria","year":"2020","journal-title":"Orthod. Craniofacial Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/JPER.17-0190","article-title":"Periodontal response to orthodontic tooth movement in diabetes-induced rats with or without periodontal disease","volume":"89","author":"Ferreira","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1007\/s00784-020-03446-7","article-title":"Effects of diabetes on oxidative stress, periodontal ligament fiber orientation, and matrix metalloproteinase 8 and 9 expressions during orthodontic tooth movement","volume":"25","author":"Vicente","year":"2021","journal-title":"Clin. Oral Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s10266-021-00609-0","article-title":"Pulpal outcomes in orthodontic tooth movement in diabetes mellitus","volume":"109","author":"Bagne","year":"2021","journal-title":"Odontology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s10735-016-9707-y","article-title":"Histological evidence that metformin reverses the adverse effects of diabetes on orthodontic tooth movement in rats","volume":"48","author":"Sun","year":"2017","journal-title":"J. Mol. Histol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/JPER.18-0140","article-title":"Metformin as an add-on to insulin improves periodontal response during orthodontic tooth movement in type 1 diabetic rats","volume":"90","author":"Cestari","year":"2019","journal-title":"J. Periodontol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Qi, J., Kitaura, H., Shen, W.R., Ogawa, S., Ohori, F., Noguchi, T., Marahleh, A., Nara, Y., Adya, P., and Mizoguchi, I. (2020). Effect of a DPP-4 Inhibitor on Orthodontic Tooth Movement and Associated Root Resorption. BioMed Res. Int., 2020.","DOI":"10.1155\/2020\/7189084"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Curto, A., Gomez-Polo, C., Curto, D., Munoz-Bruguier, M., Lorenzo-Luengo, M.C., and Montero, J. (2025). Influence of the metabolic control in patients with type 1 diabetes on their oral health status and the need for orthodontic treatment in a group of Spanish children (aged 6\u201312 years): A cross-sectional study. BMC Oral Health, 25.","DOI":"10.1186\/s12903-025-05541-1"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"S2285","DOI":"10.4103\/jpbs.jpbs_214_24","article-title":"Awareness of Orthodontists Toward Management of Orthodontic Patients Suffering with Diabetes Mellitus in Central India Population: A Cross-Sectional Survey","volume":"16","author":"Mhaske","year":"2024","journal-title":"J. Pharm Bioallied Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e12955","DOI":"10.1111\/eos.12955","article-title":"The onset of adenosine monophosphate-activated protein kinase activity on orthodontic tooth movement in rats with type 2 diabetes","volume":"131","author":"Huang","year":"2023","journal-title":"Eur. J. Oral Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/odi.14365","article-title":"Contribution of diabetes mellitus to periodontal inflammation during orthodontic tooth movement","volume":"30","author":"Chen","year":"2024","journal-title":"Oral Dis."},{"key":"ref_33","first-page":"570","article-title":"Correlation between HbA1c Levels and Periodontal Bacterial Load in Diabetic Patients with Fixed Retainers","volume":"50","author":"Bucur","year":"2024","journal-title":"Curr. Health Sci. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1067\/mod.2003.53","article-title":"Orthodontic treatment considerations in patients with diabetes mellitus","volume":"123","author":"Bensch","year":"2003","journal-title":"Am. J. Orthod. Dentofac. Orthop."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"77","DOI":"10.14740\/jocmr3285w","article-title":"Orthodontic Treatment Consideration in Diabetic Patients","volume":"10","author":"AlAlmadih","year":"2018","journal-title":"J. Clin. Med. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Koletsi, D., Iliadi, A., Papageorgiou, S.N., Konrad, D., and Eliades, T. (2020). Evidence on the effect of uncontrolled diabetes mellitus on orthodontic tooth movement. A systematic review with meta-analyses in pre-clinical in- vivo research. Arch Oral Biol., 115.","DOI":"10.1016\/j.archoralbio.2020.104739"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/idh.12821","article-title":"Probiotics for maintaining oral health during fixed orthodontic treatment: A systematic review and meta-analysis","volume":"23","author":"Robin","year":"2025","journal-title":"Int. J. Dent. Hyg."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/4879\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:07:23Z","timestamp":1760033243000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/14\/4879"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,9]]},"references-count":37,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14144879"],"URL":"https:\/\/doi.org\/10.3390\/jcm14144879","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,9]]}}}