{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T15:48:26Z","timestamp":1772034506686,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>The aim of the study was to critically assess and review the latest evidence relating the associations between host defence peptides (HDPs), periodontal diseases (PD) and diabetes mellitus type 2 (DM2). To explore studies on HDPs, periodontal disease, and DM2, researchers utilised specific key phrases to search the electronic databases PubMed (National Library of Medicine), Embase (Ovid), Medline (EBSCO), and Dentistry and Oral Sciences (EBSCO). Quality assessment was conducted by means of the Newcastle Ottawa scale and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Following a thorough screening process, a total of 12 papers (4 case-control, 6 cross-sectional, 1 animal, and 1 in vitro) fulfilled the selection criteria and were included. The majority of research found that HDPs were upregulated in DM2 patients with PD. Three investigations, however, found that HDPs were downregulated in DM2 patients with PD. HDPs play a part in the pathophysiology of PD and DM2. Nonetheless, more human, animal and laboratory investigations are needed to fully understand validation of the link, as the evidence is limited. Understanding HDPs as common moderators is critical, aimed at unlocking their potential as therapeutic and diagnostic agents.<\/jats:p>","DOI":"10.3390\/diagnostics11122210","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T01:49:58Z","timestamp":1638150598000},"page":"2210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Host Defence Peptides in Diabetes Mellitus Type 2 Patients with Periodontal Disease. A Systematic Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2128-9010","authenticated-orcid":false,"given":"Muhammad Saad","family":"Shaikh","sequence":"first","affiliation":[{"name":"Department of Oral Biology, Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University, Karachi 75510, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5157-7067","authenticated-orcid":false,"given":"Muhammad Sohail","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry, College of Dentistry, Taibah University, Al Madinah Al Munawwarah 41311, Saudi Arabia"},{"name":"Department of Dental Materials, Islamic International Dental College, Riphah International University, Islamabad 44000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhan","family":"Saleem","sequence":"additional","affiliation":[{"name":"General Dentistry, Edith Cowan University, Perth, WA 6027, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4041-4083","authenticated-orcid":false,"given":"Ahmad","family":"Alnazzawi","sequence":"additional","affiliation":[{"name":"Department of Substitutive Dental Sciences, College of Dentistry, Taibah University, Al Madinah Al Munawwarah 41311, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohid Abrar","family":"Lone","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Sindh Institute of Oral Health Sciences, Jinnah Sindh Medical University, Karachi 75510, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Jawad Ali","family":"Bukhari","sequence":"additional","affiliation":[{"name":"Centre for Addiction and Mental Health, University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7998-7335","authenticated-orcid":false,"given":"Zohaib","family":"Khurshid","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics and Dental Implantology, College of Dentistry, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/prd.12104","article-title":"Molecular aspects of the pathogenesis of periodontitis","volume":"69","author":"Meyle","year":"2015","journal-title":"Periodontology 2000"},{"key":"ref_2","first-page":"84","article-title":"Antimicrobial peptides in periodontal innate defense","volume":"15","author":"Gorr","year":"2012","journal-title":"J. Clin. Periodontol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.2174\/138161209788682325","article-title":"The roles of antimicrobial peptides in innate host defense","volume":"15","author":"Diamond","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1002\/pro.2274","article-title":"A common landscape for membrane-active peptides","volume":"22","author":"Last","year":"2013","journal-title":"Protein Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.1600-051X.2010.01664.x","article-title":"Antimicrobial peptides and periodontal disease","volume":"38","author":"Gorr","year":"2011","journal-title":"J. Clin. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jsps.2015.02.015","article-title":"Oral antimicrobial peptides: Types and role in the oral cavity","volume":"24","author":"Khurshid","year":"2016","journal-title":"Saudi Pharm. J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Khurshid, Z., Naseem, M., Asiri, Y.I., Mali, M., Sannam Khan, R., Sahibzada, H.A., Zafar, M.S., Faraz Moin, S., and Khan, E. (2017). Significance and diagnostic role of antimicrobial cathelicidins (LL-37) peptides in oral health. Biomolecules, 7.","DOI":"10.3390\/biom7040080"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.2174\/1381612824666180403114615","article-title":"Human oral defensins antimicrobial peptides: A future promising antimicrobial drug","volume":"24","author":"Khurshid","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3131","DOI":"10.2174\/138161207782110453","article-title":"Defensin participation in innate and adaptive immunity","volume":"13","author":"Yang","year":"2007","journal-title":"Curr. Pharm. Des."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15127","DOI":"10.3402\/jom.v4i0.15127","article-title":"Understanding the roles of gingival beta-defensins","volume":"4","author":"Gursoy","year":"2012","journal-title":"J. Oral Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1902\/jop.2009.080645","article-title":"Gingival transcriptome patterns during induction and resolution of experimental gingivitis in humans","volume":"80","author":"Offenbacher","year":"2009","journal-title":"J. Periodontol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1902\/jop.2012.120321","article-title":"Influence of periodontal status and periodontopathogens on levels of oral human b-defensin-2 in saliva","volume":"84","author":"Pereira","year":"2013","journal-title":"J. Periodontol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.archoralbio.2013.01.003","article-title":"Salivary concentration of free LL-37 in edentulism, chronic periodontitis and healthy periodontium","volume":"58","author":"Davidopoulou","year":"2013","journal-title":"Arch. Oral Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/jcpe.13084","article-title":"The guardians of the periodontium-sequential and differential expression of antimicrobial peptides during gingival inflammation. Results from in vivo and in vitro studies","volume":"46","author":"Dommisch","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2020). 2. Classification and diagnosis of diabetes: Standards of Medical Care in Diabetes\u20142020. Diabetes Care, 43, S14\u2013S31.","DOI":"10.2337\/dc20-S002"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1600-0757.2012.00457.x","article-title":"Risk factors for periodontal disease","volume":"62","author":"Genco","year":"2013","journal-title":"Periodontology 2000"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/prd.12235","article-title":"Periodontal complications of hyperglycemia\/diabetes mellitus: Epidemiologic complexity and clinical challenge","volume":"78","author":"Kocher","year":"2018","journal-title":"Periodontol. 2000"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6497","DOI":"10.1111\/j.1742-4658.2009.07360.x","article-title":"Multifunctional host defense peptides: Antimicrobial peptides, the small yet big players in innate and adaptive immunity","volume":"276","author":"Auvynet","year":"2009","journal-title":"FEBS J."},{"key":"ref_19","first-page":"1098","article-title":"Functions of antimicrobial peptides in vertebrates","volume":"18","year":"2017","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S335","DOI":"10.2337\/dc11-s238","article-title":"Antimicrobial-sensing proteins in obesity and type 2 diabetes: The buffering efficiency hypothesis","volume":"34","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.humimm.2011.03.027","article-title":"Differential expression of antimicrobial peptides in active and latent tuberculosis and its relationship with diabetes mellitus","volume":"72","author":"Araujo","year":"2011","journal-title":"Hum. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1617-9625-11-10","article-title":"Cigarette smoke extract induces differential expression levels of beta-defensin peptides in human alveolar epithelial cells","volume":"11","author":"Pierson","year":"2013","journal-title":"Tob. Induc. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1172\/JCI31726","article-title":"Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice","volume":"117","author":"Aberg","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_24","first-page":"93","article-title":"Natural antimicrobial peptides as promising anti-HIV candidates","volume":"13","author":"Wang","year":"2012","journal-title":"Curr. Top. Pept. Protein Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"n160","DOI":"10.1136\/bmj.n160","article-title":"PRISMA 2020 explanation and elaboration: Updated guidance and exemplars for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"Br. Med. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"276","DOI":"10.11613\/BM.2012.031","article-title":"Interrater reliability: The kappa statistic","volume":"22","author":"McHugh","year":"2012","journal-title":"Biochem. Med."},{"key":"ref_27","unstructured":"Wells, G.A., Shea, B., O\u2019Connell, D.a., Peterson, J., Welch, V., Losos, M., and Tugwell, P. (2021, June 10). The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. Available online: www.ohri.ca\/programs\/clinical_epidemiology\/oxford.asp."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Modesti, P.A., Reboldi, G., Cappuccio, F.P., Agyemang, C., Remuzzi, G., Rapi, S., Perruolo, E., Parati, G., and ESH Working Group on CV Risk in Low Resource Settings (2016). Panethnic differences in blood pressure in Europe: A systematic review and meta-analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147601"},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"454","DOI":"10.4103\/0976-237X.123040","article-title":"Adrenomedullin, periodontitis, diabetes-unraveling the equivocal relationship: A clinicobiochemical cross-sectional study","volume":"4","author":"Suchetha","year":"2013","journal-title":"Contemp. Clin. Dent."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/jre.12029","article-title":"Gingival crevicular fluid levels of human beta-defensins 1 and 3 in subjects with periodontitis and\/or type 2 diabetes mellitus: A cross-sectional study","volume":"48","author":"Ertugrul","year":"2013","journal-title":"J. Periodontal Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.imbio.2015.06.013","article-title":"Overexpressions of hBD-2, hBD-3, and hCAP18\/LL-37 in gingiva of diabetics with periodontitis","volume":"220","author":"Gursoy","year":"2015","journal-title":"Immunobiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/scd.12296","article-title":"Evaluation of DEFB1 polymorphisms in individuals with chronic periodontitis and diabetes mellitus type 2 in a population of northeastern Brazil","volume":"38","author":"Almeida","year":"2018","journal-title":"Spec. Care Dent."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1007\/s00784-018-2469-z","article-title":"Gingival crevicular fluid levels of human beta-defensin-1 in type 2 diabetes mellitus and periodontitis","volume":"22","author":"Yilmaz","year":"2018","journal-title":"Clin. Oral Investig."},{"key":"ref_35","first-page":"813","article-title":"Comparison of salivary beta-defensin-2 levels in chronic periodontitis with or without diabetes","volume":"12","author":"Alex","year":"2019","journal-title":"Drug Invent. Today"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/jre.12013","article-title":"Gingival crevicular fluid adrenomedullin level in individuals with and without diabetes mellitus type 2","volume":"48","author":"Ertugrul","year":"2013","journal-title":"J. Periodontal Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1111\/odi.12996","article-title":"Quantitative gingival crevicular fluid proteome in type 2 diabetes mellitus and chronic periodontitis","volume":"25","author":"Marinho","year":"2019","journal-title":"Oral Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"92","DOI":"10.4103\/aam.aam_40_18","article-title":"Effect of scaling and root planing on gingival crevicular fluid levels of adrenomedullin in chronic periodontitis patients with and without diabetes mellitus type 2: A clinico-biochemical study","volume":"18","author":"Pragada","year":"2019","journal-title":"Ann. Afr. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1080\/00016357.2020.1715471","article-title":"Salivary human beta-defensins and cathelicidin levels in relation to periodontitis and type 2 diabetes mellitus","volume":"78","author":"Yilmaz","year":"2020","journal-title":"Acta Odontol. Scand."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1177\/1535370218766512","article-title":"Changes in advanced glycation end products, beta-defensin-3, and interleukin-17 during diabetic periodontitis development in rhesus monkeys","volume":"243","author":"Jiang","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1111\/jre.12741","article-title":"Advanced glycation end-products increase lipocalin 2 expression in human oral epithelial cells","volume":"55","author":"Kido","year":"2020","journal-title":"J. Periodontal Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2014). Diagnosis and classification of diabetes mellitus. Diabetes Care, 37, S81\u2013S90.","DOI":"10.2337\/dc14-S081"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"a007724","DOI":"10.1101\/cshperspect.a007724","article-title":"Connecting type 1 and type 2 diabetes through innate immunity","volume":"2","author":"Odegaard","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"S106","DOI":"10.1902\/jop.2013.1340011","article-title":"Diabetes and periodontal diseases: Consensus report of the Joint EFP\/AAP Workshop on Periodontitis and Systemic Diseases","volume":"84","author":"Chapple","year":"2013","journal-title":"J. Periodontol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"771","DOI":"10.2119\/molmed.2010.00091","article-title":"High-glucose environment inhibits p38MAPK signaling and reduces human \u03b2-3 expression in keratinocytes","volume":"17","author":"Lan","year":"2011","journal-title":"Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.bbrc.2006.12.037","article-title":"Glucose regulation of \u03b2-defensin-1 mRNA in human renal cells","volume":"353","author":"Malik","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1111\/cei.12316","article-title":"Markers of innate immune activity in patients with type 1 and type 2 diabetes mellitus and the effect of the anti-oxidant coenzyme Q 10 on inflammatory activity","volume":"177","author":"Brauner","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_48","first-page":"9128","article-title":"Relevance of \u03b1-defensins (HNP1-3) and defensin \u03b2-1 in diabetes","volume":"20","author":"Lengyel","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1177\/0022034513504217","article-title":"Beta-defensin-2 genomic copy number variation and chronic periodontitis","volume":"92","author":"Jaradat","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kiselar, J.G., Wang, X., Dubyak, G.R., El Sanadi, C., Ghosh, S.K., Lundberg, K., and Williams, W.M. (2015). Modification of \u03b2-Defensin-2 by dicarbonyls methylglyoxal and glyoxal inhibits antibacterial and chemotactic function in vitro. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130533"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1902\/jop.2006.050459","article-title":"Diabetes mellitus and periodontal diseases","volume":"77","author":"Mealey","year":"2006","journal-title":"J. Periodontol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12087","DOI":"10.1074\/jbc.M406313200","article-title":"Advanced glycation end products enhance expression of pro-apoptotic genes and stimulate fibroblast apoptosis through cytoplasmic and mitochondrial pathways","volume":"280","author":"Alikhani","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.2337\/diabetes.50.6.1495","article-title":"Requirement for p38 and p44\/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-\u03baB transcriptional activation and cytokine secretion","volume":"50","author":"Yeh","year":"2001","journal-title":"Diabetes"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/12\/2210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:36:25Z","timestamp":1760168185000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/12\/2210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,26]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["diagnostics11122210"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11122210","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,26]]}}}