{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:59:46Z","timestamp":1790373586094,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spexin and galanin are neuropeptides involved in glucose homeostasis, insulin sensitivity, appetite, and energy metabolism. We conducted a systematic review and meta\u2010analysis to synthesise evidence on circulating spexin and galanin concentrations in patients with type 2 diabetes mellitus (T2DM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed\/MEDLINE, Scopus, and Web of Science were systematically searched from inception to March 22, 2026. Observational studies reporting circulating spexin and\/or galanin levels in adults with T2DM and non\u2010diabetic controls were included. Random\u2010effects meta\u2010analyses were performed to calculate pooled standardised mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses, meta\u2010regression, sensitivity analyses, prediction intervals, and publication bias assessments were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nineteen studies met the inclusion criteria. Thirteen studies (1453 T2DM and 850 controls) showed significantly lower circulating spexin levels in T2DM (SMD\u2009=\u2009\u22122.37, 95% CI: \u22123.21 to \u22121.53;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), with substantial heterogeneity (I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200998.3%). Four studies further showed reduced spexin levels in patients with diabetic complications compared with uncomplicated T2DM (SMD\u2009=\u2009\u22121.12, 95% CI: \u22121.75 to \u22120.49;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0005). Meta\u2010regression identified age as a significant moderator (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007), whereas BMI, HbA1c, sex, and publication year were not significant. Four studies (171 T2DM and 172 controls) revealed significantly elevated circulating galanin levels in T2DM (SMD\u2009=\u20091.35, 95% CI: 1.02\u20131.68;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) with moderate heterogeneity (I\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200947.2%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Circulating spexin levels are significantly decreased, whereas galanin levels are significantly increased in T2DM. These neuropeptides show potential as biomarkers of metabolic dysregulation and diabetic complications; however, the findings should be interpreted with caution owing to the very low certainty of the available evidence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70303","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:27:47Z","timestamp":1786364867000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuropeptide Alterations in Type 2 Diabetes Mellitus: A Meta\u2010Analysis of Circulating Spexin and Galanin Levels"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1202-6227","authenticated-orcid":false,"given":"Roshan Kumar","family":"Mahat","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Teerthanker Mahaveer Medical College &amp; Research Centre Teerthanker Mahaveer University  Moradabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8025-282X","authenticated-orcid":false,"given":"Sushil","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Teerthanker Mahaveer Medical College &amp; Research Centre Teerthanker Mahaveer University  Moradabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2737-2356","authenticated-orcid":false,"given":"Kahkashan","family":"Naaz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Shri Balaji Institute of Medical Sciences  Raipur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5223-7825","authenticated-orcid":false,"given":"Nand Kishor Prasad","family":"Sah","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy Teerthanker Mahaveer University  Moradabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3666-4090","authenticated-orcid":false,"given":"Amrendra P.","family":"Kushwaha","sequence":"additional","affiliation":[{"name":"Nepal Medical College and Teaching Hospital  Kathmandu Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43042\u2010025\u201000676\u2010w"},{"key":"e_1_2_13_3_1","volume-title":"IDF Diabetes Atlas","author":"International Diabetes Federation","year":"2025"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000035285"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2023.171096"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semerg.2025.102510"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010025\u201006596\u2010z"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986\u2010024\u201000790\u20103"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1086497"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201067624\u2010z"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255\u2010025\u201004556\u20105"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/4538199"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2021.170728"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.6026\/97320630017790"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.3.8661"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2004.08.029"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2011.02.023"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2012.05.016"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.03.001"},{"key":"e_1_2_13_20_1","unstructured":"G.Wells B.Shea D.O'Connell et\u00a0al. 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