{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T15:13:25Z","timestamp":1782832405013,"version":"3.54.5"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Diabetic nephropathy (DN) is a major complication of diabetes, contributing significantly to end - stage renal disease. Irisin, an exercise - induced myokine, has been linked to metabolic disorders, but its relationship with DN remains unclear. This study aims to comprehensively and accurately explore the association between serum irisin levels and DN through a systematic review and meta - analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The research was conducted following the Meta - analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Multiple electronic databases, including Cochrane Library, Embase, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), and Wanfang Database, were systematically searched using relevant keywords related to irisin and DN. Studies were included if they were randomized controlled trials (RCTs) or observational studies that stratified Type 2 diabetes mellitus (T2DM) patients based on the presence or absence of DN, measured serum irisin levels in both groups, and provided data in a suitable format. Two independent reviewers performed literature screening, data extraction, and quality assessment. The Jadad scale was used for RCTs, and the Newcastle - Ottawa Scale (NOS) was applied for cohort and case - control studies. Statistical analysis was carried out using RevMan 5.3 software, with heterogeneity evaluated by Q and I\u00b2 tests, and appropriate models (fixed - effects or random - effects) selected accordingly. INPLASY registration number:202530056.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of seven studies, comprising 453 DN patients and 346 non-DN controls, were included in the final meta-analysis. The pooled results demonstrated that serum irisin levels were significantly lower in patients with diabetic nephropathy, particularly those with more advanced stages of albuminuria. Specifically, irisin levels were significantly reduced in patients with microalbuminuria (MD = 30.84, 95% CI: 7.81 to 53.87, I\u00b2 = 96%) and macroalbuminuria (MD = 30.84, 95% CI: 7.81 to 53.87, I\u00b2 = 98%) compared to those with normoalbuminuria. Furthermore, a direct comparison between microalbuminuria and macroalbuminuria also revealed significantly lower irisin levels in the latter group (MD = 12.53, 95% CI: 3.46 to 21.59, I\u00b2 = 89%). In terms of renal function, patients with eGFR &amp;lt; 60 mL\/min\/1.73 m\u00b2 exhibited lower irisin concentrations than those with preserved renal function (MD = 3.43, 95% CI: \u20132.90 to 9.75, I\u00b2 = 90%), though this difference was not statistically significant. Given the substantial heterogeneity among the included studies, random-effects models were applied for all analyses. Funnel plot assessment showed general symmetry in most comparisons, indicating a low to moderate risk of publication bias, although asymmetry was observed in the microalbuminuria vs. macroalbuminuria subgroup, suggesting potential small-study effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This meta-analysis provides evidence for an association between serum irisin levels and DN. Lower serum irisin levels were related to more severe albuminuria and decreased eGFR in T2DM patients. However, considering the limitations of this study, such as potential missing data and methodological differences, further large - scale, multi-center, and high-quality RCTs are needed to validate these findings and elucidate the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p><jats:uri>INPLASY.COM<\/jats:uri>, identifier 202530056.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1599423","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:13:45Z","timestamp":1756268025000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Correlation of serum irisin levels with diabetic nephropathy: an exhaustive systematic appraisal and meta-analytical investigation"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuan","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhui","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-020-00739-8","article-title":"Atherogenic dyslipidemia and diabetic nephropathy","volume":"33","author":"Russo","year":"2020","journal-title":"J Nephrol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"458","DOI":"10.3390\/jcm9020458","article-title":"Inflammatory targets in diabetic nephropathy","volume":"9","author":"Donate-Correa","year":"2020","journal-title":"J Clin Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2021.09.003","article-title":"Pyroptosis in diabetic nephropathy","volume":"523","author":"Al","year":"2021","journal-title":"Clin Chim Acta"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-4939-9841-8_1","article-title":"Diabetic nephropathy: an overview","volume":"2067","author":"Sagoo","year":"2020","journal-title":"Methods Mol Biol"},{"key":"B5","first-page":"1202","article-title":"Up-date on diabetic nephropathy","volume":"12","author":"elle","year":"2022","journal-title":"Life (Basel)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00943","article-title":"Diabetic nephropathy: perspective on extracellular vesicles","volume":"11","author":"Lu","year":"2020","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"378","DOI":"10.3390\/jcm11020378","article-title":"Therapeutic advances in diabetic nephropathy","volume":"11","author":"Sawaf","year":"2022","journal-title":"J Clin Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3319056","DOI":"10.1155\/2022\/3319056","article-title":"Irisin Promotes Osteogenesis by Modulating Oxidative Stress and Mitophagy through SIRT3 Signaling under Diabetic Conditions","volume":"2022","author":"Li","year":"2022","journal-title":"Oxid Med Cell LONGEV"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1042\/CS20150009","article-title":"Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K\/Akt pathway in type 2 diabetic mice and hepatocytes","volume":"129","author":"Liu","year":"2015","journal-title":"Clin Sci (Lond)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9743","article-title":"Irisin regulates the expression of BDNF and glycometabolism in diabetic rats","volume":"19","author":"Huang","year":"2019","journal-title":"Mol Med Rep"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13813455.2023.2173785","article-title":"Irisin expression and FNDC5 (rs3480) gene polymorphism in type 2 diabetic patients with and without CAD","volume":"2023","author":"Foad","year":"","journal-title":"Arch Physiol Biochem"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/902186","article-title":"Irisin enhances osteoblast differentiation in vitro","volume":"2014","author":"Colaianni","year":"2014","journal-title":"Int J Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2013.09.011","article-title":"Relationship between circulating irisin, renal function and body composition in type 2 diabetes","volume":"28","author":"Liu","year":"2014","journal-title":"J Diabetes Complicat"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2015.01.001","article-title":"Relationship between serum irisin levels and urinary albumin excretion in patients with type 2 diabetes","volume":"29","author":"Wang","year":"2015","journal-title":"J Diabetes Complicat"},{"key":"B15","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1177\/0004563215582072","article-title":"Association of irisin concentrations with the presence of diabetic nephropathy and retinopathy","volume":"53","author":"Hu","year":"2016","journal-title":"Ann Clin Biochem"},{"key":"B16","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.gene.2017.05.010","article-title":"Association of irisin and FNDC5 rs16835198 G > T gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy. An Egyptian pilot study","volume":"626","author":"Khidr","year":"2017","journal-title":"Gene"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2016.114","article-title":"Long-term study of the association of adipokines and glucose variability with diabetic complications","volume":"33","author":"Cha","year":"2018","journal-title":"Korean J Intern Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-018-0749-7","article-title":"Irisin and visfatin predicts severity of diabetic nephropathy","volume":"34","author":"Mageswari","year":"2019","journal-title":"Indian J Clin Biochem"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2174\/1573399813666170829163442","article-title":"Study of irisin hormone level in type 2 diabetic patients and patients with diabetic nephropathy","volume":"14","author":"Shelbaya","year":"2018","journal-title":"Curr Diabetes Rev"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.3390\/biomedicines12081827","article-title":"Trajectory of irisin as a predictor of kidney-related outcomes in patients with asymptomatic heart failure","volume":"12","author":"Berezina","year":"2024","journal-title":"Biomedicines"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13810","article-title":"Transcriptional Intermediary Factor 1\u03b3-Induced Irisin in Skeletal Muscle Attenuates Renal Fibrosis in Diabetic Nephropathy","volume":"16","author":"Kim","year":"2025","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2379432","DOI":"10.1155\/2017\/2379432","article-title":"Diabetic nephropathy: from pathophysiology to treatment","volume":"2017","author":"Shen","year":"2017","journal-title":"J Diabetes Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2016.06.005","article-title":"Complication in diabetic nephropathy","volume":"10","author":"John","year":"2016","journal-title":"Diabetes Metab Syndr"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.21873\/invivo.13962","article-title":"High serum levels of irisin, visfatin and adiponectin as potential independent risk factors for diabetic nephropathy progression in patients with type 2 diabetes mellitus","volume":"39","author":"Elesawy","year":"2025","journal-title":"In Vivo"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.3390\/antiox12051088","article-title":"Diabetic nephropathy and gaseous modulators","volume":"12","author":"Juin","year":"2023","journal-title":"Antioxidants (Basel)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.yjmcc.2021.06.013","article-title":"FNDC5\/Irisin attenuates diabetic cardiomyopathy in a type 2 diabetes mouse model by activation of integrin alphaV\/beta5-AKT signaling and reduction of oxidative\/nitrosative stress","volume":"160","author":"Lin","year":"2021","journal-title":"J Mol Cell Cardiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1055\/a-1676-4118","article-title":"Serum irisin and diabetic nephropathy in patients with diabetes mellitus","volume":"53","author":"Kawada","year":"2021","journal-title":"Horm Metab Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1055\/a-1475-4444","article-title":"Association between serum irisin and diabetic nephropathy in patients with type 2 diabetes mellitus: A meta-analysis","volume":"53","author":"Wang","year":"2021","journal-title":"Horm Metab Res"},{"key":"B29","doi-asserted-by":"publisher","first-page":"9062","DOI":"10.1038\/s41598-022-13054-y","article-title":"Renal protection induced by physical exercise may be mediated by the irisin\/AMPK axis in diabetic nephropathy","volume":"12","author":"Formigari","year":"2022","journal-title":"Sci Rep"},{"key":"B30","doi-asserted-by":"publisher","first-page":"9062","DOI":"10.1038\/s41598-022-13054-y","article-title":"Renal protection induced by physical exercise may be mediated by the irisin\/AMPK axis in diabetic nephropathy","volume":"12","author":"Formigari","year":"2022","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1567179","DOI":"10.1155\/2019\/1567179","article-title":"Irisin attenuates neuroinflammation and prevents the memory and cognitive deterioration in streptozotocin-induced diabetic mice","volume":"2019","author":"Wang","year":"2019","journal-title":"Mediators Inflammation"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.3390\/antiox11071369","article-title":"Hydrogen sulfide regulates irisin and glucose metabolism in myotubes and muscle of HFD-fed diabetic mice","volume":"11","author":"Parsanathan","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2018.11.050","article-title":"The association between serum irisin levels and cardiovascular disease in diabetic patients","volume":"13","author":"Khorasani","year":"2019","journal-title":"Diabetes Metab Syndr"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e21859","DOI":"10.1016\/j.heliyon.2023.e21859","article-title":"Lower circulating irisin levels in type 2 diabetes mellitus patients with chronic complications: A meta-analysis","volume":"9","author":"Hou","year":"2023","journal-title":"Heliyon"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_202102_25095","article-title":"Cord blood and maternal serum preptin and irisin concentrations are regulated independently in GDM","volume":"25","author":"Ersahin","year":"2021","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B36","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/nrneph.2017.142","article-title":"Modelling diabetic nephropathy in mice","volume":"14","author":"Azushima","year":"2018","journal-title":"Nat Rev Nephrol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1599423\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:13:46Z","timestamp":1756268026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1599423\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,27]]},"references-count":36,"alternative-id":["10.3389\/fendo.2025.1599423"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1599423","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,27]]},"article-number":"1599423"}}