Deng Yuan, Shen Yinhui, Wu Yuchen, Wen Min, Wang Fang
Department of Nursing, Yueyang Vocational Technical College, Yueyang, China.
School of Health Management, Xianning Vocational Technical College, Xianning, China.
Front Endocrinol (Lausanne). 2025 Aug 27;16:1599423. doi: 10.3389/fendo.2025.1599423. eCollection 2025.
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.
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 I² tests, and appropriate models (fixed - effects or random - effects) selected accordingly. INPLASY registration number:202530056.
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, I² = 96%) and macroalbuminuria (MD = 30.84, 95% CI: 7.81 to 53.87, I² = 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, I² = 89%). In terms of renal function, patients with eGFR < 60 mL/min/1.73 m² exhibited lower irisin concentrations than those with preserved renal function (MD = 3.43, 95% CI: -2.90 to 9.75, I² = 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.
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.
INPLASY.COM, identifier 202530056.
糖尿病肾病（DN）是糖尿病的主要并发症，是终末期肾病的重要原因。鸢尾素是一种运动诱导的肌动蛋白，与代谢紊乱有关，但其与DN的关系尚不清楚。本研究旨在通过系统评价和荟萃分析全面、准确地探讨血清鸢尾素水平与DN之间的关联。
本研究按照流行病学观察性研究的荟萃分析（MOOSE）指南进行。使用与鸢尾素和DN相关的关键词，对多个电子数据库进行系统检索，包括Cochrane图书馆、Embase、Web of Science、PubMed、中国知网（CNKI）、中国生物医学光盘数据库（CBM）和万方数据库。纳入的研究需为随机对照试验（RCT）或观察性研究，这些研究根据2型糖尿病（T2DM）患者是否存在DN进行分层，测量两组患者的血清鸢尾素水平，并以合适的格式提供数据。两名独立的评审员进行文献筛选、数据提取和质量评估。RCT使用Jadad量表，队列研究和病例对照研究使用纽卡斯尔-渥太华量表（NOS）。使用RevMan 5.3软件进行统计分析，通过Q检验和I²检验评估异质性，并相应选择合适的模型（固定效应或随机效应）。INPLASY注册号：202530056。
最终的荟萃分析共纳入7项研究，包括453例DN患者和346例非DN对照。汇总结果表明，糖尿病肾病患者的血清鸢尾素水平显著降低，尤其是白蛋白尿较严重阶段的患者。具体而言，与正常白蛋白尿患者相比，微量白蛋白尿患者（MD = 30.84，95%CI：7.81至53.87，I² = 96%）和大量白蛋白尿患者（MD = 30.84，95%CI：7.81至53.87，I² = 98%）的鸢尾素水平显著降低。此外，微量白蛋白尿和大量白蛋白尿之间的直接比较也显示，后者的鸢尾素水平显著较低（MD = 12.53，95%CI：3.46至21.59，I² = 89%）。在肾功能方面，估算肾小球滤过率（eGFR）<60 mL/min/1.73 m²的患者的鸢尾素浓度低于肾功能正常的患者（MD = 3.43，95%CI：-2.90至9.75，I² = 90%），尽管这种差异无统计学意义。鉴于纳入研究之间存在显著异质性，所有分析均采用随机效应模型。漏斗图评估显示，大多数比较具有总体对称性，表明发表偏倚风险较低至中等，尽管在微量白蛋白尿与大量白蛋白尿亚组中观察到不对称性，提示可能存在小研究效应。
本荟萃分析为血清鸢尾素水平与DN之间的关联提供了证据。较低的血清鸢尾素水平与T2DM患者更严重的白蛋白尿和eGFR降低有关。然而，考虑到本研究的局限性，如可能存在的数据缺失和方法学差异，需要进一步开展大规模、多中心和高质量的RCT来验证这些发现并阐明潜在机制。
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