Are circulating levels of the myokine irisin linked to type 2 diabetes? A systematic review and meta-analysis

BackgroundType II diabetes (T2DM) is one of the most prevalent metabolic disorders, and its multisystemic health consequences are widely known. Due to skeletal muscles ability to sequester a vast amount of glucose, muscle function and exercise have become a subject of much research into strategies to prevent and treat T2DM. Myokines are bioactive molecules released by muscle during contraction and involved in several biological processes such as metabolism, inflammation and behavior. Irisin, a recently discovered myokine, has been implicated in a vast array of physiological roles, including the ability to induce fat beiging. Since beige and brown fat both serve important roles in metabolic regulation, irisins role in the context of T2DM is the subject of ongoing investigations. MethodsWe systematically reviewed articles indexed in PubMed, Scopus and Web of Science that were published between 2011 and 2024, and compared circulating irisin levels in patients affected by T2DM and healthy subjects. As part of our systematic review of the literature, we performed meta-analysis of the data across all included articles, as well as stratified by body mass index (BMI), country of origin and by average irisin concentration in the control group. ResultsWe discovered great variability across the included studies in the average irisin levels detected, which spanned four orders of magnitude, hence the attempt at reducing variability by stratifying based on average levels in the control group. While the statistical power of our meta-analysis was decreased by the great variability in reported irisin concentrations, we nonetheless detected a consistent trend of decreased irisin concentration in T2DM patients compared with healthy controls, regardless of BMI, country of origin or average irisin concentration in the control group. ConclusionWith almost 60 articles included, ours is the first extensive systematic review and meta-analysis of irisin in T2DM, yet a highly statistically significant association between circulating irisin levels and T2DM could not be established due to the great variability of the data across include articles. Nonetheless we noticed a trend that is independent of BMI, suggesting a direct relationship between T2DM and irisin that is likely not secondary to diabetic sarcopenia. While our work encourages further research into irisins potential role in T2DM pathogenesis, the reproducibility of irisin detection methods in biological samples should be determined and standardized protocols should be made available to the research and clinical communities.