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Horm Metab Res 2021; 53(05): 293-300
DOI: 10.1055/a-1475-4444
Review

Association Between Serum Irisin and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis

Rui Wang
1   Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
,
Hongyan Liu
1   Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
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Abstract

Irisin, an emerging adipokine, has been involved in the pathogenesis of type 2 diabetes mellitus (T2DM). However, previous studies evaluating the association between irisin and diabetic nephropathy (DN) showed inconsistent results. We performed a meta-analysis to evaluate the above association. Matched case-control studies evaluating the difference of serum irisin between T2DM patients with and without DN were identified via systematic search of PubMed, Embase, Cochranes’ Library, China National Knowledge Infrastructure, and WanFang databases from inception to December 5, 2020. A random-effects model or a fixed-effects model was used to pool the results according to the heterogeneity. Overall, thirteen matched case-control studies including 1735 T2DM patients were included. Results of meta-analysis showed that compared to T2DM patients with normoalbuminuria, those with microalbuminuria [10 studies, standard mean difference (SMD): 1.12, 95% confidence interval (CI): 0.48–1.77, p<0.001; I2=94%] and macroalbuminuria (10 studies, SMD: 1.86, 95% CI: 0.93–2.79, p<0.001; I2=97%) had significantly lower serum irisin. Besides, the serum level of irisin was significantly lower in T2DM patients with macroalbuminuria than those with microalbuminuria (10 studies, SMD: 0.91, 95% CI: 0.44–1.38, p<0.001; I2=90%). In addition, patients with estimated glomerular infiltration rate (eGFR)<60 ml/min 1.73 m2 had lower serum irisin compared to those with eGFR≥60 ml/min 1.73 m2 (4 studies, SMD: 0.89, 95% CI: 0.32–1.46, p=0.002; I2=91%). In conclusion, serum irisin may be associated with albuminuria and reduced eGFR in T2DM patients.

Key words

type 2 diabetes mellitus - diabetic nephropathy - irisin - adipokines - meta-analysis


Publication History

Received: 10 January 2021

Accepted after revision: 01 April 2021

Article published online:
07 May 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Bonner R, Albajrami O, Hudspeth J. et al. Diabetic Kidney Disease. Prim Care 2020; 47: 645-659
    CrossrefPubMedGoogle Scholar
  • 2 Pugliese G, Penno G, Natali A. et al. Diabetic kidney disease: New clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on “The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function”. Nutr Metab Cardiovasc Dis 2019; 29: 1127-1150
    CrossrefPubMedGoogle Scholar
  • 3 Abdelhafiz AH. Diabetic kidney disease in older people with type 2 diabetes mellitus: Improving prevention and treatment options. Drugs Aging 2020; 37: 567-584
    CrossrefPubMedGoogle Scholar
  • 4 Selby NM, Taal MW. An updated overview of diabetic nephropathy: Diagnosis, prognosis, treatment goals and latest guidelines. Diabetes Obes Metab 2020; 22: 3-15
    CrossrefPubMedGoogle Scholar
  • 5 Zhang XX, Kong J, Yun K. Prevalence of diabetic nephropathy among patients with type 2 diabetes mellitus in China: A meta-analysis of observational studies. J Diabetes Res. 2020 2315607.
    PubMedGoogle Scholar
  • 6 Jerums G, Panagiotopoulos S, Premaratne E. et al. Integrating albuminuria and GFR in the assessment of diabetic nephropathy. Nat Rev Nephrol 2009; 5: 397-406
    CrossrefPubMedGoogle Scholar
  • 7 Lin YC, Chang YH, Yang SY. et al. Update of pathophysiology and management of diabetic kidney disease. J Formos Med Assoc 2018; 117: 662-675
    CrossrefPubMedGoogle Scholar
  • 8 Fu H, Liu S, Bastacky SI. et al. Diabetic kidney diseases revisited: A new perspective for a new era. Mol Metab 2019; 30: 250-263
    CrossrefPubMedGoogle Scholar
  • 9 Maciorkowska M, Musialowska D, Malyszko J. Adropin and irisin in arterial hypertension, diabetes mellitus and chronic kidney disease. Adv Clin Exp Med 2019; 28: 1571-1575
    CrossrefPubMedGoogle Scholar
  • 10 Du XL, Jiang WX, Lv ZT. Lower circulating irisin level in patients with diabetes mellitus: A systematic review and meta-analysis. Horm Metab Res 2016; 48: 644-652
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Perakakis N, Triantafyllou GA, Fernandez-Real JM. et al. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol 2017; 13: 324-337
    CrossrefPubMedGoogle Scholar
  • 12 Polyzos SA, Anastasilakis AD, Efstathiadou ZA. et al. Irisin in metabolic diseases. Endocrine 2018; 59: 260-274
    CrossrefPubMedGoogle Scholar
  • 13 Martinez Munoz IY, Camarillo Romero EDS, Garduno Garcia JJ. Irisin a novel metabolic biomarker: present knowledge and future directions. Int J Endocrinol. 2018 7816806.
    PubMedGoogle Scholar
  • 14 Korta P, Pochec E, Mazur-Bialy A. Irisin as a multifunctional protein: implications for health and certain diseases. Medicina (Kaunas) 2019; 55: 485
    CrossrefPubMedGoogle Scholar
  • 15 Byun K, Lee S. The potential role of irisin in vascular function and atherosclerosis: A review. Int J Mol Sci 2020; 21: 7184
    CrossrefPubMedGoogle Scholar
  • 16 Zhang M, Chen P, Chen S. et al. The association of new inflammatory markers with type 2 diabetes mellitus and macrovascular complications: a preliminary study. Eur Rev Med Pharmacol Sci 2014; 18: 1567-1572
    PubMedGoogle Scholar
  • 17 Ali EY, Hegazy GA, Hashem EM. Evaluation of irisin, retinol-binding protein 4, and leptin serum levels as biomarkers of macrovascular complications involvement in Saudi type 2 diabetes mellitus. A case-control study. Saudi Med J 2020; 41: 1369-1374
    CrossrefPubMedGoogle Scholar
  • 18 Liu JJ, Liu S, Wong MD. et al. Relationship between circulating irisin, renal function and body composition in type 2 diabetes. J Diabetes Complicat 2014; 28: 208-213
    CrossrefPubMedGoogle Scholar
  • 19 Wang HH, Zhang XW, Chen WK. et al. Relationship between serum irisin levels and urinary albumin excretion in patients with type 2 diabetes. J Diabetes Complicat 2015; 29: 384-389
    CrossrefPubMedGoogle Scholar
  • 20 Hu W, Wang R, Li J. et al. Association of irisin concentrations with the presence of diabetic nephropathy and retinopathy. Ann Clin Biochem 2016; 53: 67-74
    CrossrefPubMedGoogle Scholar
  • 21 Liu Y, Jian L, Pan J. Study on the correlation between serum irisin and type 2 diabetic nephropathy. Chongqing Med J 2016; 45: 4243-4245
    PubMedGoogle Scholar
  • 22 Wang W, Wang S, Liu J. et al. The level of serum irisin and its influencing factors in diabetic kidney disease. Chin J Integr Tradit West Nephrol 2016; 17: 403-406
    PubMedGoogle Scholar
  • 23 Khidr EG, Ali SS, Elshafey MM. et al. Association of irisin and FNDC5 rs16835198 G>T gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy. An Egyptian pilot study. Gene 2017; 626: 26-31
    CrossrefPubMedGoogle Scholar
  • 24 Cha JJ, Min HS, Kim K. et al. Long-term study of the association of adipokines and glucose variability with diabetic complications. Korean J Intern Med 2018; 33: 367-382
    CrossrefPubMedGoogle Scholar
  • 25 Liu S, Duan R, Wu Y. et al. Correlation between irisin, betatrophin and type 2 diabetic nephropathy. Chin J Integr Tradit West Nephrol 2018; 19: 861-865
    PubMedGoogle Scholar
  • 26 Shelbaya S, Abu Shady MM, Nasr MS. et al. Study of irisin hormone level in type 2 diabetic patients and patients with diabetic nephropathy. Curr Diabetes Rev 2018; 14: 481-486
    CrossrefPubMedGoogle Scholar
  • 27 Zhang Y, Chen Y, Huang Y. et al. Relationship between serum irisin and senile diabetic nephropathy. Chin J Pract Med 2018; 45: 1-4
    PubMedGoogle Scholar
  • 28 Mageswari R, Sridhar MG, Nandeesha H. et al. Irisin and Visfatin Predicts Severity of Diabetic Nephropathy. Indian J Clin Biochem 2019; 34: 342-346
    CrossrefPubMedGoogle Scholar
  • 29 Xu Z, Jiang H, Chen X. et al. Correlation between irisin and type 2 diabetic nephropathy in elderly patients. Jiangsu Med J 2019; 45: 916-919
    PubMedGoogle Scholar
  • 30 Chen J, Liu M, Shan X. et al. Correlations of serum irisin with serum uric acids and urinary albumin-creatinine ratio in patients with type 2 diabetes mellitus. Chin J Gerontol 2020; 40: 716-719
    PubMedGoogle Scholar
  • 31 Stroup DF, Berlin JA, Morton SC. et al. Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008-2012
    CrossrefPubMedGoogle Scholar
  • 32 Higgins J, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration. 2011 www.cochranehandbook.org
    PubMedGoogle Scholar
  • 33 Jia W, Weng J, Zhu D. et al. Standards of medical care for type 2 diabetes in China 2019. Diabetes Metab Res Rev 2019; 35: e3158
    CrossrefPubMedGoogle Scholar
  • 34 Buse JB, Wexler DJ, Tsapas A. et al. Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2019; 2020: 487-493
    PubMedGoogle Scholar
  • 35 Wells GA, Shea B, O'Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2010 http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
    PubMedGoogle Scholar
  • 36 Higgins JP, Thompson SG, Deeks JJ. et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560
    CrossrefPubMedGoogle Scholar
  • 37 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558
    CrossrefPubMedGoogle Scholar
  • 38 Egger M, Davey Smith G, Schneider M. et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
    CrossrefPubMedGoogle Scholar
  • 39 Peng H, Wang Q, Lou T. et al. Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys. Nat Commun 2017; 8: 1493
    CrossrefPubMedGoogle Scholar
  • 40 Zhang R, Ji J, Zhou X. et al. Irisin Pretreatment Protects Kidneys against Acute Kidney Injury Induced by Ischemia/Reperfusion via Upregulating the Expression of Uncoupling Protein 2. Biomed Res Int 2020; 6537371
    PubMedGoogle Scholar
  • 41 Liu Y, Fu Y, Liu Z. et al. Irisin is induced in renal ischemia-reperfusion to protect against tubular cell injury via suppressing p53. Biochim Biophys Acta Mol Basis Dis 2020; 1866: 165792
    CrossrefPubMedGoogle Scholar
  • 42 Jin YH, Li ZY, Jiang XQ. et al. Irisin alleviates renal injury caused by sepsis via the NF-kappaB signaling pathway. Eur Rev Med Pharmacol Sci 2020; 24: 6470-6476
    PubMedGoogle Scholar
  • 43 Zhang J, Bi J, Ren Y. et al. Involvement of GPX4 in irisin's protection against ischemia reperfusion-induced acute kidney injury. J Cell Physiol 2021; 236: 931-945
    CrossrefPubMedGoogle Scholar
  • 44 Jia J, Yu F, Wei WP. et al. Relationship between circulating irisin levels and overweight/obesity: A meta-analysis. World J Clin Cases 2019; 7: 1444-1455
    CrossrefPubMedGoogle Scholar