Association of Irisin Circulating Level with Diabetic Retinopathy: A Case-Control Study

Abstract

Obesity and obesity induced type 2 diabetes development and progression have been associated with sedentary lifestyle. Irisin, a newly discovered myokine, has been demonstrated at lower levels in obese and type 2 diabetes patients compared to controls. The main aim of this study is to explore association of Irisin with diabetic retinopathy (DR). A total of 233 healthy and adults participated in this study. Participants were divided into four categories: a healthy control group and an age-match subset of patients with type 2 diabetes; a positive control group of patients with type 2 diabetes not affected by DR (No DR); and patients with type 2 diabetes affected by DR (non-proliferative DR (NPDR) and proliferative DR (PDR)). Plasma samples were quantified for Irisin measurement, lipid profile and HbA1c. Comparison of the age-matched groups of healthy controls and patients with type 2 diabetes revealed lower Irisin plasma level in type 2 diabetes group. Analyses revealed negative correlations of Irisin to HbA1c and LDL levels and positive correlation to HDL level. Comparing Irisin level in No DR and DR groups revealed a higher level in No DR group and analysis per DR classification indicated higher Irisin level in NPDR group. Our results demonstrate not only correlation of plasma Irisin level with DR stages, but also significantly different Irisin level among them. This is promising in terms of researching Irisin as a potential associating marker for type 2 diabetes and DR development and progression.

Key words

irisin - diabetes - diabetic retinopathy - metabolism - adipose tissue

Publikationsverlauf

Eingereicht: 15. Juni 2018
Eingereicht: 30. Juli 2018

Angenommen: 29. August 2018

Artikel online veröffentlicht:
17. September 2018

• References

• 1 Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world—a growing challenge. N Engl J Med 2007; 356: 213-215
• 2 Bjørge T, Engeland A, Tverdal A. Body mass index in adolescence in relation to cause-specific mortality: a follow-up of 230,000 Norwegian adolescents. Am J Epidemiol 2008; 168: 30-37
• 3 World Health Organization. Obesity and overweight. Retrieved from http://www.who.int/mediacentre/factsheets/en/ 2016;
• 4 World Health Organization. Prevalence of Obesity by Country. Retrieved from http://www.who.int/mediacentre/factsheets/en/ 2014;
• 5 Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes 2005; 54: 1615-1625
• 6 Nentwich MM, Ulbig MW. Diabetic retinopathy—ocular complications of diabetes mellitus. World J Diabetes 2015; 6: 489-499
• 7 International Diabetes Federation. IDF Diabetes Atlas. 8th edn Brussels, Belgium Retrieved from: http://www.diabetesatlas.org 2015
• 8 Frank RN. The Galactosemic Dog - a valid model for both early and late stages of diabetic-retinopathy. Arch Ophthalmol 1995; 113: 275-276
• 9 Crick RP, Khaw PT. The Retina. A textbook of clinical ophthalmology: a practical guide to disorders of the eyes and their management. New Jersey: World Scientific Publishing Co Inc.; 2003: 517-533
• 10 Pieczynski J, Grzybowski A. Review of diabetic retinopathy screening methods and programs adopted in different parts of the world. European Ophthalmic Review 2015; 9: 49-55
• 11 Zorena K, Raczynska D, Raczynska K. Biomarkers in diabetic retinopathy and the therapeutic implications. Mediators of inflammation 2013 Article ID 193604, 11 pages, 2013
• 12 Duh E, Aiello LP. Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox. Diabetes 1999; 48: 1899-1906
• 13 Jusufbegovic D, Mugavin MO, Schaal S. Evolution of controlling diabetic retinopathy: Changing trends in the management of diabetic macular edema at a single institution over the past decade. Retina 2015; 35: 929-934
• 14 Kriechbaum K, Prager S, Mylonas G. et al. Intravitreal bevacizumab (Avastin) versus triamcinolone (Volon A) for treatment of diabetic macular edema: one-year results. Eye (Lond) 2014; 28: 9-15
• 15 Schneider S, Ruderman N. Exercise and NIDDM (technical review). Diabetes care 1990; 13: 785-789
• 16 Horton ES. Exercise and physical training: effects on insulin sensitivity and glucose metabolism. Diabetes Metab Rev 1986; 2: 1-17
• 17 Reusch JE. Focus on insulin resistance in type 2 diabetes: therapeutic implications. Diabetes Educ 1998; 24: 188-193
• 18 Castillo-Quan JI. From white to brown fat through the PGC-1α-dependent myokine irisin: implications for diabetes and obesity. Dis Model Mech 2012; 5: 293-295
• 19 Bostrom P, Wu J, Jedrychowski MP. et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481: 463-468
• 20 Wenz T, Rossi SG, Rotundo RL. et al. Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging. Proc Natl Acad Sci USA 2009; 106: 20405-20410
• 21 Handschin C, Spiegelman BM. The role of exercise and PGC1α in inflammation and chronic disease. Nature 2008; 454: 463-469
• 22 Liu J. Irisin as an exercise-stimulated hormone binding crosstalk between organs. Eur Rev Med Pharmacol Sci 2015; 19: 316-321
• 23 Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84: 277-359
• 24 Huh JY, Panagiotou G, Mougios V. et al. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism 2012; 61: 1725-1738
• 25 Sanchis-Gomar F, Lippi G, Mayero S. et al. Irisin: A new potential hormonal target for the treatment of obesity and type 2 diabetes. J Diabetes 2012; 4: 196-196
• 26 Wu J, Spiegelman BM. Irisin ERKs the Fat. Diabetes 2014; 63: 381-383
• 27 Moreno-Navarrete JM, Ortega F, Serrano M. et al. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab 2013; 98: E769-E778
• 28 Liu JJ, Wong MD, Toy WC. et al. Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complications 2013; 27: 365-369
• 29 Liu JJ, Liu S, Wong MD. et al. Relationship between circulating irisin, renal function and body composition in type 2 diabetes. J Diabetes Complications 2014; 28: 208-213
• 30 Zhang Y, Li R, Meng Y. et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes 2014; 63: 514-525
• 31 Xiang L, Xiang G, Yue L. et al. Circulating irisin levels are positively associated with endothelium-dependent vasodilation in newly diagnosed type 2 diabetic patients without clinical angiopathy. Atherosclerosis 2014; 235: 328-333
• 32 Choi YK, Kim MK, Bae KH. et al. Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract 2013; 100: 96-101
• 33 Assyov Y, Gateva A, Tsakovaet A. et al. Irisin in the glucose continuum. Exp Clin Endocrinol Diabetes 2016; 124: 22-27
• 34 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
• 35 Rana KS, Arif M, Hill EJ. et al. Plasma irisin levels predict telomere length in healthy adults. Age (Dordr) 2014; 36: 995-1001
• 36 Zhang W, Chang L, Zhang C. et al. Irisin: A myokine with locomotor activity. Neurosci Lett 2015; 595: 7-11
• 37 Wu J, Boström P, Sparks LM. et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012; 150: 366-376
• 38 Oelmann S, Nauck M, Völzke H. et al. Circulating irisin concentrations are associated with a favourable lipid profile in the general population. PLoS One 2016; 11: e0154319
• 39 Ebert T, Focke D, Petroff D. et al. Serum levels of the myokine irisin in relation to metabolic and renal function. Eur J Endocrinol 2014; 170: 501-506
• 40 Wen MS, Wang CY, Lin SL. et al. Decrease in irisin in patients with chronic kidney disease. PLoS One 2013; 8: e64025
• 41 Zhu G, Wang J, Song M. et al. Irisin increased the number and improved the function of endothelial progenitor cells in diabetes mellitus mice. J Cardiovasc Pharmacol 2016; 68: 67-73
• 42 Li Z, Wang G, Zhu Y. et al. The relationship between circulating irisin levels and tissues AGE accumulation in type 2 diabetes patients. Biosci Rep 2017; 37: BSR20170213
• 43 Jenkins A, Joglekar MV, Hardikar AA. et al. Biomarkers in diabetic retinopathy. Rev Diabet Stud 2014; 12: 159-195
• 44 Ozturk BT, Bozkurt B, Kerimogluet H. et al. Effect of serum cytokines and VEGF levels on diabetic retinopathy and macular thickness. Mol Vis 2009; 15: 1906-1914
• 45 Gouni-Berthold I, Berthold HK, Huh JY. et al. Effects of lipid-lowering drugs on irisin in human subjects in vivo and in human skeletal muscle cells ex vivo. PLoS One 2013; 8: e72858