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Horm Metab Res 2018; 50(11): 803-810
DOI: 10.1055/a-0748-6170
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Plasma Irisin Levels in Subjects with Type 1 Diabetes: Comparison with Healthy Controls

Anastasios Tentolouris
1   Diabetes Center, National and Kapodistrian University of Athens, Athens, Greece
,
Ioanna Eleftheriadou
1   Diabetes Center, National and Kapodistrian University of Athens, Athens, Greece
,
Dimitrios Tsilingiris
1   Diabetes Center, National and Kapodistrian University of Athens, Athens, Greece
,
Ioanna A. Anastasiou
1   Diabetes Center, National and Kapodistrian University of Athens, Athens, Greece
,
Ourania A. Kosta
1   Diabetes Center, National and Kapodistrian University of Athens, Athens, Greece
,
Iordanis Mourouzis
2   Department of Pharmacology, National and Kapodistrian University of Athens, Athens Greece
,
Alexandros Kokkinos
1   Diabetes Center, National and Kapodistrian University of Athens, Athens, Greece
,
Constantinos Pantos
2   Department of Pharmacology, National and Kapodistrian University of Athens, Athens Greece
,
Nikolaos Katsilambros
1   Diabetes Center, National and Kapodistrian University of Athens, Athens, Greece
,
Nikolaos Tentolouris
1   Diabetes Center, National and Kapodistrian University of Athens, Athens, Greece
› Author Affiliations
Further Information

Publication History

received 03 May 2018

accepted 11 September 2018

Publication Date:
04 October 2018 (online)

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Abstract

Irisin is a myokine that increases energy expenditure. In this cross-sectional study, we examined for differences in plasma irisin concentrations between subjects with type 1 diabetes mellitus and healthy individuals and searched for associations between plasma irisin levels and clinical and biochemical characteristics as well as self-reported physical activity. A total of 79 subjects with type 1 diabetes [age 38.2±12.5 years, men/women (n): 27/52], were consecutively recruited. Moreover, 53 healthy controls, matched for age and body mass index with those with diabetes were recruited. Plasma irisin was measured with ELISA. Participants were asked about their physical activity during the last week. We also measured trunk and visceral fat. Circulating irisin levels were lower in subjects with diabetes than in controls [median value (interquartile range): 53.0 (35.2, 106.3) vs. 178.1 (42.6, 641.6) ng/ml, respectively, p<0.001]. In the group of diabetes, univariate analysis showed that irisin levels were associated with waist circumference (beta=–0.283, p=0.023), serum triglycerides (beta=–0.282, p=0.031), and trunk fat (beta=–0.324, p=0.012). In multivariate analysis after adjustment for potential confounders, irisin levels were associated independently only with waist circumference (beta=–0.403, p=0.005). Among controls, multivariate analysis demonstrated that irisin levels were associated with pack-years of smoking (beta=–0.563, p=0.012) and fasting triglycerides (beta=–0.338, p=0.041). Circulating irisin levels were lower in subjects with diabetes in comparison with healthy-matched controls. In conclusion, plasma irisin concentrations in subjects with diabetes were associated with waist circumference, while in controls with serum triglycerides and pack-years of smoking.

Key words

type 1 diabetes - irisin - myokine - body fat
 

  • References

  • 1 Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481: 463-468
    PubMedGoogle Scholar
  • 2 Polyzos SA, Anastasilakis AD, Efstathiadou ZA, Makras P, Perakakis N, Kountouras J, Mantzoros CS. Irisin in metabolic diseases. Endocrine 2018; 59: 260-274
    CrossrefPubMedGoogle Scholar
  • 3 Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, Belen Crujeiras A, Seoane LM, Casanueva FF, Pardo M. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One 2013; 8: e60563
    Google Scholar
  • 4 Perakakis N, Triantafyllou GA, Fernandez-Real JM, Huh JY, Park KH, Seufert J, Mantzoros CS. Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol 2017; 13: 324-337
    CrossrefPubMedGoogle Scholar
  • 5 Castillo-Quan JI. From white to brown fat through the PGC-1alpha-dependent myokine irisin: implications for diabetes and obesity. Dis Model Mech 2012; 5: 293-295
    CrossrefPubMedGoogle Scholar
  • 6 Sahin-Efe A, Upadhyay J, Ko BJ, Dincer F, Park KH, Migdal A, Vokonas P, Mantzoros C. Irisin and leptin concentrations in relation to obesity, and developing type 2 diabetes: A cross sectional and a prospective case-control study nested in the Normative Aging Study. Metabolism 2018; 79: 24-32
    CrossrefPubMedGoogle Scholar
  • 7 Liu JJ, Wong MD, Toy WC, Tan CS, Liu S, Ng XW, Tavintharan S, Sum CF, Lim SC. Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complicat 2013; 27: 365-369
    Google Scholar
  • 8 Hu W, Wang R, Li J, Zhang J, Wang W. Association of irisin concentrations with the presence of diabetic nephropathy and retinopathy. Ann Clin Biochem 2016; 53: 67-74
    CrossrefPubMedGoogle Scholar
  • 9 Assyov Y, Gateva A, Tsakova A, Kamenov Z. Irisin in the Glucose Continuum. Exp Clin Endocrinol Diabetes 2016; 124: 22-27
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Shoukry A, Shalaby SM, El-Arabi Bdeer S, Mahmoud AA, Mousa MM, Khalifa A. Circulating serum irisin levels in obesity and type 2 diabetes mellitus. IUBMB Life 2016; 68: 544-556
    Google Scholar
  • 11 Moreno-Navarrete JM, Ortega F, Serrano M, Guerra E, Pardo G, Tinahones F, Ricart W, Fernandez-Real JM. 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
    CrossrefPubMedGoogle Scholar
  • 12 Zhang C, Ding Z, Lv G, Li J, Zhou P, Zhang J. Lower irisin level in patients with type 2 diabetes mellitus: A case-control study and meta-analysis. J Diabetes 2016; 8: 56-62
    CrossrefPubMedGoogle Scholar
  • 13 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
  • 14 Duran ID, Gulcelik NE, Unal M, Topcuoglu C, Sezer S, Tuna MM, Berker D, Guler S. Irisin levels in the progression of diabetes in sedentary women. Clin Biochem 2015; 48: 1268-1272
    CrossrefPubMedGoogle Scholar
  • 15 Akour A, Kasabri V, Boulatova N, Bustanji Y, Naffa R, Hyasat D, Khawaja N, Bustanji H, Zayed A, Momani M. Levels of metabolic markers in drug-naive prediabetic and type 2 diabetic patients. Acta Diabetol 2017; 54: 163-170
    CrossrefPubMedGoogle Scholar
  • 16 Espes D, Lau J, Carlsson PO. Increased levels of irisin in people with long-standing Type 1 diabetes. Diabet Med 2015; 32: 1172-1176
    CrossrefPubMedGoogle Scholar
  • 17 Ates I, Arikan MF, Erdogan K, Kaplan M, Yuksel M, Topcuoglu C, Yilmaz N, Guler S. Factors associated with increased irisin levels in the type 1 diabetes mellitus. Endocr Regul 2017; 51: 1-7
    CrossrefPubMedGoogle Scholar
  • 18 Buscemi S, Corleo D, Vasto S, Buscemi C, Massenti MF, Nuzzo D, Lucisano G, Barile AM, Rosafio G, Maniaci V, Giordano C. Factors associated with circulating concentrations of irisin in the general population cohort of the ABCD study. Int J Obes (Lond) 2018; 42: 398-404
    CrossrefPubMedGoogle Scholar
  • 19 Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, Mantzoros CS. 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
    Google Scholar
  • 20 American Diabetes Association . 2. Classification and Diagnosis of Diabetes. Diabetes Care 2017; 40 (Suppl. 01) S11-S24
    CrossrefPubMedGoogle Scholar
  • 21 World Medical Association . World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013; 310: 2191-2194
    Google Scholar
  • 22 Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F. Task Force M . 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2013; 31: 1281-1357
    CrossrefPubMedGoogle Scholar
  • 23 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
    CrossrefPubMedGoogle Scholar
  • 24 Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461-470
    CrossrefPubMedGoogle Scholar
  • 25 American Diabetes Association . Erratum. Microvascular Complications and Foot Care. Sec. 10. In Standards of Medical Care in Diabetes-2017. Diabetes Care 2017; 40 01 S88-S98 Diabetes Care 2017; 40: 986
    CrossrefPubMedGoogle Scholar
  • 26 Panagiotakos DB, Pitsavos C, Arvaniti F, Stefanadis C. Adherence to the Mediterranean food pattern predicts the prevalence of hypertension, hypercholesterolemia, diabetes and obesity, among healthy adults; The accuracy of the MedDietScore. Prev Med 2007; 44: 335-340
    CrossrefPubMedGoogle Scholar
  • 27 Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 2003; 35: 1381-1395
    CrossrefPubMedGoogle Scholar
  • 28 Handschin C, Choi CS, Chin S, Kim S, Kawamori D, Kurpad AJ, Neubauer N, Hu J, Mootha VK, Kim YB, Kulkarni RN, Shulman GI, Spiegelman BM. Abnormal glucose homeostasis in skeletal muscle-specific PGC-1alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk. J Clin Invest 2007; 117: 3463-3474
    CrossrefPubMedGoogle Scholar
  • 29 Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T, Schering L, Lee S, Brenmoehl J, Thomas S, Drevon CA, Erickson HP, Maak S. Irisin - A myth rather than an exercise-inducible myokine. Sci Rep 2015; 5: 8889
    CrossrefPubMedGoogle Scholar
  • 30 Polyzos SA, Mantzoros CS. An update on the validity of irisin assays and the link between irisin and hepatic metabolism. Metabolism 2015; 64: 937-942
    CrossrefPubMedGoogle Scholar
  • 31 Bostrom PA, Fernandez-Real JM, Mantzoros C. Irisin in humans: recent advances and questions for future research. Metabolism 2014; 63: 178-180
    CrossrefPubMedGoogle Scholar
  • 32 Sanchis-Gomar F, Alis R, Pareja-Galeano H, Romagnoli M, Perez-Quilis C. Inconsistency in circulating irisin levels: what is really happening?. Horm Metab Res 2014; 46: 591-596
    Google Scholar
  • 33 Xie X, Gao T, Yang M, Chen P, Jin H, Yang L, Yu X. Associations of betatrophin levels with irisin in Chinese women with normal glucose tolerance. Diabetol Metab Syndr 2015; 7: 26
    CrossrefPubMedGoogle Scholar
  • 34 Stengel A, Hofmann T, Goebel-Stengel M, Elbelt U, Kobelt P, Klapp BF. Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity–correlation with body mass index. Peptides 2013; 39: 125-130
    Google Scholar
  • 35 Pardo M, Crujeiras AB, Amil M, Aguera Z, Jimenez-Murcia S, Banos R, Botella C, de la Torre R, Estivill X, Fagundo AB, Fernandez-Real JM, Fernandez-Garcia JC, Fruhbeck G, Gomez-Ambrosi J, Rodriguez R, Tinahones FJ, Fernandez-Aranda F, Casanueva FF. Association of irisin with fat mass, resting energy expenditure, and daily activity in conditions of extreme body mass index. Int J Endocrinol 2014; 857270:
    PubMed
  • 36 Deng W. Association of Serum Irisin Concentrations with Presence and Severity of Coronary Artery Disease. Med Sci Monit 2016; 22: 4193-4197
    CrossrefPubMedGoogle Scholar
  • 37 Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U, Brockmann B, Jung R, Wisloff U, Tjonna AE, Raastad T, Hallen J, Norheim F, Drevon CA, Romacho T, Eckardt K, Eckel J. Evidence against a beneficial effect of irisin in humans. PLoS One 2013; 8: e73680
    CrossrefPubMedGoogle Scholar
  • 38 Kurdiova T, Balaz M, Mayer A, Maderova D, Belan V, Wolfrum C, Ukropec J, Ukropcova B. Exercise-mimicking treatment fails to increase Fndc5 mRNA & irisin secretion in primary human myotubes. Peptides 2014; 56: 1-7
    CrossrefPubMedGoogle Scholar
  • 39 Peterson JM, Mart R, Bond CE. Effect of obesity and exercise on the expression of the novel myokines, Myonectin and Fibronectin type III domain containing 5. Peer J 2014; 2: e605
    CrossrefPubMedGoogle Scholar
  • 40 Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, Gulseth HL, Birkeland KI, Jensen J, Drevon CA. The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J 2014; 281: 739-749
    CrossrefPubMedGoogle Scholar
  • 41 Pekkala S, Wiklund PK, Hulmi JJ, Ahtiainen JP, Horttanainen M, Pollanen E, Makela KA, Kainulainen H, Hakkinen K, Nyman K, Alen M, Herzig KH, Cheng S. Are skeletal muscle FNDC5 gene expression and irisin release regulated by exercise and related to health?. J Physiol 2013; 591: 5393-5400
    CrossrefPubMedGoogle Scholar
  • 42 Moraes C, Leal VO, Marinho SM, Barroso SG, Rocha GS, Boaventura GT, Mafra D. Resistance exercise training does not affect plasma irisin levels of hemodialysis patients. Horm Metab Res 2013; 45: 900-904
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Huh JY, Siopi A, Mougios V, Park KH, Mantzoros CS. Irisin in response to exercise in humans with and without metabolic syndrome. J Clin Endocrinol Metab 2015; 100: E453-E457
    Google Scholar
  • 44 Loffler D, Muller U, Scheuermann K, Friebe D, Gesing J, Bielitz J, Erbs S, Landgraf K, Wagner IV, Kiess W, Korner A. Serum irisin levels are regulated by acute strenuous exercise. J Clin Endocrinol Metab 2015; 100: 1289-1299
    CrossrefPubMedGoogle Scholar
  • 45 Huh JY, Mougios V, Skraparlis A, Kabasakalis A, Mantzoros CS. Irisin in response to acute and chronic whole-body vibration exercise in humans. Metabolism 2014; 63: 918-921
    CrossrefPubMedGoogle Scholar
  • 46 Al-Daghri NM, Alokail MS, Rahman S, Amer OE, Al-Attas OS, Alfawaz H, Tripathi G, Sabico S, Chrousos GP, McTernan PG, Piya MK. Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2. Eur J Clin Invest 2015; 45: 775-781
    CrossrefPubMedGoogle Scholar
  • 47 Kraemer RR, Shockett P, Webb ND, Shah U, Castracane VD. A transient elevated irisin blood concentration in response to prolonged, moderate aerobic exercise in young men and women. Horm Metab Res 2014; 46: 150-154
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Bonfante IL, Chacon-Mikahil MP, Brunelli DT, Gaspari AF, Duft RG, Lopes WA, Bonganha V, Libardi CA, Cavaglieri CR. Combined training, FNDC5/irisin levels and metabolic markers in obese men: A randomised controlled trial. Eur J Sport Sci 2017; 17: 629-637
    CrossrefPubMedGoogle Scholar
  • 49 Anastasilakis AD, Polyzos SA, Saridakis ZG, Kynigopoulos G, Skouvaklidou EC, Molyvas D, Vasiloglou MF, Apostolou A, Karagiozoglou-Lampoudi T, Siopi A, Mougios V, Chatzistavridis P, Panagiotou G, Filippaios A, Delaroudis S, Antzoros CS. Circulating irisin in healthy, young individuals: day-night rhythm, effects of food intake and exercise, and associations with gender, physical activity, diet, and body composition. J Clin Endocrinol Metab 2014; 99: 3247-3255
    CrossrefPubMedGoogle Scholar