Skip to main content
Erschienen in: Acta Diabetologica 5/2014

01.10.2014 | Original Article

High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects

verfasst von: G. Sesti, F. Andreozzi, T. V. Fiorentino, G. C. Mannino, A. Sciacqua, M. A. Marini, F. Perticone

Erschienen in: Acta Diabetologica | Ausgabe 5/2014

Einloggen, um Zugang zu erhalten

Abstract

Irisin, a novel myokine, was proposed to be able to regulate glucose homeostasis and obesity in mice. Whether irisin levels are associated with cardio-metabolic variables, insulin sensitivity, and vascular atherosclerosis in humans remain unsettled. To determine the associations between circulating irisin levels, cardio-metabolic variables, insulin sensitivity, and common carotid intima-media thickness (IMT), an indicator of vascular atherosclerosis, a cross-sectional evaluation of circulating irisin levels and cardio-metabolic variables in 192 White adults was conducted. Insulin sensitivity and insulin clearance were assessed by euglycemic–hyperinsulinemic clamp. Common carotid IMT was measured by ultrasound. After adjusting for age and gender, irisin levels were positively correlated with body fat mass (r = 0.12, P < 0.05), fasting (r = 0.17, P < 0.01), 2 h post-load insulin (r = 0.15, P < 0.02) levels, and IMT (r = 0.29, P < 0.0001) and were negatively correlated with insulin-stimulated glucose disposal (r = −0.18, P = 0.007), Matsuda index (r = −0.13, P < 0.04), disposition index (r = −0.278, P < 0.0001), and insulin clearance (r = −0.26, P < 0.0001). After adjusting for age, gender, and BMI, individuals in the highest tertile of irisin levels exhibited higher body fat mass (P < 0.01), fasting (P < 0.05), 2 h post-load (P < 0.01) insulin levels, carotid IMT (P < 0.001), lower insulin-stimulated glucose disposal (P < 0.001), Matsuda index (P < 0.01), disposition index (P < 0.01), and insulin clearance (P < 0.001) as compared with subjects in the lowest tertile of circulating irisin levels. Irisin is inversely associated with insulin sensitivity and positively associated with carotid IMT in humans, suggesting either increased release by adipose/muscle tissue in response to deterioration of insulin sensitivity or a compensatory increase in irisin to overcome an underlying irisin resistance.
Literatur
1.
Zurück zum Zitat Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief 82:1–8PubMed Ogden CL, Carroll MD, Kit BK, Flegal KM (2012) Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief 82:1–8PubMed
2.
Zurück zum Zitat Alberti KG, Eckel RH, Grundy SM et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645CrossRefPubMed Alberti KG, Eckel RH, Grundy SM et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645CrossRefPubMed
3.
Zurück zum Zitat Prospective Studies Collaboration, Whitlock G, Lewington S et al (2009) Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 73:1083–1096 Prospective Studies Collaboration, Whitlock G, Lewington S et al (2009) Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 73:1083–1096
4.
Zurück zum Zitat Meigs JB, Wilson PW, Fox CS et al (2006) Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab 91:2906–2912CrossRefPubMed Meigs JB, Wilson PW, Fox CS et al (2006) Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab 91:2906–2912CrossRefPubMed
5.
Zurück zum Zitat Arnlöv J, Ingelsson E, Sundström J, Lind L (2010) Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation 121(2):230–236CrossRefPubMed Arnlöv J, Ingelsson E, Sundström J, Lind L (2010) Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation 121(2):230–236CrossRefPubMed
6.
Zurück zum Zitat Ford ES (2005) Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 28:1769–1778CrossRefPubMed Ford ES (2005) Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 28:1769–1778CrossRefPubMed
7.
8.
Zurück zum Zitat Tuomilehto J, Lindström J, Eriksson JG et al (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350CrossRefPubMed Tuomilehto J, Lindström J, Eriksson JG et al (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350CrossRefPubMed
9.
Zurück zum Zitat Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8:457–465CrossRefPubMed Pedersen BK, Febbraio MA (2012) Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol 8:457–465CrossRefPubMed
10.
Zurück zum Zitat Boström P, Wu J, Jedrychowski MP et al (2012) A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463–468CrossRefPubMedCentralPubMed Boström P, Wu J, Jedrychowski MP et al (2012) A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463–468CrossRefPubMedCentralPubMed
11.
Zurück zum Zitat Timmons JA, Baar K, Davidsen PK, Atherton PJ (2012) Is irisin a human exercise gene? Nature 488:E9–E10CrossRefPubMed Timmons JA, Baar K, Davidsen PK, Atherton PJ (2012) Is irisin a human exercise gene? Nature 488:E9–E10CrossRefPubMed
12.
Zurück zum Zitat Huh JY, Panagiotou G, Mougios V et al (2012) 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 61:1725–1738CrossRefPubMedCentralPubMed Huh JY, Panagiotou G, Mougios V et al (2012) 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 61:1725–1738CrossRefPubMedCentralPubMed
13.
Zurück zum Zitat Hee Park K, Zaichenko L, Brinkoetter M et al (2013) Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab 98:4899–4907CrossRef Hee Park K, Zaichenko L, Brinkoetter M et al (2013) Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab 98:4899–4907CrossRef
14.
Zurück zum Zitat Stengel A, Hofmann T, Goebel-Stengel M, Elbelt U, Kobelt P, Klapp BF (2013) Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity–correlation with body mass index. Peptides 39:125–130CrossRefPubMed Stengel A, Hofmann T, Goebel-Stengel M, Elbelt U, Kobelt P, Klapp BF (2013) Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity–correlation with body mass index. Peptides 39:125–130CrossRefPubMed
15.
Zurück zum Zitat Liu JJ, Wong MD, Toy WC et al (2013) Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complicat 27:365–369CrossRefPubMed Liu JJ, Wong MD, Toy WC et al (2013) Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complicat 27:365–369CrossRefPubMed
16.
Zurück zum Zitat Moreno-Navarrete JM, Ortega F, Serrano M et al (2013) Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab 98:E769–E778CrossRefPubMed Moreno-Navarrete JM, Ortega F, Serrano M et al (2013) Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab 98:E769–E778CrossRefPubMed
17.
Zurück zum Zitat Choi YK, Kim MK, Bae KH et al (2013) Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract 100:96–101CrossRefPubMed Choi YK, Kim MK, Bae KH et al (2013) Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract 100:96–101CrossRefPubMed
18.
Zurück zum Zitat Staiger H, Böhm A, Scheler M et al (2013) Common genetic variation in the human FNDC5 locus, encoding the novel muscle-derived ‘browning’ factor irisin, determines insulin sensitivity. PLoS One 25(8):e61903CrossRef Staiger H, Böhm A, Scheler M et al (2013) Common genetic variation in the human FNDC5 locus, encoding the novel muscle-derived ‘browning’ factor irisin, determines insulin sensitivity. PLoS One 25(8):e61903CrossRef
19.
Zurück zum Zitat Staiger H, Stančáková A, Zilinskaite J et al (2008) A candidate type 2 diabetes polymorphism near the HHEX locus affects acute glucose-stimulated insulin release in European populations: results from the EUGENE2 study. Diabetes 57:514–517CrossRefPubMed Staiger H, Stančáková A, Zilinskaite J et al (2008) A candidate type 2 diabetes polymorphism near the HHEX locus affects acute glucose-stimulated insulin release in European populations: results from the EUGENE2 study. Diabetes 57:514–517CrossRefPubMed
20.
Zurück zum Zitat Stancáková A, Pihlajamäki J, Kuusisto J et al (2008) SNP rs7754840 of CDKAL1 is associated with impaired insulin secretion in non-diabetic offspring of type 2 diabetic subjects (the EUGENE2 study) and in a large sample of men with normal glucose tolerance. J Clin Endocrinol Metab 93:1924–1930CrossRefPubMed Stancáková A, Pihlajamäki J, Kuusisto J et al (2008) SNP rs7754840 of CDKAL1 is associated with impaired insulin secretion in non-diabetic offspring of type 2 diabetic subjects (the EUGENE2 study) and in a large sample of men with normal glucose tolerance. J Clin Endocrinol Metab 93:1924–1930CrossRefPubMed
21.
Zurück zum Zitat Marini MA, Succurro E, Frontoni S et al (2012) Insulin sensitivity, β-cell function, and incretin effect in individuals with elevated 1-h postload plasma glucose levels. Diabetes Care 35:868–872CrossRefPubMedCentralPubMed Marini MA, Succurro E, Frontoni S et al (2012) Insulin sensitivity, β-cell function, and incretin effect in individuals with elevated 1-h postload plasma glucose levels. Diabetes Care 35:868–872CrossRefPubMedCentralPubMed
22.
Zurück zum Zitat Marini MA, Frontoni S, Mineo D et al (2003) The Arg972 variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients. J Clin Endocrinol Metab 88:3368–3371CrossRefPubMed Marini MA, Frontoni S, Mineo D et al (2003) The Arg972 variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients. J Clin Endocrinol Metab 88:3368–3371CrossRefPubMed
23.
Zurück zum Zitat Succurro E, Marini MA, Arturi F et al (2009) Elevated one-hour post-load plasma glucose levels identifies subjects with normal glucose tolerance but early carotid atherosclerosis. Atherosclerosis 207:245–249CrossRefPubMed Succurro E, Marini MA, Arturi F et al (2009) Elevated one-hour post-load plasma glucose levels identifies subjects with normal glucose tolerance but early carotid atherosclerosis. Atherosclerosis 207:245–249CrossRefPubMed
24.
Zurück zum Zitat Marini MA, Frontoni S, Succurro E et al (2013) Insulin clearance is associated with carotid artery intima–media thickness. Atherosclerosis 229:453–458CrossRefPubMed Marini MA, Frontoni S, Succurro E et al (2013) Insulin clearance is associated with carotid artery intima–media thickness. Atherosclerosis 229:453–458CrossRefPubMed
25.
Zurück zum Zitat Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA (2007) Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care 30:89–94CrossRefPubMed Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA (2007) Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care 30:89–94CrossRefPubMed
26.
Zurück zum Zitat The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160–3167 CrossRef The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26:3160–3167 CrossRef
27.
Zurück zum Zitat Faber OK, Christensen K, Kehlet H, Madsbad S, Binder C (1981) Decreased insulin removal contributes to hyperinsulinemia in obesity. J Clin Endocrinol Metab 53:618–621CrossRefPubMed Faber OK, Christensen K, Kehlet H, Madsbad S, Binder C (1981) Decreased insulin removal contributes to hyperinsulinemia in obesity. J Clin Endocrinol Metab 53:618–621CrossRefPubMed
28.
Zurück zum Zitat Marini MA, Frontoni S, Succurro E et al (2013) Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels. PLoS One 8:e77440CrossRefPubMedCentralPubMed Marini MA, Frontoni S, Succurro E et al (2013) Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels. PLoS One 8:e77440CrossRefPubMedCentralPubMed
29.
Zurück zum Zitat Mittelman SD, Van Citters GW, Kim SP et al (2000) Longitudinal compensation for fat-induced insulin resistance includes reduced insulin clearance and enhanced β cell response. Diabetes 49:2116–2125CrossRefPubMed Mittelman SD, Van Citters GW, Kim SP et al (2000) Longitudinal compensation for fat-induced insulin resistance includes reduced insulin clearance and enhanced β cell response. Diabetes 49:2116–2125CrossRefPubMed
30.
Zurück zum Zitat O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotid artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22CrossRefPubMed O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotid artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22CrossRefPubMed
31.
Zurück zum Zitat Nigro J, Osman N, Dart AM, Little PJ (2006) Insulin resistance and atherosclerosis. Endocr Rev 27:242–259CrossRefPubMed Nigro J, Osman N, Dart AM, Little PJ (2006) Insulin resistance and atherosclerosis. Endocr Rev 27:242–259CrossRefPubMed
32.
Zurück zum Zitat Madonna R, Pandolfi A, Massaro M, Consoli A, De Caterina R (2004) Insulin enhances vascular cell adhesion molecule-1 expression in human cultured endothelial cells through a pro-atherogenic pathway mediated by p38 mitogen activated protein-kinase. Diabetologia 47:532–536CrossRefPubMed Madonna R, Pandolfi A, Massaro M, Consoli A, De Caterina R (2004) Insulin enhances vascular cell adhesion molecule-1 expression in human cultured endothelial cells through a pro-atherogenic pathway mediated by p38 mitogen activated protein-kinase. Diabetologia 47:532–536CrossRefPubMed
33.
Zurück zum Zitat Madonna R, De Caterina R (2009) Prolonged exposure to high insulin impairs the endothelial PI3-kinase/Akt/nitric oxide signalling. Thromb Haemost 101:345–350PubMed Madonna R, De Caterina R (2009) Prolonged exposure to high insulin impairs the endothelial PI3-kinase/Akt/nitric oxide signalling. Thromb Haemost 101:345–350PubMed
34.
Zurück zum Zitat Koh YJ, Park BH, Park JH, Han J, Lee IK, Park JW, Koh GY (2009) Activation of PPARγ induces profound multilocularization of adipocytes in adult mouse white adipose tissues. Exp Mol Med 41:880–895CrossRefPubMedCentralPubMed Koh YJ, Park BH, Park JH, Han J, Lee IK, Park JW, Koh GY (2009) Activation of PPARγ induces profound multilocularization of adipocytes in adult mouse white adipose tissues. Exp Mol Med 41:880–895CrossRefPubMedCentralPubMed
35.
Zurück zum Zitat Daniele G, Guardado Mendoza R et al (2014) The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol 51:123–131CrossRefPubMed Daniele G, Guardado Mendoza R et al (2014) The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol 51:123–131CrossRefPubMed
36.
Zurück zum Zitat Tripathy D, Daniele G, Fiorentino TV et al (2013) Pioglitazone improves glucose metabolism and modulates skeletal muscle TIMP-3–TACE dyad in type 2 diabetes mellitus: a randomised, double-blind, placebo-controlled, mechanistic study. Diabetologia 56:2153–2163CrossRefPubMed Tripathy D, Daniele G, Fiorentino TV et al (2013) Pioglitazone improves glucose metabolism and modulates skeletal muscle TIMP-3–TACE dyad in type 2 diabetes mellitus: a randomised, double-blind, placebo-controlled, mechanistic study. Diabetologia 56:2153–2163CrossRefPubMed
Metadaten
Titel
High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects
verfasst von
G. Sesti
F. Andreozzi
T. V. Fiorentino
G. C. Mannino
A. Sciacqua
M. A. Marini
F. Perticone
Publikationsdatum
01.10.2014
Verlag
Springer Milan
Erschienen in
Acta Diabetologica / Ausgabe 5/2014
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-014-0576-0

Weitere Artikel der Ausgabe 5/2014

Acta Diabetologica 5/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.