Adiponectin in relation to exercise and physical performance in patients with type 2 diabetes and coronary artery disease

Hani Zaidi, Rune Byrkjeland, Ida U Njerve, Sissel Åkra, Svein Solheim, Harald Arnesen, Ingebjørg Seljeflot, Trine B Opstad, Hani Zaidi, Rune Byrkjeland, Ida U Njerve, Sissel Åkra, Svein Solheim, Harald Arnesen, Ingebjørg Seljeflot, Trine B Opstad

Abstract

Introduction: Adipokines, expressed by adipose tissue (AT), have been associated with metabolic disturbances and coronary artery disease (CAD). The impact of exercise training on the AT in patients suffering from both diabetes and CAD is unknown. To gain knowledge on changes in ATs' inflammatory profile in such a population, we investigated the effects of long-term exercise on selected adipokines and their associations with physical performance and glucometabolic variables. Adiponectin was selected based on its anti-atherogenic and anti-diabetic properties and visfatin and tumour necrosis factor (TNF) for their association with atherosclerosis and metabolic disorders. Not many studies have focused on the effects of long-term exercise training on adipokines in patients with concomitant T2DM and CAD.

Methods: Patients with type 2 diabetes and CAD (n = 137), 41-81 years, 17.2% females, were randomized in a 1:1 manner to an exercise group, who underwent 1 year of 150 min weekly combined strength and endurance exercise, or a control group. AT from the gluteal region and blood samples were obtained at baseline and after 12 months, along with a physical performance test, assessed by the VO2 peak. Circulating protein levels were measured by ELISA. RNA was extracted from AT and expression levels were relatively quantified by PCR.

Results: After 1 year, no significant difference in the change in the investigated markers between the intervention group and the control group was observed. Changes in circulating adiponectin and VO2 peak correlated in the total population (r = 0.256, p = 0.008). At baseline, circulating adiponectin and TNF correlated inversely with insulin and with C-peptide and VO2peak, respectively (p < 0.001, all).

Conclusion: In this population with concomitant diabetes and CAD, ATs' inflammatory profile remained unchanged apparently after 1 year of exercise intervention. Changes in the VO2peak were nevertheless, related to changes in circulating adiponectin levels.

Trial registration: http://www.clinicaltrials.gov NCT01232608.

Keywords: Adiponectin; coronary artery disease; exercise-training; type 2 diabetes; vo2peak.

Conflict of interest statement

No potential conflict of interest was reported by the author(s).

References

    1. Takeda Y, Nakanishi K, Tachibana I, et al. Chapter sixteen - adiponectin: a novel link between adipocytes and COPD. In: Litwack G, editors. Vitamins & hormones. Academic Press; 2012:419–435.
    1. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20:1595–1599.
    1. Laughlin GA, Barrett-Connor E, May S, et al. Association of adiponectin with coronary heart disease and mortality: the Rancho Bernardo study. Am J Epidemiol. 2007;165:164–174.
    1. Bahia L, Aguiar LG, Villela N, et al. Relationship between adipokines, inflammation, and vascular reactivity in lean controls and obese subjects with metabolic syndrome. Clinics (Sao Paulo). 2006;61:433–440.
    1. Yadav A, Kataria MA, Saini V, et al. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta. 2013;417:80–84.
    1. Kim Y, Park CW.. Mechanisms of adiponectin action: implication of adiponectin receptor agonism in diabetic kidney disease. Int J Mol Sci. 2019;20:1782.
    1. Hotamisligil GS, Murray DL, Choy LN, et al. Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Nat Acad Sci. 1994;91:4854–4858.
    1. Mizia-Stec K, Zahorska-Markiewicz B, Mandecki T, et al. Hyperlipidaemias and serum cytokines in patients with coronary artery disease. Acta Cardiol. 2003;58:9–15.
    1. Swaroop JJ, Rajarajeswari D, Naidu JN.. Association of TNF-α with insulin resistance in type 2 diabetes mellitus. Indian J Med Res. 2012;135:127–130.
    1. Ruan H, Hacohen N, Golub TR, et al. Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes. 2002;51:1319–1336.
    1. Campbell IL, Iscaro A, Harrison LC. IFN-gamma and tumor necrosis factor-alpha. Cytotoxicity to murine islets of Langerhans. J Immunol. 1988;141:2325.
    1. Ibfelt T, Fischer CP, Plomgaard P, et al. The acute effects of low-dose TNF-α on glucose metabolism and β-cell function in humans. Mediators Inflamm. 2014;2014:295478.
    1. Adeghate E. Visfatin: structure, function and relation to diabetes mellitus and other dysfunctions. Curr Med Chem. 2008;15:1851–1862.
    1. Sethi JK, Vidal-Puig A. Visfatin: the missing link between intra-abdominal obesity and diabetes? Trends Mol Med. 2005;11:344–347.
    1. Kadoglou NP, Sailer N, Moumtzouoglou A, et al. Visfatin (nampt) and ghrelin as novel markers of carotid atherosclerosis in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes. 2010;118:75–80.
    1. Zheng L-Y, Xu X, Wan R-H, et al. Association between serum visfatin levels and atherosclerotic plaque in patients with type 2 diabetes. Diabetol Metab Syndr. 2019;11:60.
    1. Romacho T, Sánchez-Ferrer CF, Peiró C. Visfatin/Nampt: an adipokine with cardiovascular impact. Mediators Inflamm. 2013;2013:946427.
    1. Uslu S, Kebapçı N, Kara M, et al. Relationship between adipocytokines and cardiovascular risk factors in patients with type 2 diabetes mellitus. Exp Ther Med. 2012;4:113–120.
    1. Aheed B. Association of adiponectin and visfatin in obesity with insulin resistance: a Non-systemic Review. Rawal Med J. 2014;39:92–95.
    1. Chang X, Jiao Y, Lu J, et al. Adiponectin and visfatin may serve as diagnosis markers for metabolic syndrome in Uygur population. Int J Clin Exp Med. 2014;7:4322–4326.
    1. Mattu HS, Randeva HS. Role of adipokines in cardiovascular disease. J Endocrinol. 2013;216:T17–T36.
    1. Hector J, Schwarzloh B, Goehring J, et al. TNF-alpha alters visfatin and adiponectin levels in human fat. Horm Metab Res. 2007;39:250–255.
    1. Golbidi S, Mesdaghinia A, Laher I. Exercise in the metabolic syndrome. Oxid Med Cell Longev. 2012;2012:349710.
    1. Winzer EB, Woitek F, Linke A. Physical activity in the prevention and treatment of coronary artery disease. J Am Heart Assoc. 2018;7:e007725.
    1. Oberbach A, Tonjes A, Klooting N, et al. Effect of a 4 week physical training program on plasma concentrations of inflammatory markers in patients with abnormal glucose tolerance. Eur J Endocrinol. 2006;154(4):577–585.
    1. Esposito K, Pontillo A, Di Palo C, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. Jama. 2003;289(14):1799–1804.
    1. Ghanbarzadeh M, Omidi M. The effects of physical activity on serum visfatin level: a literature review. Int J Basic Sci Med. 2017;2(2):83–89.
    1. Zouhal H, Zare-kookandeh N, Haghighi MM, et al. Physical activity and adipokine levels in individuals with type 2 diabetes: a literature review and practical applications. Rev Endocr Metab Disord. 2021. 10.1007/s11154-021-09657-x
    1. Byrkjeland R, Njerve IU, Anderssen S, et al. Effects of exercise training on HbA 1c and VO 2peak in patients with type 2 diabetes and coronary artery disease: a randomised clinical trial. Diab Vasc Dis Res. 2015;12(5):325–333.
    1. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25(4):402–408.
    1. Wang X, You T, Murphy K, et al. Addition of exercise increases plasma adiponectin and release from adipose tissue. Med Sci Sports Exerc. 2015;47:2450–2455.
    1. Kriketos AD, Gan SK, Poynten AM, et al. Exercise increases adiponectin levels and insulin sensitivity in humans. Diabetes Care. 2004;27:629–630.
    1. Saunders TJ, Palombella A, McGuire KA, et al. Acute exercise increases adiponectin levels in abdominally obese men. J Nutr Metab. 2012;2012:148729.
    1. Chen X, Sun X, Wang C, et al. Effects of exercise on inflammatory cytokines in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Oxid Med Cell Longev. 2020;2020:6660557.
    1. Bjornstad P, Truong U, Dorosz JL, et al. Cardiopulmonary dysfunction and adiponectin in adolescents with type 2 diabetes. J Am Heart Assoc. 2016;5:e002804.
    1. Nigro E, Scudiero O, Monaco ML, et al. New insight into adiponectin role in obesity and obesity-related diseases. Biomed Res Int. 2014;2014:658913.
    1. Hui X, Lam KSL, Vanhoutte PM, et al. Adiponectin and cardiovascular health: an update. Br J Pharmacol. 2012;165:574–590.
    1. Shibata R, Izumiya Y, Sato K, et al. Adiponectin protects against the development of systolic dysfunction following myocardial infarction. J Mol Cell Cardiol. 2007;42:1065–1074.
    1. Miyatake N, Numata T, Murakami H, et al. Circulating adiponectin levels are associated with peak oxygen uptake in Japanese. Environ Health Prev Med. 2014;19:279–285.
    1. Wannamethee SG, Tchernova J, Whincup P, et al. Associations of adiponectin with metabolic and vascular risk parameters in the British Regional Heart Study reveal stronger links to insulin resistance-related than to coronory heart disease risk-related parameters. Int J Obesity. 2007;31:1089–1098.
    1. Yadav A, Jyoti P, Jain SK, et al. Correlation of adiponectin and leptin with insulin resistance: a pilot study in healthy north Indian population. Indian J Clin Biochem. 2011;26:193–196.
    1. Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86:1930–1935.
    1. Suzuki K, Nakaji S, Yamada M, et al. Systemic inflammatory response to exhaustive exercise. Cytokine kinetics. Exerc Immunol Rev. 2002;8:6–48.
    1. Jahromi AS, Zar A, Ahmadi F, et al. Effects of endurance training on the serum levels of tumour necrosis factor-α and interferon-γ in sedentary men. Immune Netw. 2014;14:255–259.
    1. Conraads VM, Beckers P, Bosmans J, et al. Combined endurance/resistance training reduces plasma TNF-alpha receptor levels in patients with chronic heart failure and coronary artery disease. Eur Heart J. 2002;23:1854–1860.
    1. Ryan AS, Nicklas BJ. Reductions in plasma cytokine levels with weight loss improve insulin sensitivity in overweight and obese postmenopausal women. Diabetes Care. 2004;27:1699–1705.
    1. Çapkın E, Keskin SB, Karkucak M, et al. A prospective clinical investigation of the effects of anti-TNF alpha therapy on exercise capacity in patients with ankylosing spondylitis. Turk J Med Sci. 2019;49:27–32.
    1. Choi KM, Kim JH, Cho GJ, et al. Effect of exercise training on plasma visfatin and eotaxin levels. Eur J Endocrinol. 2007;157:437–442.
    1. Seo D-I, So W-Y, Ha S, et al. Effects of 12 weeks of combined exercise training on visfatin and metabolic syndrome factors in obese middle-aged women. J Sports Sci Med. 2011;10:222–226.
    1. Brema I, Hatunic M, Finucane F, et al. Plasma visfatin is reduced after aerobic exercise in early onset type 2 diabetes mellitus. Diabetes Obes Metab. 2008;10:600–602.
    1. Haider DG, Pleiner J, Francesconi M, et al. Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes. J Clin Endocrinol Metab. 2006;91:4702–4704.
    1. van Andel M, Heijboer AC, Drent ML. Adiponectin and Its Isoforms in Pathophysiology. Adv Clin Chem. 2018;85:115–147.
    1. Chruściel P, Sahebkar A, Rembek-Wieliczko M, et al. Impact of statin therapy on plasma adiponectin concentrations: a systematic review and meta-analysis of 43 randomized controlled trial arms. Atherosclerosis. 2016;253:194–208.
    1. Tarkun I, Dikmen E, Cetinarslan B, et al. Impact of treatment with metformin on adipokines in patients with polycystic ovary syndrome. Eur Cytokine Netw. 2010;21:272–277.

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