Skip to main content
Top
Published in: Sports Medicine 11/2016

01-11-2016 | Review Article

The Type 2 Diabetic Heart: Its Role in Exercise Intolerance and the Challenge to Find Effective Exercise Interventions

Authors: J. Chris Baldi, Genevieve A. Wilson, Luke C. Wilson, Gerard T. Wilkins, Regis R. Lamberts

Published in: Sports Medicine | Issue 11/2016

Login to get access

Abstract

The metabolic and microvascular benefits of regular exercise for people with diabetes are unequivocal. However, cardiovascular disease, which disproportionately affects people with diabetes, is not reduced by regular exercise, and heart disease remains the leading cause of death for people with type 2 diabetes. ‘Subclinical’ changes in the function of the diabetic left ventricle are common and reduce cardiac reserve and exercise capacity. This review describes the changes in resting and exercising left ventricular function, and the possible causes of these changes, and introduces the possibility that more vigorous exercise may be needed to improve left ventricular function and reduce rates of cardiovascular disease in people with type 2 diabetes.
Literature
1.
go back to reference Green S, Egańa M, Baldi JC, Lamberts R, Regensteiner JG. Cardiovascular control during exercise in type 2 diabetes mellitus. J Diabetes Res. 2015;2015:654204.PubMedPubMedCentralCrossRef Green S, Egańa M, Baldi JC, Lamberts R, Regensteiner JG. Cardiovascular control during exercise in type 2 diabetes mellitus. J Diabetes Res. 2015;2015:654204.PubMedPubMedCentralCrossRef
2.
go back to reference Baldi JC, Aoina JL, Oxenham HC, Bagg W, Doughty RN. Reduced exercise arteriovenous O2 difference in type 2 diabetes. J Appl Physiol. 2003;94:1033–8.PubMedCrossRef Baldi JC, Aoina JL, Oxenham HC, Bagg W, Doughty RN. Reduced exercise arteriovenous O2 difference in type 2 diabetes. J Appl Physiol. 2003;94:1033–8.PubMedCrossRef
3.
go back to reference Gusso S, Hofman P, Lalande S, Cutfield W, Robinson E, Baldi JC. Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus. Diabetologia. 2008;51:1317–20.PubMedCrossRef Gusso S, Hofman P, Lalande S, Cutfield W, Robinson E, Baldi JC. Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus. Diabetologia. 2008;51:1317–20.PubMedCrossRef
4.
go back to reference MacAnaney O, Malone J, Warmington S, O’Shea D, Green S, Egana M. Cardiac output responses are not related to the slowed oxygen uptake kinetics in type 2 diabetes. Med Sci Sports Exerc. 2011;43:935–42.CrossRef MacAnaney O, Malone J, Warmington S, O’Shea D, Green S, Egana M. Cardiac output responses are not related to the slowed oxygen uptake kinetics in type 2 diabetes. Med Sci Sports Exerc. 2011;43:935–42.CrossRef
5.
go back to reference Lee MJ, Coast JR, Hempleman SC, Baldi JC. Type 1 diabetes duration decreases pulmonary diffusing capacity during exercise. Respiration. 2016;91(2):164–70.PubMedCrossRef Lee MJ, Coast JR, Hempleman SC, Baldi JC. Type 1 diabetes duration decreases pulmonary diffusing capacity during exercise. Respiration. 2016;91(2):164–70.PubMedCrossRef
6.
go back to reference Niranjan V, McBrayer DG, Ramirez LC, Rasking P, Hsia CCW. Glycemic control and cardiopulmonary function in patients with insulin-dependent diabetes mellitus. Am J Med. 1997;103:504–13.PubMedCrossRef Niranjan V, McBrayer DG, Ramirez LC, Rasking P, Hsia CCW. Glycemic control and cardiopulmonary function in patients with insulin-dependent diabetes mellitus. Am J Med. 1997;103:504–13.PubMedCrossRef
7.
go back to reference O’Connor E, Green S, Kiely C, O’Shea D, Egana M. Differential effects of age and type 2 diabetes on dynamic versus peak response of pulmonary oxygen uptake during exercise. J Appl Phys. 2015;118:1031–9. O’Connor E, Green S, Kiely C, O’Shea D, Egana M. Differential effects of age and type 2 diabetes on dynamic versus peak response of pulmonary oxygen uptake during exercise. J Appl Phys. 2015;118:1031–9.
8.
go back to reference Baldi JC, Cassuto NA, Foxx-Lupo WT, Wheatley CM, Snyder EM. Glycemic status affects cardiopulmonary exercise response in athletes with type 1 diabetes. Med Sci Sports Exerc. 2010;42:1454–9.PubMedCrossRef Baldi JC, Cassuto NA, Foxx-Lupo WT, Wheatley CM, Snyder EM. Glycemic status affects cardiopulmonary exercise response in athletes with type 1 diabetes. Med Sci Sports Exerc. 2010;42:1454–9.PubMedCrossRef
9.
go back to reference Pinto TE, Gusso S, Hofman PL, Derraik JG, Hornung TS, Cutfield WS, Baldi JC. Systolic and diastolic abnormalities reduce the cardiac response to exercise in adolescents with type 2 diabetes. Diabetes Care. 2014;37:1439–46.PubMedCrossRef Pinto TE, Gusso S, Hofman PL, Derraik JG, Hornung TS, Cutfield WS, Baldi JC. Systolic and diastolic abnormalities reduce the cardiac response to exercise in adolescents with type 2 diabetes. Diabetes Care. 2014;37:1439–46.PubMedCrossRef
10.
go back to reference Regan TJ, Lyons MM, Ahmed SS, Levinson GE, Oldewurtel HA, Ahmad MR, Haider B. Evidence for cardiomyopathy in familial diabetes mellitus. J Clin Invest. 1977;60:884–99.PubMedCrossRef Regan TJ, Lyons MM, Ahmed SS, Levinson GE, Oldewurtel HA, Ahmad MR, Haider B. Evidence for cardiomyopathy in familial diabetes mellitus. J Clin Invest. 1977;60:884–99.PubMedCrossRef
11.
go back to reference Keytsman C, Dendale P, Hansen D. Chronotropic incompetence during exercise in type 2 diabetes: aetiology, assessment methodology, prognostic impact and therapy. Sports Med. 2015;45:985–95.PubMedCrossRef Keytsman C, Dendale P, Hansen D. Chronotropic incompetence during exercise in type 2 diabetes: aetiology, assessment methodology, prognostic impact and therapy. Sports Med. 2015;45:985–95.PubMedCrossRef
12.
go back to reference Gerson MC, Khoury JC, Hertzberg VS, et al. Prediction of coronary artery disease in a population of insulin-requiring diabetic patients: results of an 8-year follow up study. Am Heart J. 1988;116:820–6.PubMedCrossRef Gerson MC, Khoury JC, Hertzberg VS, et al. Prediction of coronary artery disease in a population of insulin-requiring diabetic patients: results of an 8-year follow up study. Am Heart J. 1988;116:820–6.PubMedCrossRef
13.
go back to reference Felsher J, Meissner MD, Hakki AH. Exercise thallium imaging in patients with diabetes mellitus: prognostic implications. Arch Intern Med. 1987;147:313–7.PubMedCrossRef Felsher J, Meissner MD, Hakki AH. Exercise thallium imaging in patients with diabetes mellitus: prognostic implications. Arch Intern Med. 1987;147:313–7.PubMedCrossRef
14.
go back to reference Roy TM, Peterson HR, Snider HL, Cyrus J, Broadstone VL, Fell RD, Rothchild AH, Samois E, Pfeifer MA. Autonomic influence on cardiovascular performance in diabetic subjects. Am J Med. 1989;87:382–8.PubMedCrossRef Roy TM, Peterson HR, Snider HL, Cyrus J, Broadstone VL, Fell RD, Rothchild AH, Samois E, Pfeifer MA. Autonomic influence on cardiovascular performance in diabetic subjects. Am J Med. 1989;87:382–8.PubMedCrossRef
15.
go back to reference van Heerebeek L, Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, Kupreishvili K, Ijsselmuiden AJJ, Schalkwijk CG, Bronzwaer JGF, Diamant M, Borbely A, van der Velden J, Stienen GJM, Laarman GJ, Miessen HWM, Paulus WJ. Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation. 2008;117:43–51.PubMedCrossRef van Heerebeek L, Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, Kupreishvili K, Ijsselmuiden AJJ, Schalkwijk CG, Bronzwaer JGF, Diamant M, Borbely A, van der Velden J, Stienen GJM, Laarman GJ, Miessen HWM, Paulus WJ. Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation. 2008;117:43–51.PubMedCrossRef
16.
go back to reference van Hoeven KH, Factor SM. A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive–diabetic heart disease. Circulation. 1990;82:848–55.PubMedCrossRef van Hoeven KH, Factor SM. A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive–diabetic heart disease. Circulation. 1990;82:848–55.PubMedCrossRef
17.
go back to reference Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988;318:1315–21.PubMedCrossRef Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988;318:1315–21.PubMedCrossRef
18.
go back to reference Asif M, Egan J, Vasan S, Jyothirmayi GN, Masurekar MR, Lopez S, Williams C, Torres RL, Wagle D, Ulrich P, Cerami A, Brines M, Regan TJ. An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proc Natl Acad Sci. 2000;97:2809–13.PubMedPubMedCentralCrossRef Asif M, Egan J, Vasan S, Jyothirmayi GN, Masurekar MR, Lopez S, Williams C, Torres RL, Wagle D, Ulrich P, Cerami A, Brines M, Regan TJ. An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proc Natl Acad Sci. 2000;97:2809–13.PubMedPubMedCentralCrossRef
19.
go back to reference Campbell DJ, Somaratne JB, Jenkins AJ, Prior DL, Yii M, Kenny JF, Newcomb AE, Schalkwijk CG, Black MJ, Kelly DJ. Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease. Cardiovasc Diabetol. 2011;10:80.PubMedPubMedCentralCrossRef Campbell DJ, Somaratne JB, Jenkins AJ, Prior DL, Yii M, Kenny JF, Newcomb AE, Schalkwijk CG, Black MJ, Kelly DJ. Impact of type 2 diabetes and the metabolic syndrome on myocardial structure and microvasculature of men with coronary artery disease. Cardiovasc Diabetol. 2011;10:80.PubMedPubMedCentralCrossRef
20.
go back to reference Hamdani N, Franssen C, Lourenço A, Falcão-Pires I, Fontoura D, Leite S, Plettig L, López B, Ottenheijm CA, Becher PM, González A, Tschöpe C, Diez J, Linke WA, Leite-Moreira AF, Paulus WJ. Myocardial titin hypophosphorylation importantly contributes to heart failure with preserved ejection fraction in a rat metabolic risk model. Circ Heart Fail. 2013;6:1239–49.PubMedCrossRef Hamdani N, Franssen C, Lourenço A, Falcão-Pires I, Fontoura D, Leite S, Plettig L, López B, Ottenheijm CA, Becher PM, González A, Tschöpe C, Diez J, Linke WA, Leite-Moreira AF, Paulus WJ. Myocardial titin hypophosphorylation importantly contributes to heart failure with preserved ejection fraction in a rat metabolic risk model. Circ Heart Fail. 2013;6:1239–49.PubMedCrossRef
21.
go back to reference Lalande S, Hofman PL, Baldi JC. Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes. Acta Physiol. 2010;199:23–30.CrossRef Lalande S, Hofman PL, Baldi JC. Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes. Acta Physiol. 2010;199:23–30.CrossRef
22.
go back to reference Regensteiner JG, Bauer TA, Reusch JEB, Quaife RA, Chen MY, Smith SC, Miller TM, Groves BM, Wolfel EE. Cardiac dysfunction during exercise in uncomplicated type 2 diabetes. Med Sci Sport Exerc. 2009;41:977–84.CrossRef Regensteiner JG, Bauer TA, Reusch JEB, Quaife RA, Chen MY, Smith SC, Miller TM, Groves BM, Wolfel EE. Cardiac dysfunction during exercise in uncomplicated type 2 diabetes. Med Sci Sport Exerc. 2009;41:977–84.CrossRef
23.
go back to reference Regan TJ, Ettinger PO, Khan MI, Jesrani MU, Lyons MM, Oldewurtel HA, Weber M. Altered myocardial function and metabolism in chronic diabetes mellitus without ischemia in dogs. Circ Res. 1974;35:222–37.CrossRef Regan TJ, Ettinger PO, Khan MI, Jesrani MU, Lyons MM, Oldewurtel HA, Weber M. Altered myocardial function and metabolism in chronic diabetes mellitus without ischemia in dogs. Circ Res. 1974;35:222–37.CrossRef
24.
go back to reference Baldi JC, Aoina JL, Whalley GA, Carrick-Ranson G, Walsh HA, O’Shaughnessy H, Bagg W, Doughty RN. The effect of type 2 diabetes on diastolic function. Med Sci Sports Exerc. 2006;38:1384–8.PubMedCrossRef Baldi JC, Aoina JL, Whalley GA, Carrick-Ranson G, Walsh HA, O’Shaughnessy H, Bagg W, Doughty RN. The effect of type 2 diabetes on diastolic function. Med Sci Sports Exerc. 2006;38:1384–8.PubMedCrossRef
25.
go back to reference Belke DD, Swanson EA, Dillmann WH. Decreased sarcoplasmic reticulum activity and contractility in diabetic db/db mouse heart. Diabetes. 2004;53:3201–8.PubMedCrossRef Belke DD, Swanson EA, Dillmann WH. Decreased sarcoplasmic reticulum activity and contractility in diabetic db/db mouse heart. Diabetes. 2004;53:3201–8.PubMedCrossRef
26.
go back to reference Lamberts RR, Lingam SJ, Wang HY, Bollen IA, Hughes G, Galvin IF, Bunton RW, Bahn A, Katare R, Baldi JC, Williams MJ, Saxena P, Coffey S, Jones PP. Impaired relaxation despite upregulated calcium-handling protein atrial myocardium from type 2 diabetic patients with preserved ejection fraction. Cardiovasc Diabetol. 2014;13:72.PubMedPubMedCentralCrossRef Lamberts RR, Lingam SJ, Wang HY, Bollen IA, Hughes G, Galvin IF, Bunton RW, Bahn A, Katare R, Baldi JC, Williams MJ, Saxena P, Coffey S, Jones PP. Impaired relaxation despite upregulated calcium-handling protein atrial myocardium from type 2 diabetic patients with preserved ejection fraction. Cardiovasc Diabetol. 2014;13:72.PubMedPubMedCentralCrossRef
27.
go back to reference Whalley GA, Gusso S, Hofman P, Cutfield W, Poppe KK, Doughty RN, Baldi JC. Structural and functional cardiac abnormalities in adolescent girls with poorly controlled type 2 diabetes. Diabetes Care. 2009;32:883–8.PubMedPubMedCentralCrossRef Whalley GA, Gusso S, Hofman P, Cutfield W, Poppe KK, Doughty RN, Baldi JC. Structural and functional cardiac abnormalities in adolescent girls with poorly controlled type 2 diabetes. Diabetes Care. 2009;32:883–8.PubMedPubMedCentralCrossRef
28.
go back to reference Gledhill N, Cox D, Jamnik R. Endurance athletes’ stroke volume does not plateau: major advantage is diastolic function. Med Sci Sports Exerc. 1994;26:1116–21.PubMedCrossRef Gledhill N, Cox D, Jamnik R. Endurance athletes’ stroke volume does not plateau: major advantage is diastolic function. Med Sci Sports Exerc. 1994;26:1116–21.PubMedCrossRef
29.
go back to reference Stolen TO, Høydal MA, Kemi OJ, Catalucci D, Ceci M, Aasum E, Larsen T, Rolim N, Condorelli G, Smith GL, Wisløff U. Interval training normalizes cardiomyocyte function, diastolic Ca2+ control, and SR Ca2+ release synchronicity in a mouse model of diabetic cardiomyopathy. Circ Res. 2009;105:527–36.PubMedCrossRef Stolen TO, Høydal MA, Kemi OJ, Catalucci D, Ceci M, Aasum E, Larsen T, Rolim N, Condorelli G, Smith GL, Wisløff U. Interval training normalizes cardiomyocyte function, diastolic Ca2+ control, and SR Ca2+ release synchronicity in a mouse model of diabetic cardiomyopathy. Circ Res. 2009;105:527–36.PubMedCrossRef
30.
go back to reference Bussey CT, Hughes G, Saxena P, Galvin IF, Bunton RW, Noye MK, Coffey S, Williams MJ, Baldi JC, Jones PP, Lamberts RR. Chamber-specific changes in calcium-handling proteins in the type 2 diabetic human heart with preserved ejection fraction. Int J Cardiol. 2015;193:53–5.PubMedCrossRef Bussey CT, Hughes G, Saxena P, Galvin IF, Bunton RW, Noye MK, Coffey S, Williams MJ, Baldi JC, Jones PP, Lamberts RR. Chamber-specific changes in calcium-handling proteins in the type 2 diabetic human heart with preserved ejection fraction. Int J Cardiol. 2015;193:53–5.PubMedCrossRef
31.
go back to reference Reuter H, Grönke S, Adam C, Ribati M, Brabender J, Zobel C, Frank KF, Wippermann J, Schwinger RH, Brixius K, Müller-Ehmsen J. Sarcoplasmic Ca+ release is prolonged in nonfailing myocardium of diabetic patients. Mol Cell Biochem. 2008;308:141–9.PubMedCrossRef Reuter H, Grönke S, Adam C, Ribati M, Brabender J, Zobel C, Frank KF, Wippermann J, Schwinger RH, Brixius K, Müller-Ehmsen J. Sarcoplasmic Ca+ release is prolonged in nonfailing myocardium of diabetic patients. Mol Cell Biochem. 2008;308:141–9.PubMedCrossRef
32.
go back to reference Poirier P, Bogaty P, Garneau C, Marois L, Dumesnil JG. Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. Diabetes Care. 2001;24:5–10.PubMedCrossRef Poirier P, Bogaty P, Garneau C, Marois L, Dumesnil JG. Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. Diabetes Care. 2001;24:5–10.PubMedCrossRef
33.
go back to reference Sohn DW, Chai H, Lee DJ, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol. 1997;30:474–80.PubMedCrossRef Sohn DW, Chai H, Lee DJ, et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol. 1997;30:474–80.PubMedCrossRef
34.
go back to reference Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997;30:1527–33.PubMedCrossRef Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol. 1997;30:1527–33.PubMedCrossRef
35.
go back to reference Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler–catheterization study. Circulation. 2000;102:1788–94.PubMedCrossRef Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous Doppler–catheterization study. Circulation. 2000;102:1788–94.PubMedCrossRef
36.
go back to reference Firstenberg MS, Levine BD, Garcia MJ, Greenberg NL, Cardon L, Morehead AJ, Zuckerman J, Thomas JD. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers. J Am Coll Cardiol. 2000;36:1664–9.PubMedCrossRef Firstenberg MS, Levine BD, Garcia MJ, Greenberg NL, Cardon L, Morehead AJ, Zuckerman J, Thomas JD. Relationship of echocardiographic indices to pulmonary capillary wedge pressures in healthy volunteers. J Am Coll Cardiol. 2000;36:1664–9.PubMedCrossRef
37.
go back to reference Sasso FC, Carbonara O, Cozzolino D, Rambaldi P, Mansi L, Torella D, Gentile S, Turco S, Torella R, Salvatore T. Effects of insulin–glucose infusion on left ventricular function at rest and during dynamic exercise in healthy subjects and noninsulin dependent diabetic patients. J Am Coll Cardiol. 2000;36:219–26.PubMedCrossRef Sasso FC, Carbonara O, Cozzolino D, Rambaldi P, Mansi L, Torella D, Gentile S, Turco S, Torella R, Salvatore T. Effects of insulin–glucose infusion on left ventricular function at rest and during dynamic exercise in healthy subjects and noninsulin dependent diabetic patients. J Am Coll Cardiol. 2000;36:219–26.PubMedCrossRef
38.
go back to reference Carrick-Ranson G, Doughty RN, Whalley GA, Walsh HJ, Gamble GD, Baldi JC. The larger exercise stroke volume in endurance-trained men does not result from increased left ventricular early or late inflow or tissue velocities. Acta Physiol. 2012;205:521–31.CrossRef Carrick-Ranson G, Doughty RN, Whalley GA, Walsh HJ, Gamble GD, Baldi JC. The larger exercise stroke volume in endurance-trained men does not result from increased left ventricular early or late inflow or tissue velocities. Acta Physiol. 2012;205:521–31.CrossRef
39.
go back to reference Thackery JT, Beanlands RS, DaSilva JN. Altered sympathetic nervous sytem signalling in the diabetic heart: emerging targets for molecular imaging. Am J Nucl Med Mol Imaging. 2012;2:314–34. Thackery JT, Beanlands RS, DaSilva JN. Altered sympathetic nervous sytem signalling in the diabetic heart: emerging targets for molecular imaging. Am J Nucl Med Mol Imaging. 2012;2:314–34.
40.
go back to reference Alvarez JA, Reyes M, Escobedo D, Freeman GL, Steinhelper ME, Feldman MD. Enhanced left ventricular systolic function early in type 2 diabetic mice: clinical implications. Diab Vasc Dis Res. 2004;1:89–94.PubMedCrossRef Alvarez JA, Reyes M, Escobedo D, Freeman GL, Steinhelper ME, Feldman MD. Enhanced left ventricular systolic function early in type 2 diabetic mice: clinical implications. Diab Vasc Dis Res. 2004;1:89–94.PubMedCrossRef
41.
go back to reference Fredersdorf S, Thumann C, Ulucan C, Griese DP, Luchner A, Riegger GA, Kromer EP, Weil J. Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats. Cardiovasc Pathol. 2004;13:11–9.PubMedCrossRef Fredersdorf S, Thumann C, Ulucan C, Griese DP, Luchner A, Riegger GA, Kromer EP, Weil J. Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats. Cardiovasc Pathol. 2004;13:11–9.PubMedCrossRef
42.
go back to reference Rösen P, Herberg L, Reinauer H, Adriean M, Feuerstein J, Topütt B. Different types of post insulin receptor defects contribute to insulin resistance in hearts of obese Zucker rats. Endocrinology. 1986;119:1285–91.PubMedCrossRef Rösen P, Herberg L, Reinauer H, Adriean M, Feuerstein J, Topütt B. Different types of post insulin receptor defects contribute to insulin resistance in hearts of obese Zucker rats. Endocrinology. 1986;119:1285–91.PubMedCrossRef
43.
go back to reference Celentano A, Vaccaro O, Tammaro P, Galderisi M, Crivaro M, Oliviero M, Imperatore G, Palmieri V, Iovino V, Riccardi G, Devitiis O. Early abnormalities of cardiac function in non-insulin dependent diabetes mellitus and impaired glucose tolerance. Am J Cardiol. 1995;76:1173–6.PubMedCrossRef Celentano A, Vaccaro O, Tammaro P, Galderisi M, Crivaro M, Oliviero M, Imperatore G, Palmieri V, Iovino V, Riccardi G, Devitiis O. Early abnormalities of cardiac function in non-insulin dependent diabetes mellitus and impaired glucose tolerance. Am J Cardiol. 1995;76:1173–6.PubMedCrossRef
44.
go back to reference Mustonen JN, Uusitupa MIJ, Tahvanainen K, Talwar S, Laakso M, Länsimies E, Kuikka JT, Pyörälä K. Impaired left ventricular systolic function during exercise in middle-aged insulin-dependent and noninsulin-dependent diabetic subjects without clinically evident cardiovascular disease. Am J Cardiol. 1988;62:1273–9.PubMedCrossRef Mustonen JN, Uusitupa MIJ, Tahvanainen K, Talwar S, Laakso M, Länsimies E, Kuikka JT, Pyörälä K. Impaired left ventricular systolic function during exercise in middle-aged insulin-dependent and noninsulin-dependent diabetic subjects without clinically evident cardiovascular disease. Am J Cardiol. 1988;62:1273–9.PubMedCrossRef
45.
go back to reference Ferraro S, Perrone-Filardi P, Maddalena G, Desiderio A, Gravina E, Turco S, Chiariello M. Comparison of left ventricular function in insulin- and non-insulin dependent diabetes mellitus. Am J Cardiol. 1993;71:409–14.PubMedCrossRef Ferraro S, Perrone-Filardi P, Maddalena G, Desiderio A, Gravina E, Turco S, Chiariello M. Comparison of left ventricular function in insulin- and non-insulin dependent diabetes mellitus. Am J Cardiol. 1993;71:409–14.PubMedCrossRef
46.
go back to reference Ehl NF, Kühne M, Brinkert M, Müller-Brand J, Zellweger MJ. Diabetes reduces left ventricular ejection fraction—irrespective of presence and extent of coronary artery disease. Eur J Endocrinol. 2011;165:945–51.PubMedCrossRef Ehl NF, Kühne M, Brinkert M, Müller-Brand J, Zellweger MJ. Diabetes reduces left ventricular ejection fraction—irrespective of presence and extent of coronary artery disease. Eur J Endocrinol. 2011;165:945–51.PubMedCrossRef
47.
go back to reference Ha JW, Lee HC, Kang ES, Aghn CM, Kim JM, Ahn JA, Lee SW, Choi EY, Rim SJ, Oh JK, Chung N. Abnormal left ventricular longitudinal functional reserve in patients with diabetes mellitus: implication for detecting subclinical myocardial dysfunction using exercise tissue Doppler echocardiography. Heart. 2007;93:1571–6.PubMedPubMedCentralCrossRef Ha JW, Lee HC, Kang ES, Aghn CM, Kim JM, Ahn JA, Lee SW, Choi EY, Rim SJ, Oh JK, Chung N. Abnormal left ventricular longitudinal functional reserve in patients with diabetes mellitus: implication for detecting subclinical myocardial dysfunction using exercise tissue Doppler echocardiography. Heart. 2007;93:1571–6.PubMedPubMedCentralCrossRef
48.
go back to reference Zhen Z, Chen Y, Shih K, Liu JH, Yuen M, Wong DS, Lam KS, Tse HF, Yiu KH. Altered myocardial response in patients with diabetic retinopathy: an exercise echocardiography study. Cardiovasc Diabetol. 2015;14:123.PubMedPubMedCentralCrossRef Zhen Z, Chen Y, Shih K, Liu JH, Yuen M, Wong DS, Lam KS, Tse HF, Yiu KH. Altered myocardial response in patients with diabetic retinopathy: an exercise echocardiography study. Cardiovasc Diabetol. 2015;14:123.PubMedPubMedCentralCrossRef
49.
go back to reference Aboukhoudir F, Rekik S. Left ventricular systolic function deterioration during dobutamine stress echocardiography as an early manifestation of diabetic cardiomyopathy and reversal by optimized therapeutic approach. Int J Cardiovasc Imaging. 2012;6:1329–39.CrossRef Aboukhoudir F, Rekik S. Left ventricular systolic function deterioration during dobutamine stress echocardiography as an early manifestation of diabetic cardiomyopathy and reversal by optimized therapeutic approach. Int J Cardiovasc Imaging. 2012;6:1329–39.CrossRef
50.
go back to reference Vinereanu D, Nicolaides E, Tweddel AC, Mädler CF, Holst B, Boden LE, Cinteza M, Rees AE, Fraser AG. Subclinical left ventricular dysfunction in asymptomatic patients with type II diabetes mellitus, related to serum lipids and glycated haemoglobin. Clin Sci (Lond). 2003;105:591–9.CrossRef Vinereanu D, Nicolaides E, Tweddel AC, Mädler CF, Holst B, Boden LE, Cinteza M, Rees AE, Fraser AG. Subclinical left ventricular dysfunction in asymptomatic patients with type II diabetes mellitus, related to serum lipids and glycated haemoglobin. Clin Sci (Lond). 2003;105:591–9.CrossRef
51.
go back to reference Galderisi M, de Simone G, Innelli P, Turco A, Turco S, Capaldo B, Riccardi G, de Divitiis O. Impaired inotropic response in type 2 diabetes mellitus: a strain rate imaging study. Am J Hypertens. 2007;20:548–55.PubMedCrossRef Galderisi M, de Simone G, Innelli P, Turco A, Turco S, Capaldo B, Riccardi G, de Divitiis O. Impaired inotropic response in type 2 diabetes mellitus: a strain rate imaging study. Am J Hypertens. 2007;20:548–55.PubMedCrossRef
52.
53.
go back to reference Robinson BF, Epstein SE, Beiser GD, Braunwald E. Control of heart rate by the autonomic nervous system: studies in man on the inter-relation between baroreceptor mechanisms and exercise. Circ Res. 1966;19:400–11.PubMedCrossRef Robinson BF, Epstein SE, Beiser GD, Braunwald E. Control of heart rate by the autonomic nervous system: studies in man on the inter-relation between baroreceptor mechanisms and exercise. Circ Res. 1966;19:400–11.PubMedCrossRef
55.
go back to reference Bottini P, Tantucci C, Scionti L, et al. Cardiovascular response to exercise in diabetic patients: influence of autonomic neuropathy of different severity. Diabetologia. 1995;38:244–50.PubMedCrossRef Bottini P, Tantucci C, Scionti L, et al. Cardiovascular response to exercise in diabetic patients: influence of autonomic neuropathy of different severity. Diabetologia. 1995;38:244–50.PubMedCrossRef
56.
go back to reference Hilsted J. Pathophysiology in diabetic autonomic neuropathy: cardiovascular, hormonal, and metablic studies. Diabetes. 1982;31:730–7.PubMedCrossRef Hilsted J. Pathophysiology in diabetic autonomic neuropathy: cardiovascular, hormonal, and metablic studies. Diabetes. 1982;31:730–7.PubMedCrossRef
57.
58.
go back to reference Scott JA, Coombes JS, Prins JB, Leano RL, Marwick TH, Sharman JE. Patients with type 2 diabetes have exaggerated brachial and central exercise blood pressure: relation to left ventricular relative wall thickness. Am J Hypertension. 2008;21:715–21.CrossRef Scott JA, Coombes JS, Prins JB, Leano RL, Marwick TH, Sharman JE. Patients with type 2 diabetes have exaggerated brachial and central exercise blood pressure: relation to left ventricular relative wall thickness. Am J Hypertension. 2008;21:715–21.CrossRef
59.
go back to reference Liao D, Cai J, Brancati FL, Folsom A, Barnes RW, Tyroler HA, Heiss G. Association of vagal tone with serum insulin, glucose, and diabetes mellitus—the ARIC study. Diabetes Res Clin Pract. 1995;30:211–21.PubMedCrossRef Liao D, Cai J, Brancati FL, Folsom A, Barnes RW, Tyroler HA, Heiss G. Association of vagal tone with serum insulin, glucose, and diabetes mellitus—the ARIC study. Diabetes Res Clin Pract. 1995;30:211–21.PubMedCrossRef
60.
go back to reference Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta J, Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes. 1981;30:219–25.PubMedCrossRef Rowe JW, Young JB, Minaker KL, Stevens AL, Pallotta J, Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes. 1981;30:219–25.PubMedCrossRef
61.
go back to reference Schroeder EB, Chambless LE, Liao D, Prineas RJ, Evans GW, Rosamond WD, Heiss G. Diabetes, glucose, insulin, and heart rate variability. Diabetes Care. 2005;28:668–74.PubMedCrossRef Schroeder EB, Chambless LE, Liao D, Prineas RJ, Evans GW, Rosamond WD, Heiss G. Diabetes, glucose, insulin, and heart rate variability. Diabetes Care. 2005;28:668–74.PubMedCrossRef
62.
go back to reference Carnethon MR, Golden SH, Folsom AR, Haskell W, Liao D. Prospective investigation of autonomic nervous system function and the development of type 2 diabetes: the Atheroslcerosis Risk In Communities study, 1987, 1998. Circulation. 2003;107:2190–5.PubMedCrossRef Carnethon MR, Golden SH, Folsom AR, Haskell W, Liao D. Prospective investigation of autonomic nervous system function and the development of type 2 diabetes: the Atheroslcerosis Risk In Communities study, 1987, 1998. Circulation. 2003;107:2190–5.PubMedCrossRef
63.
go back to reference Facchini FS, Stoohs RA, Reaven GM. Enhanced sympathetic nervous system activity: the linchpin between insulin resistance, hyperinsulinemia, and heart rate. Am J Hypertens. 1996;9:1013–7.PubMedCrossRef Facchini FS, Stoohs RA, Reaven GM. Enhanced sympathetic nervous system activity: the linchpin between insulin resistance, hyperinsulinemia, and heart rate. Am J Hypertens. 1996;9:1013–7.PubMedCrossRef
64.
go back to reference Flaa A, Aksnes TA, Kjeldsen SE, Eide I, Rostrup M. Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study. Metabolism. 2008;57:1422–7.PubMedCrossRef Flaa A, Aksnes TA, Kjeldsen SE, Eide I, Rostrup M. Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study. Metabolism. 2008;57:1422–7.PubMedCrossRef
65.
go back to reference Landsberg L, Saville ME, Young JB. Sympathoadrenal system and regulation of thermogenesis. Am J Physiol. 1986;247:E181–9. Landsberg L, Saville ME, Young JB. Sympathoadrenal system and regulation of thermogenesis. Am J Physiol. 1986;247:E181–9.
66.
go back to reference Thaung HP, Baldi JC, Wang HY, Hughes G, Cook RF, Bussey CT, Sheard PW, Bahn A, Jones PP, Schwenke DO, Lamberts RR. Increased efferent cardiac sympathetic nerve activity and defective intrinsic heart rate regulation in type 2 diabetes. Diabetes. 2015;64:2944–56.PubMedCrossRef Thaung HP, Baldi JC, Wang HY, Hughes G, Cook RF, Bussey CT, Sheard PW, Bahn A, Jones PP, Schwenke DO, Lamberts RR. Increased efferent cardiac sympathetic nerve activity and defective intrinsic heart rate regulation in type 2 diabetes. Diabetes. 2015;64:2944–56.PubMedCrossRef
67.
go back to reference Christensen TE, Kjaer A, Hasbak P. The clinical value of cardiac sympathetic imaging in heart failure. Clin Physiol Funct Imaging. 2014;334:178–82.CrossRef Christensen TE, Kjaer A, Hasbak P. The clinical value of cardiac sympathetic imaging in heart failure. Clin Physiol Funct Imaging. 2014;334:178–82.CrossRef
68.
go back to reference Yufu K, Takahashi N, Okada N, Shinohara T, Nakagawa M, Hara M, Yoshimatsu H, Saikawa T. Cardiac iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy parameter predicts cardiac and cerebrovascular events in type 2 diabetic patients without structural heart disease. Circ J. 2012;76:399–404.PubMedCrossRef Yufu K, Takahashi N, Okada N, Shinohara T, Nakagawa M, Hara M, Yoshimatsu H, Saikawa T. Cardiac iodine-123 metaiodobenzylguanidine (123I-MIBG) scintigraphy parameter predicts cardiac and cerebrovascular events in type 2 diabetic patients without structural heart disease. Circ J. 2012;76:399–404.PubMedCrossRef
69.
go back to reference Nagamachi S, Fujita S, Nishii R, Futami S, Tamura S, Mizuta M, et al. Prognostic value of cardiac I-123 metaiodobenzylguanidine imaging in patients with non-insulin-dependent diabetes mellitus. J Nucl Cardiol. 2006;13:34–42.PubMedCrossRef Nagamachi S, Fujita S, Nishii R, Futami S, Tamura S, Mizuta M, et al. Prognostic value of cardiac I-123 metaiodobenzylguanidine imaging in patients with non-insulin-dependent diabetes mellitus. J Nucl Cardiol. 2006;13:34–42.PubMedCrossRef
70.
go back to reference Scognamiglio R, Avogaro A, Casara D, Crepaldi C, Marin M, Palisi M, Mingardi R, Erle G, Fasoli G, Volta SD. Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol. 1998;31:404–12.PubMedCrossRef Scognamiglio R, Avogaro A, Casara D, Crepaldi C, Marin M, Palisi M, Mingardi R, Erle G, Fasoli G, Volta SD. Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol. 1998;31:404–12.PubMedCrossRef
71.
go back to reference Bristow MR. Changes in myocardial and vascular receptors in heart failure. J Am Coll Cardiol. 1993;22:61A–71A.PubMedCrossRef Bristow MR. Changes in myocardial and vascular receptors in heart failure. J Am Coll Cardiol. 1993;22:61A–71A.PubMedCrossRef
72.
go back to reference Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, Zera P, Menlove R, Shas P, Jamieson S, Stinson EB. β1- and β2-adrenergic receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective β1-receptor down-regulation in heart failure. Circ Res. 1986;59:297–309.PubMedCrossRef Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, Zera P, Menlove R, Shas P, Jamieson S, Stinson EB. β1- and β2-adrenergic receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective β1-receptor down-regulation in heart failure. Circ Res. 1986;59:297–309.PubMedCrossRef
73.
go back to reference Gautier C, Tavernier G, Charpentier F, Le Langin D, Marec H. Functional beta3-adrenoceptor in the human heart. J Clin Invest. 1996;98:556–62.CrossRef Gautier C, Tavernier G, Charpentier F, Le Langin D, Marec H. Functional beta3-adrenoceptor in the human heart. J Clin Invest. 1996;98:556–62.CrossRef
75.
go back to reference Dincer UD, Bidasee KR, Guner S, Tay A, Ozcelikay AT, Altan VM. The effect of diabetes on expression of beta1-, beta2, and beta3-adrenoreceptors in rat hearts. Diabetes. 2001;50:455–61.PubMedCrossRef Dincer UD, Bidasee KR, Guner S, Tay A, Ozcelikay AT, Altan VM. The effect of diabetes on expression of beta1-, beta2, and beta3-adrenoreceptors in rat hearts. Diabetes. 2001;50:455–61.PubMedCrossRef
76.
go back to reference Savarese JJ, Berkowitz BA. Β-adrenergic receptor decrease in diabetic rat hearts. Life Sci. 1979;25:2075–8.PubMedCrossRef Savarese JJ, Berkowitz BA. Β-adrenergic receptor decrease in diabetic rat hearts. Life Sci. 1979;25:2075–8.PubMedCrossRef
77.
go back to reference Sellers DJ, Chess-Williams R. The effect of streptozotocin-induced diabetes on cardiac beta-adrenoceptor subtypes in the rat. J Auton Pharmacol. 2001;21:15–21.PubMedCrossRef Sellers DJ, Chess-Williams R. The effect of streptozotocin-induced diabetes on cardiac beta-adrenoceptor subtypes in the rat. J Auton Pharmacol. 2001;21:15–21.PubMedCrossRef
78.
go back to reference Dincer UD, Guner S, Tay A, Arioglu E, Tasdelen A, Aslamaci S, Bidasee KR. Decreased expression of beta1- and beta2-adrenoceptors in human diabetic atrial appendage. Cardiovasc Diabetol. 2003;2:6.PubMedPubMedCentralCrossRef Dincer UD, Guner S, Tay A, Arioglu E, Tasdelen A, Aslamaci S, Bidasee KR. Decreased expression of beta1- and beta2-adrenoceptors in human diabetic atrial appendage. Cardiovasc Diabetol. 2003;2:6.PubMedPubMedCentralCrossRef
79.
go back to reference Haley JM, Thackeray JT, Thorn SL, DaSilva JN. Cardiac β-adrenoceptor expression is reduced in Zucker diabetic fatty rats as type 2 diabetes progresses. PLoS One. 2015;10:e0127581.PubMedPubMedCentralCrossRef Haley JM, Thackeray JT, Thorn SL, DaSilva JN. Cardiac β-adrenoceptor expression is reduced in Zucker diabetic fatty rats as type 2 diabetes progresses. PLoS One. 2015;10:e0127581.PubMedPubMedCentralCrossRef
80.
go back to reference Dutta K, Podolin DA, Davidson MB, Davidoff AJ. Cardiomyocyte dysfunction in sucrose-fed rats is associated with insulin resistance. Diabetes. 2001;50:1186–92.PubMedCrossRef Dutta K, Podolin DA, Davidson MB, Davidoff AJ. Cardiomyocyte dysfunction in sucrose-fed rats is associated with insulin resistance. Diabetes. 2001;50:1186–92.PubMedCrossRef
81.
go back to reference Radovits T, Korkmaz S, Loganathan S, Barnucz E, Bömicke T, Arif R, Karck M, Szabó G. Comparative investigation of the left ventricular pressure–volume relationship in rat models of type 1 and type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol. 2009;297:H125–33.PubMedCrossRef Radovits T, Korkmaz S, Loganathan S, Barnucz E, Bömicke T, Arif R, Karck M, Szabó G. Comparative investigation of the left ventricular pressure–volume relationship in rat models of type 1 and type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol. 2009;297:H125–33.PubMedCrossRef
82.
go back to reference Pereira L, Matthes J, Schuster I, Valdivia HH, Herzig S, Richard S, Gómez AM. Mechanisms of [Ca2+]i transient decrease in cardiomyopathy of db/db type 2 diabetic mice. Diabetes. 2006;55:608–15.PubMedCrossRef Pereira L, Matthes J, Schuster I, Valdivia HH, Herzig S, Richard S, Gómez AM. Mechanisms of [Ca2+]i transient decrease in cardiomyopathy of db/db type 2 diabetic mice. Diabetes. 2006;55:608–15.PubMedCrossRef
83.
go back to reference Bidasee KR, Nallani K, Henry B, Dincer UD, Besch HR Jr. Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts. Mol Cell Biochem. 2003;249:113–23.PubMedCrossRef Bidasee KR, Nallani K, Henry B, Dincer UD, Besch HR Jr. Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts. Mol Cell Biochem. 2003;249:113–23.PubMedCrossRef
84.
go back to reference Jweied EE, McKinney RD, Walker LA, Brodsky I, Geha AS, Massad MG, Buttrick PM, de Tombe PP. Depressed cardiac myofilament function in human diabetes mellitus. Am J Physiol Heart Circ Physiol. 2005;289:H2478–83.PubMedCrossRef Jweied EE, McKinney RD, Walker LA, Brodsky I, Geha AS, Massad MG, Buttrick PM, de Tombe PP. Depressed cardiac myofilament function in human diabetes mellitus. Am J Physiol Heart Circ Physiol. 2005;289:H2478–83.PubMedCrossRef
85.
go back to reference Landzberg JS, Parker JD, Gauthier DF, Colucci WS. Effects of intracoronary acetylcholine and atropine on basal and dobutamine-stimulated left ventricular contractility. Circulation. 1994;89:164–8.PubMedCrossRef Landzberg JS, Parker JD, Gauthier DF, Colucci WS. Effects of intracoronary acetylcholine and atropine on basal and dobutamine-stimulated left ventricular contractility. Circulation. 1994;89:164–8.PubMedCrossRef
86.
go back to reference Ewing DJ, Campbell IW, Clarke BF. Heart rate changes in diabetes mellitus. Lancet. 1981;317:183–6.CrossRef Ewing DJ, Campbell IW, Clarke BF. Heart rate changes in diabetes mellitus. Lancet. 1981;317:183–6.CrossRef
87.
go back to reference Ewing DJ, Irving JB, Kerr F, Wildsmith JAW, Clarke BF. Cardiovascular responses to sustained handgrip in normal subjects and in patients with diabetes mellitus: a test of autonomic function. Clin Sci Mol Med. 1974;46:295–306.PubMed Ewing DJ, Irving JB, Kerr F, Wildsmith JAW, Clarke BF. Cardiovascular responses to sustained handgrip in normal subjects and in patients with diabetes mellitus: a test of autonomic function. Clin Sci Mol Med. 1974;46:295–306.PubMed
88.
89.
go back to reference Koh J, Brown TE, Beightol LA, Ha CY, Eckberg DL. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects. J Physiol (Lond). 1994;474:483–95.PubMedCentralCrossRef Koh J, Brown TE, Beightol LA, Ha CY, Eckberg DL. Human autonomic rhythms: vagal cardiac mechanisms in tetraplegic subjects. J Physiol (Lond). 1994;474:483–95.PubMedCentralCrossRef
90.
go back to reference Pomeranz B, Macaulay RJB, Caudill MA, Kutz I, Adam D, Gordon D, Kilborn KM, Barger AC, Shannon DC, Cohen RJ, Benson H. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol. 1985;248:H151–3.PubMed Pomeranz B, Macaulay RJB, Caudill MA, Kutz I, Adam D, Gordon D, Kilborn KM, Barger AC, Shannon DC, Cohen RJ, Benson H. Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol. 1985;248:H151–3.PubMed
91.
go back to reference Lahiri MK, Kannankeril PJ, Goldberger JJ. Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications. J Am Coll Cardiol. 2008;51:1725–33.PubMedCrossRef Lahiri MK, Kannankeril PJ, Goldberger JJ. Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications. J Am Coll Cardiol. 2008;51:1725–33.PubMedCrossRef
92.
go back to reference Fang ZY, Prins JB, Sharman J, Marwick TH. Determinants of exercise capacity in patients with type 2 diabetes. Diabetes Care. 2005;28:1643–8.PubMedCrossRef Fang ZY, Prins JB, Sharman J, Marwick TH. Determinants of exercise capacity in patients with type 2 diabetes. Diabetes Care. 2005;28:1643–8.PubMedCrossRef
93.
go back to reference UKPDS Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.CrossRef UKPDS Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.CrossRef
94.
go back to reference UKPDS Study Group. Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care. 2002;25(Suppl 1):S28–32. UKPDS Study Group. Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care. 2002;25(Suppl 1):S28–32.
95.
go back to reference Holman RR, Paul SK, Bethel MS, Matthews DR, Neil AW. 10-year follow-up of intensive glycose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89.PubMedCrossRef Holman RR, Paul SK, Bethel MS, Matthews DR, Neil AW. 10-year follow-up of intensive glycose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89.PubMedCrossRef
96.
go back to reference University Group Diabetes Program. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. Diabetes. 1970;19(Suppl 2):747–830. University Group Diabetes Program. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. Diabetes. 1970;19(Suppl 2):747–830.
97.
go back to reference Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kohima Y, Furuyoshi N, Shichiri M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28:103–17.PubMedCrossRef Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kohima Y, Furuyoshi N, Shichiri M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28:103–17.PubMedCrossRef
98.
go back to reference Abraira C, Colwell J, Nuttall F, Sawin CT, Henderson W, Comstock JP, Emanuele NV, Levin SR, Pacold I, Lee HS. Cardiovascular events and correlates in the Veterans Affairs Diabetes Feasibility Trial: Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes. Arch Intern Med. 1997;157:181–8.PubMedCrossRef Abraira C, Colwell J, Nuttall F, Sawin CT, Henderson W, Comstock JP, Emanuele NV, Levin SR, Pacold I, Lee HS. Cardiovascular events and correlates in the Veterans Affairs Diabetes Feasibility Trial: Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes. Arch Intern Med. 1997;157:181–8.PubMedCrossRef
99.
go back to reference The ACCORD Study Group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364:818–28.PubMedCentralCrossRef The ACCORD Study Group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364:818–28.PubMedCentralCrossRef
100.
go back to reference The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.PubMedCentralCrossRef The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.PubMedCentralCrossRef
101.
go back to reference Saltin B, Blomqvist G, Mitchell JH, Johnson RL Jr, Wildenthal K, Chapman CB. Response to exercise after bed rest and after training. Circulation. 1968;38(5 Suppl):VII1–78.PubMed Saltin B, Blomqvist G, Mitchell JH, Johnson RL Jr, Wildenthal K, Chapman CB. Response to exercise after bed rest and after training. Circulation. 1968;38(5 Suppl):VII1–78.PubMed
102.
go back to reference Myers J, Prakash M, Froelicher V, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med. 2002;346:793–801.PubMedCrossRef Myers J, Prakash M, Froelicher V, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med. 2002;346:793–801.PubMedCrossRef
103.
go back to reference Tanasescu M, Leitzmann MF, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Exercise type and intensity in relation to coronary heart disease in men. JAMA. 2002;288:1994–2000.PubMedCrossRef Tanasescu M, Leitzmann MF, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Exercise type and intensity in relation to coronary heart disease in men. JAMA. 2002;288:1994–2000.PubMedCrossRef
104.
go back to reference Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham Study. Am J Cardiol. 1974;34:29–34.PubMedCrossRef Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham Study. Am J Cardiol. 1974;34:29–34.PubMedCrossRef
105.
go back to reference Boule’ NG, Kenny GP, Haddad E, Wells GA, Sigal RJ. Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia. 2003;46:1071–81.CrossRef Boule’ NG, Kenny GP, Haddad E, Wells GA, Sigal RJ. Meta-analysis of the effect of structured exercise training on cardiorespiratory fitness in type 2 diabetes mellitus. Diabetologia. 2003;46:1071–81.CrossRef
106.
go back to reference Trovati M, Carta Q, Franco Cavalot SV, Banaudi C, Lucchina PG, Fiocchi F, Emanuelli G, Lenti G. Influence of physical training on blood glucose control, glucose tolerance, insulin secretion, and insulin action in non-insulin-dependent diabetic patients. Diabetes Care. 1984;7:416–20.PubMedCrossRef Trovati M, Carta Q, Franco Cavalot SV, Banaudi C, Lucchina PG, Fiocchi F, Emanuelli G, Lenti G. Influence of physical training on blood glucose control, glucose tolerance, insulin secretion, and insulin action in non-insulin-dependent diabetic patients. Diabetes Care. 1984;7:416–20.PubMedCrossRef
107.
go back to reference Saltin B, Lindgarde F, Houston M, Horlin R, Nygaard E, Gad P. Physical training and glucose tolerance in middle-aged men with chemical diabetes. Diabetes. 1979;28(Suppl 1):30–2.PubMedCrossRef Saltin B, Lindgarde F, Houston M, Horlin R, Nygaard E, Gad P. Physical training and glucose tolerance in middle-aged men with chemical diabetes. Diabetes. 1979;28(Suppl 1):30–2.PubMedCrossRef
108.
go back to reference Brandenburg SL, Reusch JEB, Bauer TA, Jeffers BW, Hiatt WR, Regensteiner JG. Effects of exercise training on oxygen uptake kinetic responses in women with type 2 diabetes. Diabetes Care. 1999;22:1620–46.CrossRef Brandenburg SL, Reusch JEB, Bauer TA, Jeffers BW, Hiatt WR, Regensteiner JG. Effects of exercise training on oxygen uptake kinetic responses in women with type 2 diabetes. Diabetes Care. 1999;22:1620–46.CrossRef
109.
go back to reference The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369:145–54.PubMedCentralCrossRef The Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369:145–54.PubMedCentralCrossRef
110.
go back to reference Andrews RC, Cooper AR, Montgomery AA, Norcross AJ, Peters TJ, Sharp DJ, Jackson N, Fitzsimons K, Bright J, Coulman K, England CY, Gorton J, McLenaghan A, Paxton E, Polet A, Thompson C, Dayan CM. Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID Randomised Controlled Trial. Lancet. 2011;378:129–39.PubMedCrossRef Andrews RC, Cooper AR, Montgomery AA, Norcross AJ, Peters TJ, Sharp DJ, Jackson N, Fitzsimons K, Bright J, Coulman K, England CY, Gorton J, McLenaghan A, Paxton E, Polet A, Thompson C, Dayan CM. Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID Randomised Controlled Trial. Lancet. 2011;378:129–39.PubMedCrossRef
111.
go back to reference Bogardus C, Ravussin E, Robbins DC, Wolfe RR, Horton ES, Sims EAH. Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin-dependent diabetes mellitus. Diabetes. 1984;33:311–8.PubMedCrossRef Bogardus C, Ravussin E, Robbins DC, Wolfe RR, Horton ES, Sims EAH. Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin-dependent diabetes mellitus. Diabetes. 1984;33:311–8.PubMedCrossRef
112.
go back to reference Wycherley TP, Brinkworth GD, Noakes M, Buckley JD, Clifton PM. Effect of caloric restriction with and without exercise training on oxidative stress and endothelial function in obese subjects with type 2 diabetes. Diabetes Obes Metab. 2008;10:1062–73.PubMedCrossRef Wycherley TP, Brinkworth GD, Noakes M, Buckley JD, Clifton PM. Effect of caloric restriction with and without exercise training on oxidative stress and endothelial function in obese subjects with type 2 diabetes. Diabetes Obes Metab. 2008;10:1062–73.PubMedCrossRef
113.
go back to reference Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, Chasan-Taber L, Albright AL, Braun B. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care. 2010;33:e147–67.PubMedPubMedCentralCrossRef Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, Chasan-Taber L, Albright AL, Braun B. Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care. 2010;33:e147–67.PubMedPubMedCentralCrossRef
114.
go back to reference Pate RR, Pratt M, Blair SN, Haskell WL, Macera CA, Bouchard C, Buchner D, Ettinger W, Heath GW, King AC, et al. Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. JAMA. 1995;273:402–7.PubMedCrossRef Pate RR, Pratt M, Blair SN, Haskell WL, Macera CA, Bouchard C, Buchner D, Ettinger W, Heath GW, King AC, et al. Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. JAMA. 1995;273:402–7.PubMedCrossRef
115.
go back to reference Haskell WL, Lee I-M, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD, Bauman A. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation. 2007;116:1081–93.PubMedCrossRef Haskell WL, Lee I-M, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD, Bauman A. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation. 2007;116:1081–93.PubMedCrossRef
116.
go back to reference Lakka TA, Venäläinen JM, Rauramaa R, Salonen R, Tuomilehto J, Salonen JT. Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction. N Engl J Med. 1994;330:1549–54.PubMedCrossRef Lakka TA, Venäläinen JM, Rauramaa R, Salonen R, Tuomilehto J, Salonen JT. Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction. N Engl J Med. 1994;330:1549–54.PubMedCrossRef
117.
go back to reference Lee I-M, Sesso HD, Oguma Y, Paffenbarger RS Jr. Relative intensity of physical activity and risk of coronary heart disease. Circulation. 2003;107:1110–6.PubMedCrossRef Lee I-M, Sesso HD, Oguma Y, Paffenbarger RS Jr. Relative intensity of physical activity and risk of coronary heart disease. Circulation. 2003;107:1110–6.PubMedCrossRef
118.
go back to reference Manson JE, Colditz GA, Stampfer MJ, Willett WC, Krolewski AS, Rosner B, Arky RA, Speizer FE, Hennekens CH. A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med. 1991;151:1141–7.PubMedCrossRef Manson JE, Colditz GA, Stampfer MJ, Willett WC, Krolewski AS, Rosner B, Arky RA, Speizer FE, Hennekens CH. A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med. 1991;151:1141–7.PubMedCrossRef
119.
go back to reference Sesso HD, Stampfer MJ, Rosner B, Baziano JM, Hennekens CH. Two-year changes in blood pressure and subsequent risk of cardiovascular disease in men. Circulation. 2000;102:975–80.PubMedCrossRef Sesso HD, Stampfer MJ, Rosner B, Baziano JM, Hennekens CH. Two-year changes in blood pressure and subsequent risk of cardiovascular disease in men. Circulation. 2000;102:975–80.PubMedCrossRef
120.
go back to reference Swain DP, Franklin BA. Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise. Am J Cardiol. 2006;97:141–7.PubMedCrossRef Swain DP, Franklin BA. Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise. Am J Cardiol. 2006;97:141–7.PubMedCrossRef
121.
go back to reference Bergman H, Varnauskas E. The hemodynamic effects of physical training in coronary patients. Med Sport. 1970;4:138. Bergman H, Varnauskas E. The hemodynamic effects of physical training in coronary patients. Med Sport. 1970;4:138.
122.
go back to reference Clausen JP, Larsen OA, Trap-Jensen J. Physical training in the management of coronary artery disease. Circulation. 1969;40:143–54.PubMedCrossRef Clausen JP, Larsen OA, Trap-Jensen J. Physical training in the management of coronary artery disease. Circulation. 1969;40:143–54.PubMedCrossRef
123.
go back to reference Clausen JP, Trap-Jensen J. Effects of training on the distribution of cardiac output in patients with coronary artery disease. Circulation. 1970;42:611–24.PubMedCrossRef Clausen JP, Trap-Jensen J. Effects of training on the distribution of cardiac output in patients with coronary artery disease. Circulation. 1970;42:611–24.PubMedCrossRef
124.
go back to reference Detry JM, Rousseau M, Vandenbroucke G, Kusumi F, Brasseur LA, Bruce RA. Increased arteriovenous oxygen differences after physical training in coronary heart disease. Circulation. 1971;44:109–18.PubMedCrossRef Detry JM, Rousseau M, Vandenbroucke G, Kusumi F, Brasseur LA, Bruce RA. Increased arteriovenous oxygen differences after physical training in coronary heart disease. Circulation. 1971;44:109–18.PubMedCrossRef
125.
go back to reference Hagberg JM, Ehsani AA, Holloszy JO. Effect of 12 months of exercise training on stroke volume in patients with coronary artery disease. Circulation. 1983;67:1194–9.PubMedCrossRef Hagberg JM, Ehsani AA, Holloszy JO. Effect of 12 months of exercise training on stroke volume in patients with coronary artery disease. Circulation. 1983;67:1194–9.PubMedCrossRef
126.
go back to reference Ekblom B, Åstrand P-O, Saltin B, Stenberg J, Wallström B. Effect of training on circulatory response to exercise. J Appl Physiol. 1968;24:518–28.PubMed Ekblom B, Åstrand P-O, Saltin B, Stenberg J, Wallström B. Effect of training on circulatory response to exercise. J Appl Physiol. 1968;24:518–28.PubMed
127.
go back to reference Seals DR, Hagberg JM, Hurley BF, Ehsani AA, Holloszy JO. Endurance training in older men and women: cardiovascular responses to exercise. J Appl Physiol. 1984;57:1024–9.PubMed Seals DR, Hagberg JM, Hurley BF, Ehsani AA, Holloszy JO. Endurance training in older men and women: cardiovascular responses to exercise. J Appl Physiol. 1984;57:1024–9.PubMed
128.
go back to reference Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, Tjønna AE, Helgerud J, Slørdahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen Ø, Skjærpe T. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007;115:3086–94.PubMedCrossRef Wisløff U, Støylen A, Loennechen JP, Bruvold M, Rognmo Ø, Haram PM, Tjønna AE, Helgerud J, Slørdahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen Ø, Skjærpe T. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007;115:3086–94.PubMedCrossRef
129.
go back to reference Cassidy S, Thoma C, Hallsworth K, Parikh J, Hollingsworth KG, Taylor R, Jakovlejevic DG, Trenell MI. High intensity intermittent exercise improves cardiac structure and function and reduces liver fat in patients with type 2 diabetes: a randomised controlled trial. Diabetologia. 2016;59(1):56–66.PubMedCrossRef Cassidy S, Thoma C, Hallsworth K, Parikh J, Hollingsworth KG, Taylor R, Jakovlejevic DG, Trenell MI. High intensity intermittent exercise improves cardiac structure and function and reduces liver fat in patients with type 2 diabetes: a randomised controlled trial. Diabetologia. 2016;59(1):56–66.PubMedCrossRef
130.
go back to reference Rognmo Ø, Moholdt T, Bakken H, Hole T, Mølstad P, Myhr NE, Grimsmo J, Wisløff U. Cardiovascular risk of high-versus moderate-intensity aerobic exercise in coronary heart disease patients. Circulation. 2012;126:1436–40.PubMedCrossRef Rognmo Ø, Moholdt T, Bakken H, Hole T, Mølstad P, Myhr NE, Grimsmo J, Wisløff U. Cardiovascular risk of high-versus moderate-intensity aerobic exercise in coronary heart disease patients. Circulation. 2012;126:1436–40.PubMedCrossRef
131.
go back to reference Iscoe KE, Riddell MC. Continuous moderate-intensity exercise with or without intermittent high-intensity work: effects on acute and late glycaemia in athletes with type 1 diabetes mellitus. Diabet Med. 2011;28:824–32.PubMedCrossRef Iscoe KE, Riddell MC. Continuous moderate-intensity exercise with or without intermittent high-intensity work: effects on acute and late glycaemia in athletes with type 1 diabetes mellitus. Diabet Med. 2011;28:824–32.PubMedCrossRef
132.
go back to reference American College of Sports Medicine. The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness in healthy adults. Med Sci Sport Exerc. 1990;22:265–74. American College of Sports Medicine. The recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness in healthy adults. Med Sci Sport Exerc. 1990;22:265–74.
133.
go back to reference Martinez N, Kilpatrick MW, Salomon K, Jung ME, Little JP. Affective and enjoyment responses to high-intensity interval training in overweight-to-obese and insufficiently active adults. J Sport Exerc Psychol. 2015;37:138–49.PubMedCrossRef Martinez N, Kilpatrick MW, Salomon K, Jung ME, Little JP. Affective and enjoyment responses to high-intensity interval training in overweight-to-obese and insufficiently active adults. J Sport Exerc Psychol. 2015;37:138–49.PubMedCrossRef
134.
go back to reference Jung ME, Bourne JE, Beauchamp MR, Robinson E, Little JP. High-intensity interval training as an efficacious alternative to moderate-intensity continuous training for adults with prediabetes. J Diabetes Res. 2015;2015:191595.PubMedPubMedCentralCrossRef Jung ME, Bourne JE, Beauchamp MR, Robinson E, Little JP. High-intensity interval training as an efficacious alternative to moderate-intensity continuous training for adults with prediabetes. J Diabetes Res. 2015;2015:191595.PubMedPubMedCentralCrossRef
Metadata
Title
The Type 2 Diabetic Heart: Its Role in Exercise Intolerance and the Challenge to Find Effective Exercise Interventions
Authors
J. Chris Baldi
Genevieve A. Wilson
Luke C. Wilson
Gerard T. Wilkins
Regis R. Lamberts
Publication date
01-11-2016
Publisher
Springer International Publishing
Published in
Sports Medicine / Issue 11/2016
Print ISSN: 0112-1642
Electronic ISSN: 1179-2035
DOI
https://doi.org/10.1007/s40279-016-0542-9

Other articles of this Issue 11/2016

Sports Medicine 11/2016 Go to the issue