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Heart Failure Reviews
Published in: Heart Failure Reviews 2/2013

Open Access 01-03-2013

Diabetic cardiomyopathy: pathophysiology and clinical features

Authors: Takayuki Miki, Satoshi Yuda, Hidemichi Kouzu, Tetsuji Miura

Published in: Heart Failure Reviews | Issue 2/2013

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Abstract

Since diabetic cardiomyopathy was first reported four decades ago, substantial information on its pathogenesis and clinical features has accumulated. In the heart, diabetes enhances fatty acid metabolism, suppresses glucose oxidation, and modifies intracellular signaling, leading to impairments in multiple steps of excitation–contraction coupling, inefficient energy production, and increased susceptibility to ischemia/reperfusion injury. Loss of normal microvessels and remodeling of the extracellular matrix are also involved in contractile dysfunction of diabetic hearts. Use of sensitive echocardiographic techniques (tissue Doppler imaging and strain rate imaging) and magnetic resonance spectroscopy enables detection of diabetic cardiomyopathy at an early stage, and a combination of the modalities allows differentiation of this type of cardiomyopathy from other organic heart diseases. Circumstantial evidence to date indicates that diabetic cardiomyopathy is a common but frequently unrecognized pathological process in asymptomatic diabetic patients. However, a strategy for prevention or treatment of diabetic cardiomyopathy to improve its prognosis has not yet been established. Here, we review both basic and clinical studies on diabetic cardiomyopathy and summarize problems remaining to be solved for improving management of this type of cardiomyopathy.
Literature
1.
Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, Lin JK, Farzadfar F, Khang YH, Stevens GA, Rao M, Ali MK, Riley LM, Robinson CA, Ezzati M, Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Blood Glucose) (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 378:31–40PubMed
2.
Sobel BE (2007) Optimizing cardiovascular outcomes in diabetes mellitus. Am J Med 120(Suppl 2):S3–S11PubMed
3.
Gaede P, Pedersen O (2004) Intensive integrated therapy of type 2 diabetes: implications for long-term prognosis. Diabetes 53(Suppl 3):S39–S47PubMed
4.
From AM, Leibson CL, Bursi F, Redfield MM, Weston SA, Jacobsen SJ, Rodeheffer RJ, Roger VL (2006) Diabetes in heart failure: prevalence and impact on outcome in the population. Am J Med 119:591–599PubMed
5.
Bell DS (2003) Heart failure: the frequent, forgotten, and often fatal complication of diabetes. Diabetes Care 26:2433–2441PubMed
6.
Carrabba N, Valenti R, Parodi G, Santoro GM, Antoniucci D (2004) Left ventricular remodeling and heart failure in diabetic patients treated with primary angioplasty for acute myocardial infarction. Circulation 110:1974–1979PubMed
7.
Lewis EF, Velazquez EJ, Solomon SD, Hellkamp AS, McMurray JJ, Mathias J, Rouleau JL, Maggioni AP, Swedberg K, Kober L, White H, Dalby AJ, Francis GS, Zannad F, Califf RM, Pfeffer MA (2008) Predictors of the first heart failure hospitalization in patients who are stable survivors of myocardial infarction complicated by pulmonary congestion and/or left ventricular dysfunction: a VALIANT study. Eur Heart J 29:748–756PubMed
8.
Tocci G, Sciarretta S, Volpe M (2008) Development of heart failure in recent hypertension trials. J Hypertens 26:1477–1486PubMed
9.
Du X, Ninomiya T, de Galan B, Abadir E, Chalmers J, Pillai A, Woodward M, Cooper M, Harrap S, Hamet P, Poulter N, Lip GY, Patel A, ADVANCE Collaborative Group (2009) Risks of cardiovascular events and effects of routine blood pressure lowering among patients with type 2 diabetes and atrial fibrillation: results of the ADVANCE study. Eur Heart J 30:1128–1135PubMed
10.
MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, Solomon SD, Granger CB, Swedberg K, Yusuf S, Pfeffer MA, McMurray JJ, CHARM Investigators (2008) Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the candesartan in heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J 29:1377–1385PubMed
11.
Shah AM, Uno H, Køber L, Velazquez EJ, Maggioni AP, MacDonald MR, Petrie MC, McMurray JJ, Califf RM, Pfeffer MA, Solomon SD (2010) The inter-relationship of diabetes and left ventricular systolic function on outcome after high-risk myocardial infarction. Eur J Heart Fail 12:1229–1237PubMed
12.
Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A (1972) New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 30:595–602PubMed
13.
Aneja A, Tang WH, Bansilal S, Garcia MJ, Farkouh ME (2008) Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. Am J Med 121:748–757PubMed
14.
Factor SM, Minase T, Sonnenblick EH (1980) Clinical and morphological features of human hypertensive-diabetic cardiomyopathy. Am Heart J 99:446–458PubMed
15.
Van Hoeven KH, Factor SM (1990) A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive-diabetic heart disease. Circulation 82:848–855PubMed
16.
Goldin A, Beckman JA, Schmidt AM, Creager MA (2006) Advanced glycation end products. Sparking the development of diabetic vascular injury. Circulation 114:597–605PubMed
17.
Schalkwijk CG, Baidoshvili A, Stehouwer CD, van Hinsbergh VW, Niessen HW (2004) Increased accumulation of the glycoxidation product Nepsilon-(carboxymethyl)lysine in hearts of diabetic patients: generation and characterisation of a monoclonal anti-CML antibody. Biochim Biophys Acta 1636:82–89PubMed
18.
van Heerebeek L, Hamdani N, Handoko ML, Falcao-Pires I, Musters RJ, Kupreishvili K, Ijsselmuiden AJ, Schalkwijk CG, Bronzwaer JG, Diamant M, Borbély A, van der Velden J, Stienen GJ, Laarman GJ, Niessen HW, Paulus WJ (2008) Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation 117:43–51PubMed
19.
Falcão-Pires I, Hamdani N, Borbély A, Gavina C, Schalkwijk CG, van der Velden J, van Heerebeek L, Stienen GJ, Niessen HW, Leite-Moreira AF, Paulus WJ (2011) Diabetes mellitus worsens diastolic left ventricular dysfunction in aortic stenosis through altered myocardial structure and cardiomyocyte stiffness. Circulation 124:1151–1159PubMed
20.
Fischer VW, Barner HB, Larose LS (1984) Pathomorphologic aspects of muscular tissue in diabetes mellitus. Human Pathol 15:1127–1136
21.
Yarom R, Zirkin H, Stämmler G, Rose G (1992) Human coronary microvessels in diabetes and ischaemia. Morphometric study of autopsy material. J Pathol 166:265PubMed
22.
Kawaguchi M, Techigawara M, Ishihata T, Asakura T, Saito F, Maehara K, Maruyama Y (1997) A comparison of ultrastructural changes in endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension. Heart Vessels 12:267–271PubMed
23.
Sakata S, Lebeche D, Sakata Y, Sakata N, Chemaly ER, Liang L, Nakajima-Takenaka C, Tsuji T, Konishi N, del Monte F, Hajjar RJ, Takaki M (2007) Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a type 2 diabetic rat model. Am J Physiol Heart Circ Physiol 292:H1204–H1207PubMed
24.
Vahtola E, Louhelainen M, Merasto S, Martonen E, Penttinen S, Aahos I, Kytö V, Virtanen I, Mervaala E (2008) Forkhead class O transcription factor 3a activation and Sirtuin1 overexpression in the hypertrophied myocardium of the diabetic Goto-Kakizaki rat. J Hypertens 26:334–344PubMed
25.
Li J, Zhu H, Shen E, Wan L, Arnold JMO, Peng T (2010) Deficiency of Rac1 blocks NADH oxidase activation, inhibits endoplasmic reticulum stress, and reduces myocardial remodeling in a mouse model of type 1 diabetes. Diabetes 59:2033–2042PubMed
26.
Basu R, Oudit GY, Wang X, Zhang L, Ussher JR, Lopaschuk GD, Kassiri Z (2009) Type 1 diabetic cardiomyopathy in the Akita (Ins2WT/C96Y) mouse model is characterized by lipotoxicity and diastolic dysfunction with preserved systolic function. Am J Physiol Heart Circ Physiol 297:H2096–H2108PubMed
27.
Marso SP, Miller T, Rutherford BD, Gibbons RJ, Qureshi M, Kalynych A, Turco M, Schultheiss HP, Mehran R, Krucoff MW, Lansky AJ, Stone GW (2007) Comparison of myocardial reperfusion in patients undergoing percutaneous coronary intervention in ST-segment elevation acute myocardial infarction with versus without diabetes mellitus (from the EMERALD Trial). Am J Cardiol 100:206–210PubMed
28.
Algeria JR, Miller TD, Gibbons RJ, Yi QL, Yusuf S, Collaborative Organization of RheothRx Evaluation (CORE) Trial Investigators (2007) Infarct size, ejection fraction, and mortality in diabetic patients with acute myocardial infarction treated with thrombolytic therapy. Am Heart J 154:743–750
29.
Galderisi M, Anderson KM, Wilson PF, Levy D (1991) Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (The Framingham Heart Study). Am J Cardiol 68:85–89PubMed
30.
Devereux RB, Roman MJ, Paranicas M, O’Grady MJ, Lee ET, Welty TK, Fabsitz RR, Robbins D, Rhoades ER, Howard BV (2000) Impact of diabetes on cardiac structure and function: the Strong Heart Study. Circulation 101:2271–2276PubMed
31.
Bella JN, Devereux RB, Roman MJ, Palmieri V, Liu JE, Paranicas M, Welty TK, Lee ET, Fabsitz RR, Howard BV (2001) Separate and joint effects of systemic hypertension and diabetes mellitus on left ventricular structure and function in American Indians (the Strong Heart Study). Am J Cardiol 87:1260–1265PubMed
32.
Tenenbaum A, Fisman EZ, Schwammenthal E, Adler Y, Benderly M, Motro M, Shemesh J (2003) Increased prevalence of left ventricular hypertrophy in hypertensive women with type 2 diabetes mellitus. Cardiovasc Diabetol 2:14PubMed
33.
Rutter MK, Parise H, Benjamin EJ, Levy D, Larson MG, Meigs JB, Nesto RW, Wilson PW, Vasan RS (2003) Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study. Circulation 107:448–454PubMed
34.
Bertoni AG, Goff DC Jr, D’Agostino RB Jr, Liu K, Hundley WG, Lima JA, Polak JF, Saad MF, Szklo M, Tracy RP, Siscovick DS (2006) Diabetic cardiomyopathy and subclinical cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care 29:588–594PubMed
35.
Heckbert SR, Post W, Pearson GD, Arnett DK, Gomes AS, Jerosch-Herold M, Hundley WG, Lima JA, Bluemke DA (2006) Traditional cardiovascular risk factors in relation to left ventricular mass, volume, and systolic function by cardiac magnetic resonance imaging: the Multiethnic Study of Atherosclerosis. J Am Coll Cardiol 48:2285–2292PubMed
36.
Velagaleti RS, Gona P, Chuang ML, Salton CJ, Fox CS, Blease SJ, Yeon SB, Manning WJ, O’Donnell CJ (2010) Relations of insulin resistance and glycemic abnormalities to cardiovascular magnestic resonance measures of cardiac structure and function. The Framingham Heart Study. Circ Cardiovasc Imaging 3:257–263PubMed
37.
Schannwell CM, Schneppenheim M, Perings S, Plehn G, Stauer BE (2002) Left ventricular diastolic dysfunction as an early manifestation of diabetic cardiomyopathy. Cardiology 98:33–39PubMed
38.
Shishehbor MH, Hoogwerf BJ, Schoenhagen P, Marso SP, Sun JP, Li J, Klein AL, Thomas JD, Garcia MJ (2003) Relation of hemoglobin A1c to left ventricular relaxation in patients with type 1 diabetes mellitus and without overt heart disease. Am J Cardiol 91:1514–1517PubMed
39.
Grandi AM, Piantanida E, Franzetti I, Bernasconi M, Maresca A, Marnini P, Guasti L, Venco A (2006) Effect of glycemic control on left ventricular diastolic function in type 1 diabetes mellitus. Am J Cardiol 97:71–76PubMed
40.
Palmieri V, Capaldo B, Russo C, Iaccarino M, Di Minno G, Riccardi G, Celentano A (2006) Left ventricular chamber and myocardial systolic function reserve in patients with type 1 diabetes mellitus: insight from traditional and Doppler tissue imaging echocardiography. J Am Soc Echocardiogr 19:848–856PubMed
41.
Gul K, Celebi AS, Kacmaz F, Ozcan OC, Ustun I, Berker D, Aydin Y, Delibasi T, Guler S, Barazi AO (2009) Tissue Doppler imaging must be performed to detect early left ventricular dysfunction in patients with type 1 diabetes mellitus. Eur J Echocardiogr 10:841–846PubMed
42.
Nadeau KJ, Regensteiner JG, Bauer TA, Brown MS, Dorosz JL, Hull A, Zeitler P, Draznin B, Reusch JE (2010) Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function. J Clin Endocrinol Metab 95:513–521PubMed
43.
Picano E, Pelosi G, Marzilli M, Lattanzi F, Benassi A, Landini L, L’Abbate A (1990) In vivo quantitative ultrasonic evaluation of myocardial fibrosis in humans. Circulation 81:58–64PubMed
44.
Pérez JE, McGill JB, Santiago JV, Schechtman KB, Waggoner AD, Miller JG, Sobel BE (1992) Abnormal myocardial acoustic properties in diabetic patients and their correlation with the severity of disease. J Am Coll Cardiol 19:1154–1162PubMed
45.
Di Bello V, Talarico L, Picano E, Di Muro C, Landini L, Paterni M, Matteucci E, Giusti C, Giampietro O (1995) Increased echodensity of myocardial wall in the diabetic heart: an ultrasound tissue characterization study. J Am Coll Cardiol 25:1408–1415PubMed
46.
Kwong RY, Sattar H, Wu H, Vorobiof G, Gandla V, Steel K, Siu S, Brown KA (2008) Incidence and prognostic implication of unrecognized myocardial scar characterized by cardiac magnetic resonance in diabetic patients without clinical evidence of myocardial infarction. Circulation 118:1011–1020PubMed
47.
Ha JW, Lee HC, Kang ES, Ahn CM, Kim JM, Ahn JA, Lee SW, Choi EY, Rim SJ, Oh JK, Chung N (2007) Abnormal left ventricular longitudinal functional reserve in patients with diabetes mellitus: implication for detecting subclinical myocardial dysfunction using exercise tissue Doppler echocardiograpjhy. Heart 93:1571–1576PubMed
48.
Acar G, Akcay A, Sokmen A, Ozkaya M, Guler E, Sokmen G, Kaya H, Nacar B, Tuncer C (2009) Assessment of atrial electromechanical delay, diastolic functions, and left atrial mechanical functions in patients with type 1 diabetes mellitus. J Am Soc Echocardiogr 22:732–738PubMed
49.
Poirier P, Bogaty P, Garneau C, Marois L, Dumesnil JG (2001) Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. Diabetes Care 24:5–10PubMed
50.
Zabalgoitia M, Ismaeil MF, Anderson L, Maklady FA (2001) Prevalence of diastolic dysfunction in normotensive, asymptomatic patients with well-controlled type 2 diabetes mellitus. Am J Cardiol 87:320–323PubMed
51.
Boyer JK, Thanigaraj S, Schechtman KB, Pérez JE (2004) Prevalence of ventricular diastolic dysfunction in asymptomatic, normotensive patients with diabetes mellitus. Am J Cardiol 93:870–875PubMed
52.
Kosmala W, Kucharski W, Przewlocka-Kosmala M, Mazurek W (2004) Comparison of left ventricular function by tissue Doppler imaging in patients with diabetes mellitus without systemic hypertension versus diabetes mellitus with systemic hypertension. Am J Cardiol 94:395–399PubMed
53.
Di Bonito P, Moio N, Cavuto L, Covino G, Murena E, Scilla C, Turco S, Capaldo B, Sibilio G (2005) Early detection of diabetic cardiomyopathy: usefulness of tissue Doppler imaging. Diabet Med 22:1720–1725PubMed
54.
Andersen NH, Poulsen SH, Eiskjaer H, Poulsen PL, Mogensen CE (2003) Decreased left ventricular longitudinal contraction in normotensive and normoalbuminuric patients with type II diabetes mellitus: a Doppler tissue tracking and strain rate echocardiography study. Clin Sci 105:59–66PubMed
55.
Vinereanu D, Nicolaides E, Tweddel AC, Mädler CF, Holst B, Boden LE, Cinteza M, Rees AE, Fraser AG (2003) Subclinical left ventricular dysfunction in asymptomatic patients with type II diabetes mellitus, related to serum lipids and glycated haemoglobin. Clin Sci 105:591–599PubMed
56.
Muranaka A, Yuda S, Tsuchihashi K, Hashimoto A, Nakata T, Miura T, Tsuzuki M, Wakabayashi C, Watanabe N, Shimamoto K (2009) Quantitative assessment of left ventricular and left atrial functions by strain rate imaging in diabetic patients with and without hypertension. Echocardiography 26:262–271PubMed
57.
Ng AC, Delgado V, Bertini M, van der Meer RW, Rijzewijk LJ, Shanks M, Nucifora G, Smit JW, Diamant M, Romijn JA, de Roos A, Leung DY, Lamb HJ, Bax JJ (2009) Findings from left ventricular strain and strain rate imaging in asymptomatic patients with type 2 diabetes mellitus. Am J Cardiol 104:1398–1401PubMed
58.
Ernande L, Rietzschel ER, Bergerot C, De Buyzere ML, Schnell F, Groisne L, Ovize M, Croisille P, Moulin P, Gillebert TC, Derumeaux G (2010) Impaired myocardial radial function in asymptomatic patients with type 2 diabetes mellitus: a speckle-tracking imaging study. J Am Soc Echocardiogr 23:1266–1272PubMed
59.
Jellis CL, Stanton T, Leano R, Martin J, Marwick TH (2011) Usefulness of at rest and exercise hemodynamics to detect subclinical myocardial disease in type 2 diabetes mellitus. Am J Cardiol 107:615–621PubMed
60.
Palmieri V, Capaldo B, Russo C, Iaccarino M, Pezzullo S, Quintavalle G, Di Minno G, Riccardi G, Celentano A (2008) Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: insights from echocardiography and exercise cardiac performance evaluation. Diabetes Res Clin Pract 79:262–268PubMed
61.
Hare JL, Hordern MD, Leano R, Stanton T, Prins JB, Marwick TH (2011) Application of an exercise intervention on the evolution of diastolic dysfunction in patients with diabetes mellitus: efficacy and effectiveness. Circ Heart Fail 4:441–449PubMed
62.
Gallego M, Casis O (2001) Regulation of cardiac transient outward potassium current by norepinephrine in normal and diabetic rats. Diabetes Metab Res Rev 17:304–309PubMed
63.
Shimoni Y, Hunt D, Chuang M, Chen KY, Kargacin G, Severson DL (2005) Modulation of potassium currents by angiotensin and oxidative stress in cardiac cells from the diabetic rat. J Physiol 567:177–190PubMed
64.
Pereira L, Matthes J, Schuster I, Valdivia HH, Herzig S, Richard S, Gómez AM (2006) Mechanisms of [Ca2+]I transient decrease in cardiomyopathy of db/db type 2 diabetic mice. Diabetes 55:608–615PubMed
65.
Lacombe VA, Viatchenko-Karpinski S, Terentyev D, Sridhar A, Emani S, Bonagura JD, Feldman DS, Györke S, Carnes CA (2007) Mechanisms of impaired calcium handling underlying subclinical diastolic dysfunction in diabetes. Am J Physiol Regul Integr Comp Physiol 293:R1787–R1797PubMed
66.
Gallego M, Alday A, Urrutia J, Casis O (2009) Transient outward potassium channel regulation in healthy and diabetic hearts. Can J Physiol Pharmacol 87:77–83PubMed
67.
Lagadic-Gossmann D, Buckler KJ, Le Prigent K, Feuvray D (1996) Altered Ca2+ handling in ventricular myocytes isolated from diabetic rats. Am J Physiol 270:H1529–H1537PubMed
68.
Belke DD, Swanson EA, Dillmann WH (2004) Decreased sarcoplasmic reticulum activity and contractility in diabetic db/db mouse heart. Diabetes 53:3201–3208PubMed
69.
Yaras N, Bilginoglu A, Vassort G, Turan B (2007) Restoration of diabetes-induced abnormal local Ca2+ release in cardiomyocytes by angiontensin II receptor blockade. Am J Phyiol Heart Circ Physiol 292:H912–H920
70.
Ishikawa T, Kajiwara H, Kurihara S (1999) Alterations in contractile properties and Ca2+ handling in streptozotocin-induced diabetic rat myocardium. Am J Physiol 277:H2185–H2194PubMed
71.
Zhang L, Cannell MB, Phillips AR, Cooper GJ, Ward ML (2008) Altered calcium homeostasis does not explain the contractile deficit of diabetic cardiomyopathy. Diabetes 57:2158–2166PubMed
72.
Howarth FC, Shafiullah M, Qureshi MA (2007) Chronic effects of type 2 diabetes mellitus on cardiac muscle contraction in the Goto-Kakizaki rat. Exp Physiol 92:1029–1036PubMed
73.
Barth AS, Tomaselli GF (2009) Cardiac metabolism and arrhythmias. Circ Arrhythm Electrophysiol 2:327–335PubMed
74.
Howarth FC, Qureshi MA, Hassan Z, Al Kury LT, Isaev D, Parekh K, Yammahi SR, Oz M, Adrian TE, Adeghate E (2011) Changing pattern of gene expression is associated with ventricular myocyte dysfunction and altered mechanisms of Ca2+ signaling in young type 2 Zucker diabetic fatty rat heart. Exp Physiol 96:325–337PubMed
75.
Sah R, Oudit GY, Nguyen TT, Lim HW, Wickenden AD, Wilson GJ, Molkentin JD, Backx PH (2002) Inhibition of calcineurin and sarcolemmal Ca2+ influx protects cardiac morphology and ventricular function in Kv4.2N transgenic mice. Circulation 105:1850–1856PubMed
76.
Wu P, Sato J, Zhao Y, Jaskiewcz J, Popov KM, Harris RA (1998) Starvation and diabetes increase the amount of pruvate dehydrogenase kinase isoenzyme 4 in rat heart. Biochem J 329:197–201PubMed
77.
Huang B, Wu P, Popov KM, Harris RA (2003) Starvation and diabetes reduce the amount of pyruvate dehydrogenase phosphatase in rat heart and kidney. Diabetes 52:1371–1376PubMed
78.
Schroeder MA, Cochlin LE, Heather LC, Clarke K, Radda GK, Tyler DJ (2008) In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance. Proc Natl Acad Sci USA 105:12051–12056PubMed
79.
Rozanski GJ, Xu Z, Zhang K, Patel KP (1998) Altered K+ current of ventricular myocytes in rats with chronic myocardial infarction. Am J Physiol 274:H259–H265PubMed
80.
Huang B, Wu P, Bowker-Kinley MM, Harris RA (2002) Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin. Diabetes 51:276–283PubMed
81.
Sugden MC, Holness MJ (2006) Mechanisms underlying regulation of the expression and activities of the mammalian pyruvate dehydrogenase kinases. Arch Physiol Biochem 112:139–149PubMed
82.
Marionneau C, Aimond F, Brunet S, Niwa N, Finck B, Kelly DP, Nerbonne JM (2008) PPARalpha-mediated remodeling of repolarizing voltage-gated K+ (Kv) channels in a mouse model of metabolic cardiomyopathy. J Mol Cell Cardiol 44:1002–1015PubMed
83.
Belke DD, Dillmann WH (2004) Altered cardiac calcium handling in diabetes. Curr Hypertens Rep 6:424–429PubMed
84.
Bidasee KR, Zhang Y, Shao CH, Wang M, Patel KP, Dincer UD, Besch HR Jr (2004) Diabetes increases formation of advanced glycation end products on Sarco(endo)plasmic reticulum Ca2+-ATPase. Diabetes 53:463–473PubMed
85.
Clark RJ, McDonough PM, Swanson E, Trost SU, Suzuki M, Fukuda M, Dillmann WH (2003) Diabetes and the accompanying hyperglycemia impairs cardiomyocyte calcium cycling through increased nuclear O-GlcNAcylation. J Biol Chem 278:44230–44237PubMed
86.
Hu Y, Belke D, Suarez J, Swanson E, Clark R, Hoshijima M, Dillmann WH (2005) Adenovirus-mediated overexpression of O-GlcNAcase improves contractile function in the diabetic heart. Circ Res 96:1006–1013PubMed
87.
Yaras N, Ugur M, Ozdemir S, Gurdal H, Purali N, Lacampagne A, Vassort G, Turan B (2005) Effects of diabetes on ryanodine receptor Ca release channel (RyR2) and Ca2+ homeostasis in rat heart. Diabetes 54:3082–3088PubMed
88.
Malhotra A, Sanghi V (1997) Regulation of contractile proteins in diabetic heart. Cardiovasc Res 34:34–40PubMed
89.
Falcao-Pires I, Palladini G, Gonçalves N, van der Velden J, Moreira-Gonçalves D, Miranda-Silva D, Salinaro F, Paulus WJ, Niessen HW, Perlini S, Leite-Moreira AF (2011) Distinct mechanisms for diastolic dysfunction in diabetes mellitus and chronic pressure-overload. Basic Res Cardiol 106:801–814PubMed
90.
Jweied EE, McKinney RD, Walker LA, Brodsky I, Geha AS, Massad MG, Buttrick PM, de Tombe PP (2005) Depressed cardiac myofilament function in human diabetes mellitus. Am J Physiol Heart Circ Physiol 289:H2478–H2483PubMed
91.
Taegtmeyer H (1994) Energy metabolism of the heart: from basic concepts to clinical application. Curr Prob Cardiol 19:59–113
92.
Ingwall JS, Weiss RG (2004) Is the failing heart energy starved? On using chemical energy to support cardiac function. Circ Res 95:135–145PubMed
93.
Knaapen P, Germans T, Knuuti J, Paulus WJ, Dijkmans PA, Allaart CP, Lammertsma AA, Visser FC (2007) Myocardial energetics and efficiency: current status of the noninvasive approach. Circulation 15:918–927
94.
Madrazo JA, Kelly DP (2008) The PPAR trio: regulators of myocardial energy metabolism in health and disease. J Mol Cell Cardiol 44:968–975PubMed
95.
Hafstad AD, Khalid AM, Hagve M, Lund T, Larsen TS, Severson DL, Clarke K, Berge RK, Aasum E (2009) Cardiac peroxisome proliferator-activated receptor-α activation causes increased fatty acid oxidation, reducing efficiency and postischaemic functional loss. Cardiovasc Res 83:519–526PubMed
96.
Buchanan J, Mazumder PK, Hu P, Chakrabarti G, Roberts MW, Yun UJ, Cooksey RC, Litwin SE, Abel ED (2005) Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hypoglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology 146:5341–5349PubMed
97.
Hafstad AD, Solevåg GH, Severson DL, Larsen TS, Aasum E (2006) Perfused hearts from type 2 diabetic (db/db) mice show metabolic responsiveness to insulin. Am J Physiol Heart Circ Physiol 290:H1763–H1769PubMed
98.
Desrois M, Sidell RJ, Gauguier D, King LM, Radda GK, Clarke K (2004) Initial steps of insulin signaling and glucose transport are defective in the type 2 diabetic rat heart. Cardiovasc Res 61:288–296PubMed
99.
Deng JY, Huang JP, Lu LS, Hung LM (2007) Impairment of cardiac insulin signaling and myocardial contractile performance in high cholesterol/fructose-fed rats. Am J Physiol Heart Circ Physiol 293:H978–H987PubMed
100.
Hue L, Taegtmeyer H (2009) The Randle cycle revisited: a new head for and old hat. Am J Physiol Endocrinol Metab 297:E578–E591PubMed
101.
Heather LC, Clarke K (2011) Metabolism, hypoxia and the diabetic heart. J Mol Cell Cardiol 50:598–605PubMed
102.
Bugger H, Abel ED (2010) Mitochondria in the diabetic heart. Cardiovasc Res 88:229–240PubMed
103.
Echtay KS, Roussel D, St-Pierre J, Jekabsons MB, Cadenas S, Stuart JA, Harper JA, Roebuck SJ, Morrison A, Pickering S, Clapham JC, Brand MD (2002) Superoxide activates mitochondrial uncoupling proteins. Nature 415:96–99PubMed
104.
Echtay KS, Esteves TC, Pakay JL, Jekabsons MB, Lambert AJ, Portero-Otín M, Pamplona R, Vidal-Puig AJ, Wang S, Roebuck SJ, Brand MD (2003) A signaling role for 4-hydroxy-2-neonal in regulation of mitochondrial uncoupling. EMBO J 22:4103–4110PubMed
105.
Serpillon S, Floyd BC, Gupte RS, George S, Kozicky M, Neito V, Recchia F, Stanley W, Wolin MS, Gupte SA (2009) Superoxide production of NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH. Am J Physiol Heart Circ Physiol 297:H153–H162PubMed
106.
Li S, Li X, Li YL, Shao CH, Bidasee KR, Rozanski GJ (2007) Insulin regulation of glutathione and contractile phenotype in diabetic rat ventricular myocytes. Am J Physiol Heart Circ Physiol 292:H1619–H1629PubMed
107.
Scheuermann-Freestone M, Madsen PL, Manners D, Blamire AM, Buckingham RE, Styles P, Radda GK, Neubauer S, Clarke K (2003) Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes. Circulation 107:3040–3046PubMed
108.
Rijzewijk LJ, Jonker JT, van der Meer RW, Lubberink M, de Jong HW, Romijn JA, Bax JJ, de Roos A, Heine RJ, Twisk JW, Windhorst AD, Lammertsma AA, Smit JW, Diamant M, Lamb HJ (2010) Effects of hepatic triglyceride content on myocardial metabolism in type 2 diabetes. J Am Coll Cardiol 56:225–233PubMed
109.
Berg TJ, Snorgaard O, Faber J, Torjesen PA, Hildebrandt P, Mehlsen J, Hanssen KF (1999) Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes. Diabetic Care 22:1186–1190
110.
Yoshida N, Okumura K, Aso Y (2005) High serum pentosidine concentrations are associated with increased arterial stiffness and thickness in patients with type 2 diabetes. Metabolism 54:345–350PubMed
111.
Daroux M, Prévost G, Maillard-Lefebvre H, Gaxatte C, D’Agati VD, Schmidt AM, Boulanger E (2010) Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies. Diabetes Metab 36:1–10PubMed
112.
Verzijl N, DeGroot J, Thorpe SR, Bank RA, Shaw JN, Lyons TJ, Bijlsma JW, Lafeber FP, Baynes JW, TeKoppele JM (2000) Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem 275:39027–39031PubMed
113.
Lapolla A, Piarulli F, Sartore G, Ceriello A, Ragazzi E, Reitano R, Baccarin L, Laverda B, Fedele D (2007) Advanced glycation end products and antioxidant status in type 2 diabetic patients with and without peripheral artery disease. Diabetes Care 30:670–676PubMed
114.
Norton GR, Candy G, Woodiwiss AJ (1996) Aminoguanidine prevents the decreased myocardial compliance produced by streptozotocin-induced diabetes mellitus in rats. Circulation 93:1905–1912PubMed
115.
Wu MS, Liang JT, Lin YD, Wu ET, Tseng YZ, Chang KC (2008) Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide-induced type 2 diabetes. Br J Pharmacol 154:758–764PubMed
116.
Liu J, Masurekar MR, Vatner DE, Jyothirmayi GN, Regan TJ, Vatner SF, Meggs LG, Malhotra A (2003) Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. Am J Physiol Heart Circ Physiol 285:H2587–H2591PubMed
117.
Little WC, Zile MR, Kitzman DW, Hundley WG, O’Brien TX, Degroof RC (2005) The effect of alagebrium chloride (ATL-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail 11:191–195PubMed
118.
Reuter H, Adam C, Grönke S, Zobel C, Frank KF, Müller-Ehmsen J, Brabender J, Schwinger RH (2006) The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin-angiotensin system. Diabetologia 49:3067–3074PubMed
119.
Hotta H, Miura T, Miki T, Togashi N, Maeda T, Kim SJ, Tanno M, Yano T, Kuno A, Itoh T, Satoh T, Terashima Y, Ishikawa S, Shimamoto K (2010) Angiotensin II type 1 receptor-mediated upregulation of calcineurin activity underlies impairment of cardioprotective signaling in diabetic hearts. Circ Res 106:129–132PubMed
120.
Rosenkranz S (2004) TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res 63:423–432PubMed
121.
Chen K, Mehta JL, Li D, Joseph L, Joseph J (2004) Transforming growth factor beta receptor endoglin is expressed in cardiac fibroblasts and modulates profibrogenic actions of angiotensin II. Circ Res 95:1167–1173PubMed
122.
Factor SM, Okun EM, Minase T (1980) Capillary microaneurysms in the human diabetic heart. N Engl J Med 302:384–388PubMed
123.
Factor SM, Minase T, Cho S, Fein F, Capasso JM, Sonnenblick EH (1984) Coronary microvascular abnormalities in the hypertensive-diabetic rat. A primary cause of cardiomyopathy? Am J Pathol 116:9–20PubMed
124.
Yoon YS, Uchida S, Masuo O, Cejna M, Park JS, Gwon HC, Kirchmair R, Bahlman F, Walter D, Curry C, Hanley A, Isner JM, Losordo DW (2005) Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy: restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor. Circulation 111:2073–2085PubMed
125.
He Z, Opland DM, Way KJ, Ueki K, Bodyak N, Kang PM, Izumo S, Kulkarni RN, Wang B, Liao R, Kahn CR, King GL (2006) Regulation of vascular endothelial growth factor expression and vascularization in the myocardium by insulin receptor and PI3K/Akt pathways in insulin resistance and ischemia. Arterioscler Thromb Vasc Biol 26:787–793PubMed
126.
Chou E, Suzuma I, Way KJ, Opland D, Clermont AC, Naruse K, Suzuma K, Bowling NL, Vlahos CJ, Aiello LP, King GL (2002) Decreased cardiac expression of vascular endothelial growth factor and its receptors in insulin-resistant and diabetic states: a possible explanation for impaired collateral formation in cardiac tissue. Circulation 105:373–379PubMed
127.
Marfella R, Esposito K, Nappo F, Siniscalchi M, Sasso FC, Portoghese M, Di Marino MP, Baldi A, Cuzzocrea S, Di Filippo C, Barboso G, Baldi F, Rossi F, D’Amico M, Giugliano D (2004) Expression of angiogenic factors during acute coronary syndromes in human type 2 diabetes. Diabetes 53:2383–2391PubMed
128.
Sasso FC, Torella D, Carbonara O, Ellison GM, Torella M, Scardone M, Marra C, Nasti R, Marfella R, Cozzolino D, Indolfi C, Cotrufo M, Torella R, Salvatore T (2005) Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease. J Am Coll Cardiol 46:827–834PubMed
129.
Yu Y, Ohmori K, Kondo I, Yao L, Noma T, Tsuji T, Mizushige K, Kohno M (2002) Correlation of functional and structural alterations of the coronary arterioles during development of type II diabetes mellitus in rats. Cardiovasc Res 56:303–311PubMed
130.
Hayashi T, Sohmiya K, Ukimura A, Endoh S, Mori T, Shimomura H, Okabe M, Terasaki F, Kitaura Y (2003) Angiotensin II receptor blockade prevents microangiopathy and preserves diastolic function in the diabetic rat heart. Heart 89:1236–1242PubMed
131.
Mizuno R, Fujimoto S, Saito Y, Nakamura S (2010) Exercise-induced delayed onset of left ventricular early relaxation in association with coronary microcirculatory dysfunction in patients with diabetes mellitus. J Card Fail 16:211–217PubMed
132.
Zieman SJ, Melenovsky V, Clattenburg L, Corretti MC, Capriotti A, Gerstenblith G, Kass DA (2007) Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. J Hypertens 25:577–583PubMed
133.
Forrat R, Sebbag L, Wiernsperger N, Guidollet J, Renaud S, de Lorgeril M (1993) Acute myocardial infarction in dogs with experimental diabetes. Cardiovasc Res 27:1908–1912PubMed
134.
Marfella R, D’Amico M, Di Filippo C, Piegari E, Nappo F, Esposito K, Berrino L, Rossi F, Giugliano D (2002) Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1. Diabetologia 45:1172–1181PubMed
135.
Marfella R, Di Filippo C, Esposito K, Nappo F, Piegari E, Cuzzocrea S, Berrino L, Rossi F, Giugliano D, D’Amico M (2004) Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice. Diabetes 53:454–462PubMed
136.
Xiao CY, Chen M, Zsengellér Z, Szabó C (2004) Poly(ADP-ribose) polymerase contributes to the development of myocardial infarction in diabetic rats and regulates the nuclear translocation of apoptosis-inducing factor. J Pharmacol Exp Ther 310:498–504PubMed
137.
Di Filippo C, Marfella R, Cuzzocrea S, Piegari E, Petronella P, Giugliano D, Rossi F, D’Amico M (2005) Hyperglycemia in streptozotocin-induced diabetic rat increases infarct size associated with low levels of myocardial HO-1 during ischemia/reperfusion. Diabetes 54:803–810PubMed
138.
Liu X, Wei J, Peng DH, Layne MD, Yet SF (2005) Absence of heme oxygenase-1 exacerbates myocardial ischemia/reperfusion injury in diabetic mice. Diabetes 54:778–784PubMed
139.
Thirunavukkarasu M, Penumathsa SV, Koneru S, Juhasz B, Zhan L, Otani H, Bagchi D, Das DK, Maulik N (2007) Reseveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: role of nitric oxide, thioredoxin, and heme oxygenase. Free Radic Biol Med 43:720–729PubMed
140.
Jordan JE, Simandle SA, Tulbert CD, Busija DW, Miller AW (2003) Fructose-fed rats are protected against ischemia/reperfusion injury. J Pharmacol Exp Ther 307:1007–1011PubMed
141.
Katakam PV, Jordan JE, Snipes JA, Tulbert CD, Miller AW, Busija DW (2007) Myocardial preconditioning against ischemia-reperfusion injury is abolished in Zucker obese rats with insulin resistance. Am J Physiol Regul Integr Comp Physiol 292:R920–R926PubMed
142.
La Bonte LR, Davis-Gorman G, Stahl GL, McDonagh PF (2008) Complement inhibition reduces injury in the type 2 diabetic heart following ischemia/reperfusion. Am J Physiol Heart Circ Physiol 294:H1282–H1290PubMed
143.
Miki T, Miura T, Hotta H, Tanno M, Yano T, Sato T, Terashima Y, Takada A, Ishikawa S, Shimamoto K (2009) Endoplasmic reticulum stress in diabetic hearts abolishes erythropoietin-induced myocardial protection by impairment of phosphor-glycogen synthase kinase-3beta-mediated suppression of mitochondrial permeability transition. Diabetes 58:2863–2872PubMed
144.
Bouhidel O, Pons S, Souktani R, Zini R, Berdeaux A, Ghaleh B (2008) Myocardial ischemic postconditioning against ischemia-reperfusion is impaired in ob/ob mice. Am J Physiol Heart Circ Physiol 295:H1580–H1586PubMed
145.
Liu Y, Thornton JD, Cohen MV, Downey JM, Schaffer SW (1993) Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction. Circulation 88:1273–1278PubMed
146.
Hadour G, Ferrera R, Sebbag L, Forrat R, Delaye J, de Lorgeril M (1998) Improved myocardial tolerance to ischaemia in the diabetic rabbit. J Mol Cell Cardiol 30:1869–1875PubMed
147.
Ravingerová T, Neckár J, Kolár F (2003) Ischemic tolerance of rat hearts in acute and chronic phases of experimental diabetes. Mol Cell Biochem 249:167–174PubMed
148.
Mozaffari MS, Schaffer SW (2003) Effect of hypertension and hypertension-glucose intolerance on myocardial ischemic injury. Hypertension 42:1042–1049PubMed
149.
Xu G, Takashi E, Kudo M, Ishiwata T, Naito Z (2004) Contradictory effects of short- and long-term hyperglycemias on ischemic injury of myocardium via intracellular signaling pathway. Exp Mol Pathol 76:57–65PubMed
150.
Ma G, Al-Shabrawey M, Johnson JA, Datar R, Tawfik HE, Guo D, Caldwell RB, Caldwell RW (2006) Protection against myocardial ischemia/reperfusion injury by short-term diabetes: enhancement of VEGF formation, capillary density, and activation of cell survival signaling. Naunyn Schmiedebergs Arch Pharmacol 373:415–427PubMed
151.
Galagudza MM, Nekrasova MK, Syrenskii AV, Nifontov EM (2007) Resistance of the myocardium to ischemia and the efficacy of ischemic preconditioning in experimental diabetes mellitus. Neurosci Behav Physiol 37:489–493PubMed
152.
Kravchuk E, Grineva E, Bairamov A, Galagudza M, Vlasov T (2011) The effect of metformin on the myocardial tolerance to ischemia-reperfusion injury in the rat model of diabetes mellitus type II. Exp Diabetes Res 2011:907496PubMed
153.
Kristiansen SB, Løfgren B, Støttrup NB, Khatir D, Nielsen-Kudsk JE, Nielsen TT, Bøtker HE, Flyvbjerg A (2004) Ischaemic preconditioning does not protect the heart in obese and lean animal models of type 2 diabetes. Diabetologia 47:1716–1721PubMed
154.
Kristiansen SB, Løfgren B, Nielsen JM, Støttrup NB, Buhl ES, Nielsen-Kudsk JE, Nielsen TT, Rungby J, Flyvbjerg A, Bøtker HE (2011) Comparison of two sulfonylureas with high and low myocardial KATP channel affinity on myocardial infarct size and metabolism in a rat model of type 2 diabetes. Diabetologia 54:451–458PubMed
155.
Vogel WM, Apstein CS (1988) Effects of alloxan-induced diabetes on ischemia-reperfusion injury in rabbit hearts. Circ Res 62:975–982PubMed
156.
Joyeux M, Faure P, Godin-Ribuot D, Halimi S, Patel A, Yellon DM, Demenge P, Ribuot C (1999) Heat stress fails to protect myocardium of streptozotocin-induced diabetic rats against infarction. Cardiovasc Res 43:939–946PubMed
157.
Kersten JR, Toller WG, Gross ER, Pagel PS, Warltier DC (2000) Diabetes abolishes ischemic preconditioning: role of glucose, insulin, and osmolality. Am J Physiol Heart Circ Physiol 278:H1218–H1224PubMed
158.
Kersten JR, Montgomery MW, Ghassemi T, Gross ER, Toller WG, Pagel PS, Warltier DC (2001) Diabetes and hyperglycemia impair activation of mitochondrial KATP channels. Am J Physiol Heart Circ Physiol 280:H1744–H1750PubMed
159.
Nieszner E, Posa I, Kocsis E, Pogátsa G, Préda I, Koltai MZ (2002) Influence of diabetic state and that of different sulfonylureas on the size of myocardial infarction with and without ischemic preconditioning in rabbits. Exp Clin Endocrionol Diabetes 110:212–218
160.
Ebel D, Müllenheim J, Frässdorf J, Heinen A, Huhn R, Bohlen T, Ferrari J, Südkamp H, Preckel B, Schlack W, Thämer V (2003) Effect of acute hyperglycemia and diabetes mellitus with and without short-term insulin treatment on myocardial ischaemic late preconditioning in the rabbit heart in vivo. Pflugers Arch 446:175–182PubMed
161.
Gross ER, Hsu AK, Gross GJ (2007) Diabetes abolishes morphin-induced cardioprotection via multiple pathways upstream of glycogen synthase kinse-3beta. Diabetes 56:127–136PubMed
162.
Ghaboura N, Tamareille S, Ducluzeau PH, Grimaud L, Loufrani L, Croué A, Tourmen Y, Henrion D, Furber A, Prunier F (2011) Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling. Basic Res Cardiol 106:147–162PubMed
163.
Drenger B, Ostrovsky IA, Barak M, Nechemia-Arbely Y, Ziv E, Axelrod JH (2011) Diabetes blockade of sevoflurane postconditioning is not restored by insulin in the rat heart: phosphorylated signal transducer and activator of transcription 3- and phosphatidylinositol 3-kinase-mediated inhibition. Anesthesiology 114:1364–1372PubMed
164.
Okazaki T, Otani H, Shimazu T, Yoshioka K, Fujita M, Katano T, Ito S, Iwasaka T (2011) Reversal of inducible nitric oxide synthase uncoupling unmasks tolerance to ischemia/reperfusion injury in the diabetic rat heart. J Mol Cell Cardiol 50:534–544PubMed
165.
Przyklenk K, Maynard M, Greiner DL, Whittaker P (2011) Cardioprotection with postconditioning: loss of efficacy in murine models of type-2 and type-1 diabetes. Antioxid Redox Signal 14:781–790PubMed
166.
Tsang A, Hausenloy DJ, Mocanu MM, Carr RD, Yellon DM (2005) Preconditioning the diabetic heart: the importance of Akt phosphorylation. Diabetes 54:2360–2364PubMed
167.
Bhamra GS, Hausenloy DJ, Davidson SM, Carr RD, Paiva M, Wynne AM, Mocanu MM, Yellon DM (2008) Metformin protects the ischemic heart by the Akt-mediated inhibition of mitochondrial permeability transition pore opening. Basic Res Cardiol 103:274–284PubMed
168.
Bulhak AA, Jung C, Ostenson CG, Lundberg JO, Sjöquist PO, Pernow J (2009) PPAR-alpha activation protects the type 2 diabetic myocardium against ischemia-reperfusion injury: involvement of the PI3-kinase/Akt and NO pathway. Am J Physiol Heart Circ Physiol 296:H719–H727PubMed
169.
Matsumoto S, Cho S, Tosaka S, Ureshino H, Maekawa T, Hara T, Sumikawa K (2009) Pharmacological preconditioning in type 2 diabetic rat hearts: the role of mitochondrial ATP-sensitive potassium channels and the phosphatidylinositol 3-kinase-Akt pathway. Cardiovasc Drug Ther 23:263–270
170.
Kersten JR, Schmeling TG, Orth KG, Pagel PS, Warltier WC (1998) Acute hyperglycemia abolishes ischemic preconditioning in vivo. Am J Physiol 275:H721–H725PubMed
171.
Wong VW, Mardini M, Cheung NW, Mihailidou AS (2011) High-dose insulin in experimental myocardial infarction in rabbits: protection against effects of hyperglycemia. J Diabetes Complications 25:122–128PubMed
172.
Kehl F, Krolikowski JG, Mraovic B, Pagel PS, Warltier DC, Kersten JR (2002) Hyperglycemia prevents isoflurane-induced preconditioning against myocardial infarction. Anesthesiology 96:183–188PubMed
173.
Su H, Sun X, Ma H, Zhang HF, Yu QJ, Huang C, Wang XM, Luan RH, Jia GL, Wang HC, Gao F (2007) Aute hyperglycemia exacerbates myocardial ischemia/reperfusion injury and blunts cardioprotective effect of GIK. Am J Physiol Endocrinol Metab 293:E629–E635PubMed
174.
Weber NC, Goletz C, Huhn R, Grueber Y, Preckel B, Schlack W, Ebel D (2008) Blockade of anaesthetic-induced preconditioning in the hyperglycaemic myocardium: the regulation of different mitogen-activated protein kinases. Eur J Pharmacol 592:48–54PubMed
175.
Gu W, Kehl F, Krolikowski JG, Pagel PS, Warltier DC, Kersten JR (2008) Simvastatin restores ischemic preconditioning in the presence of hyperglycemia through a nitric oxide-mediated mechanism. Anesthesiology 108:634–642PubMed
176.
Huhn R, Heinen A, Weber NC, Hollmann MW, Schlack W, Preckel B (2008) Hyperglycaemia blocks sevoflurane-induced postconditioning in the rat heart in vivo: cardioprotection can be restored by blocking the mitochondrial permeability transition pore. Br J Anaesth 100:465–471PubMed
177.
Amour J, Brzezinska AK, Jager Z, Sullivan C, Weihrauch D, Du J, Vladic N, Shi Y, Warltier DC, Pratt PF Jr, Kersten JR (2010) Hyperglycemia adversely modulates endothelial nitric oxide synthase during anesthetic preconditioning through tetrahydrobiopterin- and heat shock protein 90-mediated mechanisms. Anesthesiology 112:576–585PubMed
178.
Raphael J, Gozal Y, Navot N, Zuo Z (2010) Hyperglycemia inhibits anesthetic-induced postconditioning in the rabbit heart via modulation of phosphatidylinositol-3-kinase/Akt and endothelial nitric oxide synthase signaling. J Cardiovasc Pharmacol 55:348–357PubMed
179.
Du Toit EF, Smith W, Muller C, Strijdom H, Stouthammer B, Woodiwiss AJ, Norton GR, Lochner A (2008) Myocardial susceptibility to ischemia-reperfusion injury in a prediabetic model of dietary-induced obesity. Am J Physiol Heart Circ Physiol 294:H2336–H2343PubMed
180.
Thim T, Bentzon JF, Kristiansen SB, Simonsen U, Andersen HL, Wassermann K, Falk E (2006) Size of myocardial infarction induced by ischaemia/reperfusion is unaltered in rats with metabolic syndrome. Clin Sci (Lond) 110:665–671
181.
Wagner C, Kloeting I, Strasser RH, Weinbrenner C (2008) Cardioprotection by postconditioning is lost in WOKW rats with metabolic syndrome: role of glycogen synthase kinase 3beta. J Cardiovasc Pharmacol 52:430–437PubMed
182.
Yadav HN, Singh M, Sharma PL (2010) Involvement of GSK-3β in attenuation of the cardioprotective effect of ischemic preconditioning in diabetic rat heart. Mol Cell Biochem 343:75–81PubMed
183.
Ishihara M, Inoue I, Kawagoe T, Shimatani Y, Kurisu S, Nishioka K, Kouno Y, Umemura T, Nakamura S, Sato H (2001) Diabetes mellitus prevents ischemic preconditioning in patients with a first acute anterior wall myocardial infarction. J Am Coll Cardiol 38:1007–1011PubMed
184.
Lee TM, Chou TF (2003) Impairment of myocardial protection in type 2 diabetic patients. J Clin Endocrinol Metab 88:531–537PubMed
185.
Ovünç K (2000) Effects of glibenclamide, a KATP channel blocker, on warm-up phenomenon in type II diabetic patients with chronic stable angina pectoris. Clin Cardiol 23:535–539PubMed
186.
Hassouna A, Loubani M, Matata BM, Fowler A, Standen NB, Galiñanes M (2006) Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium. Cardiovasc Res 69:450–458PubMed
187.
Sivaraman V, Hausenloy DJ, Wynne AM, Yellon DM (2010) Preconditioning the diabetic human myocardium. J Cell Mol Med 14:1740–1746PubMed
188.
Ueda Y, Kitakaze M, Komamura K, Minamino T, Asanuma H, Sato H, Kuzuya T, Takeda H, Hori M (1999) Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction. J Am Coll Cardiol 34:2120–2125PubMed
189.
Kyriakides ZS, Psychari S, Iliodromitis EK, Kolettis TM, Sbarouni E, Kremastinos DT (2002) Hyperlipidemia prevents the expected reduction of myocardial ischemia on repeated balloon inflations during angioplasty. Chest 121:1211–1215PubMed
190.
Ungi I, Ungi T, Ruzsa Z, Nagy E, Zimmermann Z, Csont T, Ferdinandy P (2005) Hypercholesterolemia attenuates the anti-ischemic effect of preconditioning during coronary angioplasty. Chest 128:1623–1628PubMed
191.
Ernande L, Bergerot C, Rietzschel ER, De Buyzere ML, Thibault H, Pignonblanc PG, Croisille P, Ovize M, Groisne L, Moulin P, Gillebert TC, Derumeaux G (2011) Diastolic dysfunction in patients with type 2 diabetes mellitus: is it really the first marker of diabetic cardiomyopathy? J Am Soc Echocardiogr 24:1268–1275PubMed
192.
McGavock JM, Lingvay I, Zib I, Tillery T, Salas N, Unger R, Levine BD, Raskin P, Victor RG, Szczepaniak LS (2007) Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation 116:1170–1175PubMed
193.
Rijzewijk LJ, van der Meer RW, Smit JW, Diamant M, Bax JJ, Hammer S, Romijn JA, de Roos A, Lamb HJ (2008) Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol 52:1793–1799PubMed
194.
Ng ACT, Delgado V, Bertini M, van der Meer RW, Rijzewijk LJ, Hooi Ewe S, Siebelink HM, Smit JW, Diamant M, Romijn JA, de Roos A, Leung DY, Lamb HJ, Bax JJ (2010) Myocardial steatosis and biventricular strain and strain rate imaging in patients with type 2 diabetes mellitus. Circulation 122:2538–2544PubMed
195.
Torffvit O, Lövestam-Adrian M, Agardh E, Agardh CD (2005) Nephropathy, but not retinopathy, is associated with the development of heart disease in type 1 diabetes: a 12-year observation study of 462 patients. Diabet Med 22:723–729PubMed
196.
Turnbull FM, Abraira C, Anderson RJ, Byington RP, Chalmers JP, Duckworth WC, Evans GW, Gerstein HC, Holman RR, Moritz TE, Neal BC, Ninomiya T, Patel AA, Paul SK, Travert F, Woodward M (2009) Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 52:2288–2298PubMed
197.
von Bibra H, Hansen A, Dounis V, Bystedt T, Malmberg K, Rydén L (2004) Augmented metabolic control improves myocardial diastolic function and perfusion in patients with non-insulin dependent diabetes. Heart 90:1483–1484
198.
Hordern MD, Coombes JS, Cooney LM, Jeffriess L, Prins JB, Marwick TH (2009) Effects of exercise intervention on myocardial function in type 2 diabetes. Heart 95:1343–1349PubMed
199.
Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383–393PubMed
200.
Eurich DT, McAlister FA, Blackburn D, Majumdar SR, Tsuyuki RT, Varney J, Johnson JA (2007) Benefits and harms of anti-diabetic agents in patients with diabetes and heart failure: systematic review. Br Med J 335:497–586
201.
Andersson C, Olesen JB, Hansen PR, Weeke P, Norgaard ML, Jørgensen CH, Lange T, Abildstrøm SZ, Schramm TK, Vaag A, Køber L, Torp-Pedersen C, Gislason GH (2010) Metformin treatment is associated with a low risk of mortality in diabetic patients with heart failure: a retrospective nationwide cohort study. Diabetologia 53:2546–2553PubMed
202.
Aguilar D, Chan W, Bozkurt B, Ramasubbu K, Deswal A (2011) Metformin use and mortality in ambulatory patients with diabetes and heart failure. Circ Heart Fail 4:53–58PubMed
203.
Tang WH, Francis GS, Hoogwerf BJ, Young JB (2003) Fluid retention after initiation of thiazolidinedione therapy in diabetic patients with established chronic heart failure. J Am Coll Cardiol 41:1394–1398PubMed
204.
Masoudi FA, Inzucchi SE, Wang Y, Havranek EP, Foody JM, Krumholz HM (2005) Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation 111:583–590PubMed
205.
Aguilar D, Bozkurt B, Pritchett A, Petersen NJ, Deswal A (2007) The impact of thiazolidinedione use on outcomes in ambulatory patients with diabetes mellitus and heart failure. J Am Coll Cardiol 50:32–36PubMed
206.
Erdmann E, Wilcox RG (2008) Weighing up the cardiovascular benefits of thiazolidinedione therapy: the impact of increased risk of heart failure. Eur Heart J 29:12–20PubMed
207.
Horio T, Suzuki M, Suzuki K, Takamisawa I, Hiuge A, Kamide K, Takiuchi S, Iwashima Y, Kihara S, Funahashi T, Yoshimasa Y, Kawano Y (2005) Pioglitazone improves left ventricular diastolic function in patients with essential hypertension. Am J Hypertens 18:949–957PubMed
208.
van der Meer RW, Rijzewijk LJ, de Jong HW, Lamb HJ, Lubberink M, Romijn JA, Bax JJ, de Roos A, Kamp O, Paulus WJ, Heine RJ, Lammertsma AA, Smit JW, Diamant M (2009) Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation 119:2069–2077PubMed
209.
Shindler DM, Kostis JB, Yusuf S, Quinones MA, Pitt B, Stewart D, Pinkett T, Ghali JK, Wilson AC (1996) Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry. Am J Cardiol 77:1017–1020PubMed
210.
Rydén L, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, Packer M, Poole-Wilson PA (2000) Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial. Eur Heart J 21:1967–1978PubMed
211.
Haas SJ, Vos T, Gilbert RE, Krum H (2003) Are beta-blockers as efficacious in patients with diabetes mellitus as in patients without diabetes mellitus who have chronic heart failure? A meta-analysis of large-scale clinical trials. Am Heart J 146:848–853PubMed
212.
de Boer RA, Doehner W, van der Horst IC, Anker SD, Babalis D, Roughton M, Coats AJ, Flather MD, van Veldhuisen DJ, SENIORS Investigators (2010) Influence of diabetes mellitus and hyperglycemia on prognosis in patients > or =70 years old with heart failure and effects of nebivolol (data from the Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure [SENIORS]). Am J Cardiol 106:78–86PubMed
213.
Komajda M, Carson PE, Hetzel S, McKelvie R, McMurray J, Ptaszynska A, Zile MR, Demets D, Massie BM (2011) Factors associated with outcome in heart failure with preserved ejection fraction: findings from the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-PRESERVE). Circ Heart Fail 4:27–35PubMed
214.
Borlaug BA, Paulus WJ (2011) Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J 2:670–679
215.
Redfiled MM, Jacobsen SJ, Burnett JC, Mahoney DW, Bailey KR, Rodeheffer RJ (2003) Burden of systolic and diastolic ventricular dysfunction in the community. JAMA 289:194–202
Metadata
Title
Diabetic cardiomyopathy: pathophysiology and clinical features
Authors
Takayuki Miki
Satoshi Yuda
Hidemichi Kouzu
Tetsuji Miura
Publication date
01-03-2013
Publisher
Springer US
Published in
Heart Failure Reviews / Issue 2/2013
Print ISSN: 1382-4147
Electronic ISSN: 1573-7322
DOI
https://doi.org/10.1007/s10741-012-9313-3

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