Herz. 2011 Mar;36(2):102-15. doi: 10.1007/s00059-011-3429-4.
Diabetic cardiomyopathy--fact or fiction?.
Herz
B Maisch, P Alter, S Pankuweit
Affiliations
Affiliations
- Klinik für Innere Medizin-Kardiologie, UKGM GmbH und Philipps-Universität Marburg, Baldingerstr., 35043, Marburg, Deutschland. [email protected]
PMID: 21424347
DOI: 10.1007/s00059-011-3429-4
Abstract
Epidemiologic as well as clinical studies confirm the close link between diabetes mellitus and heart failure. Diabetic cardiomyopathy (DCM) is still a poorly understood "entity", however, with several contributing pathogenetic factors which lead in different stages of diabetes to characteristic clinical phenotypes. Hyperglycemia with a shift from glucose metabolism to increased beta-oxidation and consecutive free fatty acid damage (lipotoxicity) to the myocardium, insulin resistance, renin-angiotensin-aldosterone system (RAAS) activation, altered calcium homeostasis and structural changes from the natural collagen network to a stiffer matrix due to advanced glycation endproduct (AGE) formation, hypertrophy and fibrosis contribute to the respective clinical phenotypes of DCM. We propose the following classification of cardiomyopathy in diabetic patients: a) Diastolic heart failure with normal ejection fraction (HFNEF) in diabetic patients often associated with hypertrophy without relevant hypertension. Relevant coronary artery disease (CAD), valvular disease and uncontrolled hypertension are not present. This is referred to as stage 1 DCM. b) Systolic and diastolic heart failure with dilatation and reduced ejection (HFREF) in diabetic patients excluding relevant CAD, valvular disease and uncontrolled hypertension as stage 2 DCM. c) Systolic and/or diastolic heart failure in diabetic patients with small vessel disease (microvascular disease) and/or microbial infection and/or inflammation and/or hypertension but without CAD as stage 3 DCM. d) If heart failure may also be attributed to infarction or ischemia and remodeling in addition to stage 3 DCM the term should be heart failure in diabetes or stage 4 DCM. These clinical phenotypes of diabetic cardiomyopathy can be separated by biomarkers, non-invasive (echocardiography, cardiac magnetic resonance imaging) and invasive imaging methods (levocardiography, coronary angiography) and further analysed by endomyocardial biopsy for concomitant viral infection. The role of specific diabetic drivers to the clinical phenotypes, to macro- and microangiopathy as well as accompanying risk factors or confounders, e.g. hypertension, autoimmune factors or inflammation with or without viral persistence, need to be identified in each individual patient separately. Thus hyperglycemia, hyperinsulinemia and insulin resistance as well as lipotoxicity by free fatty acids (FFAs) are the factors responsible for diabetic cardiomyopathy. In stage 1 and 2 DCM diabetic cardiomyopathy is clearly a fact. However, precise determination of to what degree the various underlying pathogenetic processes are responsible for the overall heart failure phenotype remains a fiction.
References
- Herz. 2010 May;35(3):161-8 - PubMed
- Coron Artery Dis. 2001 Feb;12 Suppl 1:S29-33 - PubMed
- Mol Cell Biochem. 1998 Mar;180(1-2):53-7 - PubMed
- J Clin Pathol. 1993 Jan;46(1):32-6 - PubMed
- Herz. 2004 Dec;29(8):788-93 - PubMed
- Physiology (Bethesda). 2006 Aug;21:250-8 - PubMed
- Herz. 2004 Feb;29(1):17-25 - PubMed
- J Am Coll Cardiol. 2009 Oct 13;54(16):1524-32 - PubMed
- Circ Cardiovasc Imaging. 2010 Sep;3(5):507-14 - PubMed
- Circulation. 2000 May 16;101(19):2271-6 - PubMed
- Mol Cell Biochem. 2008 Jul;314(1-2):179-91 - PubMed
- Circulation. 1996 Mar 1;93(5):841-2 - PubMed
- Rheumatology (Oxford). 2006 Oct;45 Suppl 4:iv32-8 - PubMed
- Herz. 2006 Jun;31(4):361-5 - PubMed
- Lancet. 2004 Nov 13-19;364(9447):1786-8 - PubMed
- Herz. 2006 May;31(3):200-6 - PubMed
- N Engl J Med. 2007 Mar 15;356(11):1140-51 - PubMed
- Herz. 2010 May;35(3):140-6 - PubMed
- Jpn Heart J. 1988 Jul;29(4):455-63 - PubMed
- Eur Heart J. 2007 Jan;28(1):88-136 - PubMed
- Herz. 2006 May;31(3):185-8 - PubMed
- J Mol Cell Cardiol. 2010 Mar;48(3):524-9 - PubMed
- Eur Heart J. 2008 Jan;29(2):270-6 - PubMed
- Herz. 2006 Oct;31(7):708-14 - PubMed
- Circulation. 1997 Oct 7;96(7):2190-6 - PubMed
- Cardiovasc Res. 2000 May;46(2):324-31 - PubMed
- Pflugers Arch. 2008 Jan;455(4):627-36 - PubMed
- Heart. 2007 Dec;93(12):1571-6 - PubMed
- Circulation. 2007 Jun 26;115(25):3213-23 - PubMed
- J Am Coll Cardiol. 2006 Oct 17;48(8):1688-97 - PubMed
- Diabetes. 2002 Jan;51(1):174-81 - PubMed
- JAMA. 1979 May 11;241(19):2035-8 - PubMed
- J Clin Invest. 1977 Oct;60(4):884-99 - PubMed
- Am J Physiol Heart Circ Physiol. 2002 Jan;282(1):H138-48 - PubMed
- Am Heart J. 2006 Apr;151(4):829-36 - PubMed
- Diabetes Care. 2006 Mar;29(3):588-94 - PubMed
- Herz. 2006 May;31(3):260-8 - PubMed
- Circulation. 2000 Sep 19;102(12):1388-93 - PubMed
- Am J Cardiol. 2001 Jun 1;87(11):1260-5 - PubMed
- Circ Res. 2001 May 11;88(9):918-24 - PubMed
- Ann N Y Acad Sci. 2001 Apr;928:48-53 - PubMed
- Eur Heart J. 2004 Apr;25(7):587-610 - PubMed
- Am J Cardiol. 1972 Nov 8;30(6):595-602 - PubMed
- Best Pract Res Clin Endocrinol Metab. 2009 Jun;23(3):347-60 - PubMed
- Diabetes Res Clin Pract. 2008 Feb;79(2):262-8 - PubMed
- Arch Biochem Biophys. 2003 Dec 1;420(1):176-84 - PubMed
- Diabetes. 2009 Jun;58(6):1373-81 - PubMed
- Herz. 2004 Sep;29(6):624-36 - PubMed
- J Cell Mol Med. 2009 Aug;13(8B):1751-1764 - PubMed
- Herz. 2008 Apr;33(3):223-32 - PubMed
- Circulation. 1992 Dec;86(6):1810-8 - PubMed
- J Cardiovasc Magn Reson. 2001;3(3):267-81 - PubMed
- Diabetes. 2006 Mar;55(3):798-805 - PubMed
- J Am Coll Cardiol. 2006 Feb 7;47(3):598-604 - PubMed
- Circulation. 2004 Aug 24;110(8):894-6 - PubMed
- J Biochem. 1995 Nov;118(5):1054-60 - PubMed
- Diabetologia. 2010 Jun;53(6):1033-45 - PubMed
- Internist (Berl). 2008 Apr;49(4):436-40 - PubMed
- Biochem Soc Trans. 1990 Dec;18(6):1125-7 - PubMed
- J Am Coll Cardiol. 1997 Aug;30(2):527-32 - PubMed
- Eur Heart J. 2008 Sep;29(18):2316 - PubMed
- Cardiovasc Res. 1997 Apr;34(1):34-40 - PubMed
- Circ Res. 1988 Mar;62(3):535-42 - PubMed
- Diabetes Care. 2001 Sep;24(9):1614-9 - PubMed
- Circulation. 2007 Sep 4;116(10):1170-5 - PubMed
- Am J Cardiol. 2009 Nov 15;104(10):1398-401 - PubMed
- Can J Physiol Pharmacol. 2007 Aug;85(8):790-9 - PubMed
- Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2237-45 - PubMed
- J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82 - PubMed
- Endocr Rev. 2004 Aug;25(4):543-67 - PubMed
- Chest. 1999 Mar;115(3):867-8 - PubMed
- Cardiovasc Diabetol. 2007 Feb 19;6:6 - PubMed
- Circulation. 2007 Apr 3;115(13):1769-76 - PubMed
- Lancet. 1954 Feb 20;266(6808):377-9 - PubMed
- Diabetes. 2001 Oct;50(10):2363-75 - PubMed
- Circulation. 2001 Jun 5;103(22):2668-73 - PubMed
- Cardiovasc Res. 1998 Nov;40(2):239-47 - PubMed
- Rev Endocr Metab Disord. 2010 Mar;11(1):31-9 - PubMed
- BMJ. 2000 Aug 12;321(7258):405-12 - PubMed
- Diabetes Care. 2003 Oct;26(10):2791-5 - PubMed
- Am J Cardiol. 2004 Apr 1;93(7):870-5 - PubMed
- Eur Heart J. 2007 Oct;28(20):2539-50 - PubMed
- J Am Coll Cardiol. 1998 Feb;31(2):404-12 - PubMed
- Am J Cardiol. 2001 Jul 19;88(2A):70E-73E - PubMed
- Eur J Heart Fail. 2007 May;9(5):469-76 - PubMed
- Circ Cardiovasc Imaging. 2010 Jul;3(4):392-7 - PubMed
- Am J Med. 2008 Sep;121(9):748-57 - PubMed
- Diabetes Care. 2003 Aug;26(8):2433-41 - PubMed
- Herz. 2006 Dec;31(9):881-90 - PubMed
- Circulation. 2004 May 11;109(18):2191-6 - PubMed
- Invest Radiol. 2005 Jan;40(1):19-26 - PubMed
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