Author(s): Francis GS
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.
Referred From: https://pubmed.ncbi.nlm.nih.gov/21424347/
Author(s): Zimmet P, Alberti KG, Shaw J
Author(s): Murarka S, Movahed MR
Author(s): Khavandi K, Khavandi A, Asghar O, Greenstein A, Withers S, et al.
Author(s): Giacco F, Brownlee M
Author(s): Baynes JW, Thorpe SR
Author(s): Brownlee M
Author(s): Cai L, Kang YJ
Author(s): Cai L, Wang J, Li Y, Sun X, Wang L, et al.
Author(s): He X, Kan H, Cai L, Ma Q
Author(s): Kensler TW, Wakabayashi N, Biswal S
Author(s): Leung L, Kwong M, Hou S, Lee C, Chan JY
Author(s): Ma Q
Author(s): Talalay P, Dinkova-Kostova AT, Holtzclaw WD
Author(s): Kobayashi A, Ohta T, Yamamoto M
Author(s): Nguyen T, Sherratt PJ, Pickett CB
Author(s): Ma Q, Battelli L, Hubbs AF
Author(s): Hubbs AF, Benkovic SA, Miller DB, O'Callaghan JP, Battelli L, et al.
Author(s): Ramos-Gomez M, Kwak MK, Dolan PM, Itoh K, Yamamoto M, et al.
Author(s): He X, Lin GX, Chen MG, Zhang JX, Ma Q
Author(s): He X, Chen MG, Ma Q
Author(s): Hu X, Roberts JR, Apopa PL, Kan YW, Ma Q
Author(s): Cho HY, Reddy SP, Yamamoto M, Kleeberger SR
Author(s): He X, Chen MG, Lin GX, Ma Q
Author(s): He X, Ma Q
Author(s): He X, Ma Q
Author(s): Taguchi K, Motohashi H, Yamamoto M
Author(s): Chan K, Lu R, Chang JC, Kan YW
Author(s): Ma Q, Kinneer K, Bi Y, Chan JY, Kan YW
Author(s): Kan H, Xie Z, Finkel MS
Author(s): Dobrin JS, Lebeche D
Author(s): Duncan JG
Author(s): Yates MS, Kwak MK, Egner PA, Groopman JD, Bodreddigari S, et al.
Author(s): Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, et al.
Author(s): Liby K, Royce DB, Williams CR, Risingsong R, Yore MM, et al.
Author(s): Sussan TE, Rangasamy T, Blake DJ, Malhotra D, El-Haddad H, et al.