Diabetic cardiomyopathy is a distinct primary disease process, independent of coronary artery disease, which leads to heart failure in diabetic patients. Epidemiological and clinical trial data have confirmed the greater incidence and prevalence of heart failure in diabetes. Novel echocardiographic and MR (magnetic resonance) techniques have enabled a more accurate means of phenotyping diabetic cardiomyopathy. Experimental models of diabetes have provided a range of novel molecular targets for this condition, but none have been substantiated in humans. Similarly, although ultrastructural pathology of the microvessels and cardiomyocytes is well described in animal models, studies in humans are small and limited to light microscopy. With regard to treatment, recent data with thiazoledinediones has generated much controversy in terms of the cardiac safety of both these and other drugs currently in use and under development. Clinical trials are urgently required to establish the efficacy of currently available agents for heart failure, as well as novel therapies in patients specifically with diabetic cardiomyopathy.
Keywords: diabetic cardiomyopathy, heart failure, hyperglycaemia, Type 2 diabetes
Abbreviations: ACE, angiotensin-converting enzyme; ACEI, ACE inhibitor; AGE, advanced glycosylation end-product; AngII, angiotensin II; AT1, AngII type 1 receptor; ARB, AT1 receptor blocker; BK, bradykinin; BNP, brain natriuretic peptide; BP, blood pressure; B1R, B1-receptor; B2R, B2-receptor; CHARM, Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity; CHS, Cardiovascular Health Study; CTGF, connective tissue growth factor; DAG, diacylglycerol; DGK, DAG kinase; DPP-4, dipeptidyl peptidase-4; EF, ejection fraction; ERK, extracellular-signal-regulated kinase; ET, endothelin; FA, fatty acid; GLP-1, glucagon-like peptide-1; GLUT4, glucose transporter 4; HbA1c, glycated haemoglobin; HF, heart failure; HFNEF, HF with a normal EF; HIF, hypoxia-inducible factor; KLK, kallikrein; hKLK, human KLK; KKS, KLK–kinin system; LV, left ventricular; LVED, left ventricular end-diastole; LVH, LV hypertrophy; LVM, LV mass; LVMI, LVM index; MESA, Multi-Ethnic Study of Atherosclerosis; MHC, myosin heavy chain; MI, myocardial infarction; MR, magnetic resonance; MRI, MR imaging; NCX, Na2+/Ca2+ exchange; NEFA, non-esterified FA; NF-κB, nuclear factor κB; NYHA, New York Heart Association; PARP, poly(ADP-ribose) polymerase; PKC, protein kinase C; PMCA, plasma-membrane Ca2+-ATPase; QOL, quality-of-life; RAS, renin–angiotensin system; RAAS, renin–angiotensin–aldosterone system; RAGE, receptor for AGEs; ROS, reactive oxygen species; RR, relative risk; RV, right ventricular; RyR, ryanodine receptor; SERCA, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase; SHS, Strong Heart Study; SOLVD, Studies of Left Ventricular Dysfunction; SR, sarcoplasmic reticulum; STZ, streptozotocin; TDI, tissue Doppler imaging; TGF-β1, transforming growth factor-β1; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; TZD, thiazolidinedione; UKPDS, UK Prospective Diabetes Study; VEGF, vascular endothelial growth factor; O2max, maximal oxygen consumption