Diabetic cardiomyopathy: pathophysiology and clinical features

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.

Fig. 1

Proposed mechanisms of contractile dysfunction by diabetes. EC coupling excitation–contraction coupling, APD action potential duration, SR sarcoplasmic reticulum, FFA free fatty acid, CFR coronary flow reserve, SMC smooth muscle cell

Fig. 2

Proposed mechanisms of diabetes-induced increase in susceptibility of the myocardium to ischemia/reperfusion-induced infarction. mPTP mitochondrial permeability transition pore, SMC smooth muscle cell

Fig. 3

Examples of Doppler echocardiography in a healthy subject and a T2DM patient. Transmitral flow patterns are shown for a healthy subject (a) and a T2DM patient (b). Peak velocities during early diastole (E) and late diastole (A) are shown. E/A ratios are 2.2 and 0.6 in a, b, respectively. c, d show tissue Doppler imaging, with positioning of sample volume at the septal mitral annulus, in a healthy subject and a T2DM patient, respectively. The diabetic patient (d) had lower peak velocities during systole (S′) and early diastole (E′) (7.5 and 6.0 cm/s, respectively) than those in the healthy subject (c 8.5 and 15.0 cm/s, respectively)

Fig. 4

Tissue Doppler-derived strain and strain rate of the left ventricle. a, b show strain and strain rates, respectively, in a normal control. Ss septal peak strain, SRs strain rate in systole, SRe strain rate in early diastole. c shows comparison of LV strain rates in normal controls (white bars, n = 15) and normotensive T2DM patients without coronary artery disease (black bars, n = 15). *P < 0.05 versus control. (S. Yuda, unpublished data)