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collagen type I carboxy-terminal peptide [PICP], ami- sclerosis in epicardial coronary arteries, but also pro-
no terminalpropeptide of procollagen type I [PINP], motes the appearance of structural and functional
carboxy terminalpropeptide of procollagen type III disorders in smaller vessels, resulting in an increased
[PIIICP], amino terminal propeptide of procollagen ischemic burden for the myocardium. Furthermore,
type III [PIIINP]), collagen degradation (CITP), mark- diabetic cardiomyopathy aggravates hypertension,
ers of extracellular matrix turnover (such as MMP) resulting in increased afterload and pressure over-
and their inhibitors (TIMP, tissue inhibitors of MMP), load, and, by contributing to the occurrence of renal
can be used as markers in detecting myocardial fi- failure (diabetic nephropathy), it leads to fluid reten-
brosis.25 Diabetic patients with diastolic dysfunction tion and eventually volume overload. From the patho-
demonstrated an increase in MMP-9 and a decrease physiological point of view, in diabetes, because of
in TIMP-1/MMP-9. Finally, in a small group of diabetic the lack of insulin or because of insulin resistance
patients, a correlation was found between PICP and in the tissues, the body does not use glucose but
left ventricular (LV) systolic parameters (fractional instead uses fatty acids as fuel. Although the heart
shortening and midwall fractional shortening). More tissue of normo glycemic people prefers free fatty
specifically, in diabetic patients, corrected endocardi- acids as fuel rather than glucose, in diabetic pa-
al (r=-0.56) and midwall shortening (r=0.38) was cor- tients this phenomenon is accentuated even further.
related with PICP, whereas the systolic and early dia- On the other hand, myocardial cells of normo glyce-
stolic velocities of the mitral annulus were correlated mic patients with heart failure or patients who have
with glutathione peroxidase (both r=0.44). 9 suffered a myocardial infarction use glucose as an
energy source rather than fatty acids. It seems that
Hypertrophy of myocardial cells in this case glucose exerts a protective role against
ischemia. The almost exclusive use of fatty acids in
Studies of cardiac tissue from diabetic animals un-
der the electron microscope have shown multiple diabetes patients leads to their accumulation into the
abnormalities in the structure of myocardial cells: heart muscle, which is followed by the appearance
(i) loss of microfibrils; (ii) loss of cell-to-cell connec- of lipotoxicity. Of particular note is palmitic acid, the
tion in the intermediate discs; and (iii) increased lipid accumulation of which influences myocardial con-
deposition in the cytoplasm and loss of components tractility and also induces apoptosis of myocardial
of the endoplasmic reticulum. Furthermore, it has cells. It has been found that persistent hyperglyce-
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been reported that LV hypertrophy and concentric re- mia in the myocardium of diabetic rats stimulates the
modeling are associated with diabetes mellitus, inde- expression of muscle carnitine palmitoyl transferase
12
pendently of other confounding factors such as age, enzyme 1. On the other hand, the main feature of
obesity, and hypertension. Additionally the NOMAS diabetes, hyperglycemia, can cause damage to the
Study described diabetes mellitus as an indepen- myocardium via modified proteins (advanced glyca-
dent determinant of LV mass, in addition to central tion end products, AGEs) and free oxygen radicals
obesity as assessed by waist circumference. Fisch- (ROS-reactive oxygen species). The AGEs, for exam-
er et al, working with cardiac tissue samples from ple, produced by glycation of collagen lead to its ac-
patients undergoing coronary artery bypass grafting, cumulation in the extracellular matrix and eventually
demonstrated no differences in LV hypertrophy and in fibrosis of the heart, resulting in diastolic dysfunc-
fibrosis between diabetic and non-diabetic patients. tion. Furthermore, soluble AGEs connected in related
They pointed out that the only differences observed receptors (RAGEs), trigger NADPH oxidase, leading
in cardiac tissue were related to swelling of endo- to the production of peroxide and ultimately of free
thelial cells and basement membrane thickening of oxygen radicals. These in turn cause direct damage
capillaries. to myocyte DNA.

Mechanisms of heart failure in diabetes Systolic dysfunction in diabetic
mellitus cardiomyopathy
Novel echocardiographic techniques, such as tissue
Many pathophysiological mechanisms are involved
in the stepwise progression from diabetes mellitus Doppler imaging (TDI) and speckle tracking imag-
to heart failure. These include direct myocardial in- ing (STI), can be used to detect early subclinical im-
jury (e.g. in myocardial ischemia or cardiomyopathy), pairment of LV or right ventricular (RV) function in
volume overload (e.g. in aortic valve insufficiency), asymptomatic diabetic patients without overt heart
and pressure overload (e.g. in arterial hypertension). disease. Longitudinal dysfunction was demonstrat-
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Diabetes not only intensifies the process of athero- ed in many studies using both TDI and STI. Several
authors demonstrated that longitudinal strain de-

Cardio Diabetes Medicine