Oxidative stress and fibrosis in incipient myocardial dysfunction in type 2 diabetic patients

The existence of a diabetic cardiomyopathy has been recently supported by epidemiological studies. Increased oxidative stress and myocardial fibrosis has been hypothesized as etiopathogenic mechanisms. We sought to demonstrate the existence of incipient myocardial dysfunction in type 2 diabetes and its relation with markers of oxidative stress and myocardial fibrosis.

We studied by echocardiography 25 uncomplicated type 2 diabetic patients and 12 sex- and age-matched control subjects. Stress-corrected endocardial and midwall shortening and systolic and early diastolic velocity of the lateral mitral annulus (Doppler tissue) were used as parameters of myocardial function. Serum levels of glutathione peroxidase and procollagen type I carboxy-terminal peptide were used as markers of oxidative stress and myocardial fibrosis, respectively.

Diabetics had significant lower values of corrected endocardial shortening than control subjects (P = 0.029). Both systolic and early diastolic mitral annulus velocities were significantly reduced in diabetics as compared to control subjects (P = 0.008 and P = 0.003, respectively). In diabetic patients, corrected endocardial (r = -0.56) and midwall shortening (r = -0.38) correlated with procollagen type I carboxy-terminal peptide, whereas systolic and early diastolic velocities of the mitral annulus correlated with glutathione peroxidase (both r = 0.44).

In a highly selected group of uncomplicated type 2 diabetic patients, we found evidence of systolic and diastolic myocardial dysfunction, especially with the use of pulsed Doppler tissue imaging. The correlations between parameters of myocardial function and glutathione peroxidase and procollagen type I carboxy-terminal peptide support a mechanistic role for the increased oxidative stress and myocardial fibrosis in the myocardial dysfunction of type 2 diabetes.