Abstract
Diabetic cardiomyopathy is characterized by metabolic changes in the myocardium that promote a slow and silent dysfunction of muscle fibers, leading to myocardium remodelling and heart failure, independently of the presence of coronary artery diseases or hypertension. At present, no imaging methods allow an early diagnosis of this disease. Circulating miRNAs in plasma have been proposed as biomarkers in the prognosis of several cardiac diseases. This study aimed to determine whether circulating miRNAs could be potential biomarkers of diabetic cardiomyopathy. Mice that were fed with a high fat diet for 16 months, showed metabolic syndrome manifestations, cardiac hypertrophy (without hypertension) and a progressive cardiac function decline. At 16 months, when maximal degree of cardiac dysfunction was observed, 15 miRNAs from a miRNA microarray screening in myocardium were selected. Then, selected miRNAs expression in myocardium (at 4 and 16 months) and plasma (at 4, 12 and 16 months) were measured by RT-qPCR. Circulating miR-19b-3p and miR-181b-5p levels were associated with myocardium levels during the development of diabetic cardiomyopathy (in terms of cardiac dysfunction), suggesting that these miRNAs could be suitable biomarkers of this disease in asymptomatic diabetic patients.
Highlights
Diabetes Mellitus (DM) has shown an increasing prevalence since 1980
Animals fed with a high-fat diet for 4 months were overweight (Fig. 1A), and they presented elevated plasma non-ester fatty acid (NEFA) levels (Fig. 1B), hyperglycaemia (Fig. 1C), and glucose intolerance (Fig. 1D) in comparison with mice fed with a standard diet
The obese mice had cardiac hypertrophy despite their normotensive state, which is a characteristic of diabetic cardiomyopathy
Summary
Diabetes Mellitus (DM) has shown an increasing prevalence since 1980. In 2014, it was estimated that 422 million adults lived with DM and approximately 4.9 million people died from complications related to diabetes, and positioned cardiovascular disease as the major cause of death[1]. Diabetic patients could have an asymptomatic cardiac function alteration without coronary arterial diseases, hypertension, or any congenital cardiac disease. This manifestation was defined as diabetic cardiomyopathy in 1972, and its implications in the integral treatment of cardiac disease related to DM in patients have aroused increasing interest in the scientific and clinical community[2,3]. In a population-based study performed in Olmsted County (USA), 1.1% of the community met criteria for diabetic cardiomyopathy, increasing to 16,9% in asymptomatic diabetic patients, of which 54.4% had diastolic dysfunction[5]. The diagnosis in asymptomatic diabetic patients without hypertension and coronary diseases is based on the detection of cardiac hypertrophy and diastolic dysfunction by echocardiography[8]
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