Abstract
Introduction: Insulin resistance (IR) adversely affects cardiac performance and peripheral vasodilation reserve. Metformin, prescribed to prevent the progression of IR resistance into diabetes, has been shown to improve myocardial performance and endothelial function in insulin resistant individuals. Metabolomics in the study of the metabolite profile of a biological organism proved its efficacy in detecting metabolites changes as a result of a therapeutic intervention and, so, predicting the response. Aim: To evaluate myocardial and endothelium-dependent vasodilatory functions in an IR population subsequent to treatment with metformin and to determine the metabolic changes associated. Methods: Twenty consecutive patients recently diagnosed with IR were studied. All subjects underwent echocardiography with Speckle Tracking technique, peripheral arterial tonometry to measure the endothelial flow reserve (EFR) and metabolomic analysis by 1H Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate analysis at baseline and after metformin treatment. Results: Inter-test comparison performed at baseline and after 3 months of metformin showed a significant reduction in weight (79 ± 15.4 vs 80.9 ± 16.2, P<0.05) and BMI (29.7 ± 5.3 vs 30.8 ± 5.2, p<0.05). Moreover we evidenced a significant increase in EFR (2.1 ± 0.43 vs 1.88 ± 0.47, p<0.05), and of the Global Longitudinal Strain (20.2 ± 4.21% vs 15.4 ± 3.06%, p<0.001). PLS-DA analysis of the metabolic profile detected by NMR identified two groups significantly different (cross validation p-value=0.005). More significant discriminating metabolites were: lactate, lipids, N.acetyl glycoproteins, valine, choline, betaine,creatine. Conclusions: The data obtained show that in IR subjects metformin improves myocardial and endothelial function. This effect was associated to significant metabolic changes characterized by means of a metabolomic approach.
Highlights
Insulin resistance (IR) adversely affects cardiac performance and peripheral vasodilation reserve
Inter-test comparison performed at baseline and after 3 months of metformin showed a significant reduction in weight (79 ± 15.4 vs 80.9 ± 16.2, P
We evidenced a significant increase in endothelial flow reserve (EFR) (2.1 ± 0.43 vs 1.88 ± 0.47, p
Summary
Insulin resistance (IR) adversely affects cardiac performance and peripheral vasodilation reserve. Metformin, prescribed to prevent the progression of IR resistance into diabetes, has been shown to improve myocardial performance and endothelial function in insulin resistant individuals. Insulin resistance (IR), a condition in which elevated levels of this hormone produce a sub-optimal biological response, is considered a primary etiologic factor in the development of non-ischemic heart failure [1]. A high prevalence of IR has been found in the non-ischemic heart failure population. It predates the development of the disease, and independently defines a worse prognosis [4]. Several studies have shown that a reduction in endothelial function [6] may represent the link between IR and decline in cardiovascular performance
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