Response to the letter: Angiotensin-II induced insulin resistance

Abstract

W e have examined with attention the comments of the letter to the Editor in regards to our recently published article (1), and want to thank its authors for their interest in our work.Indeed, it has been demonstrated that, upon acting on the AT1 receptor, angiotensin II activates matrix metalloproteases that release the epidermal growth factor (EGF), binding to its receptor promotes the activation of mammalian target of rapamycin (mTOR) and ribosomal S6 kinase-1, both of which inhibit phosphatidylinositol 3-kinase insulin signaling, thus favoring insulin resistance (2-4). Interestingly, some clinical studies have demonstrated that treatment with either angiotensin I-converter enzyme inhibitors (ACEI) or angiotensin II receptor antagonist (ARA) reduces the incidence of diabetes mellitus in high risk patients (5,6).Our study compared a group of metabolic syndrome (MS) patients (31 subjects) with a control group (27 subjects), and, as pointed out in the Results section, 13 out of 31 MS patients presented high blood pressure (41.9%), whereas none of the subjects in the control group were hypertensive (0%), not receiving therefore hypertension medication. As mentioned in the study, 10 of the 13 patients with high blood pressure and MS were treated with monotherapy (6 with ACEI and 4 with ARA), and the other three were on a combined therapy of ARA with calcium antagonist (2), and ACEI with a diuretic (1). Our study found that patients with MS revealed a greater thickness of epicardial adipose tissue (EAT) (5.69 ± 1.12 vs 3.52 ± 0.80 mm; p = 0.0001) in comparison with the subjects in the control group (1). As far as we know, no study has demonstrated that ARAs or ACEIs decrease EAT thickness, and although it is described that both antihypertensives drugs reduce insulin resistance, we observed that the study group had greater basal plasma insulin concentrations than those of the control group (6.08 ± 5.22 vs. 2.10 ± 0.54; p = 0.0001), and even greater trigliceryde/HDL-C ratio (4.52 ± 2.37 vs. 2.10 ± 1.15; p = 0.0001), which is considered a surrogate marker of insulin resistance (7).Furthermore, a larger left ventricular mass (60.28 ± 14.00 vs. 53.01 ± 8.40; p = 0,019) and lower adiponectin plasma levels (11.20 ± 2.65 vs. 14.95 ± 3.87; p = 0,0001) were found in subjects with MS as compared to the control group. In agreement with the comments of the letter to the Editor, both ACEI and ARA have been shown to reduce left ventricular mass; however, it is worth noting that only subjects belonging to the MS group were receiving such therapy, whereby it can be asserted that this aspect had little incidence on the results. Furthering into the beneficial effects of ACEI and ARA, new analyses were carried out, and upon comparing the patients receiving these drugs (n = 13) with those MS patients receiving different medication or not receiving antihypertensives (n = 18), the levels of insulin (5.37 ± 4.03