(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Diabetes-Mellitus--Type-1

Previously we revealed the effectiveness of a new therapeutic approach with a short-term, very-low dose fluvastatin-valsartan combination on the improvement of arterial function in type 1 diabetes mellitus patients (T1DM). In this study we explored whether this approach influences inflammation and oxidative stress and explored any association of these effects with arterial function improvement.. This was a supplementary analysis of the two previous double blind randomized studies (included 44 T1DM patients). Treatment group received very-low dose fluvastatin-valsartan, the control group received placebo. Blood samples were collected and inflammation parameters: high-sensitivity CRP (hsCRP), interleukin 6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1) and oxidative stress parameter total antioxidant status (TAS) were measured.. Treatment decreased hsCRP values (by 56.5%, P<0.05) and IL-6 values (by 33.6%, P<0.05) and increased TAS values (by 21.1%; P<0.05) after 30days of treatment. High sensitivity CRP and TAS remained decreased 3months after treatment discontinuation. Importantly, the anti-inflammatory and anti-oxidative action significantly correlated with arterial function improvement.. The approach consisting of short-term (30days) treatment with a very low-dose fluvastatin-valsartan combination acts anti-inflammatory and anti-oxidative in T1DM patients. These observations along with the improvement of arterial function support the assumption that this approach could have an important clinical benefit in T1DM patients.

Topics: Adult; Diabetes Mellitus, Type 1; Double-Blind Method; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Inflammation; Male; Oxidative Stress; Valsartan

We tested whether short-term, low-dose treatment with the fluvastatin and valsartan combination could improve impaired arterial wall characteristics in type 1 diabetes mellitus patients. A total of 44 type 1 diabetes mellitus patients were randomised into the treatment group [n = 22; received a low-dose combination of fluvastatin (10 mg daily) and valsartan (20 mg daily)] and the control group (n = 22; received placebo), both for 30 days. Brachial artery flow-mediated dilation (FMD), pulse wave velocity (PWV) and carotid artery β-stiffness were measured. Significant improvements in FMD (+73.2%), PWV (-7.5%) and β-stiffness (-10.0%) were achieved after 1-month treatment compared to the control group (all p values < 0.001). Three months after therapy discontinuation, important residual improvement in measured parameters was still present. No changes in lipids and blood pressure accompanied the beneficial improvements. We conclude that relatively simple intervention (low-dose, short-term fluvastatin/valsartan combination) produces substantial, long-term improvement of arterial wall characteristics in type 1 diabetes mellitus patients.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Anticholesteremic Agents; Blood Pressure; Carotid Arteries; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Humans; Indoles; Male; Middle Aged; Tetrazoles; Treatment Outcome; Valine; Valsartan