Short communicationEarly vascular and metabolic effects of rosuvastatin compared with simvastatin in patients with type 2 diabetes
Introduction
Type 2 diabetes (T2D) is characterized by an increased risk of cardiovascular complications. Endothelial dysfunction (ED) represents an underlying event for vascular abnormalities observed in diabetic patients, closely related to insulin-resistance (IR). An impaired nitric oxide bioavailability leading to an abnormal vasodilation may actually be triggered by multiple intracellular mechanisms resulting from an impaired sensitivity of insulin-signalling [1].
Besides modifications in lipid profile, statins have been reported to exert beneficial vascular actions, including anti-inflammatory effects and the up-regulation of nitric oxide production [2]. Moreover, some authors have reported that an improvement in ED can occur within a short period of statin administration [3]. Accordingly, even in diabetes mellitus, statins have been demonstrated to ameliorate ED and oxidative stress [4], [5].
However, the effects of statins on IR are somewhat controversial in diabetic patients and it is particularly unclear whether statins can simultaneously ameliorate ED and have an effect on IR. In individuals with T2D both simvastatin and atorvastatin have been reported to improve IR [6] while, in a recent study, high-dose simvastatin administration for 8 weeks did not show any effects on insulin action [7]. In addition, to our knowledge no study has ever evaluated the effects of rosuvastatin on IR, a synthetic statin with an extremely powerful lipid-lowering action, in diabetic patients.
This background prompted us to focus on the short-term effects of rosuvastatin and simvastatin administration on clamp-assessed IR and ED in individuals with type 2 diabetes.
Section snippets
Study design and subjects
We designed a randomized, single blind, parallel, intervention study which was approved by the local Ethics Committee and registered as a clinical trial (NCT00854503). All subjects gave their own written informed consent. Eligibility criteria were as follows: (a) known duration of diabetes of 3–10 years; (b) age 40–60 years; (c) BMI < 30; (d) good glycemic control (HbA1c < 7.0%); (e) LDL levels > 2.58 mmol/l; (f) no history of cardiovascular, neoplastic or other systemic diseases. The only allowed
Experimental results
The effects of 4 weeks of treatment with simvastatin 20 mg/daily or rosuvastatin 20 mg/daily on lipid profile, glucose metabolism, endothelial function and inflammation markers are summarized in Table 1. At baseline evaluation, no differences in all the parameters considered were detected between groups, except for slightly lower HDL levels in group R. During treatment period no patients changed their dietetic or life-style habits and no variations in oral anti-diabetic therapy were made.
Discussion
This study examined the early effects of rosuvastatin 20 mg/daily and simvastatin 20 mg/daily on insulin-resistance and endothelial dysfunction in middle-aged patients with type 2 diabetes and untreated mild dyslipidemia. Both treatments did not affect insulin sensitivity, glucose control and inflammation within 4 weeks. In addition, besides a greater improvement in lipid profile, rosuvastatin was less effective than simvastatin at improving endothelium-dependent vasodilation.
Growing evidence
Conflict of interest
No conflict of interest, potentially prejudicing the impartiality of the research reported, concerns this manuscript.
Acknowledgements
The present study has been supported by grants from the Ministero della Salute 2007 (Davide Lauro—Elena Tremoli) and PRIN-COFIN 2004 from the Ministero dell’Istruzione, Università e Ricerca (Davide Lauro—Elmo Mannarino).
References (10)
- et al.
Effects of simvastatin and atorvastatin administration on insulin resistance and respiratory quotient in aged dyslipidemic non-insulin dependent diabetic patients
Atherosclerosis
(2000) - et al.
Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms
Circulation
(2006) Beneficial cardiovascular pleiotropic effects of statins
Circulation
(2004)- et al.
Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month
Circulation
(1997) - et al.
The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes
J Clin Endocrinol Metab
(2004)
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