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- ADMA, asymmetrical dimethyl arginine
- CAD, coronary artery disease
- CRP, C-reactive protein
- DM, diabetes mellitus
- FBF, forearm blood flow
- HDL, high density lipoprotein
- IL-6, interleukin-6
- NTG%, per cent change of flow after nitrate administration
- RH%, per cent change of flow during reactive hyperaemia
- sVCAM-1, soluble vascular cell adhesion molecule-1
- TNF-α, tumour necrosis factor-α
Type 2 diabetes mellitus (DM) is characterised by increased oxidative stress as a result of the hyperglycaemic state, leading to decreased nitric oxide bioavailability.1 Similarly, type 2 DM is characterised by increased levels of proatherogenic cytokines and adhesion molecules,1 while it has been shown that the endogenous endothelial nitric oxide synthase inhibitor, asymmetrical dimethyl arginine (ADMA), is also elevated in type 2 DM.2 Although ADMA synthesis is triggered by both oxidative stress and proinflammatory stimuli, the effect of antioxidant or anti-inflammatory treatment on its release is unclear.
We compared the effects of atorvastatin (which has anti-inflammatory properties in atherosclerosis) and vitamin C (a well-known antioxidant) on the inflammatory process, endothelial function and the release of ADMA in normocholesterolaemic patients with type 2 DM.
Forty-one patients with type 2 DM and no evidence of macroangiopathy were recruited (table 1). The absence of coronary artery disease (CAD) was established by a negative exercise stress test within the last 6 months before recruitment, while peripheral artery disease was defined as an ankle brachial index <0.90. All patients had cholesterol <5.4 mmol/l at baseline, and exclusion criteria were the use of statins, insulin, antioxidant supplements, hormone replacement therapy or anti-inflammatory medication during the past year, or the presence of any chronic disease or infection. All subjects had normal renal function (normal creatinine clearance as calculated by the Cockroft-Gault formula and no macroalbuminuria). Patients were randomly allocated into groups receiving atorvastatin (10 mg/day), vitamin C (2 g/day) or no …
Competing interests: None declared.
Published Online First 16 August 2006