Abstract
It is now well established that major risk factors for cardiovascular diseases (CVD) impact upon endothelial function by decreasing nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA), an endogenous analog of l-arginine, is able to inhibit the activity of endothelial-NO synthase, promoting endothelial dysfunction. Type 2 diabetes (T2D) is characterized by a reduced endothelium-dependent vasodilation and increased ADMA levels and ADMA is strongly associated with micro- and macrovascular diabetic complications. However, there are not a lot of data about the role of ADMA on endothelial function in newly diagnosed T2D patients without cardiovascular (CV) complications. For this aim, we have enrolled forty-five newly diagnosed T2D patients, evaluated by a oral glucose tolerance test, and thirty normal subjects. Endothelium-dependent and -independent vasodilatation was investigated by intra-arterial infusion of increasing doses of acetylcholine (ACh) and sodium nitroprusside. ADMA was measured by high-performance liquid chromatography and insulin resistance (IR) by HOMA. Newly diagnosed T2D patients showed higher ADMA and l-arginine mean values in comparison with normal subjects and a significantly reduced ACh-stimulated forearm blood flow (FBF). In T2D patients FBF was significantly and inversely correlated with ADMA (r = −0.524, p < 0.0001) and in a multivariate regression analysis, ADMA resulted the stronger predictor of FBF, explaining the 27.5% of variability (p < 0.0001). In conclusion, ADMA was strongly related to endothelial dysfunction also in patients with newly diagnosed T2D, without clinically manifest vascular complications. This field is of great interest for understanding the mechanisms underlying the pathogenesis of diabetic disease and its CV complications.
Highlights
The normal endothelium, with its anatomical and functional integrity, plays a pivotal role in the prevention of the both coronary and extracoronary atherosclerosis [1,2]
With regard to the first mechanism, the activity of e-NOS may be inhibited by endogenous analogs of L-arginine, such as asymmetric dimethylarginine (ADMA) [10], that derive from the catabolism of proteins containing methylated arginine residues
There were no significant differences in gender, age, body mass index (BMI), waist circumference, blood pressure (BP), total and LDL-cholesterol and estimated glomerular filtration rate (e-GFR)
Summary
The normal endothelium, with its anatomical and functional integrity, plays a pivotal role in the prevention of the both coronary and extracoronary atherosclerosis [1,2]. It is well known that all traditional risk factors for cardiovascular diseases (CVD), such as hypertension and diabetes, [5,6] affect endothelial function by decreasing NO bioavailability. This condition known as “endothelial dysfunction” may be caused by several mechanisms including decreased NO synthesis, increased NO degradation due to oxidative stress, or reduced sensitivity of smooth muscle cell to NO [2,3,7,8]. There are several evidences that ADMA is increased in different clinical settings; as with chronic renal diseases [11], hypercholesterolemia [12], essential hypertension [13] and diabetes mellitus [14,15], all conditions are associated with the appearance and progression of atherosclerotic disease
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