Pashkovska N.V.

Bukovinian State Medical University, Chernivtsy, Ukraine

 

ENDOTHELIAL DYSFUNCTIONS IN PATIENTS WITH DIABETIC ENCEPHALOPATHY

 

The endothelium is a complex organ with a multitude of properties essential for control of vascular functions. It controls the tone of the underlying vascular smooth muscle through the production of vasodilator mediators. The endothelium-derived relaxing factors comprise nitric oxide, prostacyclin, and a still elusive endothelium-derived hyperpolarizing factor [3].

Vascular endothelium damage is known as one of the major mechanisms in pathogenesis of chronic complications in diabetes mellitus (DM). Factors associated with endothelial dysfunction in diabetes include activation of protein kinase C, overexpression of growth factors and/or cytokines, and oxidative stress [4].

Encephalopathies of various genesis tend to be the most important problem of present medicine. One of the leading causes of their development is DM. Diabetic encephalopathy (DE) is commonly considered to be a variant of dyscirculatory encephalopathy. The pathogenesis is still uncertain, but chronic hyperglycemia, vascular disease, repeated hypoglycemic episodes, and possibly direct effects of insulin on the brain have been implicated [1]. Nevertheless, the degree of endothelial dysfunction in DE, haven’t been studied by other investigators in dependence on the stage and type of basic disease.

The indices of circulating desquamated endotheliocytes and endothelium-dependent vasodilatation (EDVD) of brachial artery were studied to detect the degree of endothelial dysfunction in patients with DE in comparison with patients that suffer from discirculatory encephalopathy of non-diabetic genesis.

The aim of our study was to study differential peculiarities of EDVD in patients with diabetic and non-diabetic encephalopathy.

The study group comprised 66 patients with vascular encephalopathy (32 with DE and 20 with non-diabetic encephalopathy). EDVD was evaluated according to Celermayer-Sorensen’s test (EnVisor HD” (Philips, USA)) [2, 6]. The statistical evaluation was carried out by the t-test.

The study demonstrated, that dyscirculatory encephalopathy was followed by reliably significant (Ð<0,001) decrease of EDVD rate (5,6±0,21%) as compared with controls (10,8±0,51%).

In case of DE the rate of EDVD was more than two times decreased (4,9±0,23%) as compared with control rate (Ð<0,001).

EDVD was more affected in type 2 DM (4,5±0,29%, Ð<0,05), than in type 1 (5,5±0,31%), that indicated more severe damage of vascular endothelium in case of non-insulin-dependent DM.

It is necessary to mention, that changes of EDVD in DE were reliably more evident as compared with patients suffering from non-diabetic dyscirculatory encephalopathy (6,4±0,29%).

This is explained, as we concluded, by the direct toxic influence of increased glucose concentration on vascular endothelial cells. This toxicity may lower the endothelium-dependent vasodilatation, elevate the vasoconstriction, stimulate the hyperplasia of smooth muscles cells, lead to vascular remodeling and development of atherosclerosis.

The endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary. These cells reduce friction of the flow of blood allowing the fluid to be pumped further. Circulating endothelial cells  might be used as a surrogate non-invasive marker for the study of vascular alterations.

The objectives of our study were to reveal the peculiarities of endothelial dysfunction in patients with DE according to blood level of desquamated endotheliocytes in dependence on the stage and type of DM. The estimation of endothelaemia was carried out according to the method described previously [5].

The study concerned a group of 66 patients with DE (32 with type 1 DM and 34 with type 2 DM). Stage I DE was diagnosed in 23 patients of studied group, stage II and III – in 25 and 18 patients respectively.

The findings demonstrated, that endothelial desquamation was observed in the group of healthy individuals as well as in the group of patients, suffering from DE.

In healthy individuals blood level of desquamated endotheliocytes accounted 3,2±0,36·104/l.

In patients with stage I DE this index reached 12,8±0,64·104/l, stage II DE – 16,5±0,58·104/l, stage III DE – 19,2±0,71·104/l. Statistically significant changes were found between groups of patients with stage I and stage I DE (Ð<0,001), and with stage II and stage III DE (ð<0,01).

Consequently, the progression of DE was followed by proportional augmentation of the blood concentration of desquamated endothelioin cytes. The index of endotheliocytemia was reliably higher in type 2 DM as compared with type 1 diabetics (Ð<0,05), that indicated more significant implication of vascular endothelium damages in the pathogenesis of non-insulin-dependent DM. The role of endothelial dysfunction in type 2 diabetes is more complicated than that for type 1. The effects of aging, hyperlipidemia, hypertension, and other factors add to the complexity of the problem.

References:

1.           Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P: Risk of dementia in diabetes mellitus: a systematic review // Lancet Neurol. – 2006. - Vol. 5. - P.64–74.

2.     Celermajer D.S., Sorensen K.E., Gooch V.M. et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis // Lancet. – 1992. – Vol. 340. – P. 1111-1115.

3.Christ M., Bauersachs J., Liebetrau C. Glucose increases endothelial-dependent superoxide formation in coronary arteries by NAD(P)H oxidase activation: attenuation by the 3-hydroxy-3-methylglutaryl coenzyme A reductase  inhibitor atorvastatin // Diabetes. – 2003. - ¹51. – Ð.2648–2652.

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5.     Hladovec J. Circulating endothelial cells as a sign of vessel wall lesions // Physiol. Bohemoslov. - 1978. -Vol. 27, ¹ 2. - P. 140-144.

6.     Sorensen K.E., Celermajer D.S., Spiegelhaltcr D.J. et al. Noninvasive measurement of human endothelium-dependent arterial responses: accuracy and reproducibility // Brit. Heart J. – 1995. – Vol. 74. – P. 247-253.