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Type 2 diabetes and non-alcoholic fatty liver disease: a metabolic tandem or a coincidence?

DOI 10.18127/j20700997-201903-05


L.A. Zvenigorodskaya –
D. Sc. (Med.), Professor, Leading Research Scientist, Endocrinology Service of the Moscow Clinical Scientific Center n.a. А.S Loginov of the Moscow City Health Department
A.E. Lychkova –
D. Sc. (Med.), Head of Department of Moscow Clinical Scientific Center n.a. А.S Loginov of the Moscow City Health Department
E-mail address:

According to forecasts of the World Health Organization, non-alcoholic fatty liver disease (NAFLD) by 2020 will occupy the 1st place among all liver diseases. The pathogenetic links of the type 2 diabetes and NAFLD are insulin resistance, lipid metabolism disorders and chronic, subclinical inflammation. The implementation of these pathogenetic mechanisms is carried out primarily at the level of the hepatocyte. NAFLD is a predictor of severe cardiovascular complications, multiple polytopic drug resistance, creates difficulties in the effective treatment of not only type 2 diabetes, but also many other diseases.
Proinflammatory cytokines, interleukins-6 and -8 and tumor necrosis factor α (TNF-α), play an important role in the development of NAFLD. TNF-α is a multifunctional pro-inflammatory cytokine, secreted mainly by macrophages, predominantly adipose tissue, and has auto-and paracrine effects.
The drug Proluent is sutable for the long-term treatment of adult patients with primary hypercholesterolemia (non-family and heterozygous familial hypercholesterolemia) or mixed dyslipidemia, including patients with DM 2, Apo B, TG and LP (a) and increasing concentrations of HDL-C and Apo A-1.
A new, highly effective method for the treatment and prevention of type 2 diabetes, NAFLD and CVD may be the use of mo-noclonal antibodies – inhibitors of subtilin / kexin type 9 covertase proprotein (PCSK9) – low density lipoprotein receptors.
PCSK9 binds to LDL receptors (R-LDL) on the surface of hepatocytes, contributing to the degradation of R-LDL in the liver. Inhibiting the binding of PCSK9 to R-LDL, alirocumab increases the amount of R-LDL to remove LDL, thus reducing the con-centration of Xc-LDL in the blood. Alirocumab also reduces the concentration of lipoproteins (Lp (a)), which are an independent factor for cardiovascular risks.
In in vitro studies, alirocumab did not induce antibody-dependent cell-mediated toxicity and complement-dependent cytotoxicity (Fc-mediated effector function), both in the presence and absence of PCSK9. In alirocumab bound to PCSK9, there was no formation of insoluble immune complexes capable of binding complement proteins.DM 2 and NAFLD – tandem of consistently developing events, have the same type of pathogenetic roots. The metabolic effects of this tandem are responsible for the development of severe cardiovascular diseases.

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May 29, 2020

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