The relationship of endothelial dysfunction and metabolic manifestations of obesity

Introduction. Over the past three decades, the prevalence of overweight and obesity in the world has grown by almost 30–50% among adults and children. A number of metabolic and hemodynamic disorders, as well as the pathology of many organs and systems are often associated with obesity. The aim of our study was to compare the functional state of the endothelium in various variants of complicated obesity (СO). Materials and methods. The study included 66 people with СO whose average age was 47.3 ± 9.9 years, from this group 3 groups were formed depending on the complications of obesity (dyslipidemia, hypertension and impaired glucose tolerance). To assess the functional state of endothelium, we used the method of wavelet analysis of skin temperature fluctuations during cooling of the limb; endothelin-1 (ET-1), albuminuria (AC), and vascular endothelial growth factor (VEGF) were determined as markers of endothelial dysfunction. Results. The levels of VEGF, ET-1 and AC in the groups with СO did not differ significantly, however, they were significantly higher than in the comparison group. The results of the cold test revealed the absence of restoration of the amplitudes of fluctuations in skin temperature equally in all groups with CO compared with the control group (post-cold vasodilation indices (IPV) in group 1 – 0.45 (0.38–0.69, in group 2 – 0.59 (0.41–0.83), in group 3 – 0.66 (0.53–0.79), in the Control group – 0.91 (0.86–1.06), p<0.05). Correlations between biochemical and instrumental markers of endothelial dysfunction and insulin resistance indices were obtained: ET-1 correlated with insulin (r=0.49; p=0.02), HOMA index (r=0.55; p=0.01); AU value correlated with glycemia (r=0.70; p=0.02); The IVC vasoconstriction index correlated with the HOMA-IR index (r=0.62; p=0.05); The IPV-1 index decreased with increasing VEGF (r=–0.86; p=0.002) and HOMA-IR (r=–0.86; p=0.002). The IPV-2 index inversely correlated with the level of postprandial glycemia (r=–0.87; p=0.05), systolic blood pressure (r=–0.55; p=0.04), OT (r=–0.57; p=0.04) and ET-1 (r=–0.58; p=0.04). Conclusion. The unified basis of the revealed disorders in СO allows us to conclude that the factors of insulin resistance are complex: hyperglycemia, dyslipidemia, and arterial hypertension, which makes it difficult to identify the leading factor in the formation of endothelial dysfunction.

endothelial dysfunction, wavelet analysis of skin temperature oscillations, complicated obesity

1. Drapkina OM, Eliashevich SO, Shepel RN. Оbesity as a risk factor for chronic non-communicable diseases. Russian Journal of Cardiology. 2016;6(134):73–79. (In Russ.). Doi: 10.15829/1560-4071-2016-6-73-79.

2. Muromtseva GA, Kontsevaya AV, Konstantinov VV, Artamonova GV, Gatagonova TM et al. The prevalence of non-infectious diseases risk factors in Russian population in 2012-2013 years. The results of ECVD-RF. Cardiovascular Therapy and Prevention. 2014;13(6):4–11. (In Russ.). Doi: 10.15829/1728-8800-2014-6-4-11.

3. World Health Organization Media Centre. Obesity and overweight. Fact sheet no Geneva: World Health Organization, 2013.

4. James WPT, Jackson-Leach R, Mhurdu CN, Kalamara E, Shayeghi M, Rigby N, Nishida C, Rodgers A. Overweight and Obesity. In Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors. Eds. Ezzati M, Lopez AD, Rodgers A, Murray CJL. WHO, Geneva, 2003.

5. Klinicheskie rekomendacii. Diagnostika, lechenie, profilaktika ozhirenija i associirovannyh s nim zabolevanij. Russian Journal of Cardiology. 2017;7:6–8. (In Russ.). Doi: 10.15829/1560-4071-2017-6-7-85.

6. Razina AО, Achkasov EЕ, Runenko SD. Obesity: the modern approach to the problem. Obesity and Metabolism. 2016;3(1):3–8. (In Russ.)]. Doi: 10.14341/OMET201613-8.

7. Rey-Lopez J, de Rezende LF, ReyLópez JP, PastorValero M. The prevalence of metabolically healthy obesity: a systematic review and critical evaluation of the definitions used. Obesity Reviews. 2014;15:781–790. Doi: 10.1111/obr.12198.

8. Ding Wenqing, Cheng Hong, Chen Fangfang, Yinkun Yan et al. Adipokines are Associated With Hypertension in Metabolically Healthy Obese (MHO) Children and Adolescents: A Prospective Population-Based Cohort Study. Journal of epidemiology. 2018; 28(1):19–26. Doi: 10.2188/jea.JE20160141.

9. Shestakova MV. Disfunkcija jendotelija prichina ili sledstvie metabolicheskogo sindroma? Мedical journal of the Russian Federation. 2001;9(2):32–35. (In Russ.).

10. Vlasov TD, Nesterovich II, Shimanski DA. Endothelial dysfunction: from the particular to the general. Return to the «Old Paradigm»? Regional blood circulation and microcirculation. 2019;18(2):19–27. (In Russ.). Doi: 10.24884/1682-6655-2019-18-2-19-27.

11. Podtaev S, Morozov M, Frick P. Wavelet-based Correlations of Skin Temperature and Blood Flow Oscillations. Cardiovasc. Eng. 2008;8:185–189. Doi: 10.1007/s10558-008-9055-y.

12. Podtaev SJu. Sposob registracii mikrocirkuljacii krovi. Patent 2390306 Rossiiskaya Federatsiya; zayavl. 08.12.08; opubl. 27.05.10, Bjul. № 15. (In Russ.).

13. Popov AV, Podtaev SYu, Frick PG, Ershova AI, Jhukova EA. The study of low-amplitude oscillations of skin temperature during indirect cold pressure test. Regional blood circulation and microcirculation. 2011;10(1):89–94. (In Russ.).

14. Lazernaja dopplerovskaja floumetrija mikrocirkuljacii krovi. Rukovodstvo dlja vrachej. Pod red. A. I. Krupatkina, V. V. Sidorova. Moscow, Medicina, 2005:256. (In Russ.).

15. Roustit M et al. Reproducibility and methodological issues of skin post-occlusive and thermal hyperemia assessed by single-point laser Doppler flowmetry. Microvasc. Res. 2010; 79:102–108. Doi: 10.1016/j.mvr.2010.01.001.

16. Gómez-Ambrosi J, Catalán V, Rodríguez A et al. Involvement of serum vascular endothelial growth factor family members in the development of obesity in miceand humans. J Nutr Biochem. 2010;21:774–780. Doi: 10.1016/j.jnutbio.2009.05.004.

17. Statsenko ME, Derevyanchenko MV. Correction of endothelial dysfunction in hypertensive patients with type 2 diabetes mellitus during combined antihypertensive therapy. Therapeutic Archive. 2014;86(8):90–93. (In Russ.).

18. Konttinen J, Lindholm H, Sinisalo J, Kuosma E, Halonen J, Hopsu L, Uitti J. Association between lowered endothelial function measured by peripheral arterial tonometry and cardio-metabolic risk factors – a cross-sectional study of Finnish municipal workers at risk of diabetes and cardiovascular disease. Cardiovascular Disorders. 2013; 13:83. Doi: 10.1186/1471-2261-13-83.

19. Paltsev MA, Kvetnoy IM, Ilnitski AN et al. The obesity: the molecular mechanisms and the optimization of target therapy. Мolecular medicine. 2013;2:3–12. (In Russ.).

20. Kovesdy CP, Furth SL, Zoccali C. Obesity and kidney disease: hidden consequences of the epidemic. Future Sci OA. 2017;3(3):FSO159. Doi: 10.1007/s40620-017-0377-y.

21. Androga L, Sharma D, Amodu A et al. Sarcopenia, Obesity, and Mortality in US Adults With and Without Chronic Kidney Disease. Kidney Int Rep. 2017;2(2):201–211. Doi: 10.1016/j.ekir.2016.10.008.

22. Kovalyova JuV. Adipose tissue hormones and their role for female fertility and metabolic disorders. Аrterial hypertension. 2015;21(4):356–370. (In Russ.). Doi: 10.18705/1607-419X-2015-21-4-356-37.

23. Uchamprina VA, Romantsova TI, Kalashnikova MF. Integrated approach in the treatment of metabolic syndrome. Obesity and Metabolism. 2014;1:32–37. (In Russ.). Doi: 10.14341/OMET2014132-37.

24. Walther G, Obert P, Dutheil F, Chapier R, Lesourd B, Naughton G, Courteix D, Vinet A. Metabolic syndrome individuals with and without type 2 diabetes mellitus present generalized vascular dysfunction: cross-sectional. Arterioscler Thromb Vasc Biol. 2015;35(4):1022–1029. Doi: 10.1161/ATVBAHA.114.304591.

25. Thanigaimani S, Kichenadasse G, Mangoni A. The emerging role of vascular endothelial growth factor in vascular homeostasis: lessons from recent trials with anti-VEGF drugs. Current Vascular Pharmacology. 2011;9:358–380. Doi: 10.2174/157016111795495503.