Effects of COVID-19 and diabetes mellitus on apolipoprotein A1 level in the blood plasma of patients

Main Article Content

V.V. Pushkarev
L.K. Sokolova
S.A. Cherviakova
Yu.B. Belchina
M.V. Bigun
O.I. Kovzun
V.M. Pushkarev
M.D. Tronko


Background. Increased level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 (ApoA1) in plasma is associated with a reduced risk of developing cardiovascular diseases. In addition to its potential cardioprotective function, HDL and ApoA1, the main HDL apolipoprotein, also have antidiabetic properties. The aim of the study was to determine the level of ApoA1 in the blood of patients (n = 81) with diabetes mellitus and COVID-19. Materials and methods. ApoA1 was determined by enzyme-linked immunosorbent assay kits (Elabscience, USA). The measurements were performed at an optical density of 450 nm. Results. ApoA1 level in the blood of patients with diabetes and especially with COVID-19 was significantly lower than in healthy people. The study of the dependence of plasma ApoA1 content on the level of Hb1Ac, the gender and the type of diabetes showed that in blood of patients with type 2 diabetes the amount of ApoA1 is lower than in those with type 1 diabetes, and with an increase in the level of Hb1Ac the amount of ApoA1 decreases. There was also significant gender difference. With an increase in the body mass index, the content of ApoA1 in blood plasma decreases below normal — 0.9 g/L, and at body mass index < 25 kg/m2, the amount of ApoA1 is significantly higher than the average lipoprotein level in diabetic patients. In individuals with newly diagnosed diabetes, the level of ApoA1 is significantly higher, and in patients with more than 10 years of illness, it is below average and below normal. Biguanide treatment, either in combination with other drugs (mainly insulin) or as monothe-
rapy, does not significantly affect the level of ApoA1 compared to the entire group average. In patients treated with sulfonylurea, the level of ApoA1 is significantly lower than the average level for the group and the norm.
A significant positive effect on the amount of ApoA1 in plasma was observed in people treated with a combination of drugs with sodium-glucose cotransporter type 2 inhibitors, insulin and especially dipeptidyl peptidase-4 inhibitors. However, insulin monotherapy did not significantly affect the ApoA1 content. Possible mechanisms of ApoA1 decrease in COVID-19 and diabetes are discussed. Conclusions. Thus, the level of ApoA1 may be one of the promising markers of severe COVID-19.

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How to Cite
Pushkarev, V., L. Sokolova, S. Cherviakova, Y. Belchina, M. Bigun, O. Kovzun, V. Pushkarev, and M. Tronko. “Effects of COVID-19 and Diabetes Mellitus on Apolipoprotein A1 Level in the Blood Plasma of Patients”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 17, no. 5, Oct. 2021, pp. 411-7, doi:10.22141/2224-0721.17.5.2021.241519.
Original Researches


Lund-Katz S, Phillips MC. High density lipoprotein structure-function and role in reverse cholesterol transport. Subcell Biochem. 2010;51:183-227. doi:10.1007/978-90-481-8622-8_7.

Inoue Y, Okamoto T, Honda T, et al. Disruption in the balance between apolipoprotein A-I and mast cell chymase in chronic hypersensitivity pneumonitis. Immun Inflamm Dis. 2020 Dec;8(4):659-671. doi:10.1002/iid3.355.

Kareinen I, Baumann M, Nguyen SD, et al. Chymase released from hypoxia-activated cardiac mast cells cleaves human apoA-I at Tyr192 and compromises its cardioprotective activity. J Lipid Res. 2018 Jun;59(6):945-957. doi:10.1194/jlr.M077503.

Mineo C, Shaul PW. Regulation of signal transduction by HDL. J Lipid Res. 2013 Sep;54(9):2315-24. doi:10.1194/jlr.R039479.

Rye KA, Barter PJ, Cochran BJ. Apolipoprotein A-I interactions with insulin secretion and production. Curr Opin Lipidol. 2016 Feb;27(1):8-13. doi:10.1097/MOL.0000000000000253.

Di Bartolo BA, Cartland SP, Genner S, et al. HDL Improves Cholesterol and Glucose Homeostasis and Reduces Atherosclerosis in Diabetes-Associated Atherosclerosis. J Diabetes Res. 2021 May 6;2021:6668506. doi:10.1155/2021/6668506.

Fritzen AM, Domingo-Espín J, Lundsgaard AM, et al. ApoA-1 improves glucose tolerance by increasing glucose uptake into heart and skeletal muscle independently of AMPKα2. Mol Metab. 2020 May;35:100949. doi:10.1016/j.molmet.2020.01.013.

Mao Y, Xu Y, Lu L. The nonlinear association between apolipoprotein B to apolipoprotein A1 ratio and type 2 diabetes. Medicine (Baltimore). 2017 Jan;96(1):e5834. doi:10.1097/MD.0000000000005834.

Dong H, Chen W, Wang X, et al. Apolipoprotein A1, B levels, and their ratio and the risk of a first stroke: a meta-analysis and case-control study. Metab Brain Dis. 2015 Dec;30(6):1319-30. doi:10.1007/s11011-015-9732-7.

Chyu KY, Shah PK. HDL/ApoA-1 infusion and ApoA-1 gene therapy in atherosclerosis. Front Pharmacol. 2015 Sep 1;6:187. doi:10.3389/fphar.2015.00187.

Wolkowicz P, White CR, Anantharamaiah GM. Apolipoprotein Mimetic Peptides: An Emerging Therapy against Diabetic Inflammation and Dyslipidemia. Biomolecules. 2021 Apr 23;11(5):627. doi:10.3390/biom11050627.

Cochran BJ, Ong KL, Manandhar B, Rye KA. High Density Lipoproteins and Diabetes. Cells. 2021 Apr 9;10(4):850. doi:10.3390/cells10040850.

Gao L, Zhang Y, Wang X, Dong H. Association of apolipoproteins A1 and B with type 2 diabetes and fasting blood glucose: a cross-sectional study. BMC Endocr Disord. 2021 Apr 1;21(1):59. doi:10.1186/s12902-021-00726-5.

Retnakaran R, Ye C, Connelly PW, Hanley AJ, Sermer M, Zinman B. Serum apoA1 (Apolipoprotein A-1), Insulin Resistance, and the Risk of Gestational Diabetes Mellitus in Human Pregnancy-Brief Report. Arterioscler Thromb Vasc Biol. 2019 Oct;39(10):2192-2197. doi:10.1161/ATVBAHA.119.313195.

Hilser JR, Han Y, Biswas S, et al. Association of serum HDL-cholesterol and apolipoprotein A1 levels with risk of severe SARS-CoV-2 infection. J Lipid Res. 2021 Mar 2;62:100061. doi:10.1016/j.jlr.2021.100061.

Zamanian Azodi M, Arjmand B, Zali A, Razzaghi M. Introducing APOA1 as a key protein in COVID-19 infection: a bioinformatics approach. Gastroenterol Hepatol Bed Bench. 2020 Fall;13(4):367-373.

Zhu Z, Yang Y, Fan L, et al. Low serum level of apolipoprotein A1 may predict the severity of COVID-19: A retrospective study. J Clin Lab Anal. 2021 Jul 14:e23911. doi:10.1002/jcla.23911.

Begue F, Tanaka S, Mouktadi Z, et al. Altered high-density lipoprotein composition and functions during severe COVID-19. Sci Rep. 2021 Jan 27;11(1):2291. doi:10.1038/s41598-021-81638-1.

Wei X, Zeng W, Su J, et al. Hypolipidemia is associated with the severity of COVID-19. J Clin Lipidol. 2020 May-Jun;14(3):297-304. doi:10.1016/j.jacl.2020.04.008.

Usami Y, Kobayashi Y, Kameda T, et al. Identification of sites in apolipoprotein A-I susceptible to chymase and carboxypeptidase A digestion. Biosci Rep. 2012 Dec 6;33(1):49-56. doi:10.1042/BSR20120094.

Park JH, Park SM, Park KH, Cho KH, Lee ST. Analysis of apolipoprotein A-I as a substrate for matrix metalloproteinase-14. Biochem Biophys Res Commun. 2011 May 27;409(1):58-63. doi:10.1016/j.bbrc.2011.04.105.

Georgila K, Vyrla D, Drakos E. Apolipoprotein A-I (ApoA-I), Immunity, Inflammation and Cancer. Cancers (Basel). 2019 Aug 1;11(8):1097. doi:10.3390/cancers11081097.

Koval SM, Yushko KO, Snihurska IO, et al. Relations of angiotensin-(1-7) with hemodynamic and cardiac structural and functional parameters in patients with hypertension and type 2 diabetes. Arterial Hypertension. 2019;23(3):183-189. doi: 10.5603/AH.a2019.0012.

Calanna S, Scicali R, Di Pino A, et al. Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes. Nutr Metab Cardiovasc Dis. 2014 Jun;24(6):670-6. doi:10.1016/j.numecd.2014.01.013.

Wu X, Yu Z, Su W, et al. Low levels of ApoA1 improve risk prediction of type 2 diabetes mellitus. J Clin Lipidol. 2017 Mar-Apr;11(2):362-368. doi:10.1016/j.jacl.2017.01.009.

Zheng J, Yin Q, Cao J, Zhang B. Obesity contributes more to increasing ApoB/ApoA1 ratio than hyperandrogenism in PCOS women aged 20-38 years in China. Exp Ther Med. 2017 Apr;13(4):1337-1342. doi:10.3892/etm.2017.4094.

Da Costa LA, Arora P, García-Bailo B, Karmali M, El-Sohemy A, Badawi A. The association between obesity, cardiometabolic disease biomarkers, and innate immunity-related inflammation in Canadian adults. Diabetes Metab Syndr Obes. 2012;5:347-55. doi:10.2147/DMSO.S35115.

Li FR, Yang HL, Zhou R, et al. Diabetes duration and glycaemic control as predictors of cardiovascular disease and mortality. Diabetes Obes Metab. 2021 Jun;23(6):1361-1370. doi:10.1111/dom.14348.

Sola D, Rossi L, Schianca GP, et al. Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015 Aug 12;11(4):840-8. doi:10.5114/aoms.2015.53304.

Garratt KN, Brady PA, Hassinger NL, Grill DE, Terzic A, Holmes DR Jr. Sulfonylurea drugs increase early mortality in patients with diabetes mellitus after direct angioplasty for acute myocardial infarction. J Am Coll Cardiol. 1999 Jan;33(1):119-24. doi:10.1016/s0735-1097(98)00557-9.

Terao Y, Ayaori M, Ogura M, et al. Effect of sulfonylurea agents on reverse cholesterol transport in vitro and vivo. J Atheroscler Thromb. 2011;18(6):513-30. doi:10.5551/jat.7641.

Davies MJ, D'Alessio DA, Fradkin J, et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-2701. doi:10.2337/dci18-0033.

Scheen AJ. The safety of gliptins : updated data in 2018. Expert Opin Drug Saf. 2018 Apr;17(4):387-405. doi:10.1080/14740338.2018.1444027.

Patti AM, Giglio RV, Papanas N, Rizzo M, Rizvi AA. Future perspectives of the pharmacological management of diabetic dyslipidemia. Expert Rev Clin Pharmacol. 2019 Feb;12(2):129-143. doi:10.1080/17512433.2019.1567328.

Golshahi J, Validi E, Akbari M. The association between fasting serum insulin, apo-lipoproteins level, and severity of coronary artery involvement in non-diabetic patients. Adv Biomed Res. 2014 Sep 12;3:192. doi:10.4103/2277-9175.140624.

Sokolova LK, Belchina YuB, Pushkarev VV, et al. The effect of metformin treatment on the level of GLP-1, NT-proBNP and endothelin-1 in patients with type 2 diabetes mellitus. Mìžnarodnij endokrinologìčnij žurnal. 2020;16(8):26-31. doi:10.22141/2224-0721.16.8.2020.222882.

Sokolova LK, Belchina YB, Pushkarev VV, et al. The level of endothelin-1 in the blood of patients with diabetes, treated with hypoglycemic drugs. Endokrynologia. 2020;25(3):201-206. doi:10.31793/1680-1466.2020.25-3.201.

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