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Open Access 01-12-2023 | Fatty Liver | Research

Non-alcoholic fatty liver disease and compromised endothelial function in people with type 2 diabetes

Authors: Zeinab Montazeri, Nahid Hashemi-Madani, Hamed Iraji, Masoudreza Sohrabi, Fariba Alaei-Shahmiri, Zahra Emami, Mohammad Reza Babaei, Mojtaba Malek, Mohammad E. Khamseh

Published in: BMC Endocrine Disorders | Issue 1/2023

Abstract

Introduction

Nonalcoholic fatty liver disease (NAFLD) frequently coexists with type 2 diabetes mellitus (T2DM) and synergistically contributes to the development of atherosclerosis. Flow-mediated dilation (FMD) is a commonly used noninvasive test for assessing endothelial function. The main objective of this study was to explore FMD in patients with T2DM with and without NAFLD.

Methods

In this cross-sectional study, conducted on people with T2DM, NAFLD was defined as controlled attenuation parameter (CAP) score > 302 dB/m. Endothelial dysfunction was detected when arterial FMD of brachial artery was equal or less than 0.7%. Regression analyses were applied to assess factors associated with impaired FMD.

Result

A total of 147 patients (72 with NAFLD and 75 without NAFLD) were included in the final analysis. Patients with NAFLD were more likely to develop FMD ≤ 7% (77.8% vs. 58.7%, P = 0.01). In multivariate analysis, NAFLD (OR = 2.581, 95% CI (1.18–5.62), P = 0.017) and hypertension (HTN) (OR = 3.114, 95% CI (1.31–7.35), P = 0.010) were associated with an increased risk of impaired FMD. However, female sex was associated with a decreased risk of impaired FMD (OR = 0.371, 95% CI (0.15–0.87), P = 0.024).

Conclusion

NAFLD is associated with endothelial dysfunction in people with T2DM. This risk is comparable with the risk imposed by HTN, highlighting the importance of screening and management of NAFLD in these patients.

Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, et al. American Association of Clinical Endocrinology clinical practice guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the study of Liver Diseases (AASLD). Endocr Pract. 2022;28(5):528–62.CrossRefPubMed

Kudaravalli P, John S. Nonalcoholic fatty liver. StatPearls [Internet]: StatPearls Publishing; 2022.

Mikolasevic I, Filipec-Kanizaj T, Mijic M, Jakopcic I, Milic S, Hrstic I, Sobocan N, Stimac D, Burra P. Nonalcoholic fatty liver disease and liver transplantation - where do we stand? World J Gastroenterol. 2018;24(14):1491–506. https://doi.org/10.3748/wjg.v24.i14.1491.CrossRefPubMedPubMedCentral

Kneeman JM, Misdraji J, Corey KE. Secondary causes of nonalcoholic fatty liver disease. Th Adv Gastroenterol. 2012;5(3):199–207. https://doi.org/10.1177/1756283X11430859.CrossRef

Anstee QM, Targher G, Day CP. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol. 2013;10:330–44. https://doi.org/10.1038/nrgastro.2013.41.CrossRefPubMed

Tilg H, Moschen AR, Roden M. NAFLD and diabetes mellitus. Nat Rev Gastroenterol Hepatol. 2017;14(1):32–42. https://doi.org/10.1038/nrgastro.2016.147.CrossRefPubMed

Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med. 2000;343(20):1467–76. https://doi.org/10.1056/NEJM200011163432007.CrossRefPubMed

Zeb I, Li D, Budoff MJ, Katz R, Lloyd-Jones D, Agatston A, et al. Nonalcoholic fatty liver disease and incident cardiac events: the multi-ethnic study of atherosclerosis. J Am Coll Cardiol. 2016;67(16):1965–6. https://doi.org/10.1016/j.jacc.2016.01.070.CrossRefPubMed

Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C, et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol. 2016;65(3):589–600. https://doi.org/10.1016/j.jhep.2016.05.013.CrossRefPubMed

10.

Stahl EP, Dhindsa DS, Lee SK, Sandesara PB, Chalasani NP, Sperling LS. Nonalcoholic fatty liver Disease and the heart: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(8):948–63. https://doi.org/10.1016/j.jacc.2018.11.050.CrossRefPubMed

11.

Sitia S, Tomasoni L, Atzeni F, Ambrosio G, Cordiano C, Catapano A, et al. From endothelial dysfunction to atherosclerosis. Autoimmun Rev. 2010;9(12):830–4. https://doi.org/10.1016/j.autrev.2010.07.016.CrossRefPubMed

12.

Kasper P, Martin A, Lang S, Kütting F, Goeser T, Demir M, Steffen HM. NAFLD and cardiovascular diseases: a clinical review. Clin Res Cardiol. 2021;110(7):921–37. https://doi.org/10.1007/s00392-020-01709-7.CrossRefPubMed

13.

Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, et al. The assessment of endothelial function: from research into clinical practice. Circulation. 2012;126(6):753–67. https://doi.org/10.1161/CIRCULATIONAHA.112.093245.CrossRefPubMedPubMedCentral

14.

Theofilis P, Vordoni A, Nakas N, Kalaitzidis RG. Endothelial Dysfunction in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis. Life (Basel). 2022;11;12(5):718. https://doi.org/10.3390/life12050718.

15.

Maruhashi T, Kajikawa M, Kishimoto S, Hashimoto H, Takaeko Y, Yamaji T, et al. Diagnostic criteria of Flow-Mediated vasodilation for normal endothelial function and Nitroglycerin-Induced Vasodilation for normal vascular smooth muscle function of the Brachial artery. J Am Heart Assoc. 2020;9(2):e013915. https://doi.org/10.1161/JAHA.119.013915.CrossRefPubMedPubMedCentral

16.

Eddowes PJ, Sasso M, Allison M, Tsochatzis E, Anstee QM, Sheridan D, et al. Accuracy of FibroScan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology. 2019;156(6):1717–30.CrossRefPubMed

17.

Zhou YY, Zhou XD, Wu SJ, Hu XQ, Tang B, Poucke SV, et al. Synergistic increase in cardiovascular risk in diabetes mellitus with nonalcoholic fatty liver disease: a meta-analysis. Eur J Gastroenterol Hepatol. 2018;30(6):631–6. https://doi.org/10.1097/MEG.0000000000001075. PMID: 29351115.CrossRefPubMed

18.

Lauridsen BK, Stender S, Kristensen TS, Kofoed KF, Køber L, Nordestgaard BG, Tybjærg-Hansen A. Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease: mendelian randomization and meta-analysis of 279 013 individuals. Eur Heart J. 2018;39(5):385–93. https://doi.org/10.1093/eurheartj/ehx662.CrossRefPubMed

19.

Dongiovanni P, Petta S, Maglio C, Fracanzani AL, Pipitone R, Mozzi E, et al. Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease. Hepatology. 2015;61(2):506–14. https://doi.org/10.1002/hep.27490.CrossRefPubMed

20.

Kim J, Lee DY, Park SE, Park CY, Lee WY, Oh KW, et al. Increased risk for development of coronary artery calcification in subjects with non-alcoholic fatty liver disease and systemic inflammation. PLoS ONE. 2017;12(7):e0180118. https://doi.org/10.1371/journal.pone.0180118.CrossRefPubMedPubMedCentral

21.

Sung KC, Wild SH, Kwag HJ, Byrne CD. Fatty liver, insulin resistance, and features of metabolic syndrome: relationships with coronary artery calcium in 10,153 people. Diabetes Care. 2012;35(11):2359–64. https://doi.org/10.2337/dc12-0515.CrossRefPubMedPubMedCentral

22.

Puchner SB, Lu MT, Mayrhofer T, Liu T, Pursnani A, Ghoshhajra BB, et al. High-risk coronary plaque at coronary CT angiography is associated with nonalcoholic fatty liver disease, independent of coronary plaque and stenosis burden: results from the ROMICAT II trial. Radiology. 2015;274(3):693–701. https://doi.org/10.1148/radiol.14140933.CrossRefPubMed

23.

Francque SM, van der Graaff D, Kwanten WJ. Non-alcoholic fatty liver disease and cardiovascular risk: pathophysiological mechanisms and implications. J Hepatol. 2016;65(2):425–43. https://doi.org/10.1016/j.jhep.2016.04.005.CrossRefPubMed

24.

Abu-Shanab A, Quigley EM. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010;7(12):691–701. https://doi.org/10.1038/nrgastro.2010.172.CrossRefPubMed

25.

Kasumov T, Edmison JM, Dasarathy S, Bennett C, Lopez R, Kalhan SC. Plasma levels of asymmetric dimethylarginine in patients with biopsy-proven nonalcoholic fatty liver disease. Metabolism. 2011;60(6):776–81. https://doi.org/10.1016/j.metabol.2010.07.027.CrossRefPubMed

26.

Pacana T, Cazanave S, Verdianelli A, Patel V, Min HK, Mirshahi F, Quinlivan E, Sanyal AJ. Dysregulated hepatic methionine metabolism drives Homocysteine Elevation in Diet-Induced nonalcoholic fatty liver disease. PLoS ONE. 2015;10(8):e0136822. https://doi.org/10.1371/journal.pone.0136822.CrossRefPubMedPubMedCentral

27.

Sapmaz F, Uzman M, Basyigit S, Ozkan S, Yavuz B, Yeniova A, et al. Steatosis Grade is the most important risk factor for development of endothelial dysfunction in NAFLD. Med (Baltim). 2016;95(14):e3280. https://doi.org/10.1097/MD.0000000000003280.CrossRef

28.

Jose N, Kulirankal PKV. Study of endothelial dysfunction in patients with non-alcoholic fatty liver disease. Cureus. 2021;13(12):e20515. https://doi.org/10.7759/cureus.20515.CrossRefPubMedPubMedCentral

29.

Narayan J, Das HS, Nath P, Singh A, Mishra D, Padhi PK, Singh SP. Endothelial dysfunction, a marker of atherosclerosis, is Independent of metabolic syndrome in NAFLD Patients. Int J Hepatol. 2020;2020:1825142. https://doi.org/10.1155/2020/1825142.CrossRefPubMedPubMedCentral

30.

Loffredo L, Baratta F, Ludovica P, Battaglia S, Carnevale R, Nocella C, et al. Effects of dark chocolate on endothelial function in patients with non-alcoholic steatohepatitis. Nutr Metab Cardiovasc Dis. 2017;28(2):143–9. https://doi.org/10.1016/j.numecd.2017.10.027.CrossRefPubMed

31.

Shukla V, Fatima J, Chaudhary S, Ali M, Mishra I. A study of endothelial dysfunction in patients of non-alcoholic fatty liver disease. J Assoc Physicians India. 2017;65(9):18–22.PubMed

32.

Colak Y, Senates E, Yesil A, Yilmaz Y, Ozturk O, Doganay L, Coskunpinar E, Kahraman OT, Mesci B, Ulasoglu C, Tuncer I. Assessment of endothelial function in patients with nonalcoholic fatty liver disease. Endocrine. 2013;43(1):100–7. https://doi.org/10.1007/s12020-012-9712-1.CrossRefPubMed

33.

Villanova N, Moscatiello S, Ramilli S, Bugianesi E, Magalotti D, Vanni E, Zoli M, Marchesini G. Endothelial dysfunction and cardiovascular risk profile in nonalcoholic fatty liver disease. Hepatology. 2005;42(2):473–80. https://doi.org/10.1002/hep.20781.CrossRefPubMed

34.

Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, Kajikawa M, Matsumoto T, Hidaka T, Kihara Y, Chayama K, Noma K, Nakashima A, Goto C, Tomiyama H, Takase B, Yamashina A, Higashi Y. Relationship between flow-mediated vasodilation and cardiovascular risk factors in a large community-based study. Heart. 2013;99(24):1837–42. https://doi.org/10.1136/heartjnl-2013-304739.CrossRefPubMed

Title: Non-alcoholic fatty liver disease and compromised endothelial function in people with type 2 diabetes
Authors: Zeinab Montazeri
Nahid Hashemi-Madani
Hamed Iraji
Masoudreza Sohrabi
Fariba Alaei-Shahmiri
Zahra Emami
Mohammad Reza Babaei
Mojtaba Malek
Mohammad E. Khamseh
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Fatty Liver
Published in: BMC Endocrine Disorders / Issue 1/2023
Electronic ISSN: 1472-6823
DOI: https://doi.org/10.1186/s12902-023-01460-w

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