Association of Serum Bile Acid and Unsaturated Fatty Acid Profiles with the Risk of Diabetic Retinopathy in Type 2 Diabetic Patients

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2023 Jul 19

PMID 37465650

Authors

Susu Feng

Lin Guo

Sijing Wang

Lijuan Chen

Hang Chang

Bo Hang

Jianhua Mao

Antoine M Snijders

Yibing Lu

Dafa Ding

Affiliations

Soon will be listed here.

Abstract

Aim: We aimed to identify the ability of serum bile acids (BAs) and unsaturated fatty acids (UFAs) profiles to predict the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) patients.

Methods: We first used univariate and multivariate analysis to compare 15 serum BA and 11 UFA levels in healthy control (HC) group (n = 82), T2DM patients with DR (n = 58) and T2DM patients without DR (n = 60). Forty T2DM patients were considered for validation. Then, the receiver operating characteristic curve (ROC) and decision curve analysis were used to assess the diagnostic value and clinical benefit of serum biomarkers alone, clinical variables alone or in combination, and the area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to further assess whether the addition of biomarkers significantly improved the predictive ability of the model.

Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) of serum BAs and UFAs separated the three cohorts including HC, T2DM patients with or without DR. The difference in serum BA and UFA profiles of T2DM patients with or without DR was mainly manifested in the three metabolites of taurolithocholic acid (TLCA), tauroursodeoxycholic acid (TUDCA) and arachidonic acid (AA). Together, they had an AUC of 0.785 (0.918 for validation cohort) for predicting DR in T2DM patients. After adjusting for numerous confounding factors, TLCA, TUDCA, and AA were independent predictors that differentiated T2DM with or without DR. The results of AUC, IDI, and NRI demonstrated that adding these three biomarkers to a model with clinical variables statistically increased their predictive value and were replicated in our independent validation cohort.

Conclusion: These findings highlight the association of three metabolites, TLCA, TUDCA and AA, with DR and may indicate their potential value in the pathogenesis of DR.

Citing Articles

Unveiling the gut-eye axis: how microbial metabolites influence ocular health and disease.

Nguyen Y, Rudd Zhong Manis J, Ronczkowski N, Bui T, Oxenrider A, Jadeja R Front Med (Lausanne). 2024; 11:1377186.

PMID: 38799150 PMC: 11122920. DOI: 10.3389/fmed.2024.1377186.

References

Chung Y, Choi J, Koh J, Yoon Y . Ursodeoxycholic Acid Attenuates Endoplasmic Reticulum Stress-Related Retinal Pericyte Loss in Streptozotocin-Induced Diabetic Mice. J Diabetes Res. 2017; 2017:1763292. PMC: 5239976. DOI: 10.1155/2017/1763292. View

SanGiovanni J, Chew E . The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res. 2004; 24(1):87-138. DOI: 10.1016/j.preteyeres.2004.06.002. View

Beli E, Yan Y, Moldovan L, Vieira C, Gao R, Duan Y . Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in Mice. Diabetes. 2018; 67(9):1867-1879. PMC: 6110320. DOI: 10.2337/db18-0158. View

Wren S, Donovan M, Selmin O, Doetschman T, Romagnolo D . A -Driven Transgene Modulates Enterohepatic Bile Acid Homeostasis and Response to an -6-Enriched High-Fat Diet. Int J Mol Sci. 2020; 21(21). PMC: 7659968. DOI: 10.3390/ijms21217829. View

Therien A, Cieslak A, Verreault M, Perreault M, Trottier J, Gobeil S . Omega-3 Polyunsaturated Fatty Acid: A Pharmaco-Nutraceutical Approach to Improve the Responsiveness to Ursodeoxycholic Acid. Nutrients. 2021; 13(8). PMC: 8400581. DOI: 10.3390/nu13082617. View

Lin A, Roman R, Regan K, Bolch C, Chen C, Iyer S . Eicosanoid Profiles in the Vitreous Humor of Patients with Proliferative Diabetic Retinopathy. Int J Mol Sci. 2020; 21(20). PMC: 7589012. DOI: 10.3390/ijms21207451. View

Su Z, Liu W, Yang J . Association between Proliferative Diabetic Retinopathy and Serum Bile Acid Level in Patients with Type 2 Diabetes Mellitus. Endocr Metab Immune Disord Drug Targets. 2021; 21(11):2063-2067. DOI: 10.2174/1871530321666210112160724. View

Warner D, Warner J, Hardesty J, Song Y, King T, Kang J . Decreased ω-6:ω-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury. J Lipid Res. 2019; 60(12):2034-2049. PMC: 6889711. DOI: 10.1194/jlr.RA119000200. View

Rees G, Xie J, Fenwick E, Sturrock B, Finger R, Rogers S . Association Between Diabetes-Related Eye Complications and Symptoms of Anxiety and Depression. JAMA Ophthalmol. 2016; 134(9):1007-14. DOI: 10.1001/jamaophthalmol.2016.2213. View

10.

Milluzzo A, Maugeri A, Barchitta M, Sciacca L, Agodi A . Epigenetic Mechanisms in Type 2 Diabetes Retinopathy: A Systematic Review. Int J Mol Sci. 2021; 22(19). PMC: 8509039. DOI: 10.3390/ijms221910502. View

11.

Lei S, Huang F, Zhao A, Chen T, Chen W, Xie G . The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity. FASEB J. 2017; 31(9):3904-3912. PMC: 6191069. DOI: 10.1096/fj.201700055R. View

12.

Ulven S, Christensen J, Nygard O, Svardal A, Leder L, Ottestad I . Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat-a randomized controlled dietary intervention study. Am J Clin Nutr. 2019; 109(5):1239-1250. PMC: 6499508. DOI: 10.1093/ajcn/nqy356. View

13.

Wu Z, Liu L, Wang W, Cui H, Zhang Y, Xu J . Triglyceride-glucose index in the prediction of adverse cardiovascular events in patients with premature coronary artery disease: a retrospective cohort study. Cardiovasc Diabetol. 2022; 21(1):142. PMC: 9338459. DOI: 10.1186/s12933-022-01576-8. View

14.

Robert C, Buisson C, Laugerette F, Abrous H, Rainteau D, Humbert L . Impact of Rapeseed and Soy Lecithin on Postprandial Lipid Metabolism, Bile Acid Profile, and Gut Bacteria in Mice. Mol Nutr Food Res. 2021; 65(9):e2001068. DOI: 10.1002/mnfr.202001068. View

15.

Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M . A G protein-coupled receptor responsive to bile acids. J Biol Chem. 2003; 278(11):9435-40. DOI: 10.1074/jbc.M209706200. View

16.

Zhu X, Zhang Y, Bai L, Zhang X, Zhou J, Yang J . Prediction of risk of diabetic retinopathy for all-cause mortality, stroke and heart failure: Evidence from epidemiological observational studies. Medicine (Baltimore). 2017; 96(3):e5894. PMC: 5279092. DOI: 10.1097/MD.0000000000005894. View

17.

Kastelan S, Oreskovic I, Biscan F, Kastelan H, Gverovic Antunica A . Inflammatory and angiogenic biomarkers in diabetic retinopathy. Biochem Med (Zagreb). 2020; 30(3):030502. PMC: 7394255. DOI: 10.11613/BM.2020.030502. View

18.

Buhler A, Bucher F, Augustynik M, Wohrl J, Martin G, Schlunck G . Systemic confounders affecting serum measurements of omega-3 and -6 polyunsaturated fatty acids in patients with retinal disease. BMC Ophthalmol. 2016; 16(1):159. PMC: 5011975. DOI: 10.1186/s12886-016-0335-9. View

19.

Lobysheva E, Taylor C, Marshall G, Kisselev O . Tauroursodeoxycholic acid binds to the G-protein site on light activated rhodopsin. Exp Eye Res. 2018; 170:51-57. PMC: 5983371. DOI: 10.1016/j.exer.2018.02.015. View

20.

Patel P, Jelfs R, Carter R, Awdry P, Bron A, Mann J . Polyunsaturated fatty acids and diabetic retinopathy. Br J Ophthalmol. 1985; 69(1):15-8. PMC: 1040514. DOI: 10.1136/bjo.69.1.15. View