Serum Metabolic Signatures of Subclinical Atherosclerosis in Patients with Type 2 Diabetes Mellitus: a Preliminary Study

Overview

Journal Acta Diabetol

Specialty Endocrinology

Date 2021 Apr 19

PMID 33871690

Citations 5

Authors

Jiaorong Su

Qing Zhao

Aihua Zhao

Wei Jia

Wei Zhu

Jingyi Lu

Xiaojing Ma

Affiliations

Soon will be listed here.

Abstract

Aims: Atherosclerotic cardiovascular disease remains the leading cause of death among patients with diabetes. Early identification of subclinical atherosclerosis is essential for the management of diabetic patients. This study aimed to characterize serum metabolic signatures associated with carotid intima-media thickness (C-IMT), a proxy of subclinical atherosclerosis, in patients with type 2 diabetes mellitus (T2DM).

Methods: After 1:1 matching by sex, age, body mass index, glycated haemoglobin A, and other clinical parameters, a total of 462 T2DM patients were enrolled, consisting of 231 patients with C-IMT of ≥ 1 mm (abnormal C-IMT) and 231 patients with C-IMT of < 1 mm (normal C-IMT). C-IMT was assessed using ultrasonography. The serum metabolic profiling of fasting blood samples was performed using liquid chromatography-tandem triple quadrupole mass spectrometer coupled with the multivariate and univariate statistical analysis.

Results: Patients with abnormal C-IMT had significantly higher deoxycholic acid (DCA) and taurodeoxycholic acid (TDCA) levels, and lower levels of taurocholic acid (TCA) than those with normal C-IMT. Conditional logistic regression analysis revealed that per 1-standard deviation increase of DCA, TDCA and TCA were significantly associated with 64.7% (95% CI: 1.234-2.196) and 38.5% (95% CI: 1.124-1.706) higher, and 26.8% (95% CI: 0.597-0.897) lower risk of abnormal C-IMT, after adjustment of confounders. The addition of DCA, TCA, or DCA × TDCA/TCA ratio significantly improved the discrimination of abnormal C-IMT over traditional risk factors.

Conclusions: Serum bile acids may be potential biomarkers for subclinical atherosclerosis in T2DM patients, which needs further confirmation.

Citing Articles

Bile acids and incretins as modulators of obesity-associated atherosclerosis.

Kirsch A, Gindlhuber J, Zabini D, Osto E Front Cardiovasc Med. 2025; 11():1510148.

PMID: 39834741 PMC: 11743266. DOI: 10.3389/fcvm.2024.1510148.

Metabolomics and network pharmacology exploration of the effects of bile acids on carotid atherosclerosis and potential underlying mechanisms.

Cheng X, Zhang R, Qi X, Wang H, Gao T, Zheng L Front Endocrinol (Lausanne). 2024; 15:1430720.

PMID: 39076513 PMC: 11284041. DOI: 10.3389/fendo.2024.1430720.

Preliminary study of metabonomic changes during the progression of atherosclerosis in miniature pigs.

Jia Y, Zhao Y, Niu M, Zhao C, Li X, Chen H Animal Model Exp Med. 2024; 7(4):419-432.

PMID: 38923366 PMC: 11369038. DOI: 10.1002/ame2.12462.

Unveiling the oral-gut connection: chronic apical periodontitis accelerates atherosclerosis via gut microbiota dysbiosis and altered metabolites in apoE Mice on a high-fat diet.

Gan G, Lin S, Luo Y, Zeng Y, Lu B, Zhang R Int J Oral Sci. 2024; 16(1):39.

PMID: 38740741 PMC: 11091127. DOI: 10.1038/s41368-024-00301-3.

Serum metabolomic profiles associated with subclinical and clinical cardiovascular phenotypes in people with type 2 diabetes.

Huang Z, Klaric L, Krasauskaite J, McLachlan S, Strachan M, Wilson J Cardiovasc Diabetol. 2022; 21(1):62.

PMID: 35477395 PMC: 9047374. DOI: 10.1186/s12933-022-01493-w.

References

Grundy S, Stone N, Bailey A, Beam C, Birtcher K, Blumenthal R . 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018; 73(24):e285-e350. DOI: 10.1016/j.jacc.2018.11.003. View

Lee C, Lee S, Park S . Diabetes and Subclinical Coronary Atherosclerosis. Diabetes Metab J. 2018; 42(5):355-363. PMC: 6202561. DOI: 10.4093/dmj.2018.0041. View

Touboul P, Hennerici M, Meairs S, Adams H, Amarenco P, Desvarieux M . Mannheim intima-media thickness consensus. Cerebrovasc Dis. 2004; 18(4):346-9. DOI: 10.1159/000081812. View

Polak J, OLeary D . Carotid Intima-Media Thickness as Surrogate for and Predictor of CVD. Glob Heart. 2016; 11(3):295-312.e3. DOI: 10.1016/j.gheart.2016.08.006. View

Chambless L, Folsom A, Clegg L, Sharrett A, Shahar E, Nieto F . Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol. 2000; 151(5):478-87. DOI: 10.1093/oxfordjournals.aje.a010233. View

Chambless L, Heiss G, Folsom A, Rosamond W, Szklo M, Sharrett A . Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. Am J Epidemiol. 1997; 146(6):483-94. DOI: 10.1093/oxfordjournals.aje.a009302. View

Johnson C, Ivanisevic J, Siuzdak G . Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol. 2016; 17(7):451-9. PMC: 5729912. DOI: 10.1038/nrm.2016.25. View

Wu T, Qiao S, Shi C, Wang S, Ji G . Metabolomics window into diabetic complications. J Diabetes Investig. 2017; 9(2):244-255. PMC: 5835462. DOI: 10.1111/jdi.12723. View

Omori K, Katakami N, Arakawa S, Yamamoto Y, Ninomiya H, Takahara M . Identification of Plasma Inositol and Indoxyl Sulfate as Novel Biomarker Candidates for Atherosclerosis in Patients with Type 2 Diabetes. -Findings from Metabolome Analysis Using GC/MS. J Atheroscler Thromb. 2020; 27(10):1053-1067. PMC: 7585911. DOI: 10.5551/jat.52506. View

10.

Katakami N, Omori K, Taya N, Arakawa S, Takahara M, Matsuoka T . Plasma metabolites associated with arterial stiffness in patients with type 2 diabetes. Cardiovasc Diabetol. 2020; 19(1):75. PMC: 7291560. DOI: 10.1186/s12933-020-01057-w. View

11.

Yang G, Fan L, Tan J, Qi G, Zhang Y, Samet J . Smoking in China: findings of the 1996 National Prevalence Survey. JAMA. 1999; 282(13):1247-53. DOI: 10.1001/jama.282.13.1247. View

12.

He X, Su J, Ma X, Lu W, Zhu W, Wang Y . The association between serum growth differentiation factor 15 levels and lower extremity atherosclerotic disease is independent of body mass index in type 2 diabetes. Cardiovasc Diabetol. 2020; 19(1):40. PMC: 7103065. DOI: 10.1186/s12933-020-01020-9. View

13.

Han J, Lin K, Sequeira C, Borchers C . An isotope-labeled chemical derivatization method for the quantitation of short-chain fatty acids in human feces by liquid chromatography-tandem mass spectrometry. Anal Chim Acta. 2014; 854:86-94. DOI: 10.1016/j.aca.2014.11.015. View

14.

Ahmad T, Haeusler R . Bile acids in glucose metabolism and insulin signalling - mechanisms and research needs. Nat Rev Endocrinol. 2019; 15(12):701-712. PMC: 6918475. DOI: 10.1038/s41574-019-0266-7. View

15.

Jia W, Wei M, Rajani C, Zheng X . Targeting the alternative bile acid synthetic pathway for metabolic diseases. Protein Cell. 2020; 12(5):411-425. PMC: 8106556. DOI: 10.1007/s13238-020-00804-9. View

16.

Chavez-Talavera O, Tailleux A, Lefebvre P, Staels B . Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease. Gastroenterology. 2017; 152(7):1679-1694.e3. DOI: 10.1053/j.gastro.2017.01.055. View

17.

Jadhav K, Xu Y, Xu Y, Li Y, Xu J, Zhu Y . Reversal of metabolic disorders by pharmacological activation of bile acid receptors TGR5 and FXR. Mol Metab. 2018; 9:131-140. PMC: 5870099. DOI: 10.1016/j.molmet.2018.01.005. View

18.

Jove M, Ayala V, Ramirez-Nunez O, Serrano J, Cassanye A, Arola L . Lipidomic and metabolomic analyses reveal potential plasma biomarkers of early atheromatous plaque formation in hamsters. Cardiovasc Res. 2012; 97(4):642-52. DOI: 10.1093/cvr/cvs368. View

19.

Liu Y, Peng J, Jia H, Cai D, Zhang H, Yu C . UPLC-Q/TOF MS standardized Chinese formula Xin-Ke-Shu for the treatment of atherosclerosis in a rabbit model. Phytomedicine. 2014; 21(11):1364-72. DOI: 10.1016/j.phymed.2014.05.009. View

20.

Jia P, Wang S, Xiao C, Yang L, Chen Y, Jiang W . The anti-atherosclerotic effect of tanshinol borneol ester using fecal metabolomics based on liquid chromatography-mass spectrometry. Analyst. 2015; 141(3):1112-20. DOI: 10.1039/c5an01970b. View