Gut microbiota metabolites and insulin resistance parameters as potential indicators of the development and progression of arterial hypertension
https://doi.org/10.14341/omet13212
Abstract
BACKGROUND: The steady annual increase in publications in the field of gut microbiota (GM) and insulin resistance indicates a growing recognition of the importance of this research topic.
AIM: To study the characteristics and relationships of GM metabolites and insulin resistance (IR) parameters in patients with arterial hypertension (AH) and to determine their role as indicators of AH progression.
MATERIALS AND METHODS: The comparative study included patients with stage II AGI, aged 25 to 65 years, receiving basic antihypertensive therapy. Patients in the study groups underwent laboratory testing of a biospecimen of blood and feces at the time of hospitalization. Analysis of gut microbiota parameters: the level of TMA, TMAO, short-chain fatty acids (SCFA), endotoxin; biochemical parameters by the lipid profile, fasting glucose, c-peptide, the concentration of C-reactive protein, gomocistein were determined; 24-hour blood pressure (BP) monitoring was performed by BPLaB device, Russia; study of the elastic properties of the vascular wall by sphygmography using the Vasera VS-1000 Series, PWV — pulse wave velocity (PWV). Statistical analysis was carried out using the IBM SPSS Statistics 21 application package.
RESULTS: The study included 161 patients who met the inclusion criteria, from which 3 main groups were formed: group 1 — persons without AH (n=45); group 2 — patients with stage I-III AH (n=53); group 3 — patients with stage I-III AH and abdominal obesity (AO) (n=63), matched by age, gender and therapy. Patients in group 3 differed significantly from patients in groups 1 and 2 in terms of BMI, WC, OB, and from group 1 in the values of office SBP, DBP (p < 0.001) and pulse wave velocity (PWV) (p=0.015). The levels of TMAO and endotoxin were also significantly higher in the 3rd group of patients compared to the 1st group. The total content of monocarboxylic acids: C2 — acetic acid, C3 — propionic acid, C4 — butyric acid is significantly higher in the 2nd and 3rd groups compared to the 1st group (p < 0.002, p < 0.004, respectively to the groups). In the groups with AH, the target level of TC and LDL-C indicators was significantly exceeded, and in the group of AH with AO — the maximum level of TG p=0.001, TyG index, interleukin 1β and hs-CRP (p=0.001). The dependence of PWV on SCLC2 and TyG C2 and SBP on TyG in the 3rd groups of patients was determined using the logistic regression method.
CONCLUSION: The close relationship between the TyG index and UA metabolites with PWV and SPB parameters may confirm the complex role of these factors in the development and progression of AH, especially in the presence of AO. The introduction of these diagnostic methods into clinical practice will facilitate the implementation of early preventive and therapeutic intervention strategies.
About the Authors
T. I. PetelinaRussian Federation
Tatiana I. Petelina, MD
Researcher ID: I-8913-2017
Scopus Author ID: 6507194861
111 Melnikaite street, 625026 Tyumen; Tomsk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
K. S. Avdeeva
Russian Federation
Ksenia S. Avdeeva
Researcher ID: J-1751-2017
Scopus Author ID: 57210713674
Tomsk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
L. L. Valeeva
Russian Federation
Liana L. Valeeva
Tomsk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
A. A. Kapustina
Russian Federation
Anastasia A. Kapustina
Tomsk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
A. V. Gorbachevskii
Russian Federation
Alexandr V. Gorbachevskii
Tomsk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
L. I. Gapon
Russian Federation
Liudmila I. Gapon, MD, PhD, Professor
Researcher ID: S-6520-2016
Scopus Author ID: 7003891206
Tomsk
Competing Interests:
Авторы декларируют отсутствие явных и потенциальных конфликтов интересов, связанных с содержанием настоящей статьи
References
1. Sun S, Lulla A, Winglee K, Wu MC, Jacobs DR, Shikany DM. Gut Microbiota Composition and Blood Pressure. Hypertension. 2019;73(5):998-1006. doi: https://doi.org/10.1161/HYPERTENSIONAHA.118.12109
2. Ge Y, Wang J, Wu L, Wu J. Gut microbiota: a potential new regulator of hypertension. Front Cardiovasc Med. 2024;11:1333005. doi: https://doi.org/10.3389/fcvm.2024.1333005
3. Kim S, Goel R, Kumar F. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure. Clin Sci (Lond). 2018;132 (6):701-18. doi: https://doi.org/10.1042/CS20180087
4. O’Donnell JA, Zheng T, Meric G, Marques FZ. The gut microbiome and hypertension. Nat Rev Nephrol. 2023;19(3):153-167. doi: https://doi.org/10.1038/s41581-022-00654-0
5. Jang HR, Lee HY. Mechanisms linking gut microbial metabolites to insulin resistance. World J Diabetes. 2021;12(6):730-744. doi: https://doi.org/10.4239/wjd.v12.i6.730.
6. Würtz P, Mäkinen V-P, Soininen P, Kangas AJ, Tukiainen T, et al. Metabolic signatures of insulin resistance in 7,098 young adults. Diabetes. 2012;61:1372–1380. doi: https://doi.org/10.2337/db11-1355
7. Seldin MM, Meng Y, Qi H, Zhu W, Wang Z, Hazen SL, Lusis AJ, Shih DM. Trimethylamine N-Oxide Promotes Vascular Inflammation Through Signaling of Mitogen-Activated Protein Kinase and Nuclear Factor-κB. J Am Heart Assoc. 2016;5(2):e002767. doi: https://doi.org/10.1161/JAHA.115.002767
8. Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, et al. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Cell. 2016;165(1):111-124. doi: https://doi.org/10.1016/j.cell.2016.02.011
9. Wang PX, Deng XR, Zhang CH, Yuan HJ. Gut microbiota and metabolic syndrome. Chin Med J (Engl). 2020;133(7):808-816. doi: https://doi.org/10.1097/CM9.0000000000000696
10. Yan Y, Wang D, Sun Y, Ma Q, Wang K, Liao Y, et al. Triglyceride-glucose index trajectory and arterial stiffness: results from Hanzhong Adolescent Hypertension Cohort Study. Cardiovasc Diabetol. 2022;21(1):33. doi: https://doi.org/10.1186/s12933-022-01453-4
11. Lee SB, Ahn CW, Lee BK, Kang S, Nam JS, et al. Association between triglyceride glucose index and arterial stiffness in Korean adults. Cardiovasc Diabetol. 2018;17(1):41. doi: https://doi.org/10.1186/s12933-018-0692-1
12. Drapkina OM, Kaburova AN. Composition and metabolites of intestinal microbiota as new determinants of the development of cardiovascular pathology. Rational pharmacotherapy in cardiology. 2020;16(2):277-285 (in Russ)]. doi: https://doi.org/10.20996/1819-6446-2020-04-02
13. Yang Z, Wang Q, Liu Y, Wang L, Ge Z, Li Z, Feng S, Wu C. Gut microbiota and hypertension: association, mechanisms and treatment. Clin Exp Hypertens. 2023;45(1):2195135. doi: https://doi.org/10.1080/10641963.2023.2195135
14. Jang HR, Lee HY. Mechanisms linking gut microbial metabolites to insulin resistance. World J Diabetes. 2021;12(6):730-744. doi: https://doi.org/10.4239/wjd.v12.i6.730
15. Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018;98(4):2133-2223. doi: https://doi.org/10.1152/physrev.00063.2017
16. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest. 2006;116:115–124. doi: https://doi.org/10.1172/JCI24335
17. Würtz P, Mäkinen V-P, Soininen P, Kangas AJ, Tukiainen T, et al. Metabolic signatures of insulin resistance in 7,098 young adults. Diabetes. 2012;61:1372–1380. doi: https://doi.org/10.2337/db11-1355
18. Nagarajan A, Petersen MC, Nasiri AR, Butrico G, Fung A, et al. MARCH1 regulates insulin sensitivity by controlling cell surface insulin receptor levels. Nat Commun. 2016;7:12639. doi: https://doi.org/10.1038/ncomms12639
19. Onuma H, Osawa H, Yamada K, Ogura T, Tanabe F, Granner DK, Makino H. Identification of the insulin-regulated interaction of phosphodiesterase 3B with 14-3-3 β protein. Diabetes. 2002;51:3362–3367. doi: https://doi.org/10.2337/diabetes.51.12.3362
20. Samuel VT, Liu Z-X, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI. Mechanism of hepatic insulin resistance in nonalcoholic fatty liver disease. J Biol Chem. 2004;279:32345–32353. doi: https://doi.org/10.1074/jbc.M313478200
21. Lambert JE, Ramos-Roman MA, Browning JD, Parks EJ. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology. 2014;146:726–735. doi: https://doi.org/10.1053/j.gastro.2013.11.049
22. Le Marchand-Brustel Y, Grémeaux T, Ballotti R, Van Obberghen E. Insulin receptor tyrosine kinase is defective in skeletal muscle of insulin-resistant obese mice. Nature. 1985;315:676–679. doi: https://doi.org/10.1038/315676a0
23. Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 2008;7:45–56. doi: https://doi.org/10.1016/j.cmet.2007.10.013
24. Jaworski K, Sarkadi-Nagy E, Duncan RE, Ahmadian M, Sul HS. Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue. Am J Physiol Gastrointest Liver Physiol. 2007;293:G1–G4
25. Holt LJ, Brandon AE, Small L, Suryana E, Preston E, et al. Ablation of Grb10 Specifically in Muscle Impacts Muscle Size and Glucose Metabolism in Mice. Endocrinology. 2018;159:1339–1351. doi: https://doi.org/10.1210/en.2017-00851
26. Holland WL, Summers SA. Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev. 2008;29:381–402. doi: https://doi.org/10.1210/er.2007-0025
27. Wu S, Xu L, Wu M, Chen S, Wang Y, Tian Y. Association between triglyceride-glucose index and risk of arterial stiffness: a cohort study. Cardiovasc Diabetol. 2021;20(1):146. doi: https://doi.org/10.1186/s12933-021-01342-2
Supplementary files
Review
For citations:
Petelina T.I., Avdeeva K.S., Valeeva L.L., Kapustina A.A., Gorbachevskii A.V., Gapon L.I. Gut microbiota metabolites and insulin resistance parameters as potential indicators of the development and progression of arterial hypertension. Obesity and metabolism. 2025;22(3):145-155. (In Russ.) https://doi.org/10.14341/omet13212
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).




































