The Effect of Dulaglutide on Metabolic Adaptation in Patients with Type 2 Diabetes Mellitus and Obesity
https://doi.org/10.31550/1727-2378-2024-23-4-54-59
Abstract
Aim. To evaluate the effect of dulaglutide, a glucose-lowering drug from the group of glucagon-like peptide 1 receptor (GLP-1) agonists, on indicators of fat metabolism and irisin.
Design. Open pilot study.
Materials and methods. 85 people (56 women, 29 men) with type 2 diabetes mellitus and obesity of varying severity took part in the study. 17 of them had a history of myocardial infarction, 2 patients had stroke (acute cerebrovascular accident), and all the rest had arterial hypertension. All patients were prescribed dulaglutide, a GLP-1 agonist, for ongoing glucose-lowering therapy for the purpose of intensification.
Results. After 12 months of therapy, a statistically significant (р < 0.05) decrease in anthropometric parameters was obtained: body weight decreased from 110 (70–185) to 105.5 (60–159) kg, waist circumference decreased from 124.5 (46.4–150) to 119 (90–146) cm. The levels of glycated hemoglobin statistically significantly decreased — from 7.1% (5.4–10.6%) to 6.5% (6.2–12.4%) (р < 0.05), total cholesterol — from 4.89 (2.07–15) to 4.55 (2.19–8.33) mmol/l (р < 0.05), leptin — from 32.9 (14.9–127.6) to 24.5 (13.5–133.7) ng/ml (р < 0.05), C-reactive protein — from 3.37 (0.01–64.2) to 2.24 (0.01–54.1) mg/ml (р < 0.05), the HOMA β level statistically significantly increased — from 80 (4–359) to 110 (12.2–755) (р < 0.05). In addition, the thickness of epicardial fat according to echocardiography significantly decreased — from 11 (2.5–20) to 10 (7–15) mm (р < 0.05), as well as the amount of adipose tissue according to bioimpedance measurements from 52.3 (26.6–99.8) to 44.7 (28.2–73.9) kg (р < 0.05).
Conclusion. In patients with type 2 diabetes and obesity, therapy with GLP-1 agonist dulaglutide after 12 months contributed to a significant improvement in glycemic control and pancreatic β-cell function. In patients with type 2 diabetes and obesity, therapy with GLP-1 agonist the dulaglutide after 12 months, a significant decrease in body weight, the amount of adipose tissue, and epicardial fat was observed. Regression of adipose tissue according to bioimpedansometry data was accompanied by a significant decrease in the level of leptin, a marker of inflammation C-reactive protein, and a tendency to increase the level of adiponectin and irisin.
About the Authors
D. G. Gusenbekova
Russian Medical Academy of Continuous Professional Education; City Clinic No. 219 of the Moscow Health Department
Russian Federation
Russian Federation
Gusenbekova, D.G.
2/1 Barrikadnaya Str., build. 1, Moscow, 125993
47 Jan Raynis bulv., Moscow, 125373
A. S. Ametov
Russian Medical Academy of Continuous Professional Education; Botkin Hospital
Russian Federation
Russian Federation
Ametov, A.S.
2/1 Barrikadnaya Str., build. 1, Moscow, 125993
5 2nd Botkinsky pr-d, Moscow, 125284
T. N. Korotkova
Federal Research Centre of Nutrition, Biotechnology and Food Safety
Russian Federation
Russian Federation
Korotkova, T.N.
2/14 Ust`insky pr-d, Moscow, 109240
References
1. Engin A. The definition and prevalence of obesity and metabolic syndrome. Adv. Exp. Med. Biol. 2017;960:1–17. DOI: 10.1007/978-3-319-48382-5_1
2. Lehr S., Hartwig S., Lamers D., Famulla S. et al. Identification and validation of novel adipokines released from primary human adipocytes. Mol. Cell Proteomics. 2012;11(1):M111.010504. DOI: 10.1074/mcp.M111.010504
3. Rask-Madsen C., Kahn C.R. Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease. Arterioscler. Thromb. Vasc. Biol. 2012;32(9):2052–9. DOI: 10.1161/ATVBAHA.111.241919
4. Ren Y., Zhao H., Yin C., Lan X. et al. Adipokines, hepatokines and myokines: focus on their role and molecular mechanisms in adipose tissue inflammation. Front. Endocrinol. (Lausanne). 2022;13:873699. DOI: 10.3389/fendo.2022.873699
5. Friedman J. Leptin and the endocrine control of energy balance. Nat. Metab. 2019;1(8):754–64. DOI: 10.1038/s42255-019-0095-y
6. Clemente-Suárez V.J., Redondo-Flórez L., Beltrán-Velasco A.I., Martín-Rodríguez A. et al. The role of adipokines in health and disease. biomedicines. 2023;11(5):1290. DOI: 10.3390/biomedicines11051290
7. Choi H., Doss H., Kim K. Multifaceted physiological roles of adiponectin in inflammation and diseases. Int. J. Mol. Sci. 2020;21(4):1219. DOI: 10.3390/ijms21041219
8. Liu C., Feng X., Li Q., Wang Y. et al. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. Cytokine. 2016;86:100–9. DOI: 10.1016/j.cyto.2016.06.028
9. Edwardson C., Gorely T., Davies M.J., Gray L.J. et al. Association of sedentary behaviour with metabolic syndrome: a meta-analysis. PLoS One. 2012;7(4):e34916. DOI: 10.1371/journal.pone.0034916
10. Drake J.C., Wilson R.J., Yan Z. Molecular mechanisms for mitochondrial adaptation to exercise training in skeletal muscle. FASEB J. 2016;30(1):13–22. DOI: 10.1096/fj.15-276337
11. Liu S., Cui F., Ning K., Wang Z. et al. Role of irisin in physiology and pathology. Front. Endocrinol. (Lausanne). 2022;13:962968. DOI: 10.3389/fendo.2022.962968
12. Castillo-Quan J. From white to brown fat through the PGC-1α- dependent myokine irisin: implications for diabetes and obesity. Dis. Model Mech. 2012;5(3):293–5. DOI: 10.1242/dmm.009894
13. Korta P., Pocheć E., Mazur-Biały A. Irisin as a multifunctional protein: implications for health and certain diseases. Medicina (Kaunas). 2019;55(8):485. DOI: 10.3390/medicina55080485
14. Jeremic N., Chaturvedi P., Tyagi S. Browning of white fat: novel insight into factors, mechanisms, and therapeutics. J. Cell Physiol. 2017;232(1):61–8. DOI: 10.1002/jcp.25450
15. Askari H., Rajani S.F., Poorebrahim M., Haghi-Aminjan H. et al. A glance at the therapeutic potential of irisin against diseases involving inflammation, oxidative stress, and apoptosis: an introductory review. Pharmacol. Res. 2018;129:44–55. DOI: 10.1016/j.phrs.2018.01.012
16. Roth C., Molica F., Kwak B. Browning of white adipose tissue as a therapeutic tool in the fight against atherosclerosis. Metabolites. 2021;11(5):319. DOI: 10.3390/metabo11050319
17. Drab S. Glucagon-like peptide-1 receptor agonists for type 2 diabetes: a clinical update of safety and efficacy. Curr. Diabetes Rev. 2016;12(4):403–13. DOI: 10.2174/1573399812666151223093841
18. Piché M., Tchernof A., Després J. Obesity phenotypes, diabetes, and cardiovascular diseases. Circ. Res. 2020;126(11):1477–500. DOI: 10.1161/CIRCRESAHA.120.316101
19. Ebong I.A., Goff D.C. Jr, Rodriguez C.J., Chen H. et al. Mechanisms of heart failure in obesity. Obes. Res. Clin. Pract. 2014;8(6):e540–8. DOI: 10.1016/j.orcp.2013.12.005
20. Iacobellis G. Epicardial fat links obesity to cardiovascular diseases. Prog. Cardiovasc. Dis. 2023;78:27–33. DOI: 10.1016/j.pcad.2023.04.006
21. Zhu J., Su X., Li G., Chen J. et al. The incidence of acute myocardial infarction in relation to overweight and obesity: a metaanalysis. Arch. Med. Sci. 2014;10(5):855–62. DOI: 10.5114/aoms.2014.46206
22. Jia G., Aroor A.R., DeMarco V.G., Martinez-Lemus L.A. et al. Vascular stiffness in insulin resistance and obesity. Front. Physiol. 2015;6:231. DOI: 10.3389/fphys.2015.00231
23. Pestel J., Blangero F., Watson J., Pirola L. et al. Adipokines in obesity and metabolic-related-diseases. Biochimie. 2023;212:48–59. DOI: 10.1016/j.biochi.2023.04.008
24. Tirandi A., Montecucco F., Carbone F., Liberale L. Role of glucagonlike peptide-1 receptor agonists in the treatment of obesity, cardiovascular disease, and cerebrovascular disease. Pol. Arch. Intern. Med. 2024;134(2):16658. DOI: 10.20452/pamw.16658
25. Iacobellis G., Camarena V., Sant D., Wang G. Human epicardial fat expresses glucagon-like peptide 1 and 2 receptors genes. Horm. Metab. Res. 2017;49(8):625–30. DOI: 10.1055/s-0043-109563
26. Neeland I.J., Ross R., Després J.P., Matsuzawa Y. et al. Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement. Lancet Diabetes Endocrinol. 2019;7(9):715–25. DOI: 10.1016/S2213-8587(19)30084-1
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Gusenbekova D.G., Ametov A.S., Korotkova T.N. The Effect of Dulaglutide on Metabolic Adaptation in Patients with Type 2 Diabetes Mellitus and Obesity. Title. 2024;23(4):54-59. (In Russ.) https://doi.org/10.31550/1727-2378-2024-23-4-54-59
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