Abstract
The pathogenetic process of sarcopenic obesity (SO) development is multifactorial, the key of them is considered – non-specific systemic inflammation.
Objective. to assess the influence of the intensity of the course of chronic inflammation in patients with type 2 diabetes mellitus (T2DM) on the development of SO.
Material and methods. The study involved patients with type 2 diabetes (n=83), including 18 men and 65 women aged 68.73 ± 7.17 years, divided into 2 groups: type 1 diabetes mellitus and CO (decreased muscle strength, performance, excess fat mass, decreased appendicular skeletal muscle ratio index (ASMM) to body weight (MT), 2 – type 2 diabetes without CO. The diagnosis of CO was established based on the ESPEN and EASO criteria (2022) and the recommendations of EWGSOP-2019. The following tests were performed: medical history collection, objective examination, anthropometry, SARC-F completion, hand dynamometry, SPPB testing, bioimpedansometry, and laboratory tests (biochemical blood test, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), oxidation protein products (AOPP), 8-hydroxyguanosine, macrophage inflammatory protein-1α (MIP-1α), 8-isoprostanes, and glutathione).
Results. Sodium-glucose cotransporter type 2 inhibitors (iNGLT-2) and glucagon-like peptide-1 receptor agonists (aGPP-1) were more often used by participants in the second group (p < 0.001). TNF-α and MIP-1α levels were found to be higher in individuals with type 2 diabetes and SO, as well as glutathione (p=0.037). Correlation analysis revealed a significant direct relationship between glutathione and fat mass and OT; MIP-1α and HbA1c; TNF-α and ASMM, as well as TNF-α and ASMM/MT (p < 0.05). There was also a noticeable inverse relationship between MIP-1α and fat mass, as well as TNF-α and HbA1c.
Conclusion. Pro-inflammatory cytokines play a crucial role in the progression of SO. The selection of pleiotropic therapy, including hypoglycemic therapy, which affects the course of chronic inflammation (iNGLT-2, aGPP-1) will reduce the risk of developing CO in patients with type 2 diabetes
Authors and affiliations
Yu.G. Samoilova(1, 2), Е.A. Khoroshunova(3), M.V. Matveeva(1, 4), D.A. Kudlay(5–7)
1-Federal State Autonomous Educational Institution of Higher Education “Novosibirsk National Research State University”, Pirogova str., 1, Novosibirsk, 630090, Russian Federation; 2-Siberian State Medical University of the Ministry of Health of the Russian Federation, Moskovsky trakt, 2, Tomsk, 634050, Russian Federation; 3-Siberian Federal Scientific and Clinical Center of the Federal Medical
and Biological Agency, Endocrinology Department, Mira Street, 4, Seversk, 636000, Russian Federation; 4Federal Scientific and Clinical Center for Medical Rehabilitation and Balneology under Federal Medical and Biological Agency, Altufyevskoye Shosse, 1, build. 37A, Moscow, 127410, Russian Federation; 5-Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Trubetskaya str., 8, build. 2, Moscow, 119991, Russian Federation; 6-Federal State Budget Educational Institution of Higher Education M.V. Lomonosov Moscow State University, Leninskie Gory, 1, Moscow, 119991, Russian Federation; 7-The Federal Scientific “State Research Center Institute
of Immunology” of the Federal Medical and Biological Agency of Russia, Kashirskoye Shosse, 24, 115522, Moscow, Russian Federation
References
Шестакова М.В., Викулова О.К., Железнякова А.В., Кутакова Д.В., Исаков М.А., Мокрышева Н.Г. Сахарный диабет у лиц пожилого возраста: клинико-эпидемиологические характеристики всероссийской когорты пациентов старше 65 лет. Сахарный диабет. 2024; 27 (6): 504–19. [Shestakova M.V., Vikulova O.K., Zheleznyakova A.V., Kutakova D.V., Isakov M.A., Mokrysheva N.G. Diabetes mellitus in the elderly: clinical and epidemiological characteristics of the all-Russian cohort of diabetic patients over 65 years. Diabetes mellitus. 2024; 27 (6): 504–19. DOI: 10.14341/DM13261 (in Russian)].
2. Cruz-Jentoft A.J., Bahat G., Bauer J., Boirie Y., Bruyère O., Cederholm T., Cooper C. et al. Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019; 48 (1): 16–31. DOI: 10.1093/ageing/afy169.
3. Ai Y., Xu R., Liu L. The prevalence and risk factors of sarcopenia in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr. 2021; 13 (93). DOI: 10.1186/s13098-021-00707-7.
4. Бернс С.А., Шептулина А.Ф., Мамутова Э.М., Киселев А.Р., Драпкина О.М. Саркопеническое ожирение: эпидемиология, патогенез и особенности диагностики. Кардиоваскулярнаятерапия и профилактика. 2023; 22 (6): 3576. [Berns S.A., Sheptulina A.F., Mamutova E.M., Kiselev A.R., Drapkina O.M. Sarcopenic obesity: epidemiology, pathogenesis and diagnostic criteria. Cardiovascular Therapy and Prevention. 2023; 22 (6): 3576. DOI: 10.15829/1728-8800-2023-3576 (in Russian)].
5. Donini L.M., Busetto L., Bischoff S.C., Cederholm T., Ballesteros-Pomar M.D., Batsis J.A., Bauer J.M. et al. Definition and Diagnostic Criteria for Sarcopenic Obesity: ESPEN and EASO Consensus Statement. Obes Facts. 2022; 15: 321–35. DOI: 10.1159/000521241.
6. Шептулина А.Ф., Брык Д.Д., Мамутова Э.М., Яфарова А.А., Драпкина О.М. Клинические последствия саркопенического ожирения. Часть 1. Неалкогольная жировая болезнь печени, сахарный диабет 2-го типа, хроническая болезнь почек. Профилактическая медицина. 2024; 27 (8): 114–20. [Sheptulina A.F., Bryk D.D., Mamutova E.M., Yafarova A.A., Drapkina O.M. Clinical consequences of sarcopenic obesity. Part 1. Non-alcoholic fatty liver disease, type 2 diabetes mellitus, chronic kidney disease. Russian J. of Preventive Medicine. 2024; 27 (8): 114–20. DOI: 10.17116/profmed202427081114 (in Russian)].
7. Курмаев Д.П., Булгакова С.В., Тренева Е. В. Саркопеническое ожирение – актуальная проблема современной гериатрии. Российский журнал гериатрической медицины. 2022; 4 (12): 228–35. [Kurmaev D.P., Bulgakova S.V., Treneva E.V. Sarcopenic obesity – a current problem of modern geriatrics. Russian J. Geriatric Medicine. 2022; 4 (12): 228–35. DOI: 10.37586/2686-8636-4-2022-228-235 (in Russian)].
8. Picca A., Beli R., Calvani R., Coelho-Júnior H.J., Landi F., Bernabei R., Bucci C. et al. Older Adults with Physical Frailty and Sarcopenia Show Increased Levels of Circulating Small Extracellular Vesicles with a Specifi c Mitochondrial Signature. Cells. 2020; 9 (4): 973. DOI: 10.3390/cells9040973.
9. Gandham A., Mesinovic J., Jansons P., Zengin A., Bonham M.P., Ebeling P.R., Scott D. Falls, fractures, and areal bone mineral density in older adults with sarcopenic obesity: A systematic review and meta-analysis. 2021; 22 (5): e13187. DOI: 10.1111/obr.13187.
10. Yaribeygi H., Farrokhi F. R., Butler A. E., Sahebkar A. Insulin resistance: Review of the underlying molecular mechanisms. J. Cell. Physiol. 2019; 234 (6): 8152–61. DOI: 10.1002/jcp.27603.
11. Курмаев Д.П., Булгакова С.В., Тренева Е.В. Инсулинорезистентность, сахарный диабет 2 типа и саркопения. Экспериментальная и клиническая гастроэнтерология. 2024; 222 (2): 141–8. [Kurmaev D.P., Bulgakova S.V., Treneva E.V. Insulin resistance, type 2 diabetes mellitus and sarcopenia. Experimental and Clinical Gastroenterology. 2024; 222 (2): 141–8. DOI: 10.31146/1682-8658-ecg-222-2-141-148 (in Russian)].
12. Salminen A., Kaarniranta K., Kauppinen A.. Insulin/IGF-1 signaling promotes immunosuppression via the STAT3 pathway: impact on the aging process and age-related diseases. Inflamm Res. 2021; 70 (10–12): 1043–61. DOI: 10.1007/s00011-021-01498-3.
13. Goodpaster B.H., Bergman B.C., Brennan A.M., Sparks L.M. Intermuscular adipose tissue in metabolic disease. Nat Rev Endocrinol. 2023; 19 (5): 285–98. DOI: 10.1038/s41574-022-00784-2.
14. Kahn D., Macias E., Zarini S., Garfield A., Zemski Berry K., MacLean P., Gerszten R.E. et al. Exploring Visceral and Subcutaneous Adipose Tissue Secretomes in Human Obesity: Implications for Metabolic Disease. Endocrinology. 2022; 163 (11): bqac140. DOI: 10.1210/endocr/bqac140.
15. Дьяков Д.A., Акбашева О.Е. Оксидативный стресс и система протеолиза при сахарном диабете 2 типа. Сахарный диабет. 2022; 25 (1): 14–20. Dyakov D.A., Akbasheva O.E. Oxidative stress and proteolysis system in type 2 diabetes. Diabetes mellitus. 2022; 25 (1): 14–20. DOI: 10.14341/DM12402 (in Russian)].
16. Qing X., Shi D., Lv X., Wang B., Chen S., Shao Z. Prognostic significance of 8-hydroxy-2’-deoxyguanosine in solid tumors: a meta-analysis. BMC Cancer. 2019; 19 (997). DOI: 10.1186/s12885-019-6189-9.
17. Ramirez-Garza S.L., Laveriano-Santos E.P, Moreno J.J, Bodega P. Metabolic syndrome, adiposity, diet, and emotional eating are associated with oxidative stress in adolescents. Front Nutr. 2023; 10: 1216445. DOI: 10.3389/fnut.2023.1216445
18. Дедов И.И., Шестакова М.В., Майоров А.Ю. и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 10-й выпуск. Сахарный диабет. 2021; 2 (15): 13–5. [Dedov I., Shestakova M., Mayorov A. et al. Standards of Specialized Diabetes Care. 10th Edition. Diabetes mellitus. 2021; 2 (15): 13–5. DOI: 10.14341/DM12802. (in Russian)]
19. Wang M., Tan Y., Shi Y., Wang X., Liao Z., Wei P. Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments. Front. Endocrinol. 2020; 11: 568. DOI: 10.3389/fendo.2020.00568.
20. Mu Z.J., Fu J.L., Sun L.N, Chan P., Xiu S.L. Associations between homocysteine, inflammatory cytokines and sarcopenia in Chinese older adults with type 2 diabetes. BMC Geriatrics. 2021; 21 (1): 692. DOI: 10.1186/s12877-021-02622-y.
21. Akhter N., Wilson A., Arefanian H., Thomas R., Kochumon S., Al-Rashed F., AbuFarha M. et al. Endoplasmic Reticulum Stress Promotes the Expression of TNF-α in THP-1 Cells by Mechanisms Involving ROS/CHOP/HIF-1α and MAPK/NF-κB Pathways. Int J. Mol. Sci. 2023; 14: 24 (20): 15186. DOI: 10.3390/ijms242015186
22. Вульф М.А., Кузнецов Г.Л., Комар А.А., Сафиуллина Л.А., Карпеева Е.Н., Шунькина Д.А., Бограя М.М. и др. Влияние ИЛ-1β и ИЛ-8 на механизмы цитопротекции в ткани печени у больных морбидным ожирением с сопутствующими патологиями. Вестник Балтийского федерального университета им. И. Канта. Сер. Естественные и медицинские науки. 2022; 1: 108–20. [Wulf M.A., Kuznetsov G.L., Komar A.A., Safiullina L.A., Karpeeva E.N., Shunkina D.A., Bograya M.M. et al. Effect of IL-1b and IL-8 on cytoprotection mechanisms in liver tissue in morbid obese patients with concomitant pathologies. Bulletin of the Baltic Federal University named after I. Kant. Ser. Natural and medical sciences. 2022; 1: 108–20 (in Russian)]
23. Banik S., Ghosh A. The association of oxidative stress biomarkers with type 2 diabetes mellitus: A systematic review and meta-analysis. Health Science Reports. 2021; 4 (4): e389. DOI: 10.1002/hsr2.389.
24. Gallo G., Volpe M and Savoia C. Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Front Med (Lausanne). 2022; 8: 798958. DOI: 10.3389/fmed.2021.798958