Long-term effects of metformin on fat depots and insulin-glucose parameters in patients with prediabetes and chronic heart failure
https://doi.org/10.21518/ms2024-347
Abstract
Introduction. Chronic heart failure with preserved ejection fraction (CHpEF) is a heterogeneous syndrome with a variety of pathophysiological factors, including obesity and impaired carbohydrate metabolism associated with an increase in visceral adipose tissue. Due to the positive effect of metformin on weight loss, in recent years special attention has been paid to its effect on fat depots.
Aim. To study the effects of metformin XR after 12 months of administration on various fat depots and glucose metabolism parameters in patients with CHpEF, prediabetes and abdominal obesity (AO).
Materials and methods. A single-center open-label randomized prospective controlled trial included 64 people (50% men, median age 58 [55.25; 59.75] years) with CHpEF, prediabetes and AO. All patients (groups A and B) received optimal CHpEF therapy. In group A (n = 32), metformin XR 1000–1500 mg/day was additionally prescribed. All patients underwent general clinical examination, calculation of insulin resistance indices, ultrasound lipometry with determination of the size of epicardial, preperitoneal and subcutaneous fat, in addition, the thickness of epicardial fat was assessed using magnetic resonance imaging (MRI) of the heart.
Results. In group A, after 12 months of the study, fasting plasma glucose levels decreased from baseline by 7.7% (p < 0.0001), glycated hemoglobin by 3.3% (p = 0.008), fasting insulin by 20% (p = 0.004) and HOMA-IR and FIRI indices by 25.3% (p = 0.001). In the control group, on the contrary, the values of glycated hemoglobin increased by 3.4% (p = 0.021), fasting insulin by 45% (p = 0.031), HOMA-IR and FIRI by 52.4% (p = 0.020). In group A, the thickness of epicardial fat decreased by 6.1% (p = 0.020) according to ultrasound and MRI lipometry by 16.7% (p = 0.029), preperitoneal fat by 3.0% (p = 0.009), subcutaneous fat by 11.2% (p = 0.001).
Conclusion. Metformin XR therapy for 12 months in patients with prediabetes, CHpEF and AO against the background of optimal basic CHpEF therapy had a beneficial effect on glucose metabolism (decrease in fasting plasma glucose and insulin, glycated hemoglobin, insulin resistance indices HOMA-IR, FIRI) and on subcutaneous and visceral adipose tissue depots: epicardial and preperitoneal.
About the Authors
O. V. Tsygankova
Novosibirsk State Medical University;
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
Oksana V. Tsygankova, Dr. Sci. (Med.), Professor of the Department of Emergency Therapy with Endocrinology and Occupational Pathology of the Faculty of Advanced Training and Professional Retraining of Physicians, Novosibirsk State Medical University; Senior Researcher, Laboratory of Clinical Biochemical and Hormonal Research of Therapeutic Diseases, Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
52, Krasny Ave., Novosibirsk, 630091,
175/1, B. Bogatkov St., Novosibirsk, 630089
N. E. Apartseva
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
Natalia E. Apartseva, Postgraduate Student, Junior Researcher, Laboratory of Genetic and Environmental Determinants of the Human Life Cycle
175/1, B. Bogatkov St., Novosibirsk, 630089
L. D. Latyntseva
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
Lyudmila D. Latyntseva, Cand. Sci. (Med.), Senior Researcher, Laboratory of Emergency Cardiology
175/1, B. Bogatkov St., Novosibirsk, 630089
A. N. Ryabikov
Novosibirsk State Medical University;
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
Andrey N. Ryabikov, Dr. Sci. (Med.), Professor of the Department of Therapy, Hematology and Transfusiology of the Faculty of Advanced Training and Professional Retraining of Physicians, Novosibirsk State Medical University; Chief Researcher Laboratory of Ethiopathogenesis and Clinics of Internal Diseases, Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
52, Krasny Ave., Novosibirsk, 630091,
175/1, B. Bogatkov St., Novosibirsk, 630089
E. V. Kashtanova
Research Institute of Internal and Preventive Medicine, Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation
Russian Federation
Elena V. Kashtanova, Dr. Sci. (Biol.), Associate Professor, Leading Researcher with the Assigned Responsibilities of the Head of the Laboratory of Laboratory of Clinical Biochemical and Hormonal Research of Therapeutic Diseases
175/1, B. Bogatkov St., Novosibirsk, 630089
References
1. Pfeffer MA, Shah AM, Borlaug BA. Heart Failure With Preserved Ejection Fraction In Perspective. Circ Res. 2019;124(11):1598–1617. https://doi.org/10.1161/CIRCRESAHA.119.313572.
2. Packer M. Disease-treatment interactions in the management of patients with obesity and diabetes who have atrial fibrillation: the potential mediating influence of epicardial adipose tissue. Cardiovasc Diabetol. 2019;18(1):121. https://doi.org/10.1186/s12933-019-0927-9.
3. Tsygankova OV, Badin AR, Bondareva ZG, Lozhkina NG, Platonov DY. Associations of sex hormones with components of insulin-glucose homeostasis. Obesity and Metabolism. 2018;15(2):3–10. (In Russ.) https://doi.org/10.14341/omet9482.
4. Tsygankova OV, Evdokimova NE, Veretyuk VV, Latyntseva LD, Ametov AS. Insulin resistance and heart failure with preserved ejection fraction. Pathogenetic and therapeutic crossroads. Diabetes Mellitus. 2022;25(6):535–547. (In Russ.) https://doi.org/10.14341/DM12916.
5. Anthony SR, Guarnieri AR, Gozdiff A, Helsley RN, Owens AP, Tranter M. Mechanisms linking adipose tissue inflammation to cardiac hypertrophy and fibrosis. Clin Sci (Lond). 2019;133(22):2329–2344. https://doi.org/10.1042/CS20190578.
6. Christensen RH, Hansen CS, von Scholten BJ, Jensen MT, Pedersen BK, Schnohr P et al. Epicardial and pericardial adipose tissues are associated with reduced diastolic and systolic function in type 2 diabetes. Diabetes Obes Metab. 2019;21(8):2006–2011. https://doi.org/10.1111/dom.13758.
7. Baloglu I, Turkmen K, Selcuk NY, Tonbul HZ, Ozcicek A, Hamur H et al. The Relationship Between Visceral Adiposity Index and Epicardial Adipose Tissue in Patients with Type 2 Diabetes Mellitus. Exp Clin Endocrinol Diabetes. 2021;129(5):390–395. https://doi.org/10.1055/a-0892-4290.
8. Shi YJ, Dong GJ, Guo M. Targeting epicardial adipose tissue: A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus. World J Diabetes. 2023;14(6):724–740. https://doi.org/10.4239/wjd.v14.i6.724.
9. Zhang QH, Xie LH, Zhang HN, Liu JH, Zhao Y, Chen LH et al. Magnetic Resonance Imaging Assessment of Abdominal Ectopic Fat Deposition in Correlation With Cardiometabolic Risk Factors. Front Endocrinol. 2022;13:820023. https://doi.org/10.3389/fendo.2022.820023.
10. Дедов ИИ, Шестакова МВ, Майоров АЮ, Шамхалова МШ, Сухарева ОЮ, Галстян ГР и др. Клинические рекомендации. Сахарный диабет 2 типа у взрослых. 2022. https://cr.minzdrav.gov.ru/schema/290_2.
11. Mohan M, Al-Talabany S, McKinnie A, Mordi IR, Singh JSS, Gandy SJ et al. A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the METREMODEL trial. Eur Heart J. 2019;40(41):3409–3417. https://doi.org/10.1093/eurheartj/ehz203.
12. Iacobellis G, Mohseni M, Bianco SD, Banga PK. Liraglutide causes large and rapid epicardial fat reduction. Obesity. 2017;25(2):311–316. https://doi.org/10.1002/oby.21718.
13. Ziyrek M, Kahraman S, Ozdemir E, Dogan A. Metformin monotherapy significantly decreases epicardial adipose tissue thickness in newly diagnosed type 2 diabetes patients. Rev Port Cardiol (Engl Ed). 2019;38(6):419–423. https://doi.org/10.1016/j.repc.2018.08.010.
14. Tsygankova OV, Evdokimova NE, Latyntseva LD. Chronic heart failure with preserved ejection fraction amid prediabetes and abdominal obesity: fat depot compartments and cardiometabolic risk markers. RMJ. Medical Review. 2023;7(1):22–29. (In Russ.) https://doi.org/10.32364/2587-6821-2023-7-1-22-29.
15. Ageev FT, Arutyunov GP, Begrambekova YuL, Belenkov YuN, Boytsov SA, Vasyuk YuA. Russian Society of Cardiology (RSC). 2020 Clinical practice guidelines for Chronic heart failure. Russian Journal of Cardiology. 2020;25(11):4083. (In Russ.) https://doi.org/10.15829/1560-4071-2020-4083.
16. Iacobellis G, Willens HJ. Echocardiographic epicardial fat: a review of research and clinical applications. J Am Soc Echocardiogr. 2009;22(12):1311–1319. https://doi.org/10.1016/j.echo.2009.10.013.
17. Рябиков АН, Малютина СК, Гулиев ЗЗ, Шахматов СГ, Ясюкевич НВ, Толкачева НЮ. Способ диагностики метаболического синдрома путем ультразвуковой липометрии. Патент RU 2677526 С1, 17.01.2019. Режим доступа: https://www1.fips.ru/publication-web/publications/document?type=doc&tab=IZPM&id=4072D320-2902-4627-A226-38AFB19FEFB6.
18. Guliyev ZZ, Ryabikov AN, Malyutina SK, Strygin AV. Ultrasonic assessment of lipometric indicators: validization by means of MC-CT. Medicine and Education in Siberia. 2014;(3):55. (In Russ.) Available at: https://cyberleninka.ru/article/n/ultrazvukovaya-otsenkalipometricheskih-pokazateley-validizatsiya-s-pomoschyu-ms-kt.
19. Flüchter S, Haghi D, Dinter D, Heberlein W, Kühl HP, Neff W et al. Volumetric assessment of epicardial adipose tissue with cardiovascular magnetic resonance imaging. Obesity. 2007;15(4):870–878. https://doi.org/10.1038/oby.2007.591.
20. Preiss D, Lloyd SM, Ford I, McMurray JJ, Holman RR, Welsh P et al. Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial. Lancet Diabetes Endocrinol. 2014;2(2):116–124. https://doi.org/10.1016/S2213-8587(13)70152-9.
21. Ladeiras-Lopes R, Sampaio F, Leite S, Santos-Ferreira D, Vilela E, Leite-Moreira A et al. Metformin in non-diabetic patients with metabolic syndrome and diastolic dysfunction: the MET-DIME randomized trial. Endocrine. 2021;72(3):699–710. https://doi.org/10.1007/s12020-021-02687-0.
22. Wong AK, Symon R, AlZadjali MA, Ang DS, Ogston S, Choy A et al. The effect of metformin on insulin resistance and exercise parameters in patients with heart failure. Eur J Heart Fail. 2012;14(11):1303–1310. https://doi.org/10.1093/eurjhf/hfs106.
23. Larsen AH, Jessen N, Nørrelund H, Tolbod LP, Harms HJ, Feddersen S et al. A randomised, double-blind, placebo-controlled trial of metformin on myocardial efficiency in insulin-resistant chronic heart failure patients without diabetes. Eur J Heart Fail. 2020;22(9):1628–1637. https://doi.org/10.1002/ejhf.1656.
24. Kamel AM, Ismail B, Abdel Hafiz G, Sabry N, Farid S. Effect of Metformin on Oxidative Stress and Left Ventricular Geometry in Nondiabetic Heart Failure Patients: A Randomized Controlled Trial. Metab Syndr Relat Disord. 2024;22(1):49–58. https://doi.org/10.1089/met.2023.0164.
25. Issa VS, Amaral AF, Cruz FD, Ayub-Ferreira SM, Guimarães GV, Chizzola PR et al. Glycemia and prognosis of patients with chronic heart failure--subanalysis of the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial. Am Heart J. 2010;159(1):90–97. https://doi.org/10.1016/j.ahj.2009.10.027.
26. MacDonald MR, Petrie MC, Hawkins NM, Petrie JR, Fisher M, McKelvie R et al. Diabetes, left ventricular systolic dysfunction, and chronic heart failure. Eur Heart J. 2008;29(10):1224–1240. https://doi.org/10.1093/eurheartj/ehn156.
27. Song A, Zhang C, Meng X. Mechanism and application of metformin in kidney diseases: An update. Biomed Pharmacother. 2021;138:111454. https://doi.org/10.1016/j.biopha.2021.111454.
28. Lalau JD, Kajbaf F, Bennis Y, Hurtel-Lemaire AS, Belpaire F, De Broe ME. Metformin Treatment in Patients With Type 2 Diabetes and Chronic Kidney Disease Stages 3A, 3B, or 4. Diabetes Care. 2018;41(3):547–553. https://doi.org/10.2337/dc17-2231.
29. Charytan DM, Solomon SD, Ivanovich P, Remuzzi G, Cooper ME, McGill JB et al. Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab. 2019;21(5):1199–1208. https://doi.org/10.1111/dom.13642.
30. Roumie CL, Chipman J, Min JY, Hackstadt AJ, Hung AM, Greevy RA Jr et al. Association of Treatment With Metformin vs Sulfonylurea With Major Adverse Cardiovascular Events Among Patients With Diabetes and Reduced Kidney Function. JAMA. 2019;322(12):1167–1177. https://doi.org/10.1001/jama.2019.13206.
31. Vasilkova TN, Mischenko TA. Recent assessment methods of epicardial adipose tissue. The Siberian Journal of Clinical and Experimental Medicine. 2023;38(1):46–57. (In Russ.) https://doi.org/10.29001/2073-8552-2023-38-1-46-57.
32. Guglielmo M, Lin A, Dey D, Baggiano A, Fusini L, Muscogiuri G, Pontone G. Epicardial fat and coronary artery disease: Role of cardiac imaging. Atherosclerosis. 2021;321:30–38. https://doi.org/10.1016/j.atherosclerosis.2021.02.008.
33. Iacobellis G, Gra-Menendez S. Effects of Dapagliflozin on Epicardial Fat Thickness in Patients with Type 2 Diabetes and Obesity. Obesity. 2020;28(6):1068–1074. https://doi.org/10.1002/oby.22798.
34. Güneş H, Güneş H, Özmen Ş, Çelik E, Temiz F. Effects of metformin on epicardial adipose tissue and atrial electromechanical delay of obese children with insulin resistance. Cardiol Young. 2020;30(10):1429–1432. https://doi.org/10.1017/S1047951120002103.
35. Sardu C, D’Onofrio N, Torella M, Portoghese M, Loreni F, Mureddu S et al. Pericoronary fat inflammation and Major Adverse Cardiac Events (MACE) in prediabetic patients with acute myocardial infarction: effects of metformin. Cardiovasc Diabetol. 2019;18(1):126. https://doi.org/10.1186/s12933-019-0931-0.
36. Salvatore T, Galiero R, Caturano A, Vetrano E, Rinaldi L, Coviello F et al. Dysregulated Epicardial Adipose Tissue as a Risk Factor and Potential Therapeutic Target of Heart Failure with Preserved Ejection Fraction in Diabetes. Biomolecules. 2022;12(2):176. https://doi.org/10.3390/biom12020176.
37. Chen WJ, Greulich S, van der Meer RW, Rijzewijk LJ, Lamb HJ, de Roos A et al. Activin A is associated with impaired myocardial glucose metabolism and left ventricular remodeling in patients with uncomplicated type 2 diabetes. Cardiovasc Diabetol. 2013;12:150. https://doi.org/10.1186/1475-2840-12-150.
38. Yasmin T, Rahman MM, Khan F, Kabir F, Nahar K, Lasker S et al. Metformin treatment reverses high fat diet- induced non-alcoholic fatty liver diseases and dyslipidemia by stimulating multiple antioxidant and anti-inflammatory pathways. Biochem Biophys Rep. 2021;28:101168. https://doi.org/10.1016/j.bbrep.2021.101168.
Review
For citations:
Tsygankova OV, Apartseva NE, Latyntseva LD, Ryabikov AN, Kashtanova EV. Long-term effects of metformin on fat depots and insulin-glucose parameters in patients with prediabetes and chronic heart failure. Meditsinskiy sovet = Medical Council. 2024;(16):274-283. (In Russ.) https://doi.org/10.21518/ms2024-347
Views:
198
Email this article 