Статья
Избыточная масса тела и ожирение при метаболическом синдроме
В настоящей статье проанализированы современные представления о патогенезе, диагностике и влиянии на прогноз избыточной массы тела при метаболическом синдроме. Приведен обзор современных возможностей диагностики, немедикаментозной и медикаментозной терапии избыточной массы тела, а также сердечно-сосудистых преимуществ препаратов, используемых для снижения массы тела.
1. Danpanichkul P, Suparan K, Kim, D, Wijarnpreecha K. What Is New in Metabolic Dysfunction-Associated Steatotic Liver Disease in Lean Individuals: From Bench to Bedside. J. Clin. Med. 2024;13:278. doi:10.3390/jcm13010278.
2. Mukhopadhyay P, Ghosh S, Bhattacharjee K, et al. Lean Metabolic Syndrome: A Concept or a Reality? Indian J Endocrinol Metab. 2018;22(3):303-7. doi:10.4103/ijem.IJEM_639_17. Erratum in: Indian J Endocrinol Metab. 2018;22(6):868. doi:10.4103/2230-8210.246859.
3. Tang A, Ng CH, Phang PH, et al. Comparative Burden of Metabolic Dysfunction in Lean NAFLD vs Non-lean NAFLD — A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2023;21(7):1750-60.e12. doi:10.1016/j.cgh.2022.06.029.
4. Wang W, Ren J, Zhou W, et al. Lean non-alcoholic fatty liver disease (Lean-NAFLD) and the development of metabolic syndrome: a retrospective study. Sci Rep. 2022;12(1):10977. doi:10.1038/s41598-022-14701-0.
5. Osadnik K, Osadnik T, Gierlotka M, et al. Metabolic syndrome is associated with similar long-term prognosis in those living with and without obesity: an analysis of 45 615 patients from the nationwide LIPIDOGRAM 2004-2015 studies. Eur J Prev Cardiol. 2023;30(12):1195-204. doi:10.1093/eurjpc/zwad101.
6. Sanyal D. Lean Metabolic Syndrome: An Emerging Concept. Indian J Endocrinol Metab. 2018;22(3):301-2. doi:10.4103/2230-8210.236782.
7. Hall KD, Sacks G, Chandramohan D, et al. Quantification of the effect of energy imbalance on bodyweight. Lancet. 2011;378:826-37. doi:10.1016/S0140-6736(11)60812-X.
8. González-Muniesa P, Mártinez-González M-A, Hu FB, et al. Obesity. Nat. Rev. Dis. Prim. 2017;3:17034. doi:10.1038/nrdp.2017.34.
9. Bray MS, Loos R, McCaffery J, Ling C, et al. The The Conference Working Group NIH working group report–using genomic information to guide weight management: From universal to precision treatment. Obesity. 2016;24:14-22. doi:10.1002/oby.21381.
10. Elks CE, Hoed MD, Zhao JH, et al. Variability in the Heritability of Body Mass Index: A Systematic Review and Meta-Regression. Front. Endocrinol. 2012;3:29. doi:10.3389/fendo.2012.00029.
11. Winkler TW, Justice AE, Graff M, et al. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study. PLoS Genet. 2015;11:e1005378. doi:10.1371/journal.pgen.1005378.
12. Locke AE, Kahali B, Berndt SI, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518:197-206. doi:10.1038/nature14177.
13. Hetherington AW, Ranson SW. Hypothalamic lesions and adiposity in the rat. Anat. Rec. Adv. Integr. Anat. Evol. Biol. 1940;78:149-72. doi:10.1002/ar.1090780203.
14. Williams DM, Nawaz A, Evans M. Drug Therapy in Obesity: A Review of Current and Emerging Treatments. Diabetes Ther. 2020;11:1199-216. doi:10.1007/s13300-020-00816-y.
15. Yamamoto H, Kishi T, Lee CE, et al. Glucagon-Like Peptide-1-Responsive Catecholamine Neurons in the Area Postrema Link Peripheral Glucagon-Like Peptide-1 with Central Autonomic Control Sites. J. Neurosci. 2003;23:2939-46. doi:10.1523/JNEUROSCI.23-07-02939.2003.
16. Morton G, Schwartz M. The NPY/AgRP neuron and energy homeostasis. Int. J. Obes. 2001;25:S56-S62. doi:10.1038/sj.ijo.0801915.
17. Badman MK. The Gut and Energy Balance: Visceral Allies in the Obesity Wars. Science. 2005;307:1909-14. doi:10.1126/science.1109951.
18. Kuo LE, Kitlinska JB, Tilan JU, et al. Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat. Med. 2007;13:803-11. doi:10.1038/nm1611.
19. Boden G, Chen X, Mozzoli M, Ryan I. Effect of fasting on serum leptin in normal human subjects. J. Clin. Endocrinol. Metab. 1996;81:3419-23. doi:10.1210/jcem.81.9.8784108.
20. Krashes MJ, Koda S, Ye C, et al. Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J. Clin. Investig. 2011;121:1424-8. doi:10.1172/JCI46229.
21. Chen Y, Lin Y-C, Zimmerman C, et al. Hunger neurons drive feeding through a sustained, positive reinforcement signal. eLife. 2016;5:e18640. doi:10.7554/eLife.18640.
22. Betley JN, Xu S, Cao ZFH, et al. Neurons for hunger and thirst transmit a negative-valence teaching signal. Nat. Cell Biol. 2015;521:180-5. doi:10.1038/nature14416.
23. Cummings DE, Purnell JQ, Frayo RS, et al. A Preprandial Rise in Plasma Ghrelin Levels Suggests a Role in Meal Initiation in Humans. Diabetes. 2001;50:1714-9. doi:10.2337/diabetes.50.8.1714.
24. Ravussin E, Smith SR, Mitchell JA, et al. Enhanced Weight Loss With Pramlintide/ Metreleptin: An Integrated Neurohormonal Approach to Obesity Pharmacotherapy. Obesity. 2009;17:1736-43. doi:10.1038/oby.2009.184.
25. Müller T, Nogueiras R, Andermann M, et al. Ghrelin. Mol. Metab. 2015;4:437-60. doi:10.1016/j.molmet.2015.03.005.
26. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nat. Cell Biol. 2001;409:194-8. doi:10.1038/35051587.
27. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402:656-60. doi:10.1038/45230.
28. Wang W, Tao Y-X. Progress in Molecular Biology and Translational Science. Volume 140. Elsevier BV; Amsterdam, The Netherlands: 2016. Ghrelin Receptor Mutations and Human Obesity; pp. 131-50.
29. Holst B. Ghrelin receptor mutations — too little height and too much hunger. J. Clin. Investig. 2006;116:637-41. doi:10.1172/JCI27999.
30. Sun Y, Ahmed S, Smith RG. Deletion of Ghrelin Impairs neither Growth nor Appetite. Mol. Cell. Biol. 2003;23:7973-81. doi:10.1128/MCB.23.22.7973-7981.2003.
31. Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc. Natl. Acad. Sci. USA. 2004;101:4679-84. doi:10.1073/pnas.0305930101.
32. Cummings DE, Weigle DS, Frayo RS, et al. Plasma Ghrelin Levels after Diet-Induced Weight Loss or Gastric Bypass Surgery. N. Engl. J. Med. 2002;346:1623-30. doi:10.1056/NEJMoa012908.
33. Neary NM, Small CJ, Wren AM, et al. Ghrelin Increases Energy Intake in Cancer Patients with Impaired Appetite: Acute, Randomized, Placebo-Controlled Trial. J. Clin. Endocrinol. Metab. 2004;89:2832-6. doi:10.1210/jc.2003-031768.
34. Kirkham TC. Endocannabinoids in the regulation of appetite and body weight. Behav. Pharmacol. 2005;16:297-313. doi:10.1097/00008877-200509000-00004.
35. Pertwee RG. Pharmacological Actions of Cannabinoids. Handb. Exp. Pharmacol. 2005;168:1-51. doi:10.1007/3-540-26573-2_1.
36. Richey JM, Woolcott O. Revisiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases. Curr. Diabetes Rep. 2017;17:99. doi:10.1007/s11892-017-0924-x.
37. Sekar R, Wang L, Chow BKC. Central Control of Feeding Behavior by the Secretin, PACAP, and Glucagon Family of Peptides. Front. Endocrinol. 2017;8:18. doi:10.3389/fendo.2017.00018.
38. Li Y, Schnabl K, Gabler S-M, et al. Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation. Cell. 2018;175:1561-74.e12. doi:10.1016/j.cell.2018.10.016.
39. Johnson LR. Gastrointestinal Phisiology. 9th ed. Elsevier; Philadelphia, PA, USA: 2019.
40. Muurahainen N, Kissileff HR, Derogatis AJ, Pi-Sunyer FX. Effects of cholecystokinin-octapeptide (CCK-8) on food intake and gastric emptying in man. Physiol. Behav. 1988;44:645-9. doi:10.1016/0031-9384(88)90330-7.
41. Grill HJ, Hayes MR. Hindbrain Neurons as an Essential Hub in the Neuroanatomically Distributed Control of Energy Balance. Cell Metab. 2012;16:296-309. doi:10.1016/j.cmet.2012.06.015.
42. Roman CW, Derkach VA, Palmiter RD. Genetically and functionally defined NTS to PBN brain circuits mediating anorexia. Nat. Commun. 2016;7:11905. doi:10.1038/ncomms11905.
43. Schwartz MW, Seeley RJ, Zeltser LM, et al. Obesity Pathogenesis: An Endocrine Society Scientific Statement. Endocr. Rev. 2017;38:267-96. doi:10.1210/er.2017-00111.
44. Nauck MA, Meier JJ. Incretin hormones: Their role in health and disease. Diabetes Obes. Metab. 2018;20((Suppl. 1)):5-21. doi:10.1111/dom.13129.
45. Nauck MA, Heimesaat MM, Orskov C, et al. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J. Clin. Investig. 1993;91:301-7. doi:10.1172/JCI116186.
46. Kieffer TJ, McIntosh CH, Pederson RA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology. 1995;136:3585-96. doi:10.1210/endo.136.8.7628397.
47. Butler PC, Chou J, Carter WB, et al. Effects of Meal Ingestion on Plasma Amylin Concentration in NIDDM and Nondiabetic Humans. Diabetes. 1990;39:752-6. doi:10.2337/diab.39.6.752.
48. Li Z, Kelly L, Gergi I, et al. Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake. Cell Metab. 2015;22:1059-67. doi:10.1016/j.cmet.2015.10.012.
49. Mietlicki-Baase EG, Reiner DJ, Cone J, et al. Amylin Modulates the Mesolimbic Dopamine System to Control Energy Balance. Neuropsychopharmacology. 2015;40:372-85. doi:10.1038/npp.2014.180.
50. Whiting L, McCutcheon J, Boyle CN, et al. The area postrema (AP) and the parabrachial nucleus (PBN) are important sites for salmon calcitonin (sCT) to decrease evoked phasic dopamine release in the nucleus accumbens (NAc). Physiol. Behav. 2017;176:9-16. doi:10.1016/j.physbeh.2017.03.023.
51. Scherer PE, Williams S, Fogliano M, et al. A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes. J. Biol. Chem. 1995;270:26746-9. doi:10.1074/jbc.270.45.26746.
52. Achari AE, Jain SK. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int. J. Mol. Sci. 2017;18:1321. doi:10.3390/ijms18061321.
53. Fisman EZ, Tenenbaum A. Adiponectin: A manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc. Diabetol. 2014;13:103. doi:10.1186/1475-2840-13-103.
54. Qi Y, Takahashi N, Hileman SM, et al. Adiponectin acts in the brain to decrease body weight. Nat. Med. 2004;10:524-9. doi:10.1038/nm1029.
55. Hivert M-F, Sullivan L, Fox CS, et al. Associations of Adiponectin, Resistin, and Tumor Necrosis Factor-α with Insulin Resistance. J. Clin. Endocrinol. Metab. 2008;93:3165-72. doi:10.1210/jc.2008-0425.
56. Zaidi SI, Shirwany TA. Relationship of serum resistin with insulin resistance and obesity. J Ayub Med Coll Abbottabad. 2015;27(3):552-5.
57. Su K-Z, Li Y-R, Zhang D, et al. Relation of Circulating Resistin to Insulin Resistance in Type 2 Diabetes and Obesity: A Systematic Review and Meta-Analysis. Front. Physiol. 2019;10:1399. doi:10.3389/fphys.2019.01399.
58. Recinella L, Orlando G, Ferrante C, et al. Adipokines: New Potential Therapeutic Target for Obesity and Metabolic, Rheumatic, and Cardiovascular Diseases. Front. Physiol. 2020;11:578966. doi:10.3389/fphys.2020.578966.
59. Yoneshiro T, Aita S, Matsushita M, et al. Recruited brown adipose tissue as an antiobesity agent in humans. J. Clin. Investig. 2013;123:3404-8. doi:10.1172/JCI67803.
60. Van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-Activated Brown Adipose Tissue in Healthy Men. N. Engl. J. Med. 2009;360:1500-8. doi:10.1056/NEJMoa0808718.
61. Warwick PM, Busby R. Influence of mild cold on 24 h energy expenditure in ‘normally’ clothed adults. Br. J. Nutr. 1990;63:481-8. doi:10.1079/BJN19900135.
62. Planavila A, Redondo I, Hondares E, et al. Fibroblast growth factor 21 protects against cardiac hypertrophy in mice. Nat. Commun. 2013;4:2019. doi:10.1038/ncomms3019.
63. Lee P, Brychta RJ, Linderman J, et al. Mild cold exposure modulates fibroblast growth factor 21 (FGF21) diurnal rhythm in humans: Relationship between FGF21 levels, lipolysis, and cold-induced thermogenesis. J. Clin. Endocrinol. Metab. 2013;98:E98-E102. doi:10.1210/jc.2012-3107.
64. Correa-Burrows P, Rogan J, Blanco E, et al. Resolving early obesity leads to a cardiometabolic profile within normal ranges at 23 years old in a two-decade prospective follow-up study. Sci Rep. 2021;11(1):18927. doi:10.1038/s41598-021-97683-9.
65. Gutin I. In BMI We Trust: Reframing the Body Mass Index as a Measure of Health. Soc Theory Health. 2018;16(3):256-71. doi:10.1057/s41285-017-0055-0.
66. Bray GA. Beyond BMI. Nutrients. 2023;15(10):2254. doi:10.3390/nu15102254.
67. Okorodudu DO, Jumean MF, Montori VM, et al. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes (Lond). 2010;34(5):791-9. doi:10.1038/ijo.2010.5.
68. Khanna D, Peltzer C, Kahar P, Parmar MS. Body Mass Index (BMI): A Screening Tool Analysis. Cureus. 2022;14(2):e22119. doi:10.7759/cureus.22119.
69. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1-452.
70. Ross R, Berentzen T, Bradshaw AJ, et al. Does the relationship between waist circumference, morbidity and mortality depend on measurement protocol for waist circumference? Obes Rev. 2008;9(4):312-25. doi:10.1111/j.1467-789X.2007.00411.x.
71. Ross R, Neeland IJ, Yamashita S, et al. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020;16(3):177-89. doi:10.1038/s41574-019-0310-7.
72. Campana EMG, Brandão AA. Waist Circumference: A Parameter of Vascular Health. Arq Bras Cardiol. 2022;119(2):265-6. English, Portuguese. doi:10.36660/abc.20220508.
73. Jayedi A, Soltani S, Zargar MS, et al. Central fatness and risk of all cause mortality: systematic review and dose-response meta-analysis of 72 prospective cohort studies. BMJ. 2020;370:m3324. doi:10.1136/bmj.m3324.
74. Bosomworth NJ. Normal-weight central obesity: Unique hazard of the toxic waist. Can Fam Physician. 2019;65(6):399-408.
75. Fang H, Berg E, Cheng X, Shen W. How to best assess abdominal obesity. Curr Opin Clin Nutr Metab Care. 2018;21(5):360-5. doi:10.1097/MCO.0000000000000485.
76. Mawaddatina T, Budihastuti UR, Rahayu D. Waist circumference, hip circumference, arm span, and waist-to-hip ratio high risk of polycystic ovarian syndrome. Scott Med J. 2021;66(4):186-90. doi:10.1177/00369330211043206.
77. Parker ED, Pereira MA, Stevens J, Folsom AR. Association of hip circumference with incident diabetes and coronary heart disease: the Atherosclerosis Risk in Communities study. Am J Epidemiol. 2009;169(7):837-47. doi:10.1093/aje/kwn395.
78. Lanfer A, Mehlig K, Heitmann BL, Lissner L. Does change in hip circumference predict cardiovascular disease and overall mortality in Danish and Swedish women? Obesity (Silver Spring). 2014;22(3):957-63. doi:10.1002/oby.20604.
79. Bergman RN, Stefanovski D, Buchanan TA, et al. A better index of body adiposity. Obesity (Silver Spring). 2011;19(5):1083-9. doi:10.1038/oby.2011.38.
80. Tur JA, Bibiloni MDM. Anthropometry, Body Composition and Resting Energy Expenditure in Human. Nutrients. 2019;11(8):1891. doi:10.3390/nu11081891.
81. Zamaninour N, Ansar H, Pazouki A, Kabir A. Relationship Between Modified Body Adiposity Index and A Body Shape Index with Biochemical Parameters in Bariatric Surgery Candidates. Obes Surg. 2020;30(3):901-9. doi:10.1007/s11695-019-04256-x.
82. Schulze MB, Thorand B, Fritsche A, et al. Body adiposity index, body fat content and incidence of type 2 diabetes. Diabetologia. 2012;55(6):1660-7. doi:10.1007/s00125-012-2499-z.
83. Chang H, Simonsick EM, Ferrucci L, Cooper JA. Validation study of the body adiposity index as a predictor of percent body fat in older individuals: findings from the BLSA. J Gerontol A Biol Sci Med Sci. 2014;69(9):1069-75. doi:10.1093/gerona/glt165.
84. Myint PK, Kwok CS, Luben RN, et al. Body fat percentage, body mass index and waist-to-hip ratio as predictors of mortality and cardiovascular disease. Heart. 2014;100(20):1613-9. doi:10.1136/heartjnl-2014-305816.
85. Burton RF. The waist-hip ratio: a flawed index. Ann Hum Biol. 2020;47(7-8):629-31. doi:10.1080/03014460.2020.1820079.
86. Haufs MG, Zöllner YF. Waist-Hip Ratio More Appropriate Than Body Mass Index. Dtsch Arztebl Int. 2020;117(39):659. doi:10.3238/arztebl.2020.0659a.
87. Jayedi A, Soltani S, Motlagh SZ, et al. Anthropometric and adiposity indicators and risk of type 2 diabetes: systematic review and dose-response meta-analysis of cohort studies. BMJ. 2022;376:e067516. doi:10.1136/bmj-2021-067516.
88. Cao Q, Yu S, Xiong W, et al. Waist-hip ratio as a predictor of myocardial infarction risk: A systematic review and meta-analysis. Medicine (Baltimore). 2018;97(30):e11639. doi:10.1097/MD.0000000000011639.
89. Wang Y, Mao L, Zhang X. Waist-hip ratio is an independent predictor of moderate-to-severe OSA in nonobese males: a cross-sectional study. BMC Pulm Med. 2022;22(1):151. doi:10.1186/s12890-022-01886-3.
90. Xu Y, Li X, Hu T, et al. Neck circumference as a potential indicator of pre-sarcopenic obesity in a cohort of community-based individuals. Clin Nutr. 2024;43(1):11-7. doi:10.1016/j.clnu.2023.11.006.
91. Luo Y, Ma X, Shen Y, et al. Neck circumference as an effective measure for identifying cardio-metabolic syndrome: a comparison with waist circumference. Endocrine. 2017;55(3):822-30. doi:10.1007/s12020-016-1151-y.
92. Padilha CM, Pescuma JMS, Rodrigues ALCC, et al. Neck circumference as a marker of body adiposity in young to middle-aged adults. Nutrition. 2022;93:111496. doi:10.1016/j.nut.2021.111496.
93. Fosbøl MØ, Zerahn B. Contemporary methods of body composition measurement. Clin Physiol Funct Imaging. 2015;35(2):81-97. doi:10.1111/cpf.12152.
94. Holmes CJ, Racette SB. The Utility of Body Composition Assessment in Nutrition and Clinical Practice: An Overview of Current Methodology. Nutrients. 2021;13(8):2493. doi:10.3390/nu13082493.
95. Coëffier M, El Machkouri M, L’Huillier C, et al. Accuracy of bioimpedance equations for measuring body composition in a cohort of 2134 patients with obesity. Clin Nutr. 2022;41(9):2013-24. doi:10.1016/j.clnu.2022.07.032.
96. Karchynskaya V, Kopcakova J, Klein D, et al. Is BMI a Valid Indicator of Overweight and Obesity for Adolescents? Int J Environ Res Public Health. 2020;17(13):4815. doi:10.3390/ijerph17134815.
97. Mazahery H, von Hurst PR, McKinlay CJD, et al. Air displacement plethysmography (pea pod) in full-term and pre-term infants: a comprehensive review of accuracy, reproducibility, and practical challenges. Matern Health Neonatol Perinatol. 2018;4:12. doi:10.1186/s40748-018-0079-z.
98. Kuriyan R, Thomas T, Ashok S, et al. A 4-compartment model based validation of air displacement plethysmography, dual energy X-ray absorptiometry, skinfold technique & bio-electrical impedance for measuring body fat in Indian adults. Indian J Med Res. 2014;139(5):700-7.
99. Golja P, Robič Pikel T, Zdešar Kotnik K, et al. Direct Comparison of (Anthropometric) Methods for the Assessment of Body Composition. Ann Nutr Metab. 2020;76(3):183-92. doi:10.1159/000508514.
100. Heymsfield SB, Ebbeling CB, Zheng J, et al. Multi-component molecular-level body composition reference methods: evolving concepts and future directions. Obes Rev. 2015;16(4):282-94. doi:10.1111/obr.12261.
101. Liu X, He M, Li Y. Adult obesity diagnostic tool: A narrative review. Medicine (Baltimore). 2024;103(17):e37946. doi:10.1097/MD.0000000000037946.
102. Nabasenja C, Barry K, Nelson T, et al. Imaging individuals with obesity. J Med Imaging Radiat Sci. 2022;53(2):291-304. doi:10.1016/j.jmir.2022.02.003.
103. Shen W, Punyanitya M, Wang Z, et al. Visceral adipose tissue: relations between singleslice areas and total volume. Am J Clin Nutr. 2004;80(2):271-8. doi:10.1093/ajcn/80.2.271.
104. Thomas EL, Brynes AE, McCarthy J, et al. Visceral adipose tissue volume measured by single-slice MRI at the L4–L5 level is closely correlated with total visceral adipose tissue volume. International Journal of Obesity. 2002;26:535-8. doi:10.1038/sj.ijo.0801937.
105. Cypess AM, Kahn CR. Brown fat as a therapy for obesity and diabetes. Curr Opin Endocrinol Diabetes Obes. 2010;17(2):143-9. doi:10.1097/MED.0b013e328337a81f.
106. Li C, Ford ES, Zhao G, et al. Prevalence of self-reported clinically diagnosed sleep apnea according to obesity status in men and women: National Health and Nutrition Examination Survey, 2005-2006. Prev Med. 2010;51(1):18-23. doi:10.1016/j.ypmed.2010.03.016.
107. Ghimire P, Sankari A, Antoine MH, et al. Obesity-Hypoventilation Syndrome. [Updated 2025 Jun 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542216/.
108. Oreopoulos A, Padwal R, McAlister FA, et al. Association between obesity and health-related quality of life in patients with coronary artery disease. Int J Obes (Lond). 2010;34(9):1434-41. doi:10.1038/ijo.2010.73.
109. Kyrgiou M, Kalliala I, Markozannes G, et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017;356:j477. doi:10.1136/bmj.j477.
110. Renehan AG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569-78. doi:10.1016/S0140-6736(08)60269-X.
111. Guh DP, Zhang W, Bansback N, et al. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009;9:88. doi:10.1186/1471-2458-9-88.
112. Rao S, Pandey A, Garg S, et al. Effect of Exercise and Pharmacological Interventions on Visceral Adiposity: A Systematic Review and Meta-analysis of Long-term Randomized Controlled Trials. Mayo Clin Proc. 2019;94(2):211-24. doi:10.1016/j.mayocp.2018.09.019.
113. Ryan DH, Yockey SR. Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over. Curr Obes Rep. 2017;6(2):187-94. doi:10.1007/s13679-017-0262-y.
114. Zomer E, Gurusamy K, Leach R, et al. Interventions that cause weight loss and the impact on cardiovascular risk factors: a systematic review and meta-analysis. Obes Rev. 2016;17(10):1001-11. doi:10.1111/obr.12433.
115. Haase CL, Lopes S, Olsen AH, et al. Weight loss and risk reduction of obesity-related outcomes in 0.5 million people: evidence from a UK primary care database. Int J Obes (Lond). 2021;45(6):1249-58. doi:10.1038/s41366-021-00788-4.
116. Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD). Evidence-based European recommendations for the dietary management of diabetes. Diabetologia. 2023;66(6):965-85. doi:10.1007/s00125-023-05894-8.
117. Rucker D, Padwal R, Li SK, et al. Long term pharmacotherapy for obesity and overweight: updated meta-analysis. BMJ. 2007;335(7631):1194-9. doi:10.1136/bmj.39385.413113.25. Erratum in: BMJ. 2007;335(7629). doi:10.1136/bmj.39406.519132.AD.
118. Shi Q, Wang Y, Hao Q, et al. Pharmacotherapy for adults with overweight and obesity: a systematic review and network meta-analysis of randomised controlled trials. Lancet. 2024;403(10434):e21-e31. doi:10.1016/S0140-6736(24)00351-9.
119. Jastreboff AM, Aronne LJ, Ahmad NN, et al.; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-16. doi:10.1056/NEJMoa2206038.
120. Kommu S, Sharma PP, Gabor RM. Efficacy and Safety of Tirzepatide on Weight Loss in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Obes Rev. 2025:e13961. doi:10.1111/obr.13961.
121. Wen J, Syed B, Nadora D, et al. Tirzepatide Versus Semaglutide on Weight Loss in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis of Direct Comparative Studies. Endocrinol Diabetes Metab. 2025;8(3):e70045. doi:10.1002/edm2.70045.
122. Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-55. doi:10.1016/S0140-6736(21)01324-6.
123. Garvey WT, Frias JP, Jastreboff AM, et al.; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402(10402):613-26. doi:10.1016/S0140-6736(23)01200-X.
124. Chuang MH, Chen JY, Wang HY, et al. Clinical Outcomes of Tirzepatide or GLP-1 Receptor Agonists in Individuals With Type 2 Diabetes. JAMA Netw Open. 2024;7(8):e2427258. doi:10.1001/jamanetworkopen.2024.27258.
125. Packer M, Zile MR, Kramer CM, et al.; SUMMIT Trial Study Group. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2025;392(5):427-37. doi:10.1056/NEJMoa2410027.
126. Borlaug BA, Zile MR, Kramer CM, et al. Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial. Nat Med. 2025;31(2):544-51. doi:10.1038/s41591-024-03374-z.
127. Loomba R, Hartman ML, Lawitz EJ, et al.; SYNERGY-NASH Investigators. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. N Engl J Med. 2024;391(4):299-310. doi:10.1056/NEJMoa2401943.
128. Gao X, Hua X, Wang X, et al. Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials. Front Pharmacol. 2022;13:935823. doi:10.3389/fphar.2022.935823.
129. Perreault L, Davies M, Frias JP, et al. Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program. Diabetes Care. 2022;45(10):2396-405. doi:10.2337/dc21-1785.
130. Zhang R, Hou QC, Li BH, et al. Efficacy and safety of subcutaneous semaglutide in adults with overweight or obese: a subgroup meta-analysis of randomized controlled trials. Front Endocrinol (Lausanne). 2023;14:1132004. doi:10.3389/fendo.2023.11320.
131. de Oliveira Almeida G, Nienkötter TF, Balieiro CCA, et al. Cardiovascular Benefits of GLP-1 Receptor Agonists in Patients Living with Obesity or Overweight: A Meta-analysis of Randomized Controlled Trials. Am J Cardiovasc Drugs. 2024;24(4):509-21. doi:10.1007/s40256-024-00647-3.
132. Davies MJ, Aronne LJ, Caterson ID, et al.; Satiety and Clinical Adiposity — Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups. Liraglutide and cardiovascular outcomes in adults with overweight, or obesity: A post hoc analysis from SCALE randomized controlled trials. Diabetes Obes Metab. 2018;20(3):734-9. doi:10.1111/dom.13125.
133. Leite AR, Angélico-Gonçalves A, Vasques-Nóvoa F, et al. Effect of glucagon-like peptide-1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: A meta-analysis of placebo-controlled randomized trials. Diabetes Obes Metab. 2022;24(8):1676-80. doi:10.1111/dom.14707.
134. Bandyopadhyay S, Das S, Samajdar SS, Joshi SR. Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Diabetes Metab Syndr. 2023;17(10):102849. doi:10.1016/j.dsx.2023.102849.
135. Natale P, Green SC, Tunnicliffe DJ, et al. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025;2(2):CD015849. doi:10.1002/14651858.CD015849.pub2.
136. Pi-Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015;373(1):11-22. doi:10.1056/NEJMoa1411892.
137. Astrup A, Carraro R, Finer N, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes. 2012;36(6):843-54.
138. Davies MJ, Bergenstal R, Bode B, et al. NN8022-1922 Study Group. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA. 2015;314(7):687-99.
139. Lin Q, Xue Y, Zou H, et al. Efficacy and safety of liraglutide for obesity and people who are overweight: a systematic review and meta-analysis of randomized controlled trials. Expert Rev Clin Pharmacol. 2022;15(12):1461-9. doi:10.1080/17512433.2022.2130760.
140. Xie Z, Yang S, Deng W, et al. Efficacy and Safety of Liraglutide and Semaglutide on Weight Loss in People with Obesity or Overweight: A Systematic Review. Clin Epidemiol. 2022;14:1463-76. doi:10.2147/CLEP.S391819.
141. Deng Y, Park A, Zhu L, et al. Effect of semaglutide and liraglutide in individuals with obesity or overweight without diabetes: a systematic review. Ther Adv Chronic Dis. 2022;13:20406223221108064. doi:10.1177/20406223221108064.
142. le Roux CW, Astrup A, Fujioka K, et al.; SCALE Obesity Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. 2017;389(10077):1399-409. doi:10.1016/S0140-6736(17)30069-7. Erratum in: Lancet. 2017;389(10077):1398. doi:10.1016/S0140-6736(17)30705-5.
143. Song T, Jia Y, Li Z, et al. Effects of Liraglutide on Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Diabetes Ther. 2021;12(6):1735-49. doi:10.1007/s13300-021-01072-4.
144. Kalogirou MS, Patoulias D, Haidich AB, et al. Liraglutide in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials. Clinics and Research in Hepatology and Gastroenterology. 2021;45(3):101568.
145. Mantovani A, Petracca G, Beatrice G, et al. Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. Metabolites. 2021;11(2):73. doi:10.3390/metabo11020073.
146. Berg S, Stickle H, Rose SJ, Nemec EC. Discontinuing glucagon-like peptide-1 receptor agonists and body habitus: A systematic review and meta-analysis. Obes Rev. 2025:e13929. doi:10.1111/obr.13929.
147. Williamson DF, Pamuk E, Thun M, et al. Prospective Study of Intentional Weight Loss and Mortality in Overweight White Men Aged 40-64 Years. Am J Epidemiol. 1999;149(6):491-03.
148. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Study: A randomized study of orlistat as an adjunct to life-style changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155-61.
149. Singh AK, Singh R. Pharmacotherapy in obesity: a systematic review and meta-analysis of randomized controlled trials of anti-obesity drugs. Expert Rev Clin Pharmacol. 2020;13(1):53-64. doi:10.1080/17512433.2020.1698291.
150. Sahebkar A, Simental-Mendía LE, Reiner Ž, et al. Effect of orlistat on plasma lipids and body weight: A systematic review and meta-analysis of 33 randomized controlled trials. Pharmacol Res. 2017;122:53-65. doi:10.1016/j.phrs.2017.05.022.
151. Wilding JP, Jacob S. Cardiovascular outcome trials in obesity: a review. Obesity reviews. 2021;22(1):e13112.
152. James W, Philip T. The SCOUT study: risk-benefit profile of sibutramine in overweight high-risk cardiovascular patients. European heart journal. 2005; supplements 7.suppl_L: L44-L48.
153. Dedov II, Melnichenko GA, Troshina EA, et al. Body Weight Reduction Associated with the Sibutramine Treatment: Overall Results of the PRIMAVERA Primary Health Care Trial. Obes Facts. 2018;11(4):335-43.
154. Дедов И. И., Шестакова М. В., Мельниченко Г. А. и др. Междисциплинарные клинические рекомендации "Лечение ожирения и коморбидных заболеваний". Ожирение и метаболизм. 2021;18(1):5-99. doi:10.14341/omet12714.
155. Bramante CT, Raatz S, Bomberg EM, et al. Cardiovascular Risks and Benefits of Medications Used for Weight Loss. Front Endocrinol (Lausanne). 2020;10:883. doi:10.3389/fendo.2019.00883.
156. Liu L, Li Z, Ye W, et al. Safety and effects of anti-obesity medications on weight loss, cardiometabolic, and psychological outcomes in people living with overweight or obesity: a systematic review and meta-analysis. EClinicalMedicine. 2024;79:103020. doi:10.1016/j.eclinm.2024.103020.
157. James WP, Caterson ID, Coutinho W, et al.; SCOUT Investigators. Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med. 2010;363(10):905-17. doi:10.1056/NEJMoa1003114.
158. Masson W, Lobo M, Nogueira JP, et al. Anti-inflammatory effect of semaglutide: updated systematic review and meta-analysis. Front Cardiovasc Med. 2024;11:1379189. doi:10.3389/fcvm.2024.1379189.
159. Cho YK, La Lee Y, Jung CH. The Cardiovascular Effect of Tirzepatide: A Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Dual Agonist. J Lipid Atheroscler. 2023;12(3):213-22. doi:10.12997/jla.2023.12.3.213.
160. Mazidi M, Karimi E, Rezaie P, Ferns GA. Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. J Diabetes Complications. 2017;31(7):1237-42. doi:10.1016/j.jdiacomp.2016.05.022.
161. Katsiki N, Ferrannini E. Anti-inflammatory properties of antidiabetic drugs: A "promised land" in the COVID-19 era? J Diabetes Complications. 2020;34(12):107723. doi:10.1016/j.jdiacomp.2020.107723.
162. Usman MS, Davies M, Hall ME, et al. The cardiovascular effects of novel weight loss therapies. Eur Heart J. 2023;44(48):5036-48. doi:10.1093/eurheartj/ehad664.