ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet13037ometendo-13037Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESИзучение постпищевой динамики концентрации гормонов у лиц с метаболически здоровым и нездоровым ожирениемStudy of post-nutrition dynamics hormone concentrations in metabolically healthy and unhealthy obese patientshttps://orcid.org/0000-0002-2695-4924МатвеевГ. А.MatveevG. A.

Матвеев Георгий Александрович 

Author ID: 57217105577

Санкт-Петербург,

Georgy A. Matveev, MD 

Scopus Author ID: 57217105577

Saint-Petersburg

zx5000@mail.ruhttps://orcid.org/0000-0003-3185-3957ВасильеваЕ. Ю.VasilievaE. Yu.

Васильева Елена Юрьевна

Санкт-Петербург,

Elena Yu. Vasilieva, MD

Saint-Petersburg

elena-almazlab@yandex.ruhttps://orcid.org/0000-0002-0559-697XБабенкоА. Ю.BabenkoA. Y.

Бабенко Алина Юрьевна, д.м.н., профессор

 Researcher ID: Q-6714-2016

197341, Санкт-Петербург, ул. Аккуратова, д. 2

Alina Y. Babenko, MD, PhD

Researcher ID: Q-6714-2016 

2 Akkuratova street, 197341 Saint-Petersburg

alina_babenko@mail.ruhttps://orcid.org/0000-0003-2929-0980ШляхтоЕ. В.ShlyakhtoE. V.

Шляхто Евгений Владимирович, д.м.н., профессор

Санкт-Петербург,

Evgeny V. Shlyakhto, MD, PhD, Professor

Saint-Petersburg

e.shlyakhto@almazovcentre.ruНациональный медицинский исследовательский центр им. В.А. АлмазоваРоссияAlmazov National Research CentreRussian Federation202417062024212125135Copyright © Матвеев Г.А., Васильева Е.Ю., Бабенко А.Ю., Шляхто Е.В., 20242024Матвеев Г.А., Васильева Е.Ю., Бабенко А.Ю., Шляхто Е.В.Matveev G.A., Vasilieva E.Y., Babenko A.Y., Shlyakhto E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/13037Обоснование

Обоснование. Ожирение в высокой степени способствует развитию сахарного диабета 2 типа и сердечно-сосудистых заболеваний. Между тем разные фенотипы ожирения значительно различаются по степени риска, и индикация ранних предикторов, способных помочь спрогнозировать вероятность развития кардиометаболических нарушений, является важной задачей. Особенности изменения уровня гормонов, вовлеченных в энергетический гомеостаз, в постпищевом статусе при ожирении свидетельствуют в пользу развития резистентности не только к инсулину, но и к лептину, грелину, и, возможно, к инкретинам.

Цель исследования

Цель исследования. Изучить взаимосвязи между динамикой уровня гормонов, вовлеченных в энергетический гомеостаз, в пробе со стандартным углеводным завтраком и метаболическим здоровьем.

Материалы и методы

Материалы и методы. У 90 пациентов с ожирением (ИМТ 37,31±4,83 кг/м2) была выполнена оценка метаболических параметров (иНОМА-ИР и иНОМА-В, липидограмма, уровень глюкозы, АД), ряда биомаркеров (адипонектин, СРБ). Уровни лептина, грелина, ГПП1 и ГИП оценены до и через 60 минут после стандартного углеводного завтрака. Пациенты были поделены на группы метаболически здорового и метаболически нездорового ожирения: сначала по наиболее часто используемым критериям (Meigs и соавт.), затем на основании обсуждаемых в литературе критериев абсолютно здорового ожирения, при котором отсутствуют какие-либо метаболические нарушения.

Результаты

Результаты. Проведенный анализ показал, что пациенты без метаболических нарушений имели профиль уровня грелина, аналогичный таковому у здоровых людей без ожирения, в то время как у пациентов, имевших хотя бы одно из проявлений метаболического синдрома, отмечались проявления грелинорезистентности (уровень грелина натощак снижен, а после еды не происходит его адекватного снижения). Уровень адипонектина был в норме у метаболически здоровых пациентов. Уровень инкретинов носил однонаправленные изменения при ожирении вне зависимости от метаболического статуса. Уровень СРБ не отличался между группами. Уровень гликемии был достоверно ниже у метаболически здоровых пациентов (группа характеризовалась нормальным уровнем инсулина и имела меньшую степень инсулинорезистентности).

Заключение

Заключение. Полученные данные позволяют рассматривать грелинорезистентность как ранний и достаточно чувствительный индикатор развития метаболических нарушений при ожирении.

BACKGROUND

BACKGROUND: Obesity is a pathology that highly contributes to the development of type 2 diabetes mellitus and cardiovascular diseases. Meanwhile, different obesity phenotypes have varying levels of risk, and the indication of early predictors that can help determine the likelihood of developing cardiometabolic disorders is an important task. Since obesity is characterized by excessive energy intake, hormones involved in energy homeostasis (leptin and other adipokines, ghrelin, incretins) can be considered as serious candidates for the role of such predictors. The profile of changes in their level in the post-­nutrition status testifies in favor of the development of resistance not only to insulin, but also to leptin, and to ghrelin, and, possibly, to incretins.

AIM

AIM: This study aims to investigate the relationship between the dynamics of the level of hormones involved in energy homeostasis in a sample with a standard carbohydrate breakfast and metabolic health.

MATERIALS AND METHODS

MATERIALS AND METHODS: Metabolic parameters (including НОМА-IR and НОМА-B, lipid profile, glucose level, blood pressure) were assessed in 90 obese patients (BMI 37.31±4.83 kg/m2). Additionally, biomarkers such as adiponectin, CRP were measured. Levels of leptin, ghrelin, GLP1 and GIP were assessed before and 60 minutes after a standard carbohydrate breakfast. These hormone levels were classified depending on the nature of the changes, considering the physiological dynamics described in the literature in healthy people or not. Patients were divided into groups of metabolically healthy and ­metabolically unhealthy obesity, first using the most commonly known criteria (Meigs et al.), then based on the criteria discussed in the literature for perfectly healthy obesity, in which there are no metabolic disorders.

RESULTS

RESULTS: The analysis revealed that patients without metabolic disorders had a ghrelin level profile similar to that in healthy people without obesity, while patients with at least one of the manifestations of the metabolic syndrome showed evidence of ghrelin resistance (the level of ghrelin on an empty stomach was reduced, and after food it was not adequately reduced). Adiponectin levels were normal in metabolically healthy patients. Incretin levels showed unidirectional changes in obesity, regardless of metabolic status. The level of CRP did not differ between the groups. The glycemic level was significantly lower in metabolically healthy patients (the group was characterized by normal insulin levels and had a lower degree of insulin resistance).

CONCLUSION

CONCLUSION: The data obtained allow us to consider ghrelin resistance as an early and rather sensitive indicator of the development of metabolic disorders in obesity.

ожирениегрелинорезистентностьинсулинорезистентностьметаболически здоровое ожирениекритерии Мейгцаинкретиныадипоцитокиныobesityghrelin resistanceinsulin resistancemetabolically healthy obesityincretinsadipocytokinesИсследование выполнено при финансовой поддержке Министерства науки и высшего образования Российской Федерации (Соглашение №075-15-2022-301 от 20.04.2022).ReferencesMeigs JB, Wilson PW, Fox CS, et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab. 2006;91(8):2906-12. doi: https://doi.org/10.1210/jc.2006-0594Meigs JB, Wilson PW, Fox CS, et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab. 2006;91(8):2906-12. doi: https://doi.org/10.1210/jc.2006-0594Mazloomzadeh S, Karami Zarandi F, Shoghli A, et al. Metabolic syndrome, its components and mortality: A population-based study. Med J Islam Repub Iran. 2019;33:11. doi: https://doi.org/10.34171/mjiri.33.11Mazloomzadeh S, Karami Zarandi F, Shoghli A, et al. Metabolic syndrome, its components and mortality: A population-based study. Med J Islam Repub Iran. 2019;33:11. doi: https://doi.org/10.34171/mjiri.33.11Eckel N, Li Y, Kuxhaus O, et al. Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses’ Health Study): 30 year follow-up from a prospective cohort study. Lancet Diabetes Endocrinol. 2018;6(9):714-724. doi: https://doi.org/10.1016/S2213-8587(18)30137-2Eckel N, Li Y, Kuxhaus O, et al. Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses’ Health Study): 30 year follow-up from a prospective cohort study. Lancet Diabetes Endocrinol. 2018;6(9):714-724. doi: https://doi.org/10.1016/S2213-8587(18)30137-2Oussaada SM, van Galen KA, Cooiman MI, et al. The pathogenesis of obesity. Metabolism. 2019;92:26-36. doi: https://doi.org/10.1016/j.metabol.2018.12.012Oussaada SM, van Galen KA, Cooiman MI, et al. The pathogenesis of obesity. Metabolism. 2019;92:26-36. doi: https://doi.org/10.1016/j.metabol.2018.12.012Karelis AD, Brochu M, Rabasa-Lhoret R. Can we identify metabolically healthy but obese individuals (MHO)? Diabetes Metab. 2004;30(6):569-72. doi: https://doi.org/10.1016/s1262-3636(07)70156-8Karelis AD, Brochu M, Rabasa-Lhoret R. Can we identify metabolically healthy but obese individuals (MHO)? Diabetes Metab. 2004;30(6):569-72. doi: https://doi.org/10.1016/s1262-3636(07)70156-8Larsen MA, Isaksen VT, Paulssen EJ, et al. Postprandial leptin and adiponectin in response to sugar and fat in obese and normal weight individuals. Endocrine. 2019;66(3):517-525. doi: https://doi.org/10.1007/s12020-019-02102-9Larsen MA, Isaksen VT, Paulssen EJ, et al. Postprandial leptin and adiponectin in response to sugar and fat in obese and normal weight individuals. Endocrine. 2019;66(3):517-525. doi: https://doi.org/10.1007/s12020-019-02102-9Смирнова Е.Н., Шулькина С.Г. Содержание лептина, растворимых рецепторов лептина и индекса свободного лептина у больных с метаболическим синдромом // Ожирение и метаболизм. — 2017. — Т. 14. — №1. — С. 30-34. doi: https://doi.org/10.14341/omet2017130-34Smirnova EN, Shulkina SG. Leptin, soluble leptin receptor, and free leptin index in patients with metabolic syndrome. Obesity and metabolism. 2017;14(1):30-34. (In Russ.) doi: https://doi.org/10.14341/omet2017130-34Crujeiras AB, Carreira MC, Cabia B, et al. Leptin resistance in obesity: An epigenetic landscape. Life Sci. 2015;140:57-63. doi: https://doi.org/10.1016/j.lfs.2015.05.003Crujeiras AB, Carreira MC, Cabia B, et al. Leptin resistance in obesity: An epigenetic landscape. Life Sci. 2015;140:57-63. doi: https://doi.org/10.1016/j.lfs.2015.05.003Kahn SE, McCulloch DK, Porte D. Insulin secretion in the normal and diabetic human. In: Alberti KGMM, Zimmet P, Defronzo RA, editors & Keen H, (hon) editor. International Textbook of Diabetes Mellitus. (2nd ed) John Wiley & Sons, New York; 1997 p. 337–54Kahn SE, McCulloch DK, Porte D. Insulin secretion in the normal and diabetic human. In: Alberti KGMM, Zimmet P, Defronzo RA, editors & Keen H, (hon) editor. International Textbook of Diabetes Mellitus. (2nd ed) John Wiley & Sons, New York; 1997 p. 337–54Williams DL, Cummings DE. Regulation of ghrelin in physiologic and pathophysiologic states. J Nutr. 2005;135(5):1320-5. doi: https://doi.org/10.1093/jn/135.5.1320Williams DL, Cummings DE. Regulation of ghrelin in physiologic and pathophysiologic states. J Nutr. 2005;135(5):1320-5. doi: https://doi.org/10.1093/jn/135.5.1320Cummings DE, Frayo RS, Marmonier C, et al. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am J Physiol Endocrinol Metab. 2004;287(2):E297-304. doi: https://doi.org/10.1152/ajpendo.00582.2003Cummings DE, Frayo RS, Marmonier C, et al. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am J Physiol Endocrinol Metab. 2004;287(2):E297-304. doi: https://doi.org/10.1152/ajpendo.00582.2003Zwirska-Korczala K, Konturek SJ, Sodowski M, et al. Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome. J Physiol Pharmacol. 2007;58 Suppl 1:13-35Zwirska-Korczala K, Konturek SJ, Sodowski M, et al. Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin and insulin in women with moderate and morbid obesity and metabolic syndrome. J Physiol Pharmacol. 2007;58 Suppl 1:13-35Бабенко А.Ю., Матвеев Г.А. Дисбаланс гормонов, вовлеченных в регуляцию энергетического баланса у больных ожирением, — изучение вклада в нарушение пищевого поведения и метаболических параметров. Российский физиологический журнал им. И.М. Сеченова. — Т. 108.— №9. — С. 1159–1174. doi: https://doi.org/10.31857/S0869813922090047Babenko AYu, Matveev GA. Disbalans gormonov, vovlechennyh v regulyaciyu energeticheskogo balansa u bol’nyh ozhireniem — izuchenie vklada v narushenie pishchevogo povedeniya i metabolicheskih parametrov. Rossijskij fiziologicheskij zhurnal im. I.M. Sechenova. 108(9):1159–1174 (In Russ.). doi: https://doi.org/10.31857/S0869813922090047Sáinz N, Barrenetxe J, Moreno-Aliaga MJ, Martínez JA. Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism. 2015;64(1):35-46. doi: https://doi.org/10.1016/j.metabol.2014.10.015Sáinz N, Barrenetxe J, Moreno-Aliaga MJ, Martínez JA. Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism. 2015;64(1):35-46. doi: https://doi.org/10.1016/j.metabol.2014.10.015Shestakova EA, Il’in AV, Shestakova MV, Dedov II. Glucose-dependent insulinotropic polypeptide - a new link in the development of obesity. Obesity and metabolism. 2015;12(1):16-19. (In Russ.) doi: https://doi.org/10.14341/omet2015116-19Shestakova EA, Il’in AV, Shestakova MV, Dedov II. Glucose-dependent insulinotropic polypeptide - a new link in the development of obesity. Obesity and metabolism. 2015;12(1):16-19. (In Russ.) doi: https://doi.org/10.14341/omet2015116-19Yamaoka-Tojo M, Tojo T, Takahira N, et al. Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease. Cardiovasc Diabetol. 9:17. doi: https://doi.org/10.1186/1475-2840-9-17Yamaoka-Tojo M, Tojo T, Takahira N, et al. Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease. Cardiovasc Diabetol. 9:17. doi: https://doi.org/10.1186/1475-2840-9-17Carr RD, Larsen MO, Jelic K, et al. Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, nondiabetic men. J Clin Endocrinol Metab. 2010;95(2):872-8. doi: https://doi.org/10.1210/jc.2009-2054Carr RD, Larsen MO, Jelic K, et al. Secretion and dipeptidyl peptidase-4-mediated metabolism of incretin hormones after a mixed meal or glucose ingestion in obese compared to lean, nondiabetic men. J Clin Endocrinol Metab. 2010;95(2):872-8. doi: https://doi.org/10.1210/jc.2009-2054Marcus Y, Segev E, Shefer G, et al. Metabolically Healthy Obesity Is a Misnomer: Components of the Metabolic Syndrome Linearly Increase with BMI as a Function of Age and Gender. Biology (Basel). 2023;12(5):719. doi: https://doi.org/10.3390/biology12050719Marcus Y, Segev E, Shefer G, et al. Metabolically Healthy Obesity Is a Misnomer: Components of the Metabolic Syndrome Linearly Increase with BMI as a Function of Age and Gender. Biology (Basel). 2023;12(5):719. doi: https://doi.org/10.3390/biology12050719Cummings DE, Frayo RS, Marmonier C, et al. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am J Physiol Endocrinol Metab. 2004;287(2):E297-304. doi: https://doi.org/10.1152/ajpendo.00582.2003Cummings DE, Frayo RS, Marmonier C, et al. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am J Physiol Endocrinol Metab. 2004;287(2):E297-304. doi: https://doi.org/10.1152/ajpendo.00582.2003Hansen TK, Dall R, Hosoda H, et al. Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol (Oxf). 2002;56(2):203-6. doi: https://doi.org/10.1046/j.0300-0664.2001.01456.xHansen TK, Dall R, Hosoda H, et al. Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol (Oxf). 2002;56(2):203-6. doi: https://doi.org/10.1046/j.0300-0664.2001.01456.xBabenko AY, Matveev GA. Imbalance of Hormones Involved in Energy Balance Regulation in Obese Patients: a Study of Its Relationship with Disturbed Eating Behavior and Abnormal Metabolic Parameters. J Evol Biochem Phys. 2022;58:1491–1502. doi: https://doi.org/10.1134/S0022093022050192Babenko AY, Matveev GA. Imbalance of Hormones Involved in Energy Balance Regulation in Obese Patients: a Study of Its Relationship with Disturbed Eating Behavior and Abnormal Metabolic Parameters. J Evol Biochem Phys. 2022;58:1491–1502. doi: https://doi.org/10.1134/S0022093022050192Tschöp M, Weyer C, Tataranni PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50(4):707-9. doi: https://doi.org/10.2337/diabetes.50.4.707Tschöp M, Weyer C, Tataranni PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50(4):707-9. doi: https://doi.org/10.2337/diabetes.50.4.707Asakawa A, Inui A, Kaga T, et al. A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology. 2001;74(3):143-7. doi: https://doi.org/10.1159/000054680Asakawa A, Inui A, Kaga T, et al. A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology. 2001;74(3):143-7. doi: https://doi.org/10.1159/000054680Crujeiras AB, Goyenechea E, Abete I, et al. Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels. J Clin Endocrinol Metab. 2010;95(11):5037-44. doi: https://doi.org/10.1210/jc.2009-2566Crujeiras AB, Goyenechea E, Abete I, et al. Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels. J Clin Endocrinol Metab. 2010;95(11):5037-44. doi: https://doi.org/10.1210/jc.2009-2566Derevitskiia IV, Matveev GA, Babenko AYu, et al. Predictive Modelling of Weight -Loss-Therapy Results for Patients with Obesity. Procedia Computer Science. Available online 7 December 2020. doi: https://doi.org/10.1016/j.procs.2020.11.027Derevitskiia IV, Matveev GA, Babenko AYu, et al. Predictive Modelling of Weight -Loss-Therapy Results for Patients with Obesity. Procedia Computer Science. Available online 7 December 2020. doi: https://doi.org/10.1016/j.procs.2020.11.027Babenko AYu, Savitskaya DA, Kononova YuA, et al. Predictors of Effectiveness of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes and Obesity. Journal of Diabetes Research. 2019;1365162Babenko AYu, Savitskaya DA, Kononova YuA, et al. Predictors of Effectiveness of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Patients with Type 2 Diabetes and Obesity. Journal of Diabetes Research. 2019;1365162Zhang GG, Cai HQ, Li YH, et al. Ghrelin protects heart against ERS-induced injury and apoptosis by activating AMP-activated protein kinase. Peptides. 2013;48:156-65. doi: https://doi.org/10.1016/j.peptides.2013.08.015Zhang GG, Cai HQ, Li YH, et al. Ghrelin protects heart against ERS-induced injury and apoptosis by activating AMP-activated protein kinase. Peptides. 2013;48:156-65. doi: https://doi.org/10.1016/j.peptides.2013.08.015Khatib MN, Simkhada P, Gode D. Cardioprotective effects of ghrelin in heart failure: from gut to heart. Heart Views. 2014;15(3):74-6. doi: https://doi.org/10.4103/1995-705X.144792Khatib MN, Simkhada P, Gode D. Cardioprotective effects of ghrelin in heart failure: from gut to heart. Heart Views. 2014;15(3):74-6. doi: https://doi.org/10.4103/1995-705X.144792Ott V, Fasshauer M, Dalski A, et al. Direct peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res. 2002;34(11-12):640-5. doi: https://doi.org/10.1055/s-2002-38261Ott V, Fasshauer M, Dalski A, et al. Direct peripheral effects of ghrelin include suppression of adiponectin expression. Horm Metab Res. 2002;34(11-12):640-5. doi: https://doi.org/10.1055/s-2002-38261Aronson D, Bartha P, Zinder O, et al. Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome. Int J Obes Relat Metab Disord. 2004;28(5):674-9. doi: https://doi.org/10.1038/sj.ijo.0802609Aronson D, Bartha P, Zinder O, et al. Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome. Int J Obes Relat Metab Disord. 2004;28(5):674-9. doi: https://doi.org/10.1038/sj.ijo.0802609Cobos-Palacios L, Ruiz-Moreno MI, Vilches-Perez A, et al. Metabolically healthy obesity: Inflammatory biomarkers and adipokines in elderly population. PLoS One. 2022;17(6):e0265362. doi: https://doi.org/10.1371/journal.pone.0265362Cobos-Palacios L, Ruiz-Moreno MI, Vilches-Perez A, et al. Metabolically healthy obesity: Inflammatory biomarkers and adipokines in elderly population. PLoS One. 2022;17(6):e0265362. doi: https://doi.org/10.1371/journal.pone.0265362

The authors declare that there are no conflicts of interest present.