Дефицит грелина у больных сахарным диабетом 2-го типа: взаимосвязь с ожирением, дисфункцией жировой ткани и вариабельностью гликемии
Дефицит грелина у больных сахарным диабетом 2-го типа: взаимосвязь с ожирением, дисфункцией жировой ткани и вариабельностью гликемии
Климонтов В.В., Булумбаева Д.М., Фазуллина О.Н. и др. Дефицит грелина у больных сахарным диабетом 2-го типа: взаимосвязь с ожирением, дисфункцией жировой ткани и вариабельностью гликемии. Терапевтический архив. 2019; 91 (10): 28–33. DOI: 10.26442/00403660.2019.10.000150
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Аннотация
Грелин – пептидный гормон, продуцируемый главным образом в желудке, играет важную роль в регуляции пищевого поведения, энергетического баланса и гомеостаза глюкозы.
Цель исследования. Определить взаимосвязи между уровнем грелина в сыворотке крови натощак, композитным составом тела, эндокринной функцией жировой ткани и параметрами вариабельности гликемии (ВГ) у больных сахарным диабетом (СД) 2-го типа с наличием и отсутствием ожирения.
Материалы и методы. Обследовано 124 пациента с СД 2-го типа, в том числе 42 без ожирения и 82 с ожирением. Контролем являлись 30 здоровых лиц без ожирения. Концентрации грелина, лептина, резистина, висфатина в сыворотке крови натощак определяли с помощью мультиплексного анализа. Композитный состав тела исследовали с помощью двухэнергетической рентгеновской абсорбциометрии. Суточные и ночные параметры ВГ рассчитывали по данным непрерывного мониторинга уровня глюкозы.
Результаты и обсуждение. Уровень грелина у больных СД оказался достоверно ниже в сравнении с контролем (p<0,00001). Пациенты с ожирением имели более низкую концентрацию гормона, чем больные без ожирения (p=0,002). Уровень грелина обратно коррелировал с индексом массы тела, общей массой жировой ткани (ЖТ) и массой ЖТ на бедрах. Общая масса ЖТ оказалась наиболее значимым предиктором концентрации грелина в многофакторном регрессионном анализе (R2=0,18). У больных СД выявлено достоверное повышение уровня лептина, резистина и висфатина в сыворотке крови (во всех случаях p<0,001). Уровень грелина обратно коррелировал с концентрациями резистина и висфатина. Положительные корреляции зафиксированы между уровнем грелина и ночными параметрами ВГ: стандартным отклонением, средней амплитудой колебаний гликемии и индексом риска гипергликемии.
Заключение. Снижение уровня грелина в сыворотке крови натощак ассоциировано с ожирением, дисфункцией жировой ткани и ночной ВГ у больных СД 2-го типа.
Ключевые слова: сахарный диабет, ожирение, грелин, жировая ткань, адипокин, вариабельность гликемии.
Materials and methods. We observed 124 individuals with type 2 diabetes, including 42 non-obese subjects and 82 patients with obesity. Thirty non-obese healthy subjects were acted as control. The concentrations of ghrelin, leptin, resistin, and visfatin in the fasting serum were determined by Multiplex analysis. Body composition was assessed with DEXA. The 24-hour and nocturnal GV parameters were derived from continuous glucose monitoring.
Results and discussion. Ghrelin levels in patients with diabetes were decreased significantly as compared to control (p<0.00001). Subjects with obesity demonstrated lower ghrelin concentrations then non-obese patients (p=0.002). The levels of ghrelin correlated negatively with body mass index, total and gynoid fat mass. Total fat mass was most reliable predictor of ghrelin concentration in multiple regression analysis (R2=0.18). In patients with diabetes significant increase in the levels of leptin, resistin and visfatin was revealed (all p<0.001). Ghrelin correlated negatively with resistin and visfatin levels. Positive correlations were found between ghrelin and nocturnal GV parameters: SD, Mean Amplitude of Glucose Excursions, and High Blood Glucose Index.
Conclusion. The reduced fasting serum level of ghrelin is associated with obesity, adipose tissue dysfunction and nocturnal GV in subjects with type 2 diabetes.
Keywords: diabetes, obesity, ghrelin, adipose tissue, adipokine, glucose variability.
Цель исследования. Определить взаимосвязи между уровнем грелина в сыворотке крови натощак, композитным составом тела, эндокринной функцией жировой ткани и параметрами вариабельности гликемии (ВГ) у больных сахарным диабетом (СД) 2-го типа с наличием и отсутствием ожирения.
Материалы и методы. Обследовано 124 пациента с СД 2-го типа, в том числе 42 без ожирения и 82 с ожирением. Контролем являлись 30 здоровых лиц без ожирения. Концентрации грелина, лептина, резистина, висфатина в сыворотке крови натощак определяли с помощью мультиплексного анализа. Композитный состав тела исследовали с помощью двухэнергетической рентгеновской абсорбциометрии. Суточные и ночные параметры ВГ рассчитывали по данным непрерывного мониторинга уровня глюкозы.
Результаты и обсуждение. Уровень грелина у больных СД оказался достоверно ниже в сравнении с контролем (p<0,00001). Пациенты с ожирением имели более низкую концентрацию гормона, чем больные без ожирения (p=0,002). Уровень грелина обратно коррелировал с индексом массы тела, общей массой жировой ткани (ЖТ) и массой ЖТ на бедрах. Общая масса ЖТ оказалась наиболее значимым предиктором концентрации грелина в многофакторном регрессионном анализе (R2=0,18). У больных СД выявлено достоверное повышение уровня лептина, резистина и висфатина в сыворотке крови (во всех случаях p<0,001). Уровень грелина обратно коррелировал с концентрациями резистина и висфатина. Положительные корреляции зафиксированы между уровнем грелина и ночными параметрами ВГ: стандартным отклонением, средней амплитудой колебаний гликемии и индексом риска гипергликемии.
Заключение. Снижение уровня грелина в сыворотке крови натощак ассоциировано с ожирением, дисфункцией жировой ткани и ночной ВГ у больных СД 2-го типа.
Ключевые слова: сахарный диабет, ожирение, грелин, жировая ткань, адипокин, вариабельность гликемии.
________________________________________________
Materials and methods. We observed 124 individuals with type 2 diabetes, including 42 non-obese subjects and 82 patients with obesity. Thirty non-obese healthy subjects were acted as control. The concentrations of ghrelin, leptin, resistin, and visfatin in the fasting serum were determined by Multiplex analysis. Body composition was assessed with DEXA. The 24-hour and nocturnal GV parameters were derived from continuous glucose monitoring.
Results and discussion. Ghrelin levels in patients with diabetes were decreased significantly as compared to control (p<0.00001). Subjects with obesity demonstrated lower ghrelin concentrations then non-obese patients (p=0.002). The levels of ghrelin correlated negatively with body mass index, total and gynoid fat mass. Total fat mass was most reliable predictor of ghrelin concentration in multiple regression analysis (R2=0.18). In patients with diabetes significant increase in the levels of leptin, resistin and visfatin was revealed (all p<0.001). Ghrelin correlated negatively with resistin and visfatin levels. Positive correlations were found between ghrelin and nocturnal GV parameters: SD, Mean Amplitude of Glucose Excursions, and High Blood Glucose Index.
Conclusion. The reduced fasting serum level of ghrelin is associated with obesity, adipose tissue dysfunction and nocturnal GV in subjects with type 2 diabetes.
Keywords: diabetes, obesity, ghrelin, adipose tissue, adipokine, glucose variability.
Список литературы
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3. Shukla AP, Mauer E, Igel LI, Truong W, Casper A, Kumar RB, Saunders KH, Aronne LJ. Effect of Food Order on Ghrelin Suppression. Diabetes Care. 2018;41(5):e76-e77. doi: 10.2337/dc17-2244
4. Poher AL, Tschöp MH, Müller TD. Ghrelin regulation of glucose metabolism. Peptides. 2018;100:236-42. doi: 10.1016/j.peptides.2017.12.015
5. Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. 2002;8(7):643-4. doi: 10.1038/nm0702-643
6. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002;87(1):240-4. doi: 10.1210/jcem.87.1.8129
7. Cigdem Arica P, Kocael A, Tabak O, Taskin M, Zengin K, Uzun H. Plasma ghrelin, leptin, and orexin-A levels and insulin resistance after laparoscopic gastric band applications in morbidly obese patients. Minerva Med. 2013;104(3):309-16.
8. Al Qarni AA, Joatar FE, Das N, Awad M, Eltayeb M, Al-Zubair AG, Ali ME, Al Masaud A, Shire AM, Gumaa K, Giha HA. Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects. Endocrinol Metab (Seoul). 2017;32(2):230-40. doi: 10.3803/EnM.2017.32.2.230
9. Hill NR, Nick SO, Choudhary P, Levy JC, Hindmarsh P, Matthews DR. Normal reference range for mean tissue glucose and glycemic variability derived from continuous glucose monitoring for subjects without diabetes in different ethnic groups. Diabetes Technol Ther 2011;13(9):921-8. doi: 10.1089/dia.2010.0247
10. Климонтов В.В., Мякина Н.Е. Вариабельность гликемии при сахарном диабете: инструмент для оценки качества контроля гликемии и риска осложнений. Сахарный диабет. 2014;17(2):76-82 [Klimontov VV, Myakina NE. Glycaemic variability in diabetes: a tool for assessing the quality of glycaemic control and risk of complications. Sakharnyi Diabet = Diabetes Mellitus 2014;17(2):76-82 (In Russ.)]. doi: 10.14341/DM2014276-82
11. Suh S, Kim JH. Glycemic variability: How do we measure it and why is it important? Diabetes Metab J 2015;39:273-82. doi: 10.4093/dmj.2015.39.4.273
12. Ali TM, Mehanna OM, El Askary A. The association between ghrelin levels and markers of arterial stiffness and inflammatory markers in Saudi subjects with metabolic syndrome. Diabetes Metab Syndr. 2017;11(Suppl 2):S721-S725. doi: 10.1016/j.dsx.2017.05.005
13. Zhang S, Zhang Q, Zhang L, Li C, Jiang H. Expression of ghrelin and leptin during the development of type 2 diabetes mellitus in a rat model. Mol Med Rep. 2013;7(1):223-8. doi: 10.3892/mmr.2012.1154
14. Belinova L, Kahleova H, Malinska H, Topolcan O, Windrichova J, Oliyarnyk O, Kazdova L, Hill M, Pelikanova T. The effect of meal frequency in a reduced-energy regimen on the gastrointestinal and appetite hormones in patients with type 2 diabetes: A randomised crossover study. PLoS One. 2017;12(4):e0174820. doi: 10.1371/journal.pone.0174820
15. Santiago-Fernández C, García-Serrano S, Tome M, Valdes S, Ocaña-Wilhelmi L, Rodríguez-Cañete A, Tinahones FJ, García-Fuentes E, Garrido-Sánchez L. Ghrelin levels could be involved in the improvement of insulin resistance after bariatric surgery. Endocrinol Diabetes Nutr. 2017;64(7):355-62. doi: 10.1016/j.endinu.2017.05.002
16. Amato MC, Guarnotta V, Giordano C. Body composition assessment for the definition of cardiometabolic risk. J Endocrinol Invest. 2013;36(7):537-43. doi: 10.3275/8943
17. Jonas MI, Kurylowicz A, Bartoszewicz Z, Lisik W, Jonas M, Domienik-Karlowicz J, Puzianowska-Kuznicka M. Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals. Diabetol Metab Syndr. 2017;9:95. doi: 10.1186/s13098-017-0293-2
18. Terra X, Auguet T, Quesada I, Aguilar C, Luna AM, Hernández M, Sabench F, Porras JA, Martínez S, Lucas A, Pellitero S, Llutart J, del Castillo D, Richart C. Increased levels and adipose tissue expression of visfatin in morbidly obese women: the relationship with pro-inflammatory cytokines. Clin Endocrinol (Oxford). 2012;77(5):691-8. doi: 10.1111/j.1365-2265.2011.04327.x
19. Chang YH, Chang DM, Lin KC, Shin SJ, Lee YJ. Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab Res Rev. 2011;27(6):515-7. doi: 10.1002/dmrr.1201
20. Huang X, Yang Z. Resistin's, obesity and insulin resistance: the continuing disconnect between rodents and humans. J Endocrinol Invest. 2016;39(6):607-15. doi: 10.1007/s40618-015-0408-2
21. Klimontov VV, Myakina NE. Glucose variability indices predict the episodes of nocturnal hypoglycemia in elderly type 2 diabetic patients treated with insulin. Diabetes Metab Syndr. 2017;11(2):119-24. doi: 10.1016/j.dsx.2016.08.023
22. Birketvedt GS, Geliebter A, Kristiansen I, Firgenschau Y, Goll R, Florholmen JR. Diurnal secretion of ghrelin, growth hormone, insulin binding proteins, and prolactin in normal weight and overweight subjects with and without the night eating syndrome. Appetite. 2012;59(3):688-92. doi: 10.1016/j.appet.2012.07.015
23. Tong J, Davis HW, Gastaldelli A, D'Alessio D. Ghrelin Impairs Prandial Glucose Tolerance and Insulin Secretion in Healthy Humans Despite Increasing GLP-1. J Clin Endocrinol Metab. 2016;101(6):2405-14. doi: 10.1210/jc.2015-4154
24. Rizzo M, Rizvi AA, Sudar E, Soskic S, Obradovic M, Montalto G, Boutjdir M, Mikhailidis DP, Isenovic ER. A review of the cardiovascular and anti-atherogenic effects of ghrelin. Curr Pharm Des. 2013;19(27):4953-63. doi: 10.2174/1381612811319270018
25. Neale JPH, Pearson JT, Katare R, Schwenke DO. Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option. Front Endocrinol (Lausanne). 2017;8:350. doi: 10.3389/fendo.2017.00350
26. Laurila M, Santaniemi M, Kesäniemi YA, Ukkola O. High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study. Peptides. 2014;61:122-9. doi: 10.1016/j.peptides.2014.09.012
27. Барбараш О.Л., Груздева О.Л., Акбашева О.Е., Белик Е.В., Учасова Е.Г., Каретникова В.Н., Федорова Т.С. Биохимические показатели, ассоциированные с развитием сахарного диабета через год после перенесенного инфаркта миокарда. Клиническая медицина 2014;92(11):52-9 [Barbarash OL, Gruzdeva OV, Akbasheva OE, Belik EV, Uchasova EG, Karetnikova VN, Fedorova TS. Biochemical characteristics associated with diabetes mellitus one year after myocardial infarction. Klinicheskaya Meditsina (Moscow). 2014;92(11):52-9 (In Russ.)]. doi: 10.15829/1560-4071-2014-3-87-94
2. Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F, Casanueva FF, D'Alessio D, Depoortere I, Geliebter A, Ghigo E, Cole PA, Cowley M, Cummings DE, Dagher A, Diano S, Dickson SL, Diéguez C, Granata R, Grill HJ, Grove K, Habegger KM, Heppner K, Heiman ML, Holsen L, Holst B, Inui A, Jansson JO, Kirchner H, Korbonits M, Laferrère B, LeRoux CW, Lopez M, Morin S, Nakazato M, Nass R, Perez-Tilve D, Pfluger PT, Schwartz TW, Seeley RJ, Sleeman M, Sun Y, Sussel L, Tong J, Thorner MO, van der Lely AJ, van der Ploeg LH, Zigman JM, Kojima M, Kangawa K, Smith RG, Horvath T, Tschöp MH. Ghrelin. Mol Metab. 2015;4(6):437-60. doi: 10.1016/j.molmet.2015.03.005.
3. Shukla AP, Mauer E, Igel LI, Truong W, Casper A, Kumar RB, Saunders KH, Aronne LJ. Effect of Food Order on Ghrelin Suppression. Diabetes Care. 2018;41(5):e76-e77. doi: 10.2337/dc17-2244
4. Poher AL, Tschöp MH, Müller TD. Ghrelin regulation of glucose metabolism. Peptides. 2018;100:236-42. doi: 10.1016/j.peptides.2017.12.015
5. Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. 2002;8(7):643-4. doi: 10.1038/nm0702-643
6. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002;87(1):240-4. doi: 10.1210/jcem.87.1.8129
7. Cigdem Arica P, Kocael A, Tabak O, Taskin M, Zengin K, Uzun H. Plasma ghrelin, leptin, and orexin-A levels and insulin resistance after laparoscopic gastric band applications in morbidly obese patients. Minerva Med. 2013;104(3):309-16.
8. Al Qarni AA, Joatar FE, Das N, Awad M, Eltayeb M, Al-Zubair AG, Ali ME, Al Masaud A, Shire AM, Gumaa K, Giha HA. Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects. Endocrinol Metab (Seoul). 2017;32(2):230-40. doi: 10.3803/EnM.2017.32.2.230
9. Hill NR, Nick SO, Choudhary P, Levy JC, Hindmarsh P, Matthews DR. Normal reference range for mean tissue glucose and glycemic variability derived from continuous glucose monitoring for subjects without diabetes in different ethnic groups. Diabetes Technol Ther 2011;13(9):921-8. doi: 10.1089/dia.2010.0247
10. [Klimontov VV, Myakina NE. Glycaemic variability in diabetes: a tool for assessing the quality of glycaemic control and risk of complications. Sakharnyi Diabet = Diabetes Mellitus 2014;17(2):76-82 (In Russ.)]. doi: 10.14341/DM2014276-82
11. Suh S, Kim JH. Glycemic variability: How do we measure it and why is it important? Diabetes Metab J 2015;39:273-82. doi: 10.4093/dmj.2015.39.4.273
12. Ali TM, Mehanna OM, El Askary A. The association between ghrelin levels and markers of arterial stiffness and inflammatory markers in Saudi subjects with metabolic syndrome. Diabetes Metab Syndr. 2017;11(Suppl 2):S721-S725. doi: 10.1016/j.dsx.2017.05.005
13. Zhang S, Zhang Q, Zhang L, Li C, Jiang H. Expression of ghrelin and leptin during the development of type 2 diabetes mellitus in a rat model. Mol Med Rep. 2013;7(1):223-8. doi: 10.3892/mmr.2012.1154
14. Belinova L, Kahleova H, Malinska H, Topolcan O, Windrichova J, Oliyarnyk O, Kazdova L, Hill M, Pelikanova T. The effect of meal frequency in a reduced-energy regimen on the gastrointestinal and appetite hormones in patients with type 2 diabetes: A randomised crossover study. PLoS One. 2017;12(4):e0174820. doi: 10.1371/journal.pone.0174820
15. Santiago-Fernández C, García-Serrano S, Tome M, Valdes S, Ocaña-Wilhelmi L, Rodríguez-Cañete A, Tinahones FJ, García-Fuentes E, Garrido-Sánchez L. Ghrelin levels could be involved in the improvement of insulin resistance after bariatric surgery. Endocrinol Diabetes Nutr. 2017;64(7):355-62. doi: 10.1016/j.endinu.2017.05.002
16. Amato MC, Guarnotta V, Giordano C. Body composition assessment for the definition of cardiometabolic risk. J Endocrinol Invest. 2013;36(7):537-43. doi: 10.3275/8943
17. Jonas MI, Kurylowicz A, Bartoszewicz Z, Lisik W, Jonas M, Domienik-Karlowicz J, Puzianowska-Kuznicka M. Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals. Diabetol Metab Syndr. 2017;9:95. doi: 10.1186/s13098-017-0293-2
18. Terra X, Auguet T, Quesada I, Aguilar C, Luna AM, Hernández M, Sabench F, Porras JA, Martínez S, Lucas A, Pellitero S, Llutart J, del Castillo D, Richart C. Increased levels and adipose tissue expression of visfatin in morbidly obese women: the relationship with pro-inflammatory cytokines. Clin Endocrinol (Oxford). 2012;77(5):691-8. doi: 10.1111/j.1365-2265.2011.04327.x
19. Chang YH, Chang DM, Lin KC, Shin SJ, Lee YJ. Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab Res Rev. 2011;27(6):515-7. doi: 10.1002/dmrr.1201
20. Huang X, Yang Z. Resistin's, obesity and insulin resistance: the continuing disconnect between rodents and humans. J Endocrinol Invest. 2016;39(6):607-15. doi: 10.1007/s40618-015-0408-2
21. Klimontov VV, Myakina NE. Glucose variability indices predict the episodes of nocturnal hypoglycemia in elderly type 2 diabetic patients treated with insulin. Diabetes Metab Syndr. 2017;11(2):119-24. doi: 10.1016/j.dsx.2016.08.023
22. Birketvedt GS, Geliebter A, Kristiansen I, Firgenschau Y, Goll R, Florholmen JR. Diurnal secretion of ghrelin, growth hormone, insulin binding proteins, and prolactin in normal weight and overweight subjects with and without the night eating syndrome. Appetite. 2012;59(3):688-92. doi: 10.1016/j.appet.2012.07.015
23. Tong J, Davis HW, Gastaldelli A, D'Alessio D. Ghrelin Impairs Prandial Glucose Tolerance and Insulin Secretion in Healthy Humans Despite Increasing GLP-1. J Clin Endocrinol Metab. 2016;101(6):2405-14. doi: 10.1210/jc.2015-4154
24. Rizzo M, Rizvi AA, Sudar E, Soskic S, Obradovic M, Montalto G, Boutjdir M, Mikhailidis DP, Isenovic ER. A review of the cardiovascular and anti-atherogenic effects of ghrelin. Curr Pharm Des. 2013;19(27):4953-63. doi: 10.2174/1381612811319270018
25. Neale JPH, Pearson JT, Katare R, Schwenke DO. Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option. Front Endocrinol (Lausanne). 2017;8:350. doi: 10.3389/fendo.2017.00350
26. Laurila M, Santaniemi M, Kesäniemi YA, Ukkola O. High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study. Peptides. 2014;61:122-9. doi: 10.1016/j.peptides.2014.09.012
27. [Barbarash OL, Gruzdeva OV, Akbasheva OE, Belik EV, Uchasova EG, Karetnikova VN, Fedorova TS. Biochemical characteristics associated with diabetes mellitus one year after myocardial infarction. Klinicheskaya Meditsina (Moscow). 2014;92(11):52-9 (In Russ.)]. doi: 10.15829/1560-4071-2014-3-87-94
2. Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F, Casanueva FF, D'Alessio D, Depoortere I, Geliebter A, Ghigo E, Cole PA, Cowley M, Cummings DE, Dagher A, Diano S, Dickson SL, Diéguez C, Granata R, Grill HJ, Grove K, Habegger KM, Heppner K, Heiman ML, Holsen L, Holst B, Inui A, Jansson JO, Kirchner H, Korbonits M, Laferrère B, LeRoux CW, Lopez M, Morin S, Nakazato M, Nass R, Perez-Tilve D, Pfluger PT, Schwartz TW, Seeley RJ, Sleeman M, Sun Y, Sussel L, Tong J, Thorner MO, van der Lely AJ, van der Ploeg LH, Zigman JM, Kojima M, Kangawa K, Smith RG, Horvath T, Tschöp MH. Ghrelin. Mol Metab. 2015;4(6):437-60. doi: 10.1016/j.molmet.2015.03.005.
3. Shukla AP, Mauer E, Igel LI, Truong W, Casper A, Kumar RB, Saunders KH, Aronne LJ. Effect of Food Order on Ghrelin Suppression. Diabetes Care. 2018;41(5):e76-e77. doi: 10.2337/dc17-2244
4. Poher AL, Tschöp MH, Müller TD. Ghrelin regulation of glucose metabolism. Peptides. 2018;100:236-42. doi: 10.1016/j.peptides.2017.12.015
5. Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. 2002;8(7):643-4. doi: 10.1038/nm0702-643
6. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002;87(1):240-4. doi: 10.1210/jcem.87.1.8129
7. Cigdem Arica P, Kocael A, Tabak O, Taskin M, Zengin K, Uzun H. Plasma ghrelin, leptin, and orexin-A levels and insulin resistance after laparoscopic gastric band applications in morbidly obese patients. Minerva Med. 2013;104(3):309-16.
8. Al Qarni AA, Joatar FE, Das N, Awad M, Eltayeb M, Al-Zubair AG, Ali ME, Al Masaud A, Shire AM, Gumaa K, Giha HA. Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects. Endocrinol Metab (Seoul). 2017;32(2):230-40. doi: 10.3803/EnM.2017.32.2.230
9. Hill NR, Nick SO, Choudhary P, Levy JC, Hindmarsh P, Matthews DR. Normal reference range for mean tissue glucose and glycemic variability derived from continuous glucose monitoring for subjects without diabetes in different ethnic groups. Diabetes Technol Ther 2011;13(9):921-8. doi: 10.1089/dia.2010.0247
10. Климонтов В.В., Мякина Н.Е. Вариабельность гликемии при сахарном диабете: инструмент для оценки качества контроля гликемии и риска осложнений. Сахарный диабет. 2014;17(2):76-82 [Klimontov VV, Myakina NE. Glycaemic variability in diabetes: a tool for assessing the quality of glycaemic control and risk of complications. Sakharnyi Diabet = Diabetes Mellitus 2014;17(2):76-82 (In Russ.)]. doi: 10.14341/DM2014276-82
11. Suh S, Kim JH. Glycemic variability: How do we measure it and why is it important? Diabetes Metab J 2015;39:273-82. doi: 10.4093/dmj.2015.39.4.273
12. Ali TM, Mehanna OM, El Askary A. The association between ghrelin levels and markers of arterial stiffness and inflammatory markers in Saudi subjects with metabolic syndrome. Diabetes Metab Syndr. 2017;11(Suppl 2):S721-S725. doi: 10.1016/j.dsx.2017.05.005
13. Zhang S, Zhang Q, Zhang L, Li C, Jiang H. Expression of ghrelin and leptin during the development of type 2 diabetes mellitus in a rat model. Mol Med Rep. 2013;7(1):223-8. doi: 10.3892/mmr.2012.1154
14. Belinova L, Kahleova H, Malinska H, Topolcan O, Windrichova J, Oliyarnyk O, Kazdova L, Hill M, Pelikanova T. The effect of meal frequency in a reduced-energy regimen on the gastrointestinal and appetite hormones in patients with type 2 diabetes: A randomised crossover study. PLoS One. 2017;12(4):e0174820. doi: 10.1371/journal.pone.0174820
15. Santiago-Fernández C, García-Serrano S, Tome M, Valdes S, Ocaña-Wilhelmi L, Rodríguez-Cañete A, Tinahones FJ, García-Fuentes E, Garrido-Sánchez L. Ghrelin levels could be involved in the improvement of insulin resistance after bariatric surgery. Endocrinol Diabetes Nutr. 2017;64(7):355-62. doi: 10.1016/j.endinu.2017.05.002
16. Amato MC, Guarnotta V, Giordano C. Body composition assessment for the definition of cardiometabolic risk. J Endocrinol Invest. 2013;36(7):537-43. doi: 10.3275/8943
17. Jonas MI, Kurylowicz A, Bartoszewicz Z, Lisik W, Jonas M, Domienik-Karlowicz J, Puzianowska-Kuznicka M. Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals. Diabetol Metab Syndr. 2017;9:95. doi: 10.1186/s13098-017-0293-2
18. Terra X, Auguet T, Quesada I, Aguilar C, Luna AM, Hernández M, Sabench F, Porras JA, Martínez S, Lucas A, Pellitero S, Llutart J, del Castillo D, Richart C. Increased levels and adipose tissue expression of visfatin in morbidly obese women: the relationship with pro-inflammatory cytokines. Clin Endocrinol (Oxford). 2012;77(5):691-8. doi: 10.1111/j.1365-2265.2011.04327.x
19. Chang YH, Chang DM, Lin KC, Shin SJ, Lee YJ. Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab Res Rev. 2011;27(6):515-7. doi: 10.1002/dmrr.1201
20. Huang X, Yang Z. Resistin's, obesity and insulin resistance: the continuing disconnect between rodents and humans. J Endocrinol Invest. 2016;39(6):607-15. doi: 10.1007/s40618-015-0408-2
21. Klimontov VV, Myakina NE. Glucose variability indices predict the episodes of nocturnal hypoglycemia in elderly type 2 diabetic patients treated with insulin. Diabetes Metab Syndr. 2017;11(2):119-24. doi: 10.1016/j.dsx.2016.08.023
22. Birketvedt GS, Geliebter A, Kristiansen I, Firgenschau Y, Goll R, Florholmen JR. Diurnal secretion of ghrelin, growth hormone, insulin binding proteins, and prolactin in normal weight and overweight subjects with and without the night eating syndrome. Appetite. 2012;59(3):688-92. doi: 10.1016/j.appet.2012.07.015
23. Tong J, Davis HW, Gastaldelli A, D'Alessio D. Ghrelin Impairs Prandial Glucose Tolerance and Insulin Secretion in Healthy Humans Despite Increasing GLP-1. J Clin Endocrinol Metab. 2016;101(6):2405-14. doi: 10.1210/jc.2015-4154
24. Rizzo M, Rizvi AA, Sudar E, Soskic S, Obradovic M, Montalto G, Boutjdir M, Mikhailidis DP, Isenovic ER. A review of the cardiovascular and anti-atherogenic effects of ghrelin. Curr Pharm Des. 2013;19(27):4953-63. doi: 10.2174/1381612811319270018
25. Neale JPH, Pearson JT, Katare R, Schwenke DO. Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option. Front Endocrinol (Lausanne). 2017;8:350. doi: 10.3389/fendo.2017.00350
26. Laurila M, Santaniemi M, Kesäniemi YA, Ukkola O. High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study. Peptides. 2014;61:122-9. doi: 10.1016/j.peptides.2014.09.012
27. Барбараш О.Л., Груздева О.Л., Акбашева О.Е., Белик Е.В., Учасова Е.Г., Каретникова В.Н., Федорова Т.С. Биохимические показатели, ассоциированные с развитием сахарного диабета через год после перенесенного инфаркта миокарда. Клиническая медицина 2014;92(11):52-9 [Barbarash OL, Gruzdeva OV, Akbasheva OE, Belik EV, Uchasova EG, Karetnikova VN, Fedorova TS. Biochemical characteristics associated with diabetes mellitus one year after myocardial infarction. Klinicheskaya Meditsina (Moscow). 2014;92(11):52-9 (In Russ.)]. doi: 10.15829/1560-4071-2014-3-87-94
________________________________________________
2. Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, Batterham RL, Benoit SC, Bowers CY, Broglio F, Casanueva FF, D'Alessio D, Depoortere I, Geliebter A, Ghigo E, Cole PA, Cowley M, Cummings DE, Dagher A, Diano S, Dickson SL, Diéguez C, Granata R, Grill HJ, Grove K, Habegger KM, Heppner K, Heiman ML, Holsen L, Holst B, Inui A, Jansson JO, Kirchner H, Korbonits M, Laferrère B, LeRoux CW, Lopez M, Morin S, Nakazato M, Nass R, Perez-Tilve D, Pfluger PT, Schwartz TW, Seeley RJ, Sleeman M, Sun Y, Sussel L, Tong J, Thorner MO, van der Lely AJ, van der Ploeg LH, Zigman JM, Kojima M, Kangawa K, Smith RG, Horvath T, Tschöp MH. Ghrelin. Mol Metab. 2015;4(6):437-60. doi: 10.1016/j.molmet.2015.03.005.
3. Shukla AP, Mauer E, Igel LI, Truong W, Casper A, Kumar RB, Saunders KH, Aronne LJ. Effect of Food Order on Ghrelin Suppression. Diabetes Care. 2018;41(5):e76-e77. doi: 10.2337/dc17-2244
4. Poher AL, Tschöp MH, Müller TD. Ghrelin regulation of glucose metabolism. Peptides. 2018;100:236-42. doi: 10.1016/j.peptides.2017.12.015
5. Cummings DE, Clement K, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. 2002;8(7):643-4. doi: 10.1038/nm0702-643
6. Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002;87(1):240-4. doi: 10.1210/jcem.87.1.8129
7. Cigdem Arica P, Kocael A, Tabak O, Taskin M, Zengin K, Uzun H. Plasma ghrelin, leptin, and orexin-A levels and insulin resistance after laparoscopic gastric band applications in morbidly obese patients. Minerva Med. 2013;104(3):309-16.
8. Al Qarni AA, Joatar FE, Das N, Awad M, Eltayeb M, Al-Zubair AG, Ali ME, Al Masaud A, Shire AM, Gumaa K, Giha HA. Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects. Endocrinol Metab (Seoul). 2017;32(2):230-40. doi: 10.3803/EnM.2017.32.2.230
9. Hill NR, Nick SO, Choudhary P, Levy JC, Hindmarsh P, Matthews DR. Normal reference range for mean tissue glucose and glycemic variability derived from continuous glucose monitoring for subjects without diabetes in different ethnic groups. Diabetes Technol Ther 2011;13(9):921-8. doi: 10.1089/dia.2010.0247
10. [Klimontov VV, Myakina NE. Glycaemic variability in diabetes: a tool for assessing the quality of glycaemic control and risk of complications. Sakharnyi Diabet = Diabetes Mellitus 2014;17(2):76-82 (In Russ.)]. doi: 10.14341/DM2014276-82
11. Suh S, Kim JH. Glycemic variability: How do we measure it and why is it important? Diabetes Metab J 2015;39:273-82. doi: 10.4093/dmj.2015.39.4.273
12. Ali TM, Mehanna OM, El Askary A. The association between ghrelin levels and markers of arterial stiffness and inflammatory markers in Saudi subjects with metabolic syndrome. Diabetes Metab Syndr. 2017;11(Suppl 2):S721-S725. doi: 10.1016/j.dsx.2017.05.005
13. Zhang S, Zhang Q, Zhang L, Li C, Jiang H. Expression of ghrelin and leptin during the development of type 2 diabetes mellitus in a rat model. Mol Med Rep. 2013;7(1):223-8. doi: 10.3892/mmr.2012.1154
14. Belinova L, Kahleova H, Malinska H, Topolcan O, Windrichova J, Oliyarnyk O, Kazdova L, Hill M, Pelikanova T. The effect of meal frequency in a reduced-energy regimen on the gastrointestinal and appetite hormones in patients with type 2 diabetes: A randomised crossover study. PLoS One. 2017;12(4):e0174820. doi: 10.1371/journal.pone.0174820
15. Santiago-Fernández C, García-Serrano S, Tome M, Valdes S, Ocaña-Wilhelmi L, Rodríguez-Cañete A, Tinahones FJ, García-Fuentes E, Garrido-Sánchez L. Ghrelin levels could be involved in the improvement of insulin resistance after bariatric surgery. Endocrinol Diabetes Nutr. 2017;64(7):355-62. doi: 10.1016/j.endinu.2017.05.002
16. Amato MC, Guarnotta V, Giordano C. Body composition assessment for the definition of cardiometabolic risk. J Endocrinol Invest. 2013;36(7):537-43. doi: 10.3275/8943
17. Jonas MI, Kurylowicz A, Bartoszewicz Z, Lisik W, Jonas M, Domienik-Karlowicz J, Puzianowska-Kuznicka M. Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals. Diabetol Metab Syndr. 2017;9:95. doi: 10.1186/s13098-017-0293-2
18. Terra X, Auguet T, Quesada I, Aguilar C, Luna AM, Hernández M, Sabench F, Porras JA, Martínez S, Lucas A, Pellitero S, Llutart J, del Castillo D, Richart C. Increased levels and adipose tissue expression of visfatin in morbidly obese women: the relationship with pro-inflammatory cytokines. Clin Endocrinol (Oxford). 2012;77(5):691-8. doi: 10.1111/j.1365-2265.2011.04327.x
19. Chang YH, Chang DM, Lin KC, Shin SJ, Lee YJ. Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab Res Rev. 2011;27(6):515-7. doi: 10.1002/dmrr.1201
20. Huang X, Yang Z. Resistin's, obesity and insulin resistance: the continuing disconnect between rodents and humans. J Endocrinol Invest. 2016;39(6):607-15. doi: 10.1007/s40618-015-0408-2
21. Klimontov VV, Myakina NE. Glucose variability indices predict the episodes of nocturnal hypoglycemia in elderly type 2 diabetic patients treated with insulin. Diabetes Metab Syndr. 2017;11(2):119-24. doi: 10.1016/j.dsx.2016.08.023
22. Birketvedt GS, Geliebter A, Kristiansen I, Firgenschau Y, Goll R, Florholmen JR. Diurnal secretion of ghrelin, growth hormone, insulin binding proteins, and prolactin in normal weight and overweight subjects with and without the night eating syndrome. Appetite. 2012;59(3):688-92. doi: 10.1016/j.appet.2012.07.015
23. Tong J, Davis HW, Gastaldelli A, D'Alessio D. Ghrelin Impairs Prandial Glucose Tolerance and Insulin Secretion in Healthy Humans Despite Increasing GLP-1. J Clin Endocrinol Metab. 2016;101(6):2405-14. doi: 10.1210/jc.2015-4154
24. Rizzo M, Rizvi AA, Sudar E, Soskic S, Obradovic M, Montalto G, Boutjdir M, Mikhailidis DP, Isenovic ER. A review of the cardiovascular and anti-atherogenic effects of ghrelin. Curr Pharm Des. 2013;19(27):4953-63. doi: 10.2174/1381612811319270018
25. Neale JPH, Pearson JT, Katare R, Schwenke DO. Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option. Front Endocrinol (Lausanne). 2017;8:350. doi: 10.3389/fendo.2017.00350
26. Laurila M, Santaniemi M, Kesäniemi YA, Ukkola O. High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study. Peptides. 2014;61:122-9. doi: 10.1016/j.peptides.2014.09.012
27. [Barbarash OL, Gruzdeva OV, Akbasheva OE, Belik EV, Uchasova EG, Karetnikova VN, Fedorova TS. Biochemical characteristics associated with diabetes mellitus one year after myocardial infarction. Klinicheskaya Meditsina (Moscow). 2014;92(11):52-9 (In Russ.)]. doi: 10.15829/1560-4071-2014-3-87-94
Авторы
В.В. Климонтов, Д.М. Булумбаева, О.Н. Фазуллина, Н.Б. Орлов, В.И. Коненков
Научно-исследовательский институт клинической и экспериментальной лимфологии – филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, Россия
Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Novosibirsk, Russia
Научно-исследовательский институт клинической и экспериментальной лимфологии – филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, Россия
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Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Novosibirsk, Russia
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