Acute-phase serum proteins and adipocytokines in women with type 2 diabetes mellitus: Relationships with body composition and blood glucose fluctuations

Full Text

Abstract

Aim. To estimate the relationships between the serum concentrations of acute-phase proteins (APPs) and adipocytokines, body composition (BC), and blood glucose (BG) fluctuations in women with type 2 diabetes mellitus (T2DM). Subjects and methods. A total of 165 women with T2DM and 22 with a normal body mass index (BMI) at the age of 40 to 70 years were examined. The concentrations of high-sensitivity C-reactive protein (hs-CRP) and acid α1-glycoprotein (α1-AGP) were determined by ELISA. The levels of interleukins 6, 8, and 18 (IL-6, IL-8, IL-18), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor type 1 (PAI-1) were measured by a multiplex analysis. Dual energy X-ray absorptiometry was used to estimate BC parameters. BG fluctuations were estimated via continuous glucose monitoring. Results. The levels of hs-CRP, α1-AGP, IL-6, IL-8, IL-18, TNF-α, and PAI-1 were significantly higher in the obese women with T2DM than those in the control group. In the diabetic normal weight women, only hs-CRP, α1-AGP, and IL-8 concentrations exceeded those in the controls. The level of hs-CRP (other than α1-AGP) correlated positively with BMI, the mass of adipose tissue, body trunk (android), and gynoid fats. A multivariate regression analysis showed that adipose tissue mass and trunk fat proportion were independent predictors of hs-CRP levels. The concentrations of IL-6, IL-8, IL-18, PAI-1, and TNF-α correlated positively with waist-to-hip ratio, but demonstrated no associations with BMI and BC. Only the serum α1-AGP level showed a positive association with mean BG and its variability parameters. Conclusion. In the women with T2DM, the serum concentrations of APPs and adipocytokines correlate differently with the mass of adipose tissue, its distribution, and BG fluctuations. The findings indicate the multifactorial genesis of chronic inflammation in these patients.

References

  1. Hameed I, Masoodi SR, Mir SA, Nabi M, Ghazanfar K, Ganai BA. Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition. World J Diabetes. 2015;6(4):598-612. doi: 10.4239/wjd.v6.i4.598
  2. Flehmig G, Scholz M, Klöting N, Fasshauer M, Tönjes A, Stumvoll M, Youn BS, Blüher M. Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation. PLoS One. 2014;9(6):e99785. doi: 10.1371/journal.pone.0099785
  3. Andrade-Oliveira V, Câmara NO, Moraes-Vieira PM. Adipokines as drug targets in diabetes and underlying disturbances. JDiabetes Res. 2015;681612. doi: 10.1155/2015/681612
  4. Коненков В.И., Климонтов В.В., Мякина Н.Е., Тян Н.В., Фазуллина О.Н., Романов В.В. Повышенная концентрация воспалительных цитокинов в сыворотке крови у больных сахарным диабетом 2-го типа с хронической болезнью почек. Терапевтический архив. 2015;6:45-49.
  5. Cao H. Adipocytokines in obesity and metabolic disease. Endocrinol. 2014;220(2):T47-59. doi: 10.1530/JOE-13-0339
  6. Haase J, Weyer U, Immig K, Klöting N, Blüher M, Eilers J, Bechmann I, Gericke M. Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Diabetologia. 2014;57(3):562-571. doi: 10.1007/s00125-013-3139-y
  7. Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract. 2014;105(2):141-150. doi: 10.1016/j.diabres.2014.04.006
  8. Wronkowitz N, Romacho T, Sell H, Eckel J. Adipose tissue dysfunction and inflammation in cardiovascular disease. Front Horm Res.2014;43:79-92. doi: 10.1159/000360560
  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):921-928. doi: 10.1089/dia.2010.0247
  10. Service FJ. Glucose variability. Diabetes. 2013; 62(5):1398-1404. doi: 10.2337/db12-1396
  11. Климонтов В.В., Мякина Н.Е. Вариабельность гликемии при сахарном диабете: инструмент для оценки качества гликемического контроля и риска осложнений. Сахарный диабет. 2014;2:18-24. doi: 10.14341/DM20142
  12. Swift DL, Johannsen NM, Earnest CP, Blair SN, Church TS. Effect of exercise training modality on C-reactive protein in type 2 diabetes. Med Sci Sports Exerc. 2012;44(6):1028-1034. doi: 10.1249/MSS.0b013e31824526cc
  13. Saito T, Murata M, Otani T, Tamemoto H, Kawakami M, Ishikawa SE. Association of subcutaneous and visceral fat mass with serum concentrations of adipokines in subjects with type 2 diabetes mellitus. Endocr J. 2012;59(1):39-45.
  14. Litvinova L, Atochin D, Vasilenko M, Fattakhov N, Zatolokin P, Vaysbeyn I, Kirienkova E. Role of adiponectin and proinflammatory gene expression in adipose tissue chronic inflammation in women with metabolic syndrome. Diabetol Metab Syndr. 2014;6(1):137. doi: 10.1186/1758-5996-6-137
  15. Bruun JM, Lihn AS, Madan AK, Pedersen SB, Schiøtt KM, Fain JN, Richelsen B. Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. Am J Physiol Endocrinol Metab. 2004;286(1):E8-E13.
  16. Samaras K, Botelho NK, Chisholm DJ, Lord RV. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring). 2010;18(5):884-889. doi: 10.1038/oby.2009.443
  17. van Beek L, Lips MA, Visser A, Pijl H, Ioan-Facsinay A, Toes R, Berends FJ, Willems van Dijk K, Koning F, van Harmelen V. Increased systemic and adipose tissue inflammation differentiates obese women with T2DM from obese women with normal glucose tolerance. Metabolism. 2014;63(4):492-501. doi: 10.1016/j.metabol.2013.12.002
  18. Poland DC, Schalkwijk CG, Stehouwer CD, Koeleman CA, van het Hof B, van Dijk W. Increased alpha3-fucosylation of alpha1-acid glycoprotein in Type I diabetic patients is related to vascular function. Glycoconj J. 2001;18(3):261-268.
  19. Fournier T, Medjoubi-N N, Porquet D. Alpha-1-acid glycoprotein. Biochim Biophys Acta. 2000;1482(1-2):157-171. doi: 10.1016/S0167-4838(00)00153-9
  20. Alfadda AA, Fatma S, Chishti MA, Al-Naami MY, Elawad R, Mendoza CD, Jo H, Lee YS. Orosomucoid serum concentrations and fat depot-specific mRNA and protein expression in humans. Mol Cells. 2012;33(1):35-41. doi: 10.1007/s10059-012-2181-9.
  21. Lee YS., Choi JW, Hwang I, Lee JW, Lee JH, Kim AY, Huh JY, Koh YJ, Koh GY, Son HJ, Masuzaki H, Hotta K, Alfadda AA, Kim JB. Adipocytokine orosomucoid integrates inflammatory and metabolic signals to preserve energy homeostasis by resolving immoderate inflammation. J Biol Chem. 2010;285(29):22174-22185. doi: 10.1074/jbc.M109.085464
  22. Würtz P, Tiainen M, Mäkinen VP, Kangas AJ, Soininen P, Saltevo J, Keinänen-Kiukaanniemi S, Mäntyselkä P, Lehtimäki T, Laakso M, Jula A, Kähönen M, Vanhala M, Ala-Korpela M. Circulating metabolite predictors of glycemia in middle-aged men and women. Diabetes Care. 2012;35(8):1749-1756. doi: 10.2337/dc11-1838
  23. Brasacchio D, Okabe J, Tikellis C, Balcerczyk A, George P, Baker EK, Calkin AC, Brownlee M, Cooper ME, El-Osta A. Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail. Diabetes. 2009;58(5):1229-1236. doi: 10.2337/db08-1666
  24. Piconi L, Quagliaro L, Da Ros R, Assaloni R, Giugliano D, Esposito K, Szabó C, Ceriello A. Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymerase. J Thromb Haemost. 2004;2(8):1453-1459.
  25. КоненковВ.И., ШевченкоА.В., ПрокофьевВ.Ф., КлимонтовВ.В., КоролевМ.А., ФазуллинаО.Н., ЛапсинаС.А., КоролеваЕ.А. Ассоциациявариантовгенафактораростасосудистогоэндотелия (VEGF) игеновцитокинов (IL-1B, IL4, IL8, IL10, TNFA) ссахарнымдиабетом 2 типауженщин. Сахарный диабет. 2012;3:4-10. doi: 10.14341/2072-0351-6079
  26. Al-Daghri NM, Al-Attas OS, Krishnaswamy S, Mohammed AK, Alenad AM, Chrousos GP, Alokail MS. Association of Type 2 Diabetes Mellitus related SNP genotypes with altered serum adipokine levels and metabolic syndrome phenotypes. Int J Clin Exp Med. 2015;8(3):4464-4471.
  27. Daniele G, Guardado Mendoza R, Winnier D, Fiorentino TV, Pengou Z, Cornell J, Andreozzi F, Jenkinson C, Cersosimo E, Federici M, Tripathy D, Folli F. The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol. 2014;51(1):123-131. doi: 10.1007/s00592-013-0543-1
  28. Tabák AG, Kivimäki M, Brunner EJ, Lowe GD, Jokela M, Akbaraly TN, Singh-Manoux A, Ferrie JE, Witte DR. Changes in C-reactive protein levels before type 2 diabetes and cardiovascular death: the Whitehall II study. Eur J Endocrinol. 2010;163(1):89-95. doi: 10.1530/EJE-10-0277
  29. Belalcazar LM, Reboussin DM, Haffner SM, Hoogeveen RC, Kriska AM, Schwenke DC, Tracy RP, Pi-Sunyer FX, Ballantyne CM. Look AHEAD Research Group. A 1-year lifestyle intervention for weight loss in individuals with type 2 diabetes reduces high C-reactive protein levels and identifies metabolic predictors of change: from the Look AHEAD (Action for Health in Diabetes) study. Diabetes Care. 2010;33(11):2297-2303. doi: 10.2337/dc10-0728
  30. Mavros Y, Kay S, Simpson KA, Baker MK, Wang Y, Zhao RR, Meiklejohn J, Climstein M, O’Sullivan AJ, de Vos N, Baune BT, Blair SN, Simar D, Rooney K, Singh NA, Fiatarone Singh MA. Reductions in C-reactive protein in older adults with type 2 diabetes are related to improvements in body composition following a randomized controlled trial of resistance training. J Cachexia Sarcopenia Muscle. 2014;5(2):111-120. doi: 10.1007/s13539-014-0134-1
  31. Vepsäläinen T, Soinio M, Marniemi J, Lehto S, Juutilainen A, Laakso M, Rönnemaa T. Physical activity, high-sensitivity C-reactive protein, and total and cardiovascular disease mortality in type 2 diabetes. Diabetes Care. 2011;34(7):1492-1496. doi: 10.2337/dc11-0469
  32. Shirakawa J, Fujii H, Ohnuma K, Sato K, Ito Y, Kaji M, Sakamoto E, Koganei M, Sasaki H, Nagashima Y, Amo K, Aoki K, Morimoto C, Takeda E, Terauchi Y. Diet-induced adipose tissue inflammation and liver steatosis are prevented by DPP-4 inhibition in diabetic mice. Diabetes. 2011;60(4):1246-1257. doi: 10.2337/db10-1338
  33. Satoh-Asahara N, Sasaki Y, Wada H, Tochiya M, Iguchi A, Nakagawachi R, Odori S, Kono S, Hasegawa K, Shimatsu A. A dipeptidyl peptidase-4 inhibitor, sitagliptin, exerts anti-inflammatory effects in type 2 diabetic patients. Metabolism. 2013;62(3):347-351. doi: 10.1016/j.metabol.2012.09.004
  34. Rizzo MR, Barbieri M, Marfella R, Paolisso G. Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 2012;35(10):2076-2082.
  35. Andrade-Oliveira V, Câmara NO, Moraes-Vieira PM. Adipokines as drug targets in diabetes and underlying disturbances.J Diabetes Res. 2015;2015:681612. doi: 10.1155/2015/681612

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2016 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
 

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Alabyan Street, 13/1, Moscow, 127055, Russian Federation

Managing Editor:

  • Tel.: +7 (926) 905-41-26
  • E-mail: e.gorbacheva@ter-arkhiv.ru

 

© 2018-2021 "Consilium Medicum" Publishing house


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies