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Licensed Unlicensed Requires Authentication Published by De Gruyter September 11, 2014

Relationship of plasma level of chemerin and vaspin to early atherosclerotic changes and cardiac autonomic neuropathy in adolescent type 1 diabetic patients

Soha M. Abd El Dayem, Ahmed A. Battah, Abo El Magd El Bohy, Amal El Shehaby and Esmat Abd El Ghaffar

Abstract

Objective: Our objective was to evaluate the relationship of plasma level of chemerin and vaspin to early atherosclerotic changes and cardiac autonomic neuropathy (CAN) in adolescent type 1 diabetic patients.

Patients and methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood samples were taken for assessment of chemerin, vaspin, asymmetric dimenthylarginine (ADMA), and oxidized low-density lipoprotein (OxLDL) by enzyme-linked immunosorbent assay (ELISA) technique. Also, blood samples were taken for analysis of glycosylated hemoglobin; lipid profiles and urine samples were taken for assessment of albumin/creatinine ratio. Twenty-four-hour holter [for assessment of time domain heart rate variability (HRV)] and carotid intima-media thickness (CIMT) were also done. The t-test or Mann-Whitney U-test for independent variables, Pearson’s or Spearman’s correlation, and stepwise multiple regression analysis were used.

Results: The mean age of diabetic patients was 16.3±1.5 years, and mean duration of diabetes was 9.4±2.9 years. Chemerin, vaspin, OxLDL, and albumin/creatinine ratio were significantly higher, whereas ADMA was significantly lower than the controls. By stepwise multiple regression analysis, vaspin had a relation with a standard deviation difference RR (SDARR) and waist/height ratio. Conversely, chemerin had a relation with OxLDL. Albumin/creatinine ratio had a significant positive correlation with chemerin and OxLDL, and a negative correlation with ADMA.

Conclusions: Type 1 diabetic patients had impaired time domain HRV associated with increased CIMT. Vaspin had a significant relation to CAN, whereas chemerin, ADMA, and OxLDL had a significant correlation with albumin/creatinine ratio that reflects their role in renal affection.


Corresponding author: Soha M. Abd El Dayem, Professor of Pediatrics, Consultant of Diabetes and Endocrinology, Pediatrics Department, Medical Research Division, National Research Centre, Cairo, Egypt, Phone: +2 01006716852, E-mail:

Conflict of interest statement: The authors declare no conflict of interest.

References

1. Stuart AA, Schipper HS, Tasdelen I, Egan DA, Prakken BJ, et al. Altered plasma adipokine levels and in vitro adipocyte differentiation in pediatric type 1 diabetes. J Clin Endocrinol Metab 2012;97:463–72.10.1210/jc.2011-1858Search in Google Scholar PubMed

2. Leal VD, Mafra D. Adipokines in obesity. Clin Chimica Acta 2013;419:87–94.10.1016/j.cca.2013.02.003Search in Google Scholar PubMed

3. Bluher M. Vaspin in obesity and diabetes: pathophysiological and clinical significance. Endocrine 2012;41:176–82.10.1007/s12020-011-9572-0Search in Google Scholar PubMed

4. Phalitakul S, Okada M, Hara Y, Yamawaki H. Vaspin prevents TNF-α-induced intracellular adhesion molecule-1 via inhibiting reactive oxygen species-dependent NF-KB and PKCθ activation in cultured rat vascular smooth muscle cells. Pharmacol Res 2011;64:493–500.10.1016/j.phrs.2011.06.001Search in Google Scholar PubMed

5. Youn BS, Klöting N, Kratzsch J, Lee N, Park JI, et al. Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 2008;57:372–7.10.2337/db07-1045Search in Google Scholar PubMed

6. Chang HM, Park HS, Park CY, Song YS, Jang YJ. Association between serum vaspin concentrations and visceral adipose tissue in Korean subjects. Metabolism 2010;59:1276–81.10.1016/j.metabol.2009.11.021Search in Google Scholar PubMed

7. Du XY, Leung LL. Proteolytic regulatory mechanism of chemerin bioactivity. Acta Biochim Biophys Sin 2009;41:973–9.10.1093/abbs/gmp091Search in Google Scholar PubMed PubMed Central

8. Takahashi M, Takahashi Y, Takahashi K, Zolotaryov FN, Hong KS, et al. Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1adypocytes. FEBS Lett 2008;582:573–8.10.1016/j.febslet.2008.01.023Search in Google Scholar PubMed

9. Sell H, Laurencikiene J, Taube A, Eckardt K, Cramer A, et al. Chemerin is a novel adipocyte-derived factor inducing insulin resistance in primary human skeletal muscle cells. Diabetes 2009;58:2731–40.10.2337/db09-0277Search in Google Scholar PubMed PubMed Central

10. Tanner JM, Hiernaux J, Jarman S. Growth and physical studies. In: Weiner JS, Lourie JA, editors. Human biology: a guide to field methods. Oxford: Blackwell Scientific, 1969:3–41.Search in Google Scholar

11. Cameron N. The methods of auxological anthropology. In: Falkner F, Tanner JM, editors. Human growth 3 methodology. New York: Plenum Press, 1986:3–46.Search in Google Scholar

12. Marques-Vidal P, Ferrario M, Kuulasmaa K, Grafnetter D, Moltchanov V, for the WHO MONICA Project. Quality assessment of data on HDL cholesterol in the WHO MONICA Project (1999). Available at: URL:http://www.thl.fi/publications/monica/hdl/hdlqa.htm, URN:NBN:fi-fe19991137.Search in Google Scholar

13. Trivelli LA, Ranney HM, Lai HT. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 1971;284: 353–7.10.1056/NEJM197102182840703Search in Google Scholar PubMed

14. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984;310:356–60.10.1056/NEJM198402093100605Search in Google Scholar

15. Craig WY, Poulin SE, Nelson CP, Ritchie RF. An ELISA method for detection and quantitation of IgG antibody against oxidized low density lipoprotein: the effect of blocking buffer and the method of data expression on experimental findings. Clin Chem 1994;40:882–8.10.1093/clinchem/40.6.882Search in Google Scholar

16. Chiat A. Methods for assessing lipid and lipoprotein oxidation. Curr Opin Lipidol 1992;3:389–94.10.1097/00041433-199212000-00007Search in Google Scholar

17. Welch’s PD: The use of fast Fourier transform for the estimation of power spectra: a method based on time averaging over short, modified periodograms. IEEE Trans Audio Electroacoustics 1967;15:70–3.10.1109/TAU.1967.1161901Search in Google Scholar

18. Cowan MJ. Measurement of heart rate variability. Western J Nurs Res 1995;17:32–48, 101–11.10.1177/019394599501700104Search in Google Scholar

19. Faulkner MS, Quinn L, Fritschi C. Microalbuminuria and heart rate variability in adolescents with diabetes. J Pediatr Health Care 2010;24:34–47.10.1016/j.pedhc.2009.01.002Search in Google Scholar

20. Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987;59:256–62.10.1016/0002-9149(87)90795-8Search in Google Scholar

21. Kleiger RE, Stein PK, Bosner MS, Rottman JN. Time domain measurements of heart rate variability. Cardiol Clin 1992;10:487–98.10.1016/S0733-8651(18)30230-3Search in Google Scholar

22. Bazett HC. An analysis of the time relationships of the electrocardiograms. Heart 1920;7:353–7.Search in Google Scholar

23. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 2007;115:459–67.10.1161/CIRCULATIONAHA.106.628875Search in Google Scholar PubMed

24. Neuparth MJ, Proença JB, Santos-Silva A, Coimbra S. Adipokines, oxidized low-density lipoprotein, and C-reactive protein levels in lean, overweight, and obese Portuguese patients with type 2 diabetes. ISRN Obesity 2013. Available at: http://dx.doi.org/10.1155/2013/142097.10.1155/2013/142097Search in Google Scholar PubMed PubMed Central

25. Akinci A, Celiker A, Baykal E, Teziç T. Heart rate variability in diabetic children: sensitivity of the time and frequency domain methods. Pediatr Cardiol 1993;14:140–6.10.1007/BF00795641Search in Google Scholar

26. Khandoker AH, Jelinek HF, Palaniswam M. Identifying diabetic patients with cardiac autonomic neuropathy by heart rate complexity analysis. Biomed Eng Online 2009;8:3.10.1186/1475-925X-8-3Search in Google Scholar

27. Chen HS, Wu TE, Jap TS, Lee SH, Wang ML, et al. Decrease heart rate variability but preserve postural blood pressure change in type 2 diabetes with microalbuminuria. J Clin Med Assoc 2006;69:254–8.10.1016/S1726-4901(09)70252-7Search in Google Scholar

28. Gandhi RA, Marques JL, Selvarajah D, Emery CJ, Tesfaye S. Painful diabetic neuropathy is associated with greater autonomic dysfunction than painless diabetic neuropathy. Diabetes Care 2010;33:1585–90.10.2337/dc09-2314Search in Google Scholar

29. Spallone V, Menzinger G. Diagnosis of cardiovascular autonomic, neuropathy in diabetes. Diabetes 1997;46:S67.10.2337/diab.46.2.S67Search in Google Scholar

30. Johnston SC, Easton JD. Are patients with acutely recovered cerebral ischemia more unstable? Stroke 2003;4:2446.10.1161/01.STR.0000090842.81076.68Search in Google Scholar

31. Järvisalo MJ, Raitakari M, Toikka JO, Putto-Laurila A, Rontu R, et al. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation 2004;109:1750–5.10.1161/01.CIR.0000124725.46165.2CSearch in Google Scholar

32. Singh TP, Groehn H, Kazmers A. Vascular function and carotid intimal medial thickness in children with insulin-dependent diabetes mellitus. J Am Coll Cardiol 2003;41: 661–5.10.1016/S0735-1097(02)02894-2Search in Google Scholar

33. Bozaoglu K, Bolton K, McMillan J, Zimmet P, Jowett J, et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome. Endocrinology 2007;148:4687–94.10.1210/en.2007-0175Search in Google Scholar PubMed

34. Zabel BA, Silverio AM, Butcher EC, Chemokine-like receptor 1 expression and chemerin-directed chemotaxis distinguish plasmacytoid from myeloid dendritic cells in human blood. J Immunol 2005;174:244–51.10.4049/jimmunol.174.1.244Search in Google Scholar PubMed

35. Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, et al. Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem 2007;282:28175–88.10.1074/jbc.M700793200Search in Google Scholar PubMed

36. Yang M, Yang G, Dong J, Liu Y, Zong H, et al. Elevated plasma levels of chemerin in newly diagnosed type 2 diabetes mellitus with hypertension. J Investig Med 2010;58:883–6.10.2310/JIM.0b013e3181ec5db2Search in Google Scholar

37. Müssig K, Staiger H, Machicao F, Thamer C, Machann J, et al. RARRES2, encoding the novel adipokine chemerin, is a genetic determinant of disproportionate regional body fat distribution: a comparative magnetic resonance imaging study. Metabolism 2009;58:519–24.10.1016/j.metabol.2008.11.011Search in Google Scholar PubMed

38. Hashemi M, Rezaei H, Eskandari-Nasab E, Kaykhaei MA, Zakeri Z, et al. Association between chemerin rs17173608 and vaspin rs2236242 gene polymorphisms and the metabolic syndrome: a preliminary report. Gene 2012;510:113–7.10.1016/j.gene.2012.08.048Search in Google Scholar PubMed

39. Fülöp P, Seres I, Lőrincz H, Harangi M, Somodi S. Association of chemerin with oxidative stress, inflammation and classical adipokines in non-diabetic obese patients. J Cell Molec Med 2014;18:1313–20.10.1111/jcmm.12282Search in Google Scholar PubMed PubMed Central

40. Hu W, Feng P. Elevated serum chemerin concentrations are associated with renal dysfunction in type 2 diabetic patients. Diabetes Res Clin Pract 2011;91:159–63.10.1016/j.diabres.2010.11.016Search in Google Scholar PubMed

41. Lee MK, Chu SH, Lee DC, An KY, Park JH, et al. The association between chemerin and homeostasis assessment of insulin resistance at baseline and after weight reduction via lifestyle modifications in young obese adults. Clin Chimica Acta 2013;26:109–15.10.1016/j.cca.2013.02.017Search in Google Scholar PubMed

42. Wittamer V, Franssen JD, Vulcano M, Mirjolet JF, Le Poul E, et al. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J Exp Med 2003;198:977–85.10.1084/jem.20030382Search in Google Scholar PubMed PubMed Central

43. El-Mesallamy HO, Kassem DH, El-Demerdash E, Amin AI. Vaspin and visfatin/Nampt are interesting interrelated adipokines playing a role in the pathogenesis of type 2 diabetes mellitus. Metab Clin Exp 2011;60:63–70.10.1016/j.metabol.2010.04.008Search in Google Scholar PubMed

44. Gulcelik NE, Karakaya J, Gedik A, Usman A, Gurlek A. Serum vaspin levels in type 2 diabetic women in relation to microvascular complications. Eur J Endocrinol 2009;160:65–70.10.1530/EJE-08-0723Search in Google Scholar PubMed

45. Hida K, Wada J, Eguchi J, Zhang H, Baba M, et al. Visceral adipose tissue-derived serine protease inhibitor: a unique insulin sensitizing adipocytokine in obesity. Proc Natl Acad Sci USA 2005;102:10610–15.10.1073/pnas.0504703102Search in Google Scholar

46. Klöting N, Berndt J, Kralisch S, Kovacs P, Fasshauer M, et al. Vaspin gene expression in human adipose tissue: association with obesity and type 2 diabetes. Biochem Biophys Res Commun 2006;339:430–6.10.1016/j.bbrc.2005.11.039Search in Google Scholar

47. Tan BK, Heutling D, Chen J, Farhatullah S, Adya R, et al. Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance. Diabetes 2008;57:1501–7.10.2337/db08-0127Search in Google Scholar

48. Körner A, Neef M, Friebe D, Erbs S, Kratzsch J, et al. Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children. Int J Obes (London) 2011;35:578–86.10.1038/ijo.2010.196Search in Google Scholar

49. Akcay A, Akar M, Demirel G, Canpolat FE, Erdeve O, et al. Umbilical cord and fifth-day serum vaspin concentrations in small-, appropriate-, and large-for-gestational age neonates. J Pediatr Endocrinol Metab 2013;26:635–8.10.1515/jpem-2012-0111Search in Google Scholar

50. Sibal L, Agarwal SC, Schwedhelm E, Lüneburg N, Böger RH, et al. A study of endothelial function and circulating asymmetric dimethylarginine levels in people with type 1 diabetes without macrovascular disease or microalbuminuria. Cardiovasc Diabetol 2009;8:27.10.1186/1475-2840-8-27Search in Google Scholar

51. Heilman K, Zilmer M, Zilmer K, Kool P, Tillmann V. Elevated plasma adiponectin and decreased plasma homocysteine and asymmetric dimethylarginine in children with type 1 diabetes. Scand J Clin Lab Invest 2009;69:85–91.10.1080/00365510802419454Search in Google Scholar

52. Päivä H, Lehtimäki T, Laakso J, Ruokonen I, Rantalaiho V, et al. Plasma concentrations of asymmetric- dimethyl-arginine in type 2 diabetes associate with glycemic control and glomerular filtration rate but not with risk factors of vasculopathy. Metabolism 2003;52:303–7.10.1053/meta.2003.50048Search in Google Scholar

53. Altinova AE, Arslan M, Sepici-Dincel A, Akturk M, Altan N, et al. Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations. J Clin Endocrinol Metabol 2007;92:1881–5.10.1210/jc.2006-2643Search in Google Scholar

54. Boger RH, Zoccali C. ADMA: a novel risk factor that explains excess cardiovascular event rate in patients with end-stage renal disease. Atherosclerosis 2003;4:23–8.10.1016/S1567-5688(03)00030-8Search in Google Scholar

55. Tarnow L, Hovind P, Teerlink T, Stehouwer CD, Parving HH. Elevated plasma asymmetric dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in type 1 diabetes. Diabetes Care 2004;27:765–9.10.2337/diacare.27.3.765Search in Google Scholar PubMed

Received: 2014-5-22
Accepted: 2014-8-7
Published Online: 2014-9-11
Published in Print: 2015-3-1

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