Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter February 18, 2015

Resistin and right ventricular function in children with recently diagnosed type-1 diabetes mellitus: a case control study

Mohammed A. Al-Biltagi ORCID logo, Osama A. Tolba, Wegdan Mawlana, Abdallah Abd El Hamed and May Ghazy

Abstract

Background: Resistin is an adipocyte-derived signaling polypeptide described in adipose tissue, which acts as a metabolic link between inflammation and atherosclerosis. This study aimed to assess the relation between right ventricular (RV) function assessed by echocardiography and resistin levels in recently diagnosed type-1 diabetic children.

Methods: The study was conducted as a prospective cohort study and it included 30 children with type-1 diabetes mellitus as a patient group and 30 healthy children matched for age and sex as controls. It evaluated RV functions by tissue Doppler imaging, speckle tracking imaging, and real-time three-dimensional echocardiography (RT3DE), as well as assessing resistin serum level using enzyme-linked immunosorbent assay.

Results: The left ventricle (LV) showed no significant difference between the two groups in E/A ratio across the mitral valve, ejection fraction, and S wave mitral annulus. However, it showed significant decrease in the E′/A′ wave of mitral annulus, impairment of LV myocardial performance index (MPI), and decrease in LV EF measured by RT3DE in diabetic patients compared to the control group. Significant differences in the mean value of tricuspid annular systolic excursion (TASE), pulmonary artery pressure, longitudinal systolic strain (RV LSS), MPI, and RV ejection fraction were observed between the studied groups. Yet, no significant differences in E/A ratio and S value were observed between the two groups. Significant positive correlation of resistin level with age of studied group and significant negative correlation of resistin with both TASE and RV LSS values were also observed.

Conclusion: We confirmed the presence of subclinical RV systolic and diastolic dysfunction in type-1 diabetic children with positive correlation between resistin level and RV dysfunction among them.


Corresponding author: Mohammed A. Al-Biltagi, MD, PhD, Associate Professor of Paediatrics, Faculty of Medicine, Pediatric Department, Tanta University, El Bahr Str, Tanta 31527, Egypt, Phone: +97-33-9545472, Fax: +20-40-2213543, E-mail: .

References

1. Mulestein JB, Anderson JL, Horne BD. Effect of fasting glucose levels on mortality rate in patients with and without diabetes mellitus and coronary artery disease undergoing percutaneous coronary intervention. Am Heart J 2003;146:351–8.10.1016/S0002-8703(03)00235-7Search in Google Scholar

2. Ghio S, Gavazzi A, Campana C, Inserra O, KlersyC, et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 2001;37:183–8.10.1016/S0735-1097(00)01102-5Search in Google Scholar

3. Meluzin J, Spinarová L, Dusek L, Toman J, Hude P, et al. Prognostic importance of the right ventricular function assessed by Doppler tissue imaging. Eur J Echocardiogr 2003;4:262–71.10.1016/S1525-2167(02)00171-3Search in Google Scholar

4. Karamitsos TD, Karvounis HI, Dalamanga EG, Papadopoulos CE, Didangellos TP, et al. Early diastolic impairment of diabetic heart: The significance of right ventricle. Int J Cardiol 2007;114: 218–23.10.1016/j.ijcard.2006.02.003Search in Google Scholar PubMed

5. Grapsa J, Dawson D, Nihoyannopoulos P. Assessment of right ventricular structure and function in pulmonary hypertension. J Cardiovasc Ultrasound 2011;19:115–25.10.4250/jcu.2011.19.3.115Search in Google Scholar PubMed PubMed Central

6. Kim KH, Lee K, Moon YS. A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 2001;276:11252–6.10.1074/jbc.C100028200Search in Google Scholar PubMed

7. Reilly MP, Lehrke M, Wolfe LM, Rohatgi A, Lazar M, et al. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 2005;111:932–9.10.1161/01.CIR.0000155620.10387.43Search in Google Scholar PubMed

8. Jung HS, Park KH, Cho YM, Chungb SS, Cho HJ, et al. Resistin is secreted from macrophages in atheromas and promotes atherosclerosis. Cardiovasc Res 2006;69:76–85.10.1016/j.cardiores.2005.09.015Search in Google Scholar PubMed

9. Weikert C, Berger K, Heidemann C, Bergmann MM, Hoffmann K, et al. Joint effects of risk factors for stroke and transient ischemic attack in a German population: the EPIC Potsdam Study. J Neurol 2007;254:315–21.10.1007/s00415-006-0358-xSearch in Google Scholar PubMed

10. Pischon T, Mohlig M, Hoffmann K, Spranger J, Weikert C, et al. Comparison of relative an attributable risk of myocardial infarction and stroke according to C-reactive protein and low-density lipoprotein cholesterol levels. Eur J Epidemiol 2007;22:429–38.10.1007/s10654-007-9141-2Search in Google Scholar PubMed

11. Jamaluddin MS, Weakley SM, Yao Q, Chen C. Resistin functional roles and therapeutic considerations for cardiovascular disease. Br J Pharmacol 2012;165:622–32.10.1111/j.1476-5381.2011.01369.xSearch in Google Scholar

12. Costandi J, Melone M, Zhao A, Rashid S. Human resistin stimulates hepatic overproduction of atherogenicApoB-containing lipoprotein particles by enhancing ApoB stability and impairing intracellular insulin signaling. Circ Res 2011;108:727–42.10.1161/CIRCRESAHA.110.238949Search in Google Scholar

13. Momiyama Y, Ohmori R, Uto-Kondo H, Tanaka N, Kato R, et al. Serum resistin levels and cardiovascular events in patients undergoing percutaneous coronary intervention. J Atheroscler Thromb 2011;18:108–14.10.5551/jat.6023Search in Google Scholar

14. Picard MH, Adams D, Bierig SM, Dent JM, Douglas PS, et al. American Society of Echocardiography recommendations for quality echocardiography laboratory operations. J Am Soc Echocardiogr 2011;24:1–10.10.1016/j.echo.2010.11.006Search in Google Scholar

15. Cevik Y, Değertekin M, Başaran Y, Turan F, Pektaş O. A new echocardiographic formula to calculate ejection fraction by using systolic excursion of mitral annulus. Angiology 1995;46:157–63.10.1177/000331979504600210Search in Google Scholar

16. Giardini A. Limitations inherent to the simplified Bernoulli equation explain the inaccuracy of Doppler echocardiographic estimates of pulmonary artery pressures in patients with pulmonary hypertension. Chest 2011;140:270–1.10.1378/chest.11-0344Search in Google Scholar

17. Speiser U, Hirschberger M, Pilz G, Heer T, Sievers B, et al. Tricuspid annular plane systolic excursion assessed using MRI for semi-quantification of right ventricular ejection fraction. Brit J Radiol 2012;85:e716–21.10.1259/bjr/50238360Search in Google Scholar

18. Horton KD, Meece RW, Hill JC. Assessment of the right ventricle by echocardiography: a primer for cardiac sonographers. J Am Soc Echocardiogr 2009;22:776–92.10.1016/j.echo.2009.04.027Search in Google Scholar

19. Al-Biltagi M, Serag AR, Hefidah MM, Mabrouk MM. Evaluation of cardiac functions with Doppler echocardiography in children with Down syndrome and anatomically normal heart. Cardiol Young 2013;23:174–80.10.1017/S1047951112000613Search in Google Scholar

20. Tei C, Dujardin KS, Hodge DO, Bailey KR, McGoon MD, et al. Doppler echocardiographic index for assessment of global right ventricular function. J Am Soc Echocardiogr 1996;9:838–47.10.1016/S0894-7317(96)90476-9Search in Google Scholar

21. Langeland S, D’hooge J, Wouters PF, Leather HA, Claus P, et al. Experimental validation of a new ultrasound method for the simultaneous assessment of radial and longitudinal myocardial deformation independent of insonation angle. Circulation 2005;112:2157–62.10.1161/CIRCULATIONAHA.105.554006Search in Google Scholar PubMed

22. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63.10.1016/j.echo.2005.10.005Search in Google Scholar PubMed

23. Suffoletto MS, Dohi K, Cannesson M, Saba S, Gorcsan J 3rd. Novel speckle-tracking radial strain from routine black-and-white echocar-diographic images to quantify dyssynchrony and predict response to cardiac resynchronization therapy. Circulation 2006;113:960–8.10.1161/CIRCULATIONAHA.105.571455Search in Google Scholar PubMed

24. Paterson AD, Rutledge BN, Cleary PA, Lachin JM, Crow RS, et al. The effect of intensive diabetes treatment on resting heart rate in type 1 diabetes: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Diabetes Care 2007;30:2107–12.10.2337/dc06-1441Search in Google Scholar PubMed PubMed Central

25. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activating signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 2002;23:599–622.10.1210/er.2001-0039Search in Google Scholar PubMed

26. Taube A, Schlich R, Sell H, Eckardt K, Eckel J. Inflammation and metabolic dysfunction: links to cardiovascular diseases. Am J Physiol Heart Circ Physiol 2012;302:H2148–65.10.1152/ajpheart.00907.2011Search in Google Scholar PubMed

27. Verrijn 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

28. Yazıcı D, Yavuz D, Öğünç AV, Sirikçi Ö, Toprak A, et al. Serum adipokine levels in type 1 diabetic patients: association with carotid intima media thickness. Metab Syndr Relat Disord 2012;10:26–31.10.1089/met.2011.0052Search in Google Scholar PubMed

29. Rivero A, Mora C, Muros M, García J, Herrera H, et al. Pathogenic perspectives for the role of inflammation in diabetic nephropathy. Clin Sci (Lond) 2009;116:479–92.10.1042/CS20080394Search in Google Scholar PubMed

30. Thomopoulos C, Daskalaki M, Papazachou O, Rodolakis N, Bratsas A, et al. Association of resistin and adiponectin with different clinical blood pressure phenotypes. J Hum Hypertens 2011;25:38–46.10.1038/jhh.2010.22Search in Google Scholar PubMed

31. Schäffler A, Büchler C, Müller-Ladner U, Herfarth H, Ehling A, et al. Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus. Horm Metab Res 2004;36:702–7.10.1055/s-2004-826015Search in Google Scholar PubMed

32. Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin – the classical, resistin – the controversical, adiponectin – the promising, and more to come. Best Pract Res Clin Endocrinol Metab 2005;19:525–46.10.1016/j.beem.2005.07.008Search in Google Scholar PubMed

33. Bleeker GB, Steendijk P, Holman ER, Yu CM, Breithardt OA, et al. Assessing right ventricular function: the role of echocardiography and complementary technologies. Heart 2006;92(Suppl 1):i19–26.10.1136/hrt.2005.082503Search in Google Scholar PubMed PubMed Central

34. Lindqvist P, Calcutteea A, Henein M. Echocardiography in the assessment of right heart function. Eur J Echocardiogr 2008;9:225–34.Search in Google Scholar

35. Sheu JJ, Chang LT, Chiang CH, Sun CK, Chang NK, et al. Impact of diabetes on cardiomyocyte apoptosis and connexin43 gap junction integrity: role of pharmacological modulation. Int Heart J 2007;48:233–45.10.1536/ihj.48.233Search in Google Scholar PubMed

36. Elshahed GS, El-Beblawy NS, Kamal NS, Kamal HM, Ismail MF, et al. Evaluation of right and left ventricular systolic and diastolic function in patients with type I using echocardiography and tissue Doppler imaging. Suez Canal Univ Med J 2008;11:228–38.Search in Google Scholar

37. Ho CY, Solomon SD. A clinician’s guide to tissue Doppler imaging. Circulation 2006;113:e396–8.10.1161/CIRCULATIONAHA.105.579268Search in Google Scholar PubMed

38. Hsiao SH, Lin SK, Wang WC, Yang SH, Gin PL, et al. Severe tricuspid regurgitation shows significant impact in the relationship among peak systolic tricuspid annular velocity, tricuspid annular plane systolic excursion, and right ventricular ejection fraction. J Am Soc Echocardiogr 2006;19:902–10.10.1016/j.echo.2006.01.014Search in Google Scholar PubMed

39. Abdelaziz AA, Daoud EM. Assessment of right ventricular function by myocardial performance index in diabetic patients. Egyptian Heart J 2011;63:175–81.10.1016/j.ehj.2011.08.001Search in Google Scholar

40. Van den Bergh A, Flameng W, Herijgers P. Type II diabetic mice exhibit contractile dysfunction but maintain cardiac output by favourable loading conditions. Eur J Heart Fail 2006;8:777–83.10.1016/j.ejheart.2006.03.001Search in Google Scholar PubMed

41. Hadi HA, Suwaidi JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag 2007;3:853–76.Search in Google Scholar

42. Cella G, Bellotto F, Tona F, Sbarai A, Mazzaro G, et al. Plasma markers of endothelial dysfunction in pulmonary hypertension. Chest 2001;120:1226–30.10.1378/chest.120.4.1226Search in Google Scholar PubMed

43. Lopez-Lopez JG, Moral-Sanz J, Frazziano G, Gomez-Villalobos MJ, Flores-Hernandez J, et al. Diabetes induces pulmonary artery endothelial dysfunction by NADPH oxidase induction. Am J Physiol Lung Cell Mol Physiol 2008;295:L727–32.10.1152/ajplung.90354.2008Search in Google Scholar PubMed

44. Parsaee M, Bahmanziari P, Ardeshiri M, Esmaeilzadeh M. Obvious or subclinical right ventricular dysfunction in diabetes mellitus (type II): an echocardiographic tissue deformation study. J Tehran Heart Cent 2012;7:177–81.Search in Google Scholar

45. Vittos O, Toana B, Vittos A. Biomarkers and their involvement in the early diagnosis of right ventricular dysfunction in type 2 diabetes mellitus. J Med Life 2012;5:74–8.Search in Google Scholar

46. Gaber R, Kotb NA. Early diagnosis of right ventricular dysfunction in type II diabetes mellitus: value of 3 dimensional strain/strain rate. Heart Mirror J 2010;4:46–51.Search in Google Scholar

47. Gerber M, Boettner A, Seidel B, Lammert A, Bär J, et al. Serum resistin levels of obese and lean children and adolescents: biochemical analysis and clinical relevance. J Clin Endocrinol Metab 2005;90:4503–9.10.1210/jc.2005-0437Search in Google Scholar PubMed

48. Al-Suhaimi AA, Al-Kulaifi FM, Ravinayagam V, Al-Qahtani MH. Serum Adipocytokines, Metabolic and Immunological Correlations in Type 1 Diabetes mellitus (T1DM) Children. Open Endocrinol J 2012;6:110–6.10.2174/1874216501106010110Search in Google Scholar

49. Geyikli I, Keskin M, Kör Y, Akan M. Increased resistin serum concentrations in patients with type 1 diabetes mellitus. J Clin Res Pediatr Endocrinol 2013;5:189–93.10.4274/Jcrpe.1072Search in Google Scholar PubMed PubMed Central

50. Osawa H, Doi Y, Makino H, Ninomiya T, Yonemoto K, et al. Diabetes and hypertension markedly increased the risk of ischemic stroke associated with high serum resistin concentration in a general Japanese population: the Hisayama Study. Cardiovasc Diabetol 2009;8:60.10.1186/1475-2840-8-60Search in Google Scholar PubMed PubMed Central

51. Devereux RB, Roman MJ, Paranicas M, O’Grady MJ, Lee ET, et al. Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 2000;101:2271–6.10.1161/01.CIR.101.19.2271Search in Google Scholar PubMed

52. Kosmala W, Colonna P, Przewlocka-Kosmala M, Mazurek W. Right ventricular dysfunction in asymptomatic diabetic patients. Diabetes Care 2004;27:2736–8.10.2337/diacare.27.11.2736Search in Google Scholar PubMed

53. Kreçki R, Krzemińska-Pakuła M, Peruga JZ, Szcześniak P, Lipiec P, et al. Elevated resistin opposed to adiponectin or angiogenin plasma levels as a strong, independent predictive factor for the occurrence of major adverse cardiac and cerebrovascular events in patients with stable multivessel coronary artery disease over 1-year follow-up. Med Sci Monit 2011;17:CR26–32.10.12659/MSM.881325Search in Google Scholar PubMed PubMed Central

54. McManus DD, Lyass A, Ingelsson E, Massaro JM, Meigs JB, et al. Relations of circulating resistin and adiponectin and cardiac structure and function: the Framingham Offspring Study. Obesity (Silver Spring) 2012;20:1882–6.10.1038/oby.2011.32Search in Google Scholar PubMed PubMed Central

55. Kim M, Oh JK, Sakata S, Liang I, Park W, et al. Role of resistin in cardiac contractility and hypertrophy. J Mol Cell Cardiol 2008;45:270–80.10.1016/j.yjmcc.2008.05.006Search in Google Scholar PubMed PubMed Central

56. Bobbert P, Jenke A, Bobbert T, Kühl U, Rauch U, et al. High leptin and resistin expression in chronic heart failure: adverse outcome in patients with dilated and inflammatory cardiomyopathy. Eur J Heart Fail 2012;14:1265–75.10.1093/eurjhf/hfs111Search in Google Scholar PubMed

Received: 2014-6-19
Accepted: 2014-12-17
Published Online: 2015-2-18
Published in Print: 2015-3-1

©2015 by De Gruyter