Cathelicidin as a marker for subclinical cardiac changes and microvascular complications in children and adolescents with type 1 diabetes

Randa M. Matter; Marwa Waheed A. Nasef; Reham M. ShibaAlhamd; Rasha Adel Thabet

doi:10.1515/jpem-2022-0421

Article

Cathelicidin as a marker for subclinical cardiac changes and microvascular complications in children and adolescents with type 1 diabetes

Randa M. Matter , Marwa Waheed A. Nasef , Reham M. ShibaAlhamd and Rasha Adel Thabet

Published/Copyright: October 6, 2022

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information Explore this Subject

From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 12

Abstract

Objectives

To detect cathelicidin levels in pediatric patients with type 1 diabetes (T1D) as a potential marker for diabetic vascular complications and to assess its relation to diastolic dysfunction as an index for subclinical macrovasculopathy.

Methods

Totally, 84 patients with T1D were categorized into three groups; newly diagnosed diabetes group (28 patients with a mean age of 12.38 ± 1.99) years, T1D without microvascular complications group (28 patients with a mean age of 13.04 ± 2.27), and T1D with microvascular complications group (28 patients with a mean age of 13.96 ± 2.30). Patients were evaluated using serum cathelicidin levels and echocardiography.

Results

Total cholesterol, microalbuminuria, and cathelicidin levels were significantly higher in patients with microvascular complications when compared to the other two groups (p<0.001). Additionally, carotid intima-media thickness (CIMT) echocardiography values and diastolic functions were significantly higher in patients with complications (p<0.001). Cathelicidin was positively correlated to the duration of diabetes (r=0.542, p<0.001), total cholesterol (r=0.346, p=0.001), recurrence of hypoglycemia (r=0.351, p=0.001), recurrence of diabetes ketoacidosis (r=0.365, p=0.001), CIMT (r=0.544, p<0.001), and E/A values (r=0.405, p<0.001).

Conclusions

Serum cathelicidin levels can be used as an early marker for the occurrence and progression of vascular complications in patients with T1D.

Keywords: cathelicidin; CIMT; T1D vascular complications

Corresponding author: Rasha Adel Thabet, Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt, Phone: +20 01003702944, E-mail: Rasha-thabet@hotmail.com

Research funding: None declared.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: This study was approved by the local ethical committee (FWA00017585 FMASU MS 61/2020) in the Declaration of Helsinki before the start of patients’ enrollment.

References

1. Donaghue, KC, Marcovecchio, ML, Wadwa, RP, Chew, EY, Wong, TY, Calliari, LE, et al.. ISPAD clinical practice consensus guidelines 2018: microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes 2018;19(27 Suppl):262–74. https://doi.org/10.1111/pedi.12742.Search in Google Scholar PubMed PubMed Central

2. Litwak, L, Goh, SY, Hussein, Z, Malek, R, Prusty, V, Khamseh, ME. Prevalence of diabetes complications in people with type 2 diabetes mellitus and its association with baseline characteristics in the multinational A1chieve study. Diabetol Metab Syndrome 2013;5:57. https://doi.org/10.1186/1758-5996-5-57.Search in Google Scholar PubMed PubMed Central

3. Alicic, RZ, Rooney, MT, Tuttle, KR. Diabetic kidney disease. Clin J Am Soc Nephrol 2017;12:2032–45.https://doi.org/10.2215/CJN.11491116.Search in Google Scholar PubMed PubMed Central

4. Rask-Madsen, C, King, GL. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab 2013;17:20–33. https://doi.org/10.1016/j.cmet.2012.11.012.Search in Google Scholar PubMed PubMed Central

5. Ozdemir, O, Koksoy, A, Bulus, A, Andiran, N, Yagli, E. The effects of type 1 diabetes mellitus on cardiac functions in children: evaluation by conventional and tissue Doppler echocardiography. J Pediatr Endocrinol Metab 2016;29:1389–95.https://doi.org/10.1515/jpem-2016-0222.Search in Google Scholar PubMed

6. Hassan Ayman, KM, Mahmoud, AA, Abdel-Mageed, EA, Marwa, S, Soliman Mona, M, Kishk Yehia, T. Correlation between left ventricular diastolic dysfunction and dyslipidaemia in asymptomatic patients with new-onset type 2 diabetes mellitus. Egypt J Intern Med 2021;33:8.https://doi.org/10.1186/s43162-021-00037-0.Search in Google Scholar

7. Cristelo, C, Machado, A, Sarmento, B, Gama, FM. The roles of vitamin D and cathelicidin in type 1 diabetes susceptibility. Endocr Connect 2021;10:R1–12. https://doi.org/10.1530/EC-20-0484.Search in Google Scholar PubMed PubMed Central

8. El-Ashmawy, HM, Ahmed, AM. Serum cathelicidin as a marker for diabetic nephropathy in patients with type 1 diabetes. Diabetes/Metab Res Rev 2018;34:e3057. https://doi.org/10.1002/dmrr.3057.Search in Google Scholar PubMed

9. El-Nofely, AA. Anthropometry of Egyptians from birth till senility sociology research. Cairo: Centre-Cairo University Press; 2012. 53–85 pp.Search in Google Scholar

10. Wilkinson, CP, Ferris, FL3rd, Klein, RE, Lee, PP, Agardh, CD, Davis, M, et al.., Global Diabetic Retinopathy Project Group. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003;110:1677–82. https://doi.org/10.1016/s0161-6420(03)00475-5.Search in Google Scholar PubMed

11. Weintrob, N, Amitay, I, Lilos, P, Shalitin, S, Lazar, L, Josefsberg, Z. Bedside neuropathy disability score compared to quantitative sensory testing for measurement of diabetic neuropathy in children, adolescents, and young adults with type 1 diabetes. J Diabetes Its Complications 2007;21:13–9. https://doi.org/10.1016/j.jdiacomp.2005.11.002.Search in Google Scholar PubMed

12. England, JD, Gronseth, GS, Franklin, G, Miller, RG, Asbury, AK, Carter, GT, et al.. Distal symmetric polyneuropathy: a definition for clinical research: report of the American academy of neurology, the American association of electrodiagnostic medicine, and the American academy of physical medicine and rehabilitation. Neurology 2005;64:199–207. https://doi.org/10.1212/01.wnl.0000149522.32823.ea.Search in Google Scholar PubMed

13. Lopez, L, Colan, SD, Frommelt, PC, Ensing, GJ, Kendall, K, Younoszai, AK, et al.. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the pediatric measurements writing group of the American society of echocardiography pediatric and congenital heart disease council. J Am Soc Echocardiogr 2010;23:465–95. https://doi.org/10.1016/j.echo.2010.03.019.Search in Google Scholar PubMed

14. Baroncini, LA, Sylvestre Lde, C, Pecoits Filho, R. Assessment of intima-media thickness in healthy children aged 1 to 15 years. Arq Bras Cardiol 2016;106:327–32. https://doi.org/10.5935/abc.20160030.Search in Google Scholar PubMed PubMed Central

15. Breton, MD, Patek, SD, Lv, D, Schertz, E, Robic, J, Pinnata, J, et al.. Continuous glucose monitoring and insulin informed advisory system with automated titration and dosing of insulin reduces glucose variability in type 1 diabetes mellitus. Diabetes Technol Therapeut 2018;20:531–40. https://doi.org/10.1089/dia.2018.0079.Search in Google Scholar PubMed PubMed Central

16. Runge, AS, Kennedy, L, Brown, AS, Dove, AE, Levine, BJ, Koontz, SP, et al.. Does time-in-range matter? Perspectives from people with diabetes on the success of current therapies and the drivers of improved outcomes. Clin Diabetes 2018;36:112–9. https://doi.org/10.2337/cd17-0094.Search in Google Scholar PubMed PubMed Central

17. Al-Agha, AE, Alafif, M, Abd-Elhameed, IA. Glycemic control, complications, and associated autoimmune diseases in children and adolescents with type 1 diabetes in Jeddah, Saudi Arabia. Saudi Med J 2015;36:26. https://doi.org/10.15537/smj.2015.1.9829.Search in Google Scholar PubMed PubMed Central

18. Uruska, A, Michalska, A, Ostrowska, J, Skonieczna, P, Lipski, D, Uruski, P, et al.. Is cathelicidin a novel marker of diabetic microangiopathy in patients with type 1 diabetes? Clin Biochem 2017;50:1110–4. https://doi.org/10.1016/j.clinbiochem.2017.09.023.Search in Google Scholar PubMed

19. Virk, SA, Donaghue, KC, Cho, YH, Benitez-Aguirre, P, Hing, S, Pryke, A, et al.. Association between HbA1c variability and risk of microvascular complications in adolescents with type 1 diabetes. J Clin Endocrinol Metab 2016;101:3257–63. ‏https://doi.org/10.1210/jc.2015-3604.Search in Google Scholar PubMed

20. Schauber, J, Rieger, D, Weiler, F, Wehkamp, J, Eck, M, Fellermann, K, et al.. Heterogeneous expression of human cathelicidin hCAP18/LL-37 in inflammatory bowel diseases. Eur J Gastroenterol Hepatol 2006;18:615–21. https://doi.org/10.1097/00042737-200606000-00007.Search in Google Scholar PubMed

21. Brownlee, M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005;54:1615–25. https://doi.org/10.2337/diabetes.54.6.1615.Search in Google Scholar PubMed

22. Yazici, D, Yavuz, DG, Toprak, A, Deyneli, O, Akalin, S. Impaired diastolic function and elevated Nt-proBNP levels in type 1 diabetic patients without overt cardiovascular disease. Acta Diabetol 2013;50:155–61. https://doi.org/10.1007/s00592-010-0235-z.Search in Google Scholar PubMed

23. Suran, D, Sinkovic, A, Naji, F. Tissue Doppler imaging is a sensitive echocardiographic technique to detect subclinical systolic and diastolic dysfunction of both ventricles in type 1 diabetes mellitus. BMC Cardiovasc Disord 2016;16:1–10. https://doi.org/10.1186/s12872-016-0242-2.Search in Google Scholar PubMed PubMed Central

24. Jensen, MT, Sogaard, P, Andersen, HU, Bech, J, Hansen, TF, Biering, T, et al.. Prevalence of systolic and diastolic dysfunction in patients with type 1 diabetes without known heart disease: the Thousand & 1 Study. Diabetologia 2014;57:672–80. https://doi.org/10.1007/s00125-014-3164-5.Search in Google Scholar PubMed

25. Redfield, MM, Jacobsen, SJ, Burnett, JC, Mahoney, DW, Bailey, KR, Rodeheffer, RJ, et al.. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003;289:194–202. https://doi.org/10.1001/jama.289.2.194.Search in Google Scholar PubMed

26. Gul, K, Celebi, AS, Kacmaz, F, Ozcan, OC, Ustun, I, Berker, D, et al.. Tissue Doppler imaging must be performed to detect early left ventricular dysfunction in patients with type 1 diabetes mellitus. Eur J Echocardiogr 2009;10:841–6. https://doi.org/10.1093/ejechocard/jep086.Search in Google Scholar PubMed

27. Konduracka, E, Gackowski, A, Rostoff, P, Galicka-Latala, D, Frasik, W, Piwowarska, W. Diabetes-specific cardiomyopathy in type 1 diabetes mellitus: no evidence for its occurrence in the era of intensive insulin therapy. Eur Heart J 2007;28:2465–71. https://doi.org/10.1093/eurheartj/ehm361.Search in Google Scholar PubMed

28. Khattab, AA, Soliman, MA. Biventricular function and glycemic load in type 1 diabetic children: Doppler tissue-imaging study. Pediatr Cardiol 2015;36:423–31. https://doi.org/10.1007/s00246-014-1030-3.Search in Google Scholar PubMed

29. Wu, Y, Zhang, Y, Zhang, J, Zhai, T, Hu, J, Luo, H, et al.. Cathelicidin aggravates myocardial ischemia/reperfusion injury via activating TLR4 signaling and P2X7R/NLRP3 inflammasome. J Mol Cell Cardiol 2020;139:75–86. https://doi.org/10.1016/j.yjmcc.2019.12.011.Search in Google Scholar PubMed

30. Benachour, H, Zaiou, M, Samara, A. Association of human cathelicidin (hCAP-18/LL-37) gene expression with cardiovascular disease risk factors. Nutr, Metab Cardiovasc Dis 2009;19:720–8. https://doi.org/10.1016/j.numecd.2009.01.001.Search in Google Scholar PubMed

Received: 2022-08-24

Accepted: 2022-09-17

Published Online: 2022-10-06

Published in Print: 2022-12-16

You are currently not able to access this content.

Articles in the same Issue

https://doi.org/10.1515/jpem-2022-0421

Keywords for this article

cathelicidin; CIMT; T1D vascular complications