Skip to main content
SpringerLink
Log in

Early Markers of Atherosclerosis in Children and Adolescents with Type 1 Diabetes Mellitus

  • Original Article
  • Published:
Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Objectives

To detect early atherosclerosis changes using flow-mediated dilation (FMD) of the brachial artery, carotid intima–media thickness (CIMT), inflammatory markers (hs-CRP, IL-6), and endothelial markers (sICAM and sVCAM).

Methods

The authors recruited 4 to 18-y-old children with type 1 diabetes mellitus (T1DM) and age- and sex-matched normal children, excluding those with familial hypercholesterolemia, syndromic disorders, and cardiovascular disease. CIMT and FMD were measured in both the groups. Biomarkers hs-CRP, IL-6, sICAM, and sVCAM, were analyzed in the T1DM group.

Results

Forty T1DM children and 40 controls with 27 (67.5%) girls were enrolled in each group. The mean age was 9.68 y. The T1DM group had 4 (10%) obese and 4 (10%) overweight children. Among cases, 9 (22.5%) had diabetes for > 5 y, 24 (60%) required daily insulin between 0.8 and 1.2 IU/kg/d and 26 (65%) had HbA1c > 10 g/dL. The CIMT values were significantly higher in cases (0.69 mm) than in controls (0.59 mm); 29 (72.5%) cases had abnormal combined CIMT values. FMD was lesser in cases than in controls but not significant. The median values of hs-CRP, IL-6, sICAM, sVCAM were 0.81 mg/L, 6.27 pg/mL, 46.33 ng/mL and 668.81 ng/mL, respectively. A significant correlation of IL-6 with CIMT (r = 0.543, p =  < 0.001) and sICAM with FMD (r =  −0.397, p = 0.011) was observed. VCAM was low in the obese and overweight children.

Conclusion

Children with type 1 diabetes had higher CIMT than normal children, whereas FMD did not differ. The association between elevated inflammatory markers with high CIMT and low FMD indicates that inflammation plays an essential role in endothelial dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kumar KM. Incidence trends for childhood type 1 diabetes in India. Indian J Endocrinol Metab. 2015;19:S34–5.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Dahl-Jørgensen K, Larsen JR, Hanssen KF. Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment? Diabetologia. 2005;48:1445–53.

    Article  PubMed  Google Scholar 

  3. Järvisalo MJ, Rönnemaa T, Volanen I, et al. Brachial artery dilatation responses in healthy children and adolescents. Am J Physiol Heart Circ Physiol. 2002;282:H87-92.

    Article  PubMed  Google Scholar 

  4. Gökşen D, Levent E, Kar S, Ozen S, Darcan S. Serum adiponectin and hsCRP levels and non-invasive radiological methods in the early diagnosis of cardiovascular system complications in children and adolescents with type 1 diabetes mellitus. J Clin Res Pediatr Endocrinol. 2013;5:174–81.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dalla Pozza R, Beyerlein A, Thilmany C, et al. The effect of cardiovascular risk factors on the longitudinal evolution of the carotid intima medial thickness in children with type 1 diabetes mellitus. Cardiovasc Diabetol. 2011;10:53.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wiegman A, de Groot E, Hutten BA, et al. Arterial intima-media thickness in children heterozygous for familial hypercholesterolaemia. Lancet. 2004;363:369–70.

    Article  PubMed  Google Scholar 

  7. Rabago Rodriguez R, Gómez-Díaz RA, Tanus Haj J, et al. Carotid intima-media thickness in pediatric type 1 diabetic patients. Diabetes Care. 2007;30:2599–602.

    Article  PubMed  Google Scholar 

  8. Roberts WL. CDC/AHA Workshop on markers of inflammation and cardiovascular disease: application to clinical and public health practice: laboratory tests available to assess inflammation–performance and standardization: a background paper. Circulation. 2004;110:e572–6.

    Google Scholar 

  9. Järvisalo MJ, Raitakari M, Toikka JO, et al. Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes. Circulation. 2004;109:1750–5.

    Article  PubMed  Google Scholar 

  10. Rostampour N, Fekri K, Hashemi-Dehkordi E, Obodiat M. Association between Vascular Endothelial Markers and Carotid Intima-Media Thickness in Children and Adolescents with Type 1 Diabetes Mellitus. J Clin Diagn Res JCDR. 2017;11:SC01–5.

  11. Nascimento AMMAD, Sequeira IJ, Vasconcelos DF, Gandolfi L, Pratesi R, Nóbrega YKM. Endothelial dysfunction in children with type 1 diabetes mellitus. Arch Endocrinol Metab. 2017;61:476–83.

  12. Baroncini LA, Sylvestre Lde C, Pecoits FR. Assessment of intima-media thickness in healthy children aged 1 to 15 years. Arq Bras Cardiol. 2016;106:327–32.

    PubMed  PubMed Central  Google Scholar 

  13. Abdelghaffar S, El Amir M, El Hadidi A, El Mougi F. Carotid intima-media thickness: an index for subclinical atherosclerosis in type 1 diabetes. J Trop Pediatr. 2006;52:39–45.

    Article  PubMed  Google Scholar 

  14. Heilman K, Zilmer M, Zilmer K, et al. Arterial stiffness, carotid artery intima-media thickness and plasma myeloperoxidase level in children with type 1 diabetes. Diabetes Res Clin Pract. 2009;84:168–73.

    Article  CAS  PubMed  Google Scholar 

  15. Drole Torkar A, Plesnik E, Groselj U, Battelino T, Kotnik P. Carotid intima-media thickness in healthy children and adolescents: normative data and systematic literature review. Front Cardiovasc Med. 2020;7:597768.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Rodriguez-Miguelez P, Seigler N, Harris RA. Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test. J Vis Exp. 2016;54011. https://doi.org/10.3791/54011

  17. Tacito LHB, Pires AC, Yugar-Toledo JC. Impaired flow-mediated dilation response and carotid intima-media thickness in patients with type 1 diabetes mellitus with a mean disease duration of 4.1 years. Arch Endocrinol Metab. 2017;61:542–9.

  18. Kamath DY, Xavier D, Sigamani A, Pais P. High sensitivity C-reactive protein (hsCRP) & cardiovascular disease: An Indian perspective. Indian J Med Res. 2015;142:261–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pérez-Segura P, de Dios O, Herrero L, et al. Children with type 1 diabetes have elevated high-sensitivity C-reactive protein compared with a control group. BMJ Open Diabetes Res Care. 2020;8: e001424.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Snell-Bergeon JK, West NA, Mayer-Davis EJ, et al. Inflammatory markers are increased in youth with type 1 diabetes: the SEARCH case-control study. J Clin Endocrinol Metab. 2010;95:2868–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Picardi A, Valorani M, Vespasiani Gentilucci U, et al. IMDIAB Group. Raised C-reactive protein levels in patients with recent onset type 1 diabetes. Diabetes Metab Res Rev. 2007;23:211–4.

  22. Alnek K, Kisand K, Heilman K, Peet A, Varik K, Uibo R. Increased blood levels of growth factors, proinflammatory cytokines, and th17 cytokines in patients with newly diagnosed type 1 diabetes. PloS One. 2015;10:e0142976.

  23. Astrup AS, Tarnow L, Pietraszek L, et al. Markers of endothelial dysfunction and inflammation in type 1 diabetic patients with or without diabetic nephropathy followed for 10 years: association with mortality and decline of glomerular filtration rate. Diabetes Care. 2008;31:1170–6.

    Article  CAS  PubMed  Google Scholar 

  24. Klein BEK, Knudtson MD, Tsai MY, Klein R. The relation of markers of inflammation and endothelial dysfunction to the prevalence and progression of diabetic retinopathy. wisconsin epidemiologic study of diabetic retinopathy. Arch Ophthalmol. 2009;127:1175–82.

  25. Hartman J, Frishman WH. Inflammation and atherosclerosis: a review of the role of interleukin-6 in the development of atherosclerosis and the potential for targeted drug therapy. Cardiol Rev. 2014;22:147–51.

    Article  PubMed  Google Scholar 

  26. Christoffersen M, Tybjaerg-Hansen A. Targeting IL-6 in patients at high cardiovascular risk. Lancet Lond Engl. 2021;397:2025–7.

    Article  CAS  Google Scholar 

  27. Maffeis C, Birkebaek NH, Konstantinova M, et al. SWEET Study Group. Prevalence of underweight, overweight, and obesity in children and adolescents with type 1 diabetes: Data from the international SWEET registry. Pediatr Diabetes. 2018;19:1211–20.

Download references

Funding

The study was funded by JIPMER intramural research fund – grant No. JIP/Dean(R)/Intarmural/ Phs 1/ 2019–20 dated 9th October 2020.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, 605006, India

    Palanisamy Shanmugasundaram Bharathy & Delhikumar C. G.

  2. Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

    Medha Rajappa

  3. Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

    Jayaprakash Sahoo

  4. Department of Cardiology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

    Avinash Anantharaj

Authors
  1. Palanisamy Shanmugasundaram Bharathy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Delhikumar C. G.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Medha Rajappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jayaprakash Sahoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Avinash Anantharaj
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DCG and PSB conceptualized the study; PSB collected the data and drafted the initial draft of the manuscript; DCG performed the analysis of data and literature search; DCG, AA, MR and JS provided intellectual input in the final drafting of the manuscript and did overall supervision. All authors contributed to the critical revision of the article.

Guarantor

Dr Narayanan Parameswaran, Professor & Head, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India.

Corresponding author

Correspondence to Delhikumar C. G..

Ethics declarations

Ethical Approval

The study was approved by Institute Ethics committee (Human studies) with approval number—JIP/IEC/2019/157.

Consent to Participate

Informed consent was obtained from all the individual participants included in the study.

Consent to Publish

Patients signed informed consent regarding publishing their data.

Conflict of Interest

None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bharathy, P.S., Delhikumar, C., Rajappa, M. et al. Early Markers of Atherosclerosis in Children and Adolescents with Type 1 Diabetes Mellitus. Indian J Pediatr 90, 227–232 (2023). https://doi.org/10.1007/s12098-022-04314-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-022-04314-w

Keywords

Search

Navigation