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Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents

  • Mónica Reis ORCID logo EMAIL logo , Ana Teixeira , Juliana Cardoso , Teresa Borges , Alberto Caldas Afonso and Liane Correia-Costa
Published/Copyright: April 9, 2024
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 37 Issue 5

Abstract

Objectives

Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters.

Methods

Twenty-three type 1 diabetic patients, aged 12–16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid–femoral pulse wave velocity. Proinflammatory cytokines’ concentrations (TNF-α, IL-1β, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer.

Results

There were no statistically significant differences between the proinflammatory cytokines’ concentrations in the two groups. PWV [6.63 (6.23–7.07) vs. 6.07 (5.15–6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=−0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=−0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group.

Conclusions

Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.

Keywords: cytokines; type 1 diabetes mellitus; arterial stiffness; pulse wave velocity; adolescents
Corresponding author: Dr. Mónica Reis, MD, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge Viterbo Ferreira, no 228, Porto 4050-213, Portugal; and Centro Hospitalar Universitário de Santo António, Porto, Portugal, E-mail:

Funding source: Bolsa de Investigação do Centro Hospitalar Universitário do Porto 2018

Funding source: Programa Operacional Factores de Competitividade - COMPETE

Award Identifier / Grant number: FCOMP-01-0124-FEDER-028751

Funding source: Bolsa de Investigação da Sociedade Portuguesa de Pediatria 2018

Funding source: Portuguese Foundation for Science and Technology

Award Identifier / Grant number: PTDC/DTP-PIC/0239/2012

Acknowledgments

The authors gratefully acknowledge the diabetic patients and those enrolled in Generation XXI, as well as their families, for their kindness; all members of the research team for their enthusiasm and perseverance and the participating hospitals and their staff for their help and support.

  1. Research ethics: The research related to human use has complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the author’s Institutional Review Board or equivalent committee.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: Authors state no conflict of interest.

  5. Research funding: This project was supported by FEDER funds from Programa Operacional Factores de Competitividade – COMPETE [FCOMP-01-0124-FEDER-028751], by national funds from the Portuguese Foundation for Science and Technology (FCT), Lisbon, Portugal [PTDC/DTP-PIC/0239/2012], and by the Calouste Gulbenkian Foundation. Liane Correia-Costa was supported by FCT [grant SFRH/SINTD/95898/2013]. Additionally, Ana Teixeira, in 2018, received two research grants from Sociedade Portuguesa de Pediatria and from Centro Hospitalar Universitário Santo António, which were partially used to fund this project.

  6. Data availability: Not applicable.

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Received: 2023-11-27
Accepted: 2024-03-03
Published Online: 2024-04-09
Published in Print: 2024-05-27

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jpem-2023-0530
Keywords for this article
cytokines; type 1 diabetes mellitus; arterial stiffness; pulse wave velocity; adolescents

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Tackling access and payer barriers for growth hormone therapy in Saudi Arabia: a consensus statement for the Saudi Working Group for Pediatric Endocrinology
  4. Original Articles
  5. Does an episode of diabetic ketoacidosis affect thyroid function tests in pediatric patients?
  6. Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents
  7. Endocrinological and metabolic profile of Gaucher disease patients treated with enzyme replacement therapy
  8. Diurnal 11-ketotestosterone and 17-hydroxyprogesterone saliva profiles in paediatric classical congenital adrenal hyperplasia
  9. Growth after pediatric kidney transplantation: a 25-year study in a pediatric kidney transplant center
  10. Long term clinical follow up of four patients with Wolfram syndrome and urodynamic abnormalities
  11. Evaluation of copeptin in children after stimulation with clonidine or L-Dopa
  12. Examination of quality of life and psychiatric symptoms in childhood Graves’ disease
  13. Timing of onset of menses after GnRH agonist treatment for central precocious puberty
  14. Implementation of the Mind Youth Questionnaire (MY-Q) for routine health-related quality of life screening of adolescents with type 1 diabetes in a large tertiary care center
  15. Case Reports
  16. Medulloblastoma in a child with osteoma cutis – a rare association due to loss of GNAS expression
  17. Ectopic lingual thyroid with subclinical hypothyroidism in children
  18. Pituitary stalk interruption syndrome due to novel ROBO1 mutation presenting as combined pituitary hormone deficiency and central diabetes insipidus
  19. A 14-year-old girl with premature ovarian insufficiency but with a positive pregnancy test
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