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High molecular weight adiponectin as a biomarker of hypertension in children and adolescents with obesity

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Abstract

Lower HMW (high molecular weight) adiponectin levels are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. However, data on HMW levels in pediatric population with hypertension are lacking. This study aimed to examine the association and predictive capacity of HMW levels, HMW/HOMA-IR, and HMW/APN ratio with hypertension in obese children and adolescents. The 299 pediatric subjects were grouped in obese hypertensive (OH), obese normotensive (ON), and normal weight normotensive (NN). Plasma concentrations of HMW were investigated by ELISA. ANOVA was used to compare study groups, and a binary logistic regression analysis was used to verify if HMW, HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, and HOMA-IR are associated to hypertension regardless obesity in children and adolescents. To compare the strength and performance of each biomarker to classify individuals with and without hypertension, the receiver-operating characteristic (ROC) curve, area under the curve (AUC), and Youden index (J) were evaluated. Both HMW plasma levels and the HMW/HOMA-IR ratio were significantly lower in the OH group when compared to the ON group (HMW: 2.00 ± 1.33 µg/mL vs 2.48 ± 1.48 µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 1.27 ± 1.2; P < 0.05) and NN weight groups (HMW: 2.00 ± 1.33 µg/mL vs 4.02 ± 1.99 µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 2.62 ± 1.86; P < 0.05). Hypertension was associated with lowest HMW (OR = 4.50; 95% CI = 1.41–15.84) and HMW/HOMA-IR (OR = 12.13; 95% CI = 2.51–92.93) regardless of obesity. However, HOMA-IR or the HMW/APN was not significant (P > 0.05). In the ROC curve analyses, the HMW and HMW/HOM-IR were more sensitive to detect hypertension in children and adolescents with obesity.

   Conclusion: Low levels of HMW oligomer and HMW/HOM-IR are associated with hypertension in childhood obesity. Thus, these biomarkers could be clinically useful in identifying hypertension in childhood obesity.

What is Known:

• HMW has previously been reported as the most biologically active isoform of adiponectin, and lower HMW concentrations are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents.

• HMW/HOMA-IR ratio is a sensitive predictor for metabolic syndrome in adults.

What is New:

• HMW levels are associated with hypertension in children and adolescents, independently of presence of obesity.

• HMW was more sensitive to detect hypertension in children and adolescents with obesity when compared to HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, or HOMA-IR.

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Data availability

Availability of data and material on request.

Abbreviations

APN:

Adiponectin

HMW:

High molecular weight

HOMA-IR:

Homeostasis model assessment-insulin resistance

LMW:

Low molecular weight

MMW:

Medium molecular weight

NN:

Normal weight normotensive

NO:

Nitric oxide

ON:

Obese normotensive

OH:

Obese hypertensive

References

  1. Chooi YC, Ding C, Magkos F (2019) The epidemiology of obesity. Metabolism. https://doi.org/10.1016/j.metabol.2018.09.005

    Article  PubMed  Google Scholar 

  2. Ministério da Saúde (2020) Vigitel Brasil 2019. https://bvsms.saude.gov.br/bvs/publicacoes/vigitel_brasil_2019_vigilancia_fatores_risco.pdf

  3. Sommer A, Twig G (2018) The impact of childhood and adolescent obesity on cardiovascular risk in adulthood: a systematic review. Curr Diab Rep. https://doi.org/10.1007/s11892-018-1062-9

  4. Albataineh SR, Badran EF, Tayyem RF (2019) Overweight and obesity in childhood: dietary, biochemical, inflammatory and lifestyle risk factors. Obes Med. https://doi.org/10.1177/0260106018803243

  5. Orlando A, Nava E, Giussani M, Genovesi S (2019) Adiponectin and cardiovascular risk. From pathophysiology to clinic: Focus on children and adolescents. Int J Mol Sci. https://doi.org/10.3390/ijms20133228

  6. Vaiopoulos AG, Marinou K, Christodoulides C, Koutsilieris M (2012) The role of adiponectin in human vascular physiology. Int J Cardiol. https://doi.org/10.1016/j.ijcard.2011.07.047

  7. Kim DH, Kim C, Ding EL et al (2013) Adiponectin levels and the risk of hypertension: a systematic review and meta-analysis. Hypertension. https://doi.org/10.1161/HYPERTENSIONAHA.113.01453

  8. Belo VA, Souza-Costa DC, Lacchini R et al (2013) Adiponectin associates positively with nitrite levels in children and adolescents. Int J Obes 37. https://doi.org/10.1038/ijo.2012.104

  9. van Andel M, Heijboer AC, Drent ML (2018) Adiponectin and its isoforms in pathophysiology. Adv Clin Chem. https://doi.org/10.1016/bs.acc.2018.02.007

  10. Araki S, Dobashi K, Kubo K et al (2006) High molecular weight, rather than total, adiponectin levels better reflect metabolic abnormalities associated with childhood obesity. J Clin Endocrinol Metab. https://doi.org/10.1210/jc.2006-1051

    Article  PubMed  Google Scholar 

  11. Meyer DM, Brei C, Stecher L et al (2017) Cord blood and child plasma adiponectin levels in relation to childhood obesity risk and fat distribution up to 5 y. Pediatr Res. https://doi.org/10.1038/pr.2016.275

    Article  PubMed  Google Scholar 

  12. De Abreu VG, de Martins CJ, M, De Oliveira PAC, Francischetti EA (2017) High-molecular weight adiponectin/HOMA-IR ratio as a biomarker of metabolic syndrome in urban multiethnic Brazilian subjects. PLoS ONE 12:1–12. https://doi.org/10.1371/journal.pone.0180947

    Article  CAS  Google Scholar 

  13. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM et al (2000) CDC growth charts: United States. Adv Data

  14. Flynn JT, Kaelber DC, Baker-Smith CM et al (2017) Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. https://doi.org/10.1542/peds.2017-1904

  15. Matthews DR, Hosker JP, Rudenski AS et al (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. https://doi.org/10.1007/BF00280883

    Article  PubMed  Google Scholar 

  16. Brambilla P, Antolini L, Street ME et al (2013) Adiponectin and hypertension in normal-weight and obese children. Am J Hypertens. https://doi.org/10.1093/ajh/hps033

    Article  PubMed  Google Scholar 

  17. Wang H, Necheles J, Birne JS, Li Z, Xing H, Tang G, Christoffel KK, Brickman WJ, Zimmerman D, Wang X (2012) Association of adipokines with blood pressure in rural Chinese adolescents. J Hum Hypertens. https://doi.org/10.1038/jhh.2011.64

  18. Belo VA, Lacchini R, Miranda JA et al (2015) Increased activity of MMP-2 in hypertensive obese children is associated with hypoadiponectinemia. Obesity 23:177–182. https://doi.org/10.1002/oby.20939

    Article  CAS  PubMed  Google Scholar 

  19. Ciccone MM, Faienza MF, Altomare M et al (2016) Endothelial and metabolic function interactions in overweight/obese children: the role of high-molecular weight adiponectin. J Atheroscler Thromb. https://doi.org/10.5551/jat.31740

  20. Nigro E, Scudiero O, Ludovica Monaco M et al (2017) Adiponectin profile and Irisin expression in Italian obese children: association with insulin-resistance. Cytokine. https://doi.org/10.1016/j.cyto.2016.12.018

    Article  PubMed  Google Scholar 

  21. Sprague AH, Khalil RA (2009) Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol. https://doi.org/10.1016/j.bcp.2009.04.029

  22. Yamauchi T, Kamon J, Waki H et al (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. https://doi.org/10.1038/90984

    Article  PubMed  Google Scholar 

  23. Hug C, Wang J, Ahmad NS et al (2004) T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.0403382101

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wang F, Han L, Hu D (2017) Fasting insulin, insulin resistance and risk of hypertension in the general population: a meta-analysis. Clin Chim Acta. https://doi.org/10.1016/j.cca.2016.11.009

  25. Makni E, Moalla W, Lac G et al (2012) The Homeostasis Model Assessment-adiponectin (HOMA-AD) is the most sensitive predictor of insulin resistance in obese children. Ann Endocrinol (Paris). https://doi.org/10.1016/j.ando.2011.12.002

    Article  PubMed  Google Scholar 

  26. Cândido APC, Geloneze B, Calixto A et al (2021) Adiponectin, HOMA-adiponectin, HOMA-IR in children and adolescents: Ouro Preto study. Indian J Pediatr. https://doi.org/10.1007/s12098-020-03444-3

  27. Smith JD, Fu E, Kobayashi MA (2020) Prevention and management of childhood obesity and its psychological and health comorbidities. Annu Rev Clin Psychol. https://doi.org/10.1146/annurev-clinpsy-100219-060201

  28. Lee EY, Yoon KH (2018) Epidemic obesity in children and adolescents: risk factors and prevention. Front Med. https://doi.org/10.1007/s11684-018-0640-1

  29. Alp H, Karaarslan S, Eklioǧlu BS et al (2014) The effect of hypertension and obesity on left ventricular geometry and cardiac functions in children and adolescents. J Hypertens. https://doi.org/10.1097/HJH.0000000000000176

    Article  PubMed  Google Scholar 

  30. Twig G, Yaniv G, Levine H et al (2016) Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood. N Engl J Med. https://doi.org/10.1056/nejmoa1503840

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Acknowledgements

We thank all patients who agreed to participate in this study. We are grateful for the assistance provided by Instituto Mineiro de Ensino e Pesquisa em Nefrologia (Imepen) research team members.

Funding

This study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (no. 453946/2014-3).

Author information

Authors and Affiliations

  1. School of Pharmacy, Federal University of Ouro Preto, Ouro Preto, Minas Gerais, Brazil

    Warlley Rosa Cunha & Vanessa de Almeida Belo

  2. School of Medicine, Barbacena, Minas Gerais, Brazil

    Isabella Campos Gaspar, Beatriz Cazarim de Souza & Bárbara Dias Lana Martins

  3. Department of Physiology, Federal University of Juiz de Fora, 36036-900, Juiz de Fora, MG, Brazil

    Josiane Aparecida de Miranda & Carla Márcia Moreira Lanna

  4. Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil

    José Eduardo Tanus-Santos

  5. Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Ribeirão Preto, Brazil

    Riccardo Lacchini

Authors
  1. Warlley Rosa Cunha
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  2. Isabella Campos Gaspar
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  9. Vanessa de Almeida Belo
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Contributions

WRC performed the statistical analysis and wrote the paper with contributions from all authors. RL coordinated HMW isoform determinations and reviewed the paper. ICG, BCS, and BDCM were responsible for making HMW isoform determinations. CMML was responsible for recruiting research participants and taking the participants’ anamnesis. JAM was responsible for collecting anthropometric measurements and measuring blood pressure. VAB conceived and designed the cross-sectional study, coordinated the project, and reviewed the paper. All the authors critically contributed to the discussion and data interpretation, reviewed and approved the final manuscript. JETS reviewed the paper. VAB is the guarantor for this paper and is recipient of a CNPq individual research grant for productivity.

Corresponding author

Correspondence to Vanessa de Almeida Belo.

Ethics declarations

Ethics approval

All procedures were in accordance with the Helsinki Declaration of Principles and approved by the local ethics committee of the Federal University of Juiz de Fora, Juiz de Fora, Brazil (no. 1942.001.2010).

Consent to participate

Parents gave written consent and children gave verbal consent.

Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by Gregorio Milani.

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Cunha, W.R., Gaspar, I.C., de Souza, B.C. et al. High molecular weight adiponectin as a biomarker of hypertension in children and adolescents with obesity. Eur J Pediatr 182, 2925–2931 (2023). https://doi.org/10.1007/s00431-023-04962-w

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