Can we use copeptin as a biomarker for masked hypertension or metabolic syndrome in obese children and adolescents?
-
Duygu Deligözoğlu
, Caner Alparslan
Abstract
Objectives
Copeptin, the C-terminal part of arginine-vasopressin, is increased in hypertensive adolescents and closely associated with metabolic syndrome (MS). We aimed to investigate whether serum copeptin can be used to differentiate masked hypertension (MHT) and MS, and the role of sodium intake, natriuretic peptide response and renin-angiotensin-aldosterone system in MHT and MS in obese youth.
Methods
Obese children aged 10–18 years with normal office blood pressure measurements were included. Patients with MHT and normotension and those with MS and non-MS were evaluated separately. Biochemical parameters, copeptin, brain natriuretic peptide (BNP), aldosterone, renin, urine sodium, and protein were evaluated. Echocardiography, fundoscopic examination, and ambulatory blood pressure monitoring were performed.
Results
There were 80 (M/F=39/41) obese patients with a mean age of 13.78 ± 1.93 years. The cases with MHT, MS, and concomitant MHT and MS were 53,24, and 13%, respectively. Copeptin levels were similar among patients with and without MHT or MS (p>0.05). However, multivariate analysis revealed that copeptin significantly increased the probability of MHT (OR 1.01, 95% CI=1.001–1.018, p=0.033). Copeptin was positively correlated with daytime systolic and diastolic load, aldosterone, BNP, and urine microalbumin/creatinine levels (p<0.05). Linear regression analyses revealed that copeptin was significantly correlated with BNP regardless of having MHT or MS in obese youth. In the MHT group, 24-h sodium excretion was not significantly correlated with BNP.
Conclusion
Copeptin may be a beneficial biomarker to discriminate MHT, but not MS in obese children and adolescents. An insufficient BNP response to sodium intake might be one of the underlying causes of MHT in obese cases.
Research funding: This work was supported by İzmir Katip Çelebi University Scientific Research Projects Coordination Unit (Project Number: 2016-TDU-TIPF-0022).
Author Contributions: Duygu Deligözoğlu involved in the recruitment of subjects, data analysis, and manuscript preparation. Belde Kasap-Demir involved in principle investigator and involved in all aspects of the study, including study concept, study design, recruitment of subjects, data analysis, and manuscript preparation. Caner Alparslan involved in data acquisition. Huriye Erbak involved in data acquisition. Gönül Çatlı involved in study concept and data interpretation. Fatma Mutlubaş involved in data analysis. Demet Alaygut involved in statistical data analysis. Eren Soyaltın involved in data acquisition. Seçil Arslansoyu-Çamlar involved in manuscript preparation. Önder Yavaşcan involved in study design.
Conflicts of interest: The authors have no conflicts of interest to disclose.
Statement of Ethics: All procedures involved in this research study were evaluated İzmir Katip Çelebi University Clinical Studies Ethics Committee. Written informed consent was obtained from parents of all subjects. Informed consent was obtained from a parent or legal guardian and assent were obtained for children greater than 7 years of age.
References
1. Weihrauch-Blüher, S, Schwarz, P, Klusmann, JH. Childhood obesity: increased risk for cardiometabolic disease and cancer in adulthood. Metabolism 2019;92:147–52. https://doi.org/10.1016/j.metabol.2018.12.001.Suche in Google Scholar
2. Ng, M, Fleming, T, Robinson, M, Thomson, B, Graetz, N, Margono, C, et al.. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014;384:766–81. https://doi.org/10.1016/S0140-6736(14)60460-8.Suche in Google Scholar
3. Stabouli, S, Kotsis, V, Toumanidis, S, Papamichael, C, Constantopoulos, A, Zakopoulos, N. White-coat and masked hypertension in children: association with target-organ damage. Pediatr Nephrol 2005;20:1151–5. https://doi.org/10.1007/s00467-005-1979-5.Suche in Google Scholar
4. Flynn, JT, Daniels, SR, Hayman, LL, Maahs, DM, McCrindle, BW, Mitsnefes, M, et al.. American heart association atherosclerosis, hypertension and obesity in youth committee of the council on cardiovascular disease in the young. Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American heart association. Hypertension 2014;63:1116–35. https://doi.org/10.1161/hyp.0000000000000007.Suche in Google Scholar
5. Asferg, CL, Andersen, UB, Linneberg, A, Goetze, JP, Jeppesen, JL. Copeptin, a surrogate marker for arginine vasopressin secretion, is associated with higher glucose and insulin concentrations but not higher blood pressure in obese men. Diabet Med 2014;31:728–32. https://doi.org/10.1111/dme.12411.Suche in Google Scholar
6. Russell, JA. Bench-to-bedside review: vasopressin in the management of septic shock. Crit Care 2011;15:226. https://doi.org/10.1186/cc8224.Suche in Google Scholar
7. Tenderenda-Banasiuk, E, Wasilewska, A, Filonowicz, R, Jakubowska, U, Waszkiewicz-Stojda, M. Serum copeptin levels in adolescents with primary hypertension. Pediatr Nephrol 2014;29:423–9. https://doi.org/10.1007/s00467-013-2683-5.Suche in Google Scholar
8. Asferg, CL, Nielsen, SJ, Andersen, UB, Linneberg, A, Møller, DV, Hedley, PL, et al.. Relative atrial natriuretic peptide deficiency and inadequate renin and angiotensin suppression in obese hypertensive men. Hypertension 2013;62:147–53. https://doi.org/10.1161/hypertensionaha.111.00791.Suche in Google Scholar
9. Enhörning, S, Struck, J, Wirfält, E, Hedblad, B, Morgenthaler, NG, Melander, O. Plasma copeptin, a unifying factor behind the metabolic syndrome. J Clin Endocrinol Metab 2011;96:E1065–72. https://doi.org/10.1210/jc.2010-2981.Suche in Google Scholar
10. Enhörning, S, Bankir, L, Bouby, N, Struck, J, Hedblad, B, Persson, M, et al.. Copeptin, a marker of vasopressin, in abdominal obesity, diabetes and microalbuminuria: the prospective Malmö Diet and Cancer Study cardiovascular cohort. Int J Obes 2013;37:598–603. https://doi.org/10.1038/ijo.2012.88.Suche in Google Scholar
11. Cuspidi, C, Facchetti, R, Bombelli, M, Sala, C, Tadic, M, Grassi, G, et al.. Risk of new-onset metabolic syndrome associated with white-coat and masked hypertension: data from a general population. J Hypertens 2018;36:1833–9. https://doi.org/10.1097/hjh.0000000000001767.Suche in Google Scholar
12. Colantonio, LD, Anstey, DE, Carson, AP, Ogedegbe, G, Abdalla, M, Sims, M, et al.. Metabolic syndrome and masked hypertension among African Americans: the jackson heart study. J Clin Hypertens 2017;19:592–600. https://doi.org/10.1111/jch.12974.Suche in Google Scholar
13. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 1995;854:1–452. PMID: 8594834.Suche in Google Scholar PubMed
14. Chaput, JP, Katzmarzyk, PT, Barnes, JD, ISCOLE Research Group. Mid-upper arm circumference as a screening tool for identifying children with obesity: a 12-country study. Pediatr Obes 2017;12:439–45. https://doi.org/10.1111/ijpo.12162.Suche in Google Scholar
15. Rönnecke, E, Vogel, M, Bussler, S, Grafe, N, Jurkutat, A, Schlingmann, M, et al.. Age- and sex-related percentiles of skinfold thickness, waist and hip circumference, waist-to-hip ratio and waist-to-height ratio: results from a population-based pediatric cohort in Germany (LIFE Child). Obes Facts 2019;12:25–39. https://doi.org/10.1159/000494767.Suche in Google Scholar
16. Demir, K, Konakçı, E, Özkaya, G, Kasap Demir, B, Özen, S, Aydın, M, et al.. New features for Child Metrics: further growth references and blood pressure calculations. J Clin Res Pediatr Endocrinol 2020;12:125–9. https://doi.org/10.4274/jcrpe.galenos.2019.2019.0127.Suche in Google Scholar
17. Neyzi, O, Bundak, R, Gökçay, G, Günöz, H, Furman, A, Darendeliler, F, et al.. Reference values for weight, height, head circumference, and body mass index in Turkish Children. J Clin Res Pediatr Endocrinol 2015;7:280–93. https://doi.org/10.4274/jcrpe.2183.Suche in Google Scholar
18. Marshall, WA, Tanner, JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:13–23. https://doi.org/10.1136/adc.45.239.13.Suche in Google Scholar
19. Marshall, WA, Tanner, JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303. https://doi.org/10.1136/adc.44.235.291.Suche in Google Scholar
20. Maruhama, Y, Abe, R. A familial form of obesity without hyperinsulinism at the outset. Diabetes 1981;30:14–8. https://doi.org/10.2337/diab.30.1.14.Suche in Google Scholar
21. Katz, A, Nambi, SS, Mather, K, Baron, AD, Follmann, DA, Sullivan, G, et al.. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000;85:2402–10. https://doi.org/10.1210/jcem.85.7.6661.Suche in Google Scholar
22. Keskin, M, Kurtoglu, S, Kendirci, M, Atabek, ME, Yazici, C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 2005;115:500–3. https://doi.org/10.1542/peds.2004-1921.Suche in Google Scholar
23. Atabek, ME, Pirgon, O. Assessment of insulin sensitivity from measurements in fasting state and during an oral glucose tolerance test in obese children. J Pediatr Endocrinol Metab 2007;20:187–95. https://doi.org/10.1515/jpem.2007.20.2.187.Suche in Google Scholar
24. Matthews, DR, Hosker, JP, Rudenski, AS, Naylor, BA, Treacher, DF, Turner, RC. Homeostasis model assessment: insulin resistance and beta−cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–19. https://doi.org/10.1007/bf00280883.Suche in Google Scholar
25. Ten, S, Maclaren, N. Insulin resistance syndrome in children. J Clin Endocrinol Metab 2004;89:2526–39. https://doi.org/10.1210/jc.2004-0276.Suche in Google Scholar
26. Goran, MI, Gower, BA. Longitudinal study on pubertal insulin resistance. Diabetes 2001;50:2444–50. https://doi.org/10.2337/diabetes.50.11.2444.Suche in Google Scholar
27. Van der Aa, MP, Knibbe, CA, Boer, A, van der Vorst, MM. Definition of insulin resistance affects prevalence rate in pediatric patients: a systematic review and call for consensus. J Pediatr Endocrinol Metab 2017;30:123–31. https://doi.org/10.1515/jpem-2016-0242.Suche in Google Scholar
28. Hatipoglu, N, Ozturk, A, Mazicioglu, MM, Kurtoglu, S, Seyhan, S, Lokoglu, F. Waist circumference percentiles for 7- to 17-year-old Turkish children and adolescents. Eur J Pediatr 2008;167:383–9. https://doi.org/10.1007/s00431-007-0502-3.Suche in Google Scholar
29. International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome in children and adolescents; 2007. Available at: http://www.idf.org/publications/idf-consensus-definition-metabolic-syndrome-children.Suche in Google Scholar
30. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555–76. PMID: 15286277.10.1542/peds.114.S2.555Suche in Google Scholar PubMed
31. Wühl, E, Witte, K, Soergel, M, Mehls, O, Schaefer, F. German Working Group on Pediatric Hypertension. Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions. J Hypertens 2002;20:1995–2007. https://doi.org/10.1097/00004872-200210000-00019.Suche in Google Scholar
32. Devereux, RB, Reichek, N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation 1977;55:613–18. https://doi.org/10.1161/01.cir.55.4.613.Suche in Google Scholar
33. Khoury, PR, Mitsnefes, M, Daniels, SR, Kimball, TR. Age-specific reference intervals for indexed left ventricular mass in children. J Am Soc Echocardiogr 2009;22:709–14. https://doi.org/10.1016/j.echo.2009.03.003.Suche in Google Scholar
34. Aissopou, EK, Papathanassiou, M, Nasothimiou, EG, Konstantonis, GD, Tentolouris, N, Theodossiadis, PG, et al.. The Keith-Wagener-Barker and Mitchell-Wong grading systems for hypertensive retinopathy: association with target organ damage in individuals below 55 years. J Hypertens 2015;33:2303–9. https://doi.org/10.1097/hjh.0000000000000702.Suche in Google Scholar
35. Rothermel, J, Kulle, A, Holterhus, PM, Toschke, C, Lass, N, Reinehr, T. Copeptin in obese children and adolescents: relationships to body mass index, cortisol and gender. Clin Endocrinol 2016;85:868–73. https://doi.org/10.1111/cen.13235.Suche in Google Scholar
36. Vintilă, M, Gheorghiu, ML, Caragheorgheopol, A, Baculescu, N, Lichiardopol, C, Badiu, C, et al.. Increased copeptin levels in metabolic syndrome from a Romanian population. J Med Life 2016;9:353–7. PMCID: PMC5141393.Suche in Google Scholar PubMed
37. Yegül-Gülnar, G, Kasap-Demir, B, Alparslan, C, Çatli, G, Mutlubaş, F, Yavaşcan, Ö, et al.. Ambulatory blood pressure monitoring parameters in obese children and adolescents with masked hypertension. Blood Pres Monit 2019;24:277–83. https://doi.org/10.1097/mbp.0000000000000402.Suche in Google Scholar
38. Maggio, AB, Aggoun, Y, Marchand, LM, Martin, XE, Herrmann, F, Beghetti, M, et al.. Associations among obesity, blood pressure, and left ventricular mass. J Pediatr 2008;152:489–93. https://doi.org/10.1016/j.jpeds.2007.10.042.Suche in Google Scholar
39. Lurbe, E, Invitti, C, Torro, I, Maronati, A, Aguilar, F, Sartorio, A, et al.. The impact of the degree of obesity on the discrepancies between office and ambulatory blood pressure values in youth. J Hypertens 2006;24:1557–64. https://doi.org/10.1097/01.hjh.0000239291.32883.e3.Suche in Google Scholar
40. Ostrow, V, Wu, S, Aguilar, A, Bonner, R, Suarez, E, Luca, FD. Association between oxidative stress and masked hypertension in a multi-ethnic population of obese children and adolescents. J Pediatr 2011;158:628–33. https://doi.org/10.1016/j.jpeds.2010.09.081.Suche in Google Scholar
41. Urbina, E, Alpert, B, Flynn, J, Hayman, L, Harshfield, GA, Jacobson, M, et al.. American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee. Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association atherosclerosis, hypertension, and obesity in youth committee of the council on cardiovascular disease in the young and the council for high blood pressure research. Hypertension 2008;52:433–51. https://doi.org/10.1161/hypertensionaha.108.190329.Suche in Google Scholar
42. Lurbe, E, Torro, I, Alvarez, V, Nawrot, T, Paya, R, Redon, J, et al.. Prevalence, persistence, and clinical significance of masked hypertension in youth. Hypertension 2005;45:493–8. https://doi.org/10.1161/01.hyp.0000160320.39303.ab.Suche in Google Scholar
43. Rosner, B, Prineas, R, Daniels, SR, Loggie, J. Blood pressure differences between blacks and whites in relation to body size among US children and adolescents. Am J Epidemiol 2000;151:1007–19. https://doi.org/10.1093/oxfordjournals.aje.a010129.Suche in Google Scholar
44. Sarzani, R, Spannella, F, Giulietti, F, Balietti, P, Cocci, G, Bordicchia, M. Cardiac natriuretic peptides, hypertension and cardiovascular risk. High Blood Pres Cardiovasc Prev 2017;24:115–26. https://doi.org/10.1007/s40292-017-0196-1.Suche in Google Scholar
45. Wyskida, K, Ficek, J, Ficek, R, Adamska, D, Jędrzejowska, P, Wajda, J, et al.. N-terminal prohormone of brain natriuretic peptide but not C-terminal pre-pro vasopressin (copeptin) level is associated with the response to Antihypertensive therapy in haemodialysis patients. Kidney Blood Press Res 2017;42:1013–22. https://doi.org/10.1159/000485433.Suche in Google Scholar
46. Li, X, Yang, XC, Sun, QM, Chen, XD, Li, YC. Brain natriuretic peptide and copeptin levels are associated with cardiovascular disease in patients with chronic kidney disease. Chin Med J 2013;126:823–7. PMID: 23489784.10.3760/cma.j.issn.0366-6999.20122497Suche in Google Scholar
47. Goharian, TS, Goetze, JP, Faber, J, Andersen, LB, Grøntved, A, Jeppesen, JL. Associations of proatrial natriuretic peptide with components of the metabolic syndrome in adolescents and young adults from the general population. Am J Hypertens 2017;30:561–8. https://doi.org/10.1093/ajh/hpx026.Suche in Google Scholar
48. Saleem, U, Khaleghi, M, Morgenthaler, NG, Bergmann, A, Struck, J, Mosley, THJr, et al.. Plasma carboxy-terminal provasopressin (copeptin): a novel marker of insulin resistance and metabolic syndrome. J Clin Endocrinol Metab 2009;94:2558–64. https://doi.org/10.1210/jc.2008-2278.Suche in Google Scholar
49. Thomsen, CF, Dreier, R, Goharian, TS, Goetze, JP, Andersen, LB, Faber, J, et al.. Association of copeptin, a surrogate marker for arginine vasopressin secretion, with insulin resistance: influence of adolescence and psychological stress. Peptides 2019;115:8–14. https://doi.org/10.1016/j.peptides.2019.02.005.Suche in Google Scholar
50. Canivell, S, Mohaupt, M, Ackermann, D, Pruijm, M, Guessous, I, Ehret, G, et al.. Copeptin and insulin resistance: effect modification by age and 11 β-HSD2 activity in a population-based study. J Endocrinol Invest 2018;41:799–808. https://doi.org/10.1007/s40618-017-0807-7.Suche in Google Scholar
© 2020 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review Article
- Papillary thyroid carcinoma in children with Hashimoto’s thyroiditis – a review of the literature between 2000 and 2020
- Original Articles
- Tyrosine metabolism in health and disease: slow-release amino acids therapy improves tyrosine homeostasis in phenylketonuria
- Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM)
- Glycated hemoglobin variability and microvascular complications in patients with type 1 diabetes mellitus
- Delineation of the genetic and clinical spectrum, including candidate genes, of monogenic diabetes: a multicenter study in South Korea
- Can we use copeptin as a biomarker for masked hypertension or metabolic syndrome in obese children and adolescents?
- Relationship of acanthosis nigricans with metabolic syndrome in obese children
- Daily intake of macronutrients and energy in childhood and its association with cardiometabolic risk factors in Colombians
- The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): a systematic review and meta-analysis
- Growth in achondroplasia, from birth to adulthood, analysed by the JPA-2 model
- Short Communication
- Assessing disparities in barriers to attending pediatric diabetes camp
- Letter to the Editor
- Severity in pediatric type 1 diabetes mellitus debut during the COVID-19 pandemic
- Case Reports
- The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene
- Effect of recombinant human insulin-like growth factor 1 therapy in a child with 3-M syndrome-1 with CUL7 gene mutation
- A nonsense variant in FGFR1: a rare cause of combined pituitary hormone deficiency
- Treatment response to long term antiresorptive therapy in osteogenesis imperfecta type VI: does genotype matter?
Artikel in diesem Heft
- Frontmatter
- Review Article
- Papillary thyroid carcinoma in children with Hashimoto’s thyroiditis – a review of the literature between 2000 and 2020
- Original Articles
- Tyrosine metabolism in health and disease: slow-release amino acids therapy improves tyrosine homeostasis in phenylketonuria
- Evolution of Hashimoto thyroiditis in children with type 1 diabetes mellitus (TIDM)
- Glycated hemoglobin variability and microvascular complications in patients with type 1 diabetes mellitus
- Delineation of the genetic and clinical spectrum, including candidate genes, of monogenic diabetes: a multicenter study in South Korea
- Can we use copeptin as a biomarker for masked hypertension or metabolic syndrome in obese children and adolescents?
- Relationship of acanthosis nigricans with metabolic syndrome in obese children
- Daily intake of macronutrients and energy in childhood and its association with cardiometabolic risk factors in Colombians
- The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): a systematic review and meta-analysis
- Growth in achondroplasia, from birth to adulthood, analysed by the JPA-2 model
- Short Communication
- Assessing disparities in barriers to attending pediatric diabetes camp
- Letter to the Editor
- Severity in pediatric type 1 diabetes mellitus debut during the COVID-19 pandemic
- Case Reports
- The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene
- Effect of recombinant human insulin-like growth factor 1 therapy in a child with 3-M syndrome-1 with CUL7 gene mutation
- A nonsense variant in FGFR1: a rare cause of combined pituitary hormone deficiency
- Treatment response to long term antiresorptive therapy in osteogenesis imperfecta type VI: does genotype matter?