Skip to main content
Top
Published in: BMC Pediatrics 1/2018

Open Access 01-12-2018 | Research article

Insulin metabolism markers are predictors of subclinical atherosclerosis among overweight and obese children and adolescents

Authors: Golaleh Asghari, Pooneh Dehghan, Parvin Mirmiran, Emad Yuzbashian, Maryam Mahdavi, Maryam Tohidi, Tirang R. Neyestani, Farhad Hosseinpanah, Fereidoun Azizi

Published in: BMC Pediatrics | Issue 1/2018

Login to get access

Abstract

Background

To investigate the association between markers of insulin metabolism and carotid intima-media thickness(cIMT) among overweight and obese children and adolescents.

Methods

A total of 378 children and adolescents aged from 6 to 13 years, with WHO body mass index Z-Scores ≥2 were enrolled in this study. We measured fasting serum insulin and glucose, conducted a homeostatic model assessment of insulin resistance(HOMA-IR), and calculated the quantitative insulin sensitivity check index(QUICKI). Carotid intima-media thickness was measured in the common carotid artery with high-resolution ultrasonography.

Results

The study participants consisted of 198 boys and 180 girls with a mean(±SD) age of 9.3 ± 1.7 years, 18.3% being pre-pubertal. In boys, after controlling for confounders, a one-SD increase in fasting insulin and HOMA-IR were associated with 0.351 mm(P < 0.001) and 0.350 mm(P < 0.001) increases in cIMT, respectively. However, a one-SD increase in QUICKI was associated with a − 0.305 mm(P = 0.001) decrease in cIMT. When categorizing into tertiles, a one-SD increase in fasting insulin and HOMA-IR were associated with 87 and 81% increases in the odds of higher categories of cIMT(both P < 0.05). However, a one-SD increase in QUICKI was associated with 37% lower odds of higher categories of cIMT(P = 0.022). No significant associations were found among girls.

Conclusion

This study demonstrated that insulin resistance and sensitivity markers were independent predictors of cIMT in overweight and obese boys, but not in girls, highlighting the importance of chronically elevated insulin levels for predisposing these boys to alterations in their vascular structure.
Literature
1.
2.
go back to reference Perkins JM, Joy NG, Tate DB, Davis SN. Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans. American Journal of Physiology-Endocrinology and Metabolism. 2015;309(2):E168–76.CrossRef Perkins JM, Joy NG, Tate DB, Davis SN. Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans. American Journal of Physiology-Endocrinology and Metabolism. 2015;309(2):E168–76.CrossRef
3.
go back to reference Rosvall M, Persson M, Östling G, Nilsson P, Melander O, Hedblad B, Engström G. Risk factors for the progression of carotid intima-media thickness over a 16-year follow-up period: the Malmö diet and Cancer study. Atherosclerosis. 2015;239(2):615–21.CrossRef Rosvall M, Persson M, Östling G, Nilsson P, Melander O, Hedblad B, Engström G. Risk factors for the progression of carotid intima-media thickness over a 16-year follow-up period: the Malmö diet and Cancer study. Atherosclerosis. 2015;239(2):615–21.CrossRef
4.
go back to reference Kuller L, Borthani N, Furberg C, Gardin J, Manolio T, O'leary D, Psaty B, Robbins J. Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the cardiovascular health study. Am J Epidemiol. 1994;139(12):1164–79.CrossRef Kuller L, Borthani N, Furberg C, Gardin J, Manolio T, O'leary D, Psaty B, Robbins J. Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the cardiovascular health study. Am J Epidemiol. 1994;139(12):1164–79.CrossRef
5.
go back to reference Rahman TJ, Walker EA, Mayosi BM, Hall DH, Avery PJ, Connell JM, Watkins H, Stewart PM, Keavney B. Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness. PLoS One. 2011;6(8):e23248.CrossRef Rahman TJ, Walker EA, Mayosi BM, Hall DH, Avery PJ, Connell JM, Watkins H, Stewart PM, Keavney B. Genotype at the P554L variant of the hexose-6 phosphate dehydrogenase gene is associated with carotid intima-medial thickness. PLoS One. 2011;6(8):e23248.CrossRef
6.
go back to reference Tonstad S, Joakimsen O, Stensland-Bugge E, Leren TP, Ose L, Russell D, Bønaa KH. Risk factors related to carotid intima-media thickness and plaque in children with familial hypercholesterolemia and control subjects. Arterioscler Thromb Vasc Biol. 1996;16(8):984–91.CrossRef Tonstad S, Joakimsen O, Stensland-Bugge E, Leren TP, Ose L, Russell D, Bønaa KH. Risk factors related to carotid intima-media thickness and plaque in children with familial hypercholesterolemia and control subjects. Arterioscler Thromb Vasc Biol. 1996;16(8):984–91.CrossRef
7.
go back to reference Järvisalo MJ, Putto-Laurila A, Jartti L, Lehtimäki T, Solakivi T, Rönnemaa T, Raitakari OT. Carotid artery intima-media thickness in children with type 1 diabetes. Diabetes. 2002;51(2):493–8.CrossRef Järvisalo MJ, Putto-Laurila A, Jartti L, Lehtimäki T, Solakivi T, Rönnemaa T, Raitakari OT. Carotid artery intima-media thickness in children with type 1 diabetes. Diabetes. 2002;51(2):493–8.CrossRef
8.
go back to reference Lande MB, Carson NL, Roy J, Meagher CC. Effects of childhood primary hypertension on carotid intima media thickness. Hypertension. 2006;48(1):40–4.CrossRef Lande MB, Carson NL, Roy J, Meagher CC. Effects of childhood primary hypertension on carotid intima media thickness. Hypertension. 2006;48(1):40–4.CrossRef
9.
go back to reference Dalla Pozza R, Ehringer-Schetitska D, Fritsch P, Jokinen E, Petropoulos A, Oberhoffer R. Intima media thickness measurement in children: a statement from the Association for European Paediatric Cardiology (AEPC) working group on cardiovascular prevention endorsed by the Association for European Paediatric Cardiology. Atherosclerosis. 2015;238(2):380–7.CrossRef Dalla Pozza R, Ehringer-Schetitska D, Fritsch P, Jokinen E, Petropoulos A, Oberhoffer R. Intima media thickness measurement in children: a statement from the Association for European Paediatric Cardiology (AEPC) working group on cardiovascular prevention endorsed by the Association for European Paediatric Cardiology. Atherosclerosis. 2015;238(2):380–7.CrossRef
10.
go back to reference Ryder JR, Dengel DR, Jacobs DR Jr, Sinaiko AR, Kelly AS, Steinberger J. Relations among adiposity and insulin resistance with flow-mediated dilation, carotid intima-media thickness, and arterial stiffness in children. J Pediatr. 2016;168:205–11.CrossRef Ryder JR, Dengel DR, Jacobs DR Jr, Sinaiko AR, Kelly AS, Steinberger J. Relations among adiposity and insulin resistance with flow-mediated dilation, carotid intima-media thickness, and arterial stiffness in children. J Pediatr. 2016;168:205–11.CrossRef
11.
go back to reference Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, Lam CW, Metreweli C, Celermajer DS. Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening. Int J Obes Relat Metab Disord. 2004;28(7):852–7.CrossRef Woo KS, Chook P, Yu CW, Sung RY, Qiao M, Leung SS, Lam CW, Metreweli C, Celermajer DS. Overweight in children is associated with arterial endothelial dysfunction and intima-media thickening. Int J Obes Relat Metab Disord. 2004;28(7):852–7.CrossRef
12.
go back to reference Yajnik CS, Katre PA, Joshi SM, Kumaran K, Bhat DS, Lubree HG, Memane N, Kinare AS, Pandit AN, Bhave SA, et al. Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune Children's study. Diabetologia. 2015;58(7):1626–36.CrossRef Yajnik CS, Katre PA, Joshi SM, Kumaran K, Bhat DS, Lubree HG, Memane N, Kinare AS, Pandit AN, Bhave SA, et al. Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune Children's study. Diabetologia. 2015;58(7):1626–36.CrossRef
13.
go back to reference Gazolla FM, Neves Bordallo MA, Madeira IR, de Miranda Carvalho CN, Vieira Monteiro AM, Pinheiro Rodrigues NC, Borges MA, Collett-Solberg PF, Muniz BM, de Oliveira CL. Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children. J Pediatr Endocrinol Metab. 2015;28(5–6):579–87.PubMed Gazolla FM, Neves Bordallo MA, Madeira IR, de Miranda Carvalho CN, Vieira Monteiro AM, Pinheiro Rodrigues NC, Borges MA, Collett-Solberg PF, Muniz BM, de Oliveira CL. Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children. J Pediatr Endocrinol Metab. 2015;28(5–6):579–87.PubMed
14.
go back to reference Brar PC, Patel P, Katz S. The relationship between insulin resistance and endothelial dysfunction in obese adolescents. J Pediatr Endocrinol Metab. 2017;30(6):635–42.CrossRef Brar PC, Patel P, Katz S. The relationship between insulin resistance and endothelial dysfunction in obese adolescents. J Pediatr Endocrinol Metab. 2017;30(6):635–42.CrossRef
15.
go back to reference Delshad M, Ghanbarian A, Ghaleh NR, Amirshekari G, Askari S, Azizi F. Reliability and validity of the modifiable activity questionnaire for an Iranian urban adolescent population. Int J Prev Med. 2015;6:3.CrossRef Delshad M, Ghanbarian A, Ghaleh NR, Amirshekari G, Askari S, Azizi F. Reliability and validity of the modifiable activity questionnaire for an Iranian urban adolescent population. Int J Prev Med. 2015;6:3.CrossRef
16.
go back to reference Kelishadi R, Gouya MM, Ardalan G, Hosseini M, Motaghian M, Delavari A, Majdzadeh R, Heidarzadeh A, Mahmoud-Arabi MS, Riazi MM. First reference curves of waist and hip circumferences in an Asian population of youths: CASPIAN study. J Trop Pediatr. 2007;53(3):158–64.CrossRef Kelishadi R, Gouya MM, Ardalan G, Hosseini M, Motaghian M, Delavari A, Majdzadeh R, Heidarzadeh A, Mahmoud-Arabi MS, Riazi MM. First reference curves of waist and hip circumferences in an Asian population of youths: CASPIAN study. J Trop Pediatr. 2007;53(3):158–64.CrossRef
17.
go back to reference O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med. 1999;340(1):14–22.CrossRef O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med. 1999;340(1):14–22.CrossRef
18.
go back to reference Simon A, Megnien J-L, Chironi G. The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol. 2010;30(2):182–5.CrossRef Simon A, Megnien J-L, Chironi G. The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol. 2010;30(2):182–5.CrossRef
19.
go back to reference Iannuzzi A, Licenziati MR, Acampora C, Salvatore V, Auriemma L, Romano ML, Panico S, Rubba P, Trevisan M. Increased carotid intima-media thickness and stiffness in obese children. Diabetes Care. 2004;27(10):2506–8.CrossRef Iannuzzi A, Licenziati MR, Acampora C, Salvatore V, Auriemma L, Romano ML, Panico S, Rubba P, Trevisan M. Increased carotid intima-media thickness and stiffness in obese children. Diabetes Care. 2004;27(10):2506–8.CrossRef
20.
go back to reference Rathsman B, Rosfors S, Sjoholm A, Nystrom T. Early signs of atherosclerosis are associated with insulin resistance in non-obese adolescent and young adults with type 1 diabetes. Cardiovasc Diabetol. 2012;11:145.CrossRef Rathsman B, Rosfors S, Sjoholm A, Nystrom T. Early signs of atherosclerosis are associated with insulin resistance in non-obese adolescent and young adults with type 1 diabetes. Cardiovasc Diabetol. 2012;11:145.CrossRef
21.
go back to reference Urbina EM, Kimball TR, McCoy CE, Khoury PR, Daniels SR, Dolan LM. Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function. Circulation. 2009;119(22):2913–9.CrossRef Urbina EM, Kimball TR, McCoy CE, Khoury PR, Daniels SR, Dolan LM. Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function. Circulation. 2009;119(22):2913–9.CrossRef
22.
go back to reference Elkiran O, Yilmaz E, Koc M, Kamanli A, Ustundag B, Ilhan N. The association between intima media thickness, central obesity and diastolic blood pressure in obese and overweight children: a cross-sectional school-based study. Int J Cardiol. 2013;165(3):528–32.CrossRef Elkiran O, Yilmaz E, Koc M, Kamanli A, Ustundag B, Ilhan N. The association between intima media thickness, central obesity and diastolic blood pressure in obese and overweight children: a cross-sectional school-based study. Int J Cardiol. 2013;165(3):528–32.CrossRef
23.
go back to reference Reinehr T, Kiess W, de Sousa G, Stoffel-Wagner B, Wunsch R. Intima media thickness in childhood obesity: relations to inflammatory marker, glucose metabolism, and blood pressure. Metabolism. 2006;55(1):113–8.CrossRef Reinehr T, Kiess W, de Sousa G, Stoffel-Wagner B, Wunsch R. Intima media thickness in childhood obesity: relations to inflammatory marker, glucose metabolism, and blood pressure. Metabolism. 2006;55(1):113–8.CrossRef
24.
go back to reference Elshorbagy HH, Fouda ER, Kamal NM, Bassiouny MM, Fathi WM. Evaluation oF Epicardial fat and carotid intima-media thickness in obese children. Iran J Pediatr. 2016;26(1):e2968.CrossRef Elshorbagy HH, Fouda ER, Kamal NM, Bassiouny MM, Fathi WM. Evaluation oF Epicardial fat and carotid intima-media thickness in obese children. Iran J Pediatr. 2016;26(1):e2968.CrossRef
25.
go back to reference Melo X, Santa-Clara H, Pimenta NM, Carrolo M, Martins SS, Minderico CS, Fernhall B, Sardinha LB. Body composition phenotypes and carotid intima-media thickness in 11-13-year-old children. Eur J Pediatr. 2014;173(3):345–52.CrossRef Melo X, Santa-Clara H, Pimenta NM, Carrolo M, Martins SS, Minderico CS, Fernhall B, Sardinha LB. Body composition phenotypes and carotid intima-media thickness in 11-13-year-old children. Eur J Pediatr. 2014;173(3):345–52.CrossRef
26.
go back to reference Miniello VL, Faienza MF, Scicchitano P, Cortese F, Gesualdo M, Zito A, Basile M, Recchia P, Leogrande D, Viola D, et al. Insulin resistance and endothelial function in children and adolescents. Int J Cardiol. 2014;174(2):343–7.CrossRef Miniello VL, Faienza MF, Scicchitano P, Cortese F, Gesualdo M, Zito A, Basile M, Recchia P, Leogrande D, Viola D, et al. Insulin resistance and endothelial function in children and adolescents. Int J Cardiol. 2014;174(2):343–7.CrossRef
27.
go back to reference Shah AS, Gao Z, Urbina EM, Kimball TR, Dolan LM. Prediabetes: the effects on arterial thickness and stiffness in obese youth. J Clin Endocrinol Metab. 2014;99(3):1037–43.CrossRef Shah AS, Gao Z, Urbina EM, Kimball TR, Dolan LM. Prediabetes: the effects on arterial thickness and stiffness in obese youth. J Clin Endocrinol Metab. 2014;99(3):1037–43.CrossRef
28.
go back to reference Hughan KS, Tfayli H, Warren-Ulanch JG, Barinas-Mitchell E, Arslanian SA. Early biomarkers of subclinical atherosclerosis in obese adolescent girls with polycystic ovary syndrome. J Pediatr. 2016;168:104–111.e101.CrossRef Hughan KS, Tfayli H, Warren-Ulanch JG, Barinas-Mitchell E, Arslanian SA. Early biomarkers of subclinical atherosclerosis in obese adolescent girls with polycystic ovary syndrome. J Pediatr. 2016;168:104–111.e101.CrossRef
29.
go back to reference Eikendal AL, Evelein AM, Uiterwaal CS, van der Ent CK, Visseren FL, Bots ML, Hoefer IE, den Ruijter HM, Dalmeijer GW. Relation between circulating inflammatory chemokines and vascular characteristics in healthy, young children. J Am Heart Assoc. 2015;4(12). Eikendal AL, Evelein AM, Uiterwaal CS, van der Ent CK, Visseren FL, Bots ML, Hoefer IE, den Ruijter HM, Dalmeijer GW. Relation between circulating inflammatory chemokines and vascular characteristics in healthy, young children. J Am Heart Assoc. 2015;4(12).
30.
go back to reference Atabek ME, Pirgon O, Kivrak AS. Evidence for association between insulin resistance and premature carotid atherosclerosis in childhood obesity. Pediatr Res. 2007;61(3):345–9.CrossRef Atabek ME, Pirgon O, Kivrak AS. Evidence for association between insulin resistance and premature carotid atherosclerosis in childhood obesity. Pediatr Res. 2007;61(3):345–9.CrossRef
31.
go back to reference Marmot MG, Elliott P: Coronary heart disease epidemiology: from aetiology to public health: Oxford Medical Publications; 2005. Marmot MG, Elliott P: Coronary heart disease epidemiology: from aetiology to public health: Oxford Medical Publications; 2005.
32.
go back to reference Freedman DS, Patel DA, Srinivasan SR, Chen W, Tang R, Bond MG, Berenson GS. The contribution of childhood obesity to adult carotid intima-media thickness: the Bogalusa heart study. Int J Obes. 2008;32(5):749–56.CrossRef Freedman DS, Patel DA, Srinivasan SR, Chen W, Tang R, Bond MG, Berenson GS. The contribution of childhood obesity to adult carotid intima-media thickness: the Bogalusa heart study. Int J Obes. 2008;32(5):749–56.CrossRef
Metadata
Title
Insulin metabolism markers are predictors of subclinical atherosclerosis among overweight and obese children and adolescents
Authors
Golaleh Asghari
Pooneh Dehghan
Parvin Mirmiran
Emad Yuzbashian
Maryam Mahdavi
Maryam Tohidi
Tirang R. Neyestani
Farhad Hosseinpanah
Fereidoun Azizi
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2018
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-018-1347-9

Other articles of this Issue 1/2018

BMC Pediatrics 1/2018 Go to the issue