Home Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach
Article
Licensed
Unlicensed Requires Authentication

Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach

  • Irine-Ikbale Sakou EMAIL logo , Theodora Psaltopoulou , Theodoros N. Sergentanis , Kyriaki Karavanaki , Feneli Karachaliou , Ioannis Ntanasis-Stathopoulos , Stamatios Tzanninis , Triantafyllia Sdogou , Donald Greydanus and Artemis Tsitsika
Published/Copyright: March 7, 2015
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 28 Issue 5-6

Abstract

Background: This study aims to globally assess the network of insulin resistance (IR)-related factors in a sample of overweight and obese Greek youths.

Methods: A total of 185 subjects were examined, and IR was quantified by homeostasis model assessment (HOMA-IR). Multivariate hierarchical approach was performed, and five distinct levels were recognized, namely, immutable demographic features and early life parameters, current anthropometric measures, IR, unfavorable clinical conditions, and social parameters. Two analyses were performed based on HOMA-IR cut-off values (3.16 and, as an alternative, 3.99).

Results: Obesity was associated with IR (adjusted OR=3.19, 95% CI: 1.12–9.09). IR steadily predicted low HDL (adjusted OR=5.75, 95% CI: 1.58–20.87), hypertriglyceridemia (adjusted OR=10.28, 95% CI: 1.18–89.55), and systolic hypertension. At the alternative analysis, IR was also associated with older age, older age at menarche, hyperuricemia, and low school grades.

Conclusion: Emerging on the grounds of obesity, IR confers risks for dyslipidemia and hypertension at a relatively early age. Along with weight loss, interventions targeted at IR are required to prevent cardiometabolic risk in adolescence.

Keywords: adolescents; cardiometabolic risk factors; insulin resistance; obesity
Corresponding author: Irine-Ikbale Sakou, Adolescent Health Unit (AHU), University of Athens, Second Department of Pediatrics, “P&A Kyriakou”, Children’s Hospital, Athens, Greece, Phone: (0030) 210-7710824, Fax: (0030) 210-7710824, E-mail:

Acknowledgments

The authors wish to thank Ms. Eleni C. Tzavela for final editing.

Conflict of interest statement: None declared.

References

1. Dietz WH. Overweight in childhood and adolescence. N Engl J Med 2004;350:855–7.10.1056/NEJMp048008Search in Google Scholar PubMed

2. Tzotzas T, Kapantais E, Tziomalos K, Ioannidis I, Mortoglou A, et al. Epidemiological survey for the prevalence of overweight and abdominal obesity in Greek adolescents. Obesity 2008;16:1718–22.10.1038/oby.2008.247Search in Google Scholar PubMed

3. Nathan BM, Moran A. Metabolic complications of obesity in childhood and adolescence:more than just diabetes. Curr Opin Endocrinol Diabetes Obes 2008;15:21–9.10.1097/MED.0b013e3282f43d19Search in Google Scholar PubMed

4. Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, Druet C, et al. Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab 2010;95:5189–98.10.1210/jc.2010-1047Search in Google Scholar PubMed PubMed Central

5. Huang RC, Mori TA, Beilin LJ. Early life programming of cardiometabolic disease in the Western Australian pregnancy cohort (Raine) study. Clin Exp Pharmacol Physiol 2012;39:973–8.10.1111/j.1440-1681.2012.05746.xSearch in Google Scholar PubMed

6. Ten S, Maclaren N. Insulin resistance syndrome in children. J Clin Endocrinol Metab 2004;89:2526–39.10.1210/jc.2004-0276Search in Google Scholar PubMed

7. Ramachandran A, Snehalatha C, Yamuna A, Murugesan N, Narayan KM. Insulin resistance and clustering of cardiometabolic risk factors in urban teenagers in southern India. Diabetes Care 2007;30:1828–1833.10.2337/dc06-2097Search in Google Scholar PubMed

8. Sinaiko AR, Steinberger J, Moran A, Prineas RJ, Vessby B, et al. Relation of body mass index and insulin resistance to cardiovascular risk factors, inflammatory factors, and oxidative stress during adolescence. Circulation 2005;111:1985–1991.10.1161/01.CIR.0000161837.23846.57Search in Google Scholar PubMed

9. Lee JM, Okumura MJ, Davis MM, Herman WH, Gurney JG. Prevalence and determinants of insulin resistance among U.S. adolescents: a population-based study. Diabetes Care 2006;29:2427–32.10.2337/dc06-0709Search in Google Scholar PubMed

10. Cnattingius S, Villamor E, Lagerros YT, Wikström AK, Granath F. High birth weight and obesity--a vicious circle across generations. Int J Obes (Lond) 2012;36:1320–4.10.1038/ijo.2011.248Search in Google Scholar PubMed

11. Goodman E, Daniels SR, Dolan LM. Socioeconomic disparities in insulin resistance: results from the Princeton School District Study. Psychosom Med 2007;69:61–7.10.1097/01.psy.0000249732.96753.8fSearch in Google Scholar PubMed

12. Lawlor DA, Harro M, Wedderkopp N, Andersen LB, Sardinha LB, et al. Association of socioeconomic position with insulin resistance among children from Denmark, Estonia, and Portugal: cross sectional study. BMJ 2005;331:183.10.1136/bmj.331.7510.183Search in Google Scholar PubMed PubMed Central

13. Kalogeromitros D, Makris MP, Chliva C, Sergentanis TN, Church MK, et al. An internet survey on self-reported food allergy in Greece: clinical aspects and lack of appropriate medical consultation. J Eur Acad Dermatol Venereol 2013;27:558–64.10.1111/j.1468-3083.2012.04482.xSearch in Google Scholar PubMed

14. Papadodima SA, Sakelliadis EI, Sergentanis TN Giotakos O, Sergentanis IN, et al. Smoking in prison: a hierarchical approach at the crossroad of personality and childhood events. Eur J Public Health 2010;20:470–4.10.1093/eurpub/ckp209Search in Google Scholar PubMed

15. 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;115:500–3.10.1542/peds.2004-1921Search in Google Scholar PubMed

16. Wahrenberg H, Hertel K, Leijonhufvud BM, Persson LG, Toft E, et al. Use of waist circumference to predict insulin resistance: retrospective study. BMJ 2005;330:1363–4.10.1136/bmj.38429.473310.AESearch in Google Scholar PubMed PubMed Central

17. Schwartz B, Jacobs Jr DR, Moran A, Steinberger J, Hong CP, et al. Measurement of insulin sensitivity in children: comparison between the euglycemic-hyperinsulinemic clamp and surrogate measures. Diabetes Care 2008;31:783–8.10.2337/dc07-1376Search in Google Scholar PubMed

18. Jelastopulu E, Kallianezos P, Merekoulias G, Alexopoulos EC, Sapountzi-Krepia D. Prevalence and risk factors of excess weight in school children in West Greece. Nurs Health Sci 2012;14:372–80.10.1111/j.1442-2018.2012.00691.xSearch in Google Scholar PubMed

19. Papoutsakis C, Yannakoulia M, Ntalla I, Dedoussis GV. Metabolic syndrome in a Mediterranean pediatric cohort: prevalence using International Diabetes Federation-derived criteria and associations with adiponectin and leptin. Metabolism 2012;61:140–5.10.1016/j.metabol.2011.06.006Search in Google Scholar PubMed

20. Roditis ML, Parlapani ES, Tzotzas T, Hassapidou M, Krassas GE. Epidemiology and predisposing factors of obesity in Greece: from the Second World War until today. J Pediatr Endocrinol Metab 2009;22:389–405.10.1515/JPEM.2009.22.5.389Search in Google Scholar PubMed

21. Kuczmarski RJ1, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 2002;11:1–190.Search in Google Scholar

22. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.10.1007/BF00280883Search in Google Scholar PubMed

23. 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: 555–76.10.1542/peds.114.2.S2.555Search in Google Scholar

24. Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, et al. IDF Consensus Group. The metabolic syndrome in children and adolescents – an IDF consensus report. Pediatr Diabetes 2007;8:299–306.10.1111/j.1399-5448.2007.00271.xSearch in Google Scholar PubMed

25. Daniels SR, Greer FR. Committee on Nutrition. Lipid screening and cardiovascular health in childhood. Pediatrics 2008;122:198–208.10.1542/peds.2008-1349Search in Google Scholar PubMed

26. Geiger SD, Xiao J, Shankar A. Positive association between perfluoroalkyl chemicals and hyperuricemia in children. Am J Epidemiol 2013;177:1255–62.10.1093/aje/kws392Search in Google Scholar PubMed PubMed Central

27. Mayo Clinic Laboratories. Pediatric Test Reference Values. http://www.mayomedicallaboratories.com/test-info/pediatric/refvalues/ (Accessed on January 01, 2014).Search in Google Scholar

28. Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 1961;21:1440–7.10.1210/jcem-21-11-1440Search in Google Scholar PubMed

29. Gandhe MB, ML, Srinivasan AR. Evaluation of body mass index (BMI) percentile cut-off levels with reference to insulin resistance: A comparative study on south Indian obese and non-obese adolescents. J Clin Diagn Res 2013;7:1579–82.10.7860/JCDR/2013/6263.3213Search in Google Scholar PubMed PubMed Central

30. Bokor S, Frelut ML, Vania A, Hadjiathanasiou CG, Anastasakou M, et al. Prevalence of metabolic syndrome in European obese children. Int J Pediatr Obes 2008;1:3–8.10.1080/17477160802404509Search in Google Scholar PubMed

31. Rizzo AC, Goldberg TD, Silva CC, Kurokawa CS, Nunes HR, et al. Metabolic syndrome risk factors in overweight, obese and extremely obese Brazilian adolescents. Nutr J 2013;12:19.10.1186/1475-2891-12-19Search in Google Scholar PubMed PubMed Central

32. Ehtisham S, Crabtree N, Clark P, Shaw N, Barrett T. Ethnic differences in insulin resistance and body composition in United Kingdom adolescents. J Clin Endocrinol Metab 2005;90:3963–9.10.1210/jc.2004-2001Search in Google Scholar PubMed

33. Ortega FB, Ruiz JR, Labayen I, Martínez-Gómez D, Vicente-Rodriguez G, et al. Health inequalities in urban adolescents: role of physical activity, diet, and genetics. Pediatrics. 2014;133 (Abstract only).10.1542/peds.2013-1665Search in Google Scholar

34. Aguilar-Salinas CA, Olaiz G, Valles V, Torres JM, Gómez Pérez FJ, et al. High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey. J Lipid Res 2001;42:1298–307.10.1016/S0022-2275(20)31581-9Search in Google Scholar

35. Ruotolo G, Howard BV. Dyslipidemia of the metabolic syndrome. Curr Cardiol Rep 2002;4:494–500.10.1007/s11886-002-0113-6Search in Google Scholar PubMed

36. Borggreve SE, De Vries R, Dullaart RP. Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin: cholesterol acyltransferase and lipid transfer proteins. Eur J Clin Invest 2003;33:1051–69.10.1111/j.1365-2362.2003.01263.xSearch in Google Scholar PubMed

37. Kotchen TA. Obesity-related hypertension: epidemiology, pathophysiology, and clinical management. Am J Hypertens 2010;23:1170–8.10.1038/ajh.2010.172Search in Google Scholar PubMed

38. Fang C, Lei J, Zhou SX, Zhang YL, Yuan GY, et al. Association of higher resistin levels with inflammatory activation and endothelial dysfunction in patients with essential hypertension. Chin Med J (Engl) 2013;126:646–9.Search in Google Scholar

39. Makni E, Moalla W, Benezzeddine-Boussaidi L, Lac G, Tabka Z, et al. Correlation of resistin with inflammatory and cardiometabolic markers in obese adolescents with and without metabolic syndrome. Obes Facts 2013;6:393–404.10.1159/000354574Search in Google Scholar PubMed PubMed Central

40. Raab J, Haupt F, Kordonouri O, Scholz M, Wosch A, et al. Continuous rise of insulin resistance before and after the onset of puberty in children at increased risk for type 1 diabetes-a cross-sectional analysis. Diabetes Metab Res Rev 2013;29:631–5.10.1002/dmrr.2438Search in Google Scholar PubMed

41. Remsberg KE, Demerath EW, Schubert CM, Chumlea WC, Sun SS, et al. Early menarche and the development of cardiovascular disease risk factors in adolescent girls: the Fels Longitudinal Study. J Clin Endocrinol Metab 2005;90:2718–24.10.1210/jc.2004-1991Search in Google Scholar PubMed

42. Glueck CJ, Morrison JA, Wang P, Woo JG. Early and late menarche are associated with oligomenorrhea and predict metabolic syndrome 26 years later. Metabolism 2013;62:1597–1606.10.1016/j.metabol.2013.07.005Search in Google Scholar PubMed

43. Santos RD. Elevated uric acid, the metabolic syndrome and cardiovascular disease: cause, consequence, or just a not so innocent bystander? Endocrine 2012;41:350–2.10.1007/s12020-012-9657-4Search in Google Scholar PubMed

44. Cardoso AS, Gonzaga NC, Medeiros CC, Carvalho DF. Association of uric acid levels with components of metabolic syndrome and non-alcoholic fatty liver disease in overweight or obese children and adolescents. J Pediatr (Rio J) 2013;89:412–8.10.1016/j.jped.2012.12.008Search in Google Scholar PubMed

45. Wilson SM, Sato AF. Stress and paediatric obesity: what we know and where to go. Stress Health 2014;30:91–102.10.1002/smi.2501Search in Google Scholar PubMed

46. Yau PL, Castro MG, Tagani A, Tsui WH, Convit A. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics 2012;130:856–64.10.1542/peds.2012-0324Search in Google Scholar PubMed PubMed Central

Supplemental Material

The online version of this article (DOI: 10.1515/jpem-2014-0431) offers supplementary material, available to authorized users.

Received: 2014-10-13
Accepted: 2015-1-21
Published Online: 2015-3-7
Published in Print: 2015-5-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Obesity
  3. Childhood obesity at the crossroads
  4. Obesogenic environments: environmental approaches to obesity prevention
  5. Childhood obesity and eating behaviour
  6. Hypothalamic obesity in children: pathophysiology to clinical management
  7. The reliability of body mass index in the diagnosis of obesity and metabolic risk in children
  8. Determining abdominal obesity cut-offs and relevant risk factors for anthropometric indices in Turkish children and adolescents
  9. The effect of body mass index on blood pressure varies by race among obese children
  10. Insulin secretion response during oral glucose tolerance test is related to low cardiorespiratory fitness in obese adolescents
  11. Is there a relationship between cardiovascular risk factors and dehydroepiandrosterone sulfate levels in childhood obesity?
  12. The effect of lifestyle change and metformin therapy on serum arylesterase and paraoxonase activity in obese children
  13. Childhood obesity, thyroid function, and insulin resistance – is there a link? A longitudinal study
  14. Associations between IGF-I, IGF-binding proteins and bone turnover markers in prepubertal obese children
  15. Osteocalcin is inversely associated with adiposity and leptin in adolescent boys
  16. Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children
  17. Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach
  18. The role of apolipoprotein E polymorphism in improving dyslipidemia in obese adolescents following physical exercise and National Cholesterol Education Program Step II intervention
  19. Review article
  20. Is ultrasound useful in the diagnosis of adolescents with polycystic ovary syndrome?
  21. Original articles
  22. IGF-II expression and methylation in small for gestational age infants
  23. Early screening of FTO and MC4R variants in newborns of Greek origin
  24. Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency
  25. The prevalence of vitamin D deficiency among schoolchildren: a cohort study from Xinxiang, China
  26. Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?
  27. Vitamin D status and its associations with components of metabolic syndrome in healthy children
  28. Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome
  29. Patient reports
  30. Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene
  31. Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy
  32. An asymptomatic mother diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency after newborn screening
  33. A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)
  34. Ovotesticular disorder of sex development with unusual karyotype: patient report
  35. First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China
  36. Virilizing adrenal oncocytoma in a 9-year-old girl: rare neoplasm with an intriguing postoperative course
  37. Unexpected clinical features in a female patient with proopiomelanocortin (POMC) deficiency
  38. Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation
  39. Cross-reactivity of adrenal steroids with aldosterone may prevent the accurate diagnosis of congenital adrenal hyperplasia
  40. Hyperthyroidism hidden by congenital central hypoventilation syndrome
  41. The use of pamidronate for acute vitamin D intoxication, clinical experience with three cases
  42. Chondrocalcinosis related to familial hypomagnesemia with hypercalciuria and nephrocalcinosis
  43. Cushing syndrome related to leukemic infiltration of the central nervous system
  44. Hashimoto’s encephalopathy: a rare pediatric brain disease
  45. Short communication
  46. A novel ABCD1 gene mutation in a Chinese patient with X-linked adrenoleukodystrophy
https://doi.org/10.1515/jpem-2014-0431
Keywords for this article
adolescents; cardiometabolic risk factors; insulin resistance; obesity

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Obesity
  3. Childhood obesity at the crossroads
  4. Obesogenic environments: environmental approaches to obesity prevention
  5. Childhood obesity and eating behaviour
  6. Hypothalamic obesity in children: pathophysiology to clinical management
  7. The reliability of body mass index in the diagnosis of obesity and metabolic risk in children
  8. Determining abdominal obesity cut-offs and relevant risk factors for anthropometric indices in Turkish children and adolescents
  9. The effect of body mass index on blood pressure varies by race among obese children
  10. Insulin secretion response during oral glucose tolerance test is related to low cardiorespiratory fitness in obese adolescents
  11. Is there a relationship between cardiovascular risk factors and dehydroepiandrosterone sulfate levels in childhood obesity?
  12. The effect of lifestyle change and metformin therapy on serum arylesterase and paraoxonase activity in obese children
  13. Childhood obesity, thyroid function, and insulin resistance – is there a link? A longitudinal study
  14. Associations between IGF-I, IGF-binding proteins and bone turnover markers in prepubertal obese children
  15. Osteocalcin is inversely associated with adiposity and leptin in adolescent boys
  16. Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children
  17. Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach
  18. The role of apolipoprotein E polymorphism in improving dyslipidemia in obese adolescents following physical exercise and National Cholesterol Education Program Step II intervention
  19. Review article
  20. Is ultrasound useful in the diagnosis of adolescents with polycystic ovary syndrome?
  21. Original articles
  22. IGF-II expression and methylation in small for gestational age infants
  23. Early screening of FTO and MC4R variants in newborns of Greek origin
  24. Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency
  25. The prevalence of vitamin D deficiency among schoolchildren: a cohort study from Xinxiang, China
  26. Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?
  27. Vitamin D status and its associations with components of metabolic syndrome in healthy children
  28. Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome
  29. Patient reports
  30. Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene
  31. Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy
  32. An asymptomatic mother diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency after newborn screening
  33. A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)
  34. Ovotesticular disorder of sex development with unusual karyotype: patient report
  35. First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China
  36. Virilizing adrenal oncocytoma in a 9-year-old girl: rare neoplasm with an intriguing postoperative course
  37. Unexpected clinical features in a female patient with proopiomelanocortin (POMC) deficiency
  38. Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation
  39. Cross-reactivity of adrenal steroids with aldosterone may prevent the accurate diagnosis of congenital adrenal hyperplasia
  40. Hyperthyroidism hidden by congenital central hypoventilation syndrome
  41. The use of pamidronate for acute vitamin D intoxication, clinical experience with three cases
  42. Chondrocalcinosis related to familial hypomagnesemia with hypercalciuria and nephrocalcinosis
  43. Cushing syndrome related to leukemic infiltration of the central nervous system
  44. Hashimoto’s encephalopathy: a rare pediatric brain disease
  45. Short communication
  46. A novel ABCD1 gene mutation in a Chinese patient with X-linked adrenoleukodystrophy
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 18.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2014-0431/html
Scroll to top button