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Licensed Unlicensed Requires Authentication Published by De Gruyter July 27, 2017

Concentrations of leptin, adiponectin and other metabolic parameters in non-obese children with Down syndrome

Nikhil Tenneti, Devi Dayal, Sheetal Sharda, Inusha Panigrahi, Mohammed Didi, Savita Verma Attri, Naresh Sachdeva and Anil Kumar Bhalla

Abstract

Background:

Recent data indicates that adults with Down syndrome (DS) are at increased risk for cardiovascular disease (CVD) that significantly contributes to their morbidity and mortality. Although identification of cardiometabolic risk factors during childhood is desirable to design preventive interventions, the data on such risk factors in children with DS is scarce. The aim of this study was to study the cardiometabolic risk factors such as insulin resistance (IR), leptin and adiponectin concentrations, lipid abnormalities and leptin resistance in non-obese children with DS.

Methods:

This cross-sectional case control study included karyotype confirmed trisomy-21 DS children aged 2–12 years and their matched healthy controls. After detailed anthropometry, weight, height and body mass index (BMI) standard deviation scores (SDSs) were calculated with reference data. Laboratory evaluation included determination of fasting lipid parameters, insulin, glucose, leptin and adiponectin concentrations. The homeostasis model assessment method (HOMA-IR) was used to assess IR and the ratio of leptin to BMI was used as an index of leptin resistance.

Results:

Seventy-seven children (39 with DS and 38 controls) comprised the study cohort. The anthropometric parameters were similar in the two groups. Children with DS showed significantly higher mean leptin concentrations (2.098±1.68 ng/mL vs. 1.44±0.52 ng/mL, p-value: 0.00) and higher indices of leptin resistance (0.127±0.085 vs. 0.09±0.03, p-value: 0.001) as compared to controls. Fasting adiponectin concentrations were lower (20.64±19.87 ng/mL vs. 32.58±34.25 ng/mL, p-value: 0.21) and fasting glucose higher (89.25±8.12 mg/dL vs. 85.71±5.52 mg/dL, p-value: 0.06) in the DS group as compared to the controls but the differences did not reach statistical significance. The concentrations of insulin, various lipid parameters and calculated HOMA-IR values were similar in the two groups. In the DS group, five children were identified to have high (>75th centile) leptin levels and four as impaired fasting glucose as compared to none in the controls.

Conclusions:

Alterations of several cardiometabolic risk factors, in particular, leptin concentrations and leptin resistance are present in children with DS. The presence of hyperleptinemia without hyperinsulinemia suggests a probable inherent genetic basis for increased leptin resistance in patients with DS. There is a need for larger studies to further understand increased leptin resistance in DS that may contribute to increased CVD related morbidity and mortality in these patients.


Corresponding author: Dr. Devi Dayal, MD, Professor, Pediatric Endocrinology and Diabetes Unit, Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India, Phone: 0091-172-2755657 (O), 0091-172-2772777 (R), Fax: 0091-172-2744401; 2745078, E-mail:

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

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Murdoch JC, Rodger JC, Rao SS, Fletcher CD, Dunnigan MG. Down’s syndrome: an atheroma-free model? Br Med J 1977;2:226–8.Search in Google Scholar

2. Ylä-Herttuala S, Luoma J, Nikkari T, Kivimäki T. Down’s syndrome and atherosclerosis. Atherosclerosis 1989;76:269–72.Search in Google Scholar

3. Glasson EJ, Sullivan SG, Hussain R, Petterson BA, Montgomery PD, et al. The changing survival profile of people with Down’s syndrome: implications for genetic counselling. Clin Genet 2002;62:390–3.Search in Google Scholar

4. Englund A, Jonsson B, Zander CS, Gustafsson J, Annerén G. Changes in mortality and causes of death in the Swedish Down syndrome population. Am J Med Genet A 2013;161A:642–9.Search in Google Scholar

5. Hosking FJ, Carey IM, Shah SM, Harris T, DeWilde S, et al. Mortality among adults with intellectual disability in England: comparisons with the general population. Am J Public Health 2016;106:1483–90.Search in Google Scholar

6. Real de Asua D, Parra P, Costa R, Moldenhauer F, Suarez C. Evaluation of the impact of abdominal obesity on glucose and lipid metabolism disorders in adults with Down syndrome. Res Dev Disabil 2014;35:2942–9.Search in Google Scholar

7. Bertapelli F, Pitetti K, Agiovlasitis S, Guerra-Junior G. Overweight and obesity in children and adolescents with Down syndrome-prevalence, determinants, consequences, and interventions: a literature review. Res Dev Disabil 2016;57:181–92.Search in Google Scholar

8. Magge SN, O’Neill KL, Shults J, Stallings VA, Stettler N. Leptin levels among prepubertal children with Down syndrome compared with their siblings. J Pediatr 2008;152:321–6.Search in Google Scholar

9. Yahia S, El-Farahaty RM, El-Hawary AK, El-Hussiny MA, Abdel-Maseih H, et al. Leptin, insulin and thyroid hormones in a cohort of Egyptian obese Down syndrome children: a comparative study. BMC Endocr Disord 2012;12:22.Search in Google Scholar

10. Clavijo A, Guerrero-Lozano R, Camacho AE. Increased leptin levels in children with Down’s syndrome. Gastroenterology AGA 2012;142:S560.Search in Google Scholar

11. Adelekan T, Magge S, Shults J, Stallings V, Stettler N. Lipid profiles of children with Down syndrome compared with their siblings. Pediatrics 2012;129:e1382–7.Search in Google Scholar

12. Buonuomo PS, Bartuli A, Mastrogiorgio G, Vittucci A, Di Camillo C, et al. Lipid profiles in a large cohort of Italian children with Down syndrome. Eur J Med Genet 2016;59:392–5.Search in Google Scholar

13. Das R, Sarker A, Saha H, Bin Shahid AS, Shahunja KM, et al. Experience with clinically diagnosed Down syndrome children admitted with diarrhea in an urban hospital in Bangladesh. Int Sch Res Notices 2015;2015:979404.Search in Google Scholar

14. Tanner JM. Growth at adolescence, 2nd ed. Oxford: Blackwell Publications, 1962.Search in Google Scholar

15. Zemel BS, Pipan M, Stallings VA, Hall W, Schadt K, et al. Growth charts for children with Down syndrome in the United States. Pediatrics 2015;136:e1204–11.Search in Google Scholar

16. WHO AnthroPlus for Personal Computers Manual: Software for Assessing Growth of the World’s Children and Adolescents. WHO, Geneva 2009. Available at: http://www.who.int/growthref/tools/en (accessed 1–15 August, 2016).Search in Google Scholar

17. Madeira IR, Bordallo MA, Carvalho CN, Gazolla FM, de Souza FM, et al. The role of metabolic syndrome components and adipokines in insulin resistance in prepubertal children. J Pediatr Endocrinol Metab 2011;24:289–95.Search in Google Scholar

18. Singh Y, Garg MK, Tandon N, Marwaha RK. A study of insulin resistance by HOMA-IR and its cut-off value to identify metabolic syndrome in urban Indian adolescents. J Clin Res Pediatr Endocrinol 2013;5:245–51.Search in Google Scholar

19. Khalil A, Gupta S, Madan A, Venkatesan M. Lipid profile norms in Indian children. Indian Pediatr 1995;32:1177–80.Search in Google Scholar

20. Erhardt E, Foraita R, Pigeot I, Barba G, Veidebaum T, et al. Reference values for leptin and adiponectin in children below the age of 10 based on the IDEFICS cohort. Int J Obes (Lond) 2014;38:S32–8.Search in Google Scholar

21. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, et al. Serum immunoreactive leptin concentrations in normal-weight and obese humans. N Engl J Med 1996;334:292–5.Search in Google Scholar

22. Pietrobelli A, Allison DB, Faith MS, Beccaria L, Bosio L, et al. Prader-Willi syndrome: relationship of adiposity to plasma leptin levels. Obes Res 1998;6:196–201.Search in Google Scholar

23. Goldstone AP, Brynes AE, Thomas EL, Bell JD, Frost G, et al. Resting metabolic rate, plasma leptin concentrations, leptin receptor expression, and adipose tissue measured by whole-body magnetic resonance imaging in women with Prader-Willi syndrome. Am J Clin Nutr 2002;75:468–75.Search in Google Scholar

24. Kennedy L, Bittel DC, Kibiryeva N, Kalra SP, Torto R, et al. Circulating adiponectin levels, body composition and obesity-related variables in Prader-Willi syndrome: comparison with obese subjects. Int J Obes (Lond) 2006;30:382–7.Search in Google Scholar

25. Rosenbaum M, Pietrobelli A, Vasselli JR, Heymsfield SB, Leibel RL. Sexual dimorphism in circulating leptin concentrations is not accounted for by differences in adipose tissue distribution. Int J Obes Relat Metab Disord 2001;25:1365–71.Search in Google Scholar

26. Garcia-Mayor RV, Andrade MA, Rios M, Lage M, Dieguez C, et al. Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. J Clin Endocrinol Metab 1997;82:2849–55.Search in Google Scholar

27. Blum WF, Englaro P, Hanitsch S, Juul A, Hertel NT, et al. Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab 1997;82:2904–10.Search in Google Scholar

28. Shimada K, Miyazaki T, Daida H. Adiponectin and atherosclerosis disease. Clinica Chimica Acta 2004;344:1–12.Search in Google Scholar

29. Saarikoski LA, Juonala M, Huupponen R, Viikari JS, Lehtimäki T, et al. Low serum adiponectin levels in childhood and adolescence predict increased intima-media thickness in adulthood. The Cardiovascular Risk in Young Finns Study. Ann Med 2017;49:42–50.Search in Google Scholar

30. Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta 2013;417:80–4.Search in Google Scholar

31. Yamagishi SI, Nakamura N, Matsui T. Glycation and cardiovascular disease in diabetes: a perspective on the concept of metabolic memory. J Diabetes 2017;9:141–8.Search in Google Scholar

32. 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.Search in Google Scholar

33. Miras M, Ochetti M, Martín S, Silvano L, Sobrero G, et al. Serum levels of adiponectin and leptin in children born small for gestational age: relation to insulin sensitivity parameters. J Pediatr Endocrinol Metab 2010;23:463–71.Search in Google Scholar

34. Al-Harithy RN. Relationship of leptin concentration to gender, body mass index and age in Saudi adults. Saudi Med J 2004;25:1086–90.Search in Google Scholar

35. Wendel D, Weber D, Leonard MB, Magge SN, Kelly A, et al. Body composition estimation using skinfolds in children with and without health conditions affecting growth and body composition. Ann Hum Biol 2017;44:108–120.Search in Google Scholar

Received: 2016-11-6
Accepted: 2017-7-3
Published Online: 2017-7-27
Published in Print: 2017-8-28

©2017 Walter de Gruyter GmbH, Berlin/Boston