Leptin-adiponectin imbalance as a marker of metabolic syndrome among Chinese children and adolescents: The BCAMS study

Ge Li, Linxin Xu, Yanglu Zhao, Lujiao Li, Junling Fu, Qian Zhang, Naishi Li, Xinhua Xiao, Changhong Li, Jie Mi, Shan Gao, Ming Li, Ge Li, Linxin Xu, Yanglu Zhao, Lujiao Li, Junling Fu, Qian Zhang, Naishi Li, Xinhua Xiao, Changhong Li, Jie Mi, Shan Gao, Ming Li

Abstract

Purpose: Leptin and adiponectin have opposite effects on subclinical inflammation and insulin resistance, both involved in the development of metabolic syndrome (MS). We aimed to investigate whether leptin/adiponectin ratio (L/A), as a marker of these two adipokines imbalance, may improve diagnosis of MS in children and adolescents, and determined its cut-off value in the diagnosis of MS.

Methods: A total of 3,428 subjects aged 6-18 years were selected from Beijing Child and Adolescent Metabolic Syndrome study. Adipokine leptin and adiponectin were measured using enzyme-linked immunosorbent assay. Odds ratio of MS per 1 z-score of adipokine was examined using logistic regression. Diagnosis accuracy was assessed using c-statistics (AUC) and net reclassification index.

Results: The levels of leptin and L/A increased with number of positive MS components, while the levels of adiponectin declined in both boys and girls (all P <0.001). AUCs for diagnosis of MS in girls were 0.793, 0.773, and 0.689 using L/A, leptin and adiponectin, respectively; and AUCs in boys were 0.822, 0.798, and 0.697 for L/A, leptin and adiponectin, respectively. Notably, L/A outperformed individual leptin or adiponectin in discriminating a diagnosis of MS (all P < 0.02 in AUC comparisons). In addition, the optimal cut-offs of L/A by ROC curve differed by genders and pubertal stages, which were 1.63, 1.28, 1.95 and 1.53 ng/ug for total, pre-, mid- and postpubertal boys, respectively and 2.19, 0.87,1.48 and 2.27 ng/ug for total, pre-, mid- and postpubertal girls, respectively, yielding high sensitivity and moderate specificity for a screening test.

Conclusions: In this pediatric population, leptin-adiponectin imbalance, as reflected by an increase in L/A level, was found to be a better diagnostic biomarker for MS than leptin or adiponectin alone. Future longitudinal studies are needed to further validate the gender-specific cutoff values.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow chart.
Fig 1. Flow chart.

References

    1. Steinberger J, Daniels SR, Eckel RH, Hayman L, Lustig RH, McCrindle B, et al. Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2009;119(4):628–47. doi: .
    1. Tailor AM, Peeters PH, Norat T, Vineis P, Romaguera D. An update on the prevalence of the metabolic syndrome in children and adolescents. International journal of pediatric obesity. 2010;5(3):202–13. doi: .
    1. Korner A, Kratzsch J, Gausche R, Schaab M, Erbs S, Kiess W. New predictors of the metabolic syndrome in children—role of adipocytokines. Pediatric Research. 2007;61(6):640–5. doi: .
    1. Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, et al. The metabolic syndrome in children and adolescents—an IDF consensus report. Pediatric diabetes. 2007;8(5):299–306. Epub 2007/09/14. doi: .
    1. Fasshauer M, Bluher M. Adipokines in health and disease. Trends in pharmacological sciences. 2015;36(7):461–70. doi: .
    1. Perez-Perez A, Vilarino-Garcia T, Fernandez-Riejos P, Martin-Gonzalez J, Segura-Egea JJ, Sanchez-Margalet V. Role of leptin as a link between metabolism and the immune system. Cytokine & Growth Factor Reviews. 2017. doi: .
    1. Sainz N, Barrenetxe J, Moreno-Aliaga MJ, Martinez JA. Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism: clinical and experimental. 2015;64(1):35–46. Epub 2014/12/17. doi: .
    1. Erhardt E, Foraita R, Pigeot I, Barba G, Veidebaum T, Tornaritis M, et al. Reference values for leptin and adiponectin in children below the age of 10 based on the IDEFICS cohort. International journal of obesity. 2014;38 Suppl 2:S32–8. Epub 2014/09/16. doi: .
    1. Cambuli VM, Musiu MC, Incani M, Paderi M, Serpe R, Marras V, et al. Assessment of adiponectin and leptin as biomarkers of positive metabolic outcomes after lifestyle intervention in overweight and obese children. The Journal of clinical endocrinology and metabolism. 2008;93(8):3051–7. Epub 2008/05/22. doi: .
    1. Alikasifoglu A, Gonc N, Ozon ZA, Sen Y, Kandemir N. The relationship between serum adiponectin, tumor necrosis factor-alpha, leptin levels and insulin sensitivity in childhood and adolescent obesity: adiponectin is a marker of metabolic syndrome. Journal of Clinical Research in Pediatric Endocrinology. 2009;1(5):233–9. Epub 2009/09/01. doi: ; PubMed Central PMCID: PMCPMC3005745.
    1. Zhuo Q, Wang Z, Fu P, Piao J, Tian Y, Xu J, et al. Comparison of adiponectin, leptin and leptin to adiponectin ratio as diagnostic marker for metabolic syndrome in older adults of Chinese major cities. Diabetes research and clinical practice. 2009;84(1):27–33. doi: .
    1. Mirza S, Qu HQ, Li Q, Martinez PJ, Rentfro AR, McCormick JB, et al. Adiponectin/leptin ratio and metabolic syndrome in a Mexican American population. Clinical and investigative medicine. 2011;34(5):E290 Epub 2011/10/05. ; PubMed Central PMCID: PMCPmc3256930.
    1. Yoon JH, Park JK, Oh SS, Lee KH, Kim SK, Cho IJ, et al. The ratio of serum leptin to adiponectin provides adjunctive information to the risk of metabolic syndrome beyond the homeostasis model assessment insulin resistance: the Korean Genomic Rural Cohort Study. Clinica chimica acta. 2011;412(23–24):2199–205. doi: .
    1. Yun JE, Won S, Mok Y, Cui W, Kimm H, Jee SH. Association of the leptin to high-molecular-weight adiponectin ratio with metabolic syndrome. Endocrine journal. 2011;58(9):807–15. Epub 2011/08/09. .
    1. Mojiminiyi OA, Abdella NA, Al Arouj M, Ben Nakhi A. Adiponectin, insulin resistance and clinical expression of the metabolic syndrome in patients with Type 2 diabetes. International journal of obesity. 2007;31(2):213–20. doi: .
    1. Finucane FM, Luan J, Wareham NJ, Sharp SJ, O'Rahilly S, Balkau B, et al. Correlation of the leptin:adiponectin ratio with measures of insulin resistance in non-diabetic individuals. Diabetologia. 2009;52(11):2345–9. Epub 2009/09/17. doi: ; PubMed Central PMCID: PMCPmc2759015.
    1. Thorand B, Zierer A, Baumert J, Meisinger C, Herder C, Koenig W. Associations between leptin and the leptin / adiponectin ratio and incident Type 2 diabetes in middle-aged men and women: results from the MONICA / KORA Augsburg study 1984–2002. Diabetic medicine. 2010;27(9):1004–11. Epub 2010/08/21. doi: .
    1. Lopez-Jaramillo P, Gomez-Arbelaez D, Lopez-Lopez J, Lopez-Lopez C, Martinez-Ortega J, Gomez-Rodriguez A, et al. The role of leptin/adiponectin ratio in metabolic syndrome and diabetes. Hormone Molecular Biology and Clinical Investigation. 2014;18(1):37–45. doi: .
    1. Li M, Fisette A, Zhao XY, Deng JY, Mi J, Cianflone K. Serum resistin correlates with central obesity but weakly with insulin resistance in Chinese children and adolescents. International journal of obesity. 2009;33(4):424–39. doi: .
    1. Force GOCO. Body mass index reference norm for screening overweight and obesity in Chinese children and adolescents. Chinese Journal of Epidemiology. 2004;25(2):97–102.
    1. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114(2 Suppl 4th Report):555–76. Epub 2004/08/03. .
    1. Marshall WA, Tanner JM. Puberty In: Falkner F, Tanner JM, editors. Human Growth. New York: Plenum Press; 1986. p. 171–210.
    1. Li L, Yin J, Cheng H, Wang Y, Gao S, Li M, et al. Identification of Genetic and Environmental Factors Predicting Metabolically Healthy Obesity in Children: Data From the BCAMS Study. The Journal of clinical endocrinology and metabolism. 2016;101(4):1816–25. doi: .
    1. Li M, Wu C, Song A, K Z. Development and preliminary application of enzyme-linked immunosorbent assay for human net insulin in serum. Chinese Journal of Endocrinology and Metabolism. 1997;13:214–17.
    1. Li M, Yin JH, Zhang K, Wu CY. A highly sensitive enzyme-linked immunosorbent assay for measurement of leptin secretion in human adipocytes. Zhonghua yi xue za zhi. 2008;88(46):3293–7. Epub 2009/01/23. .
    1. Li Q, Lu Y, Sun L, Yan J, Yan X, Fang L, et al. Plasma adiponectin levels in relation to prognosis in patients with angiographic coronary artery disease. Metabolism: clinical and experimental. 2012;61(12):1803–8. Epub 2012/07/14. doi: .
    1. Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988–1994. Archives of Pediatrics and Adolescent Medicine. 2003;157(8):821–7. doi: .
    1. Wang Q, Yin J, Xu L, Cheng H, Zhao X, Xiang H, et al. Prevalence of metabolic syndrome in a cohort of Chinese schoolchildren: comparison of two definitions and assessment of adipokines as components by factor analysis. BMC Public Health. 2013;13:249 doi:
    1. Parker-Duffen JL, Walsh K. Cardiometabolic effects of adiponectin. Best practice & research Clinical endocrinology & metabolism. 2014;28(1):81–91. Epub 2014/01/15. doi: ; PubMed Central PMCID: PMCPmc3905311.
    1. Okamoto Y, Kihara S, Funahashi T, Matsuzawa Y, Libby P. Adiponectin: a key adipocytokine in metabolic syndrome. Clinical Science (Lond). 2006;110(3):267–78. Epub 2006/02/09. doi: .
    1. Moran O, Phillip M. Leptin: obesity, diabetes and other peripheral effects—a review. Pediatric diabetes. 2003;4(2):101–9. Epub 2003/12/06. doi: .
    1. Mohlig M. Predictors of abnormal glucose metabolism in women with polycystic ovary syndrome. European Journal of Endocrinology. 2006;154(2):295–301. doi:
    1. Wang J, Li H, Franco OH, Yu Z, Liu Y, Lin X. Adiponectin and metabolic syndrome in middle-aged and elderly Chinese. Obesity (Silver Spring, Md). 2008;16(1):172–8. Epub 2008/01/29. doi: .
    1. Patel SB, Reams GP, Spear RM, Freeman RH, Villarreal D. Leptin: linking obesity, the metabolic syndrome, and cardiovascular disease. Current hypertension reports. 2008;10(2):131–7. Epub 2008/05/14. .
    1. Juonala M, Saarikoski LA, Viikari JS, Oikonen M, Lehtimaki T, Lyytikainen LP, et al. A longitudinal analysis on associations of adiponectin levels with metabolic syndrome and carotid artery intima-media thickness. The Cardiovascular Risk in Young Finns Study. Atherosclerosis. 2011;217(1):234–9. doi: .
    1. Yoshinaga M, Sameshima K, Tanaka Y, Wada A, Hashiguchi J, Tahara H, et al. Adipokines and the prediction of the accumulation of cardiovascular risk factors or the presence of metabolic syndrome in elementary school children. Circulation journal. 2008;72(11):1874–8. Epub 2008/09/25. .
    1. Winer JC, Zern TL, Taksali SE, Dziura J, Cali AM, Wollschlager M, et al. Adiponectin in childhood and adolescent obesity and its association with inflammatory markers and components of the metabolic syndrome. The Journal of clinical endocrinology and metabolism. 2006;91(11):4415–23. Epub 2006/08/24. doi: .
    1. Nappo A, Gonzalez-Gil EM, Ahrens W, Bammann K, Michels N, Moreno LA, et al. Analysis of the association of leptin and adiponectin concentrations with metabolic syndrome in children: Results from the IDEFICS study. Nutrition, metabolism, and cardiovascular diseases. 2017;27(6):543–51. Epub 2017/05/18. doi: .
    1. 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: clinical and experimental. 2012;61(2):140–5. Epub 2011/08/06. doi: .
    1. Kang DR, Yadav D, Koh SB, Kim JY, Ahn SV. Impact of Serum Leptin to Adiponectin Ratio on Regression of Metabolic Syndrome in High-Risk Individuals: The ARIRANG Study. Yonsei medical journal. 2017;58(2):339–46. Epub 2017/01/26. doi: ; PubMed Central PMCID: PMCPMC5290013.
    1. Falahi E, Khalkhali Rad AH, Roosta S. What is the best biomarker for metabolic syndrome diagnosis? Diabetes & Metabolic Syndrome. 2015;9(4):366–72. doi: .
    1. Xu L, Li M, Yin J, Cheng H, Yu M, Zhao X, et al. Change of Body Composition and Adipokines and Their Relationship with Insulin Resistance across Pubertal Development in Obese and Nonobese Chinese Children: The BCAMS Study. International journal of endocrinology. 2012;2012:389108 doi: ; PubMed Central PMCID: PMC3534211.
    1. Ainsworth BE, Haskell WL, Herrmann SD, Meckes N, Bassett DR Jr., Tudor-Locke C, et al. 2011 Compendium of Physical Activities: a second update of codes and MET values. Medicine & Science in Sports & Exercise. 2011;43(8):1575–81. Epub 2011/06/18. doi: .
    1. Kranz S, McCabe GP. Examination of the five comparable component scores of the diet quality indexes HEI-2005 and RC-DQI using a nationally representative sample of 2–18 year old children: NHANES 2003–2006. Journal of Obesity. 2013;2013:376314 Epub 2013/10/29. doi: ; PubMed Central PMCID: PMCPMC3791824.1.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel