Background: Modifications in body fat in obese patients during puberty determine changes in adipokines that affect insulin sensitivity. Aims: We hypothesized that the leptin/adiponectin (L/A) ratio and free leptin index (FLI) are good markers of insulin resistance (IR) and total body fat (TBF) during pubertal development. Methods: A prospective study of 32 obese girls (OG) and age-matched control girls (CG) was performed. OG were divided into those that maintained a weight loss (WL) of >1 SD of initial body mass index (BMI) (WL group, n = 25) and those without WL (NWL group, n = 7). Oral glucose tolerance tests (OGTT) were performed to evaluate IR. Correlations of adipokines, L/A, and FLI with BMI, waist circumference, percentage of TBF (%TBF) and IR were performed over pubertal development. Results: The L/A ratio and FLI were increased in OG at baseline. Both indexes decreased in the WL group as puberty progressed, with no change in CG or NWL. In the WL group, a correlation between L/A and FLI with OGTT and %TBF, and L/A and homeostasis model assessment (HOMA) was found throughout the study. Conclusion: The L/A ratio and FLI are good markers to follow changes in IR and %TBF after WL during puberty. Insulin more accurately reflects the changes in IR than HOMA.

Keywords:
Adiponectin, Insulin resistance, Leptin, Obesity, Puberty, Fat mass, Cardiovascular risk
1.
L'Allemand-Jander D: Clinical diagnosis of metabolic and cardiovascular risks in overweight children: early development of chronic diseases in the obese child. Int J Obes (London) 2010;34(suppl 2):S32-S36.
2.
Romeo GR, Lee J, Shoelson SE: Metabolic syndrome, insulin resistance, and roles of inflammation: mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol 2012;32:1771-1776.
3.
Antuna-Puente B, Feve B, Fellahi S, Bastard JP: Adipokines: the missing link between insulin resistance and obesity. Diabetes Metab 2008;34:2-11.
4.
Okamoto Y, Kihara S, Funahashi T, Matsuzawa Y, Libby P: Adiponectin: a key adipocytokine in metabolic syndrome. Clin Sci 2006;110:267-278.
5.
Lang HF, Chou CY, Sheu WH, Lin JY: Weight loss increased serum adiponectin but decreased lipid levels in obese subjects whose body mass index was lower than 30 kg/m2. Nutr Res 2011;31:378-386.
6.
Shargorodsky M, Boaz M, Goldberg Y, et al: Adiponectin and vascular properties in obese patients: is it a novel biomarker of early atherosclerosis? Int J Obes (London) 2009;3:553-558.
7.
Zhuo Q, Wang Z, Fu P, 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 Res Clin Pract 2009;84:27-33.
8.
Körner A, Blüher S, Kapellen T, et al: Obesity in childhood and adolescence: a review in the interface between adipocyte physiology and clinical challenges. Hormones 2005;4:189-199.
9.
Shaibi GQ, Cruz ML, Weigensberg MJ, et al: Adiponectin independently predicts metabolic syndrome in overweight Latino youth. J Clin Endocrinol Metab 2007;92:1809-1813.
10.
Campos RM, de Mello MT, Tock L, da Silva PL, Corgosinho FC, Carnier J, de Piano A, Sanches PL, Masquio DC, Tufik S, Dâmaso AR: Interaction of bone mineral density, adipokines and hormones in obese adolescent girls submitted in an interdisciplinary therapy. J Pediatr Endocrinol Metab 2013;22:1-6.
11.
Oda N, Imamura S, Fujita T, et al: The ratio of leptin to adiponectin can be used as an index of insulin resistance. Metabolism 2008;57:268-273.
12.
Satoh N, Naruse M, Usui T, et al: Leptin-to-adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care 2004;27:2488-2490.
13.
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. Int J Obes (London) 2007;31:213-220.
14.
Zhuo Q, Wang Z, Fu P, 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 Res Clin Pract 2009;84:27-33.
15.
Brufani C, Tozzi A, Fintini D, Ciampalini P, Grossi A, Fiori R, et al: Sexual dimorphism of body composition and insulin sensitivity across pubertal development in obese Caucasian subjects. Eur J Endocrinol 2009;160:769-775.
16.
Lee JM: Insulin resistance in children and adolescents. Rev Endocr Metab Disord 2006;7:141-147.
17.
Bahíllo-Curieses MP, Hermoso-López F, Martínez-Sopena MJ, Cobreros-García P, García-Saseta P, Tríguez-García M, Marugán-Miguelsanz JM: Prevalence of insulin resistance and impaired glucose tolerance in a sample of obese Spanish children and adolescents. Endocrine 2012;41:289-295.
18.
Lecke SB, Morsch DM, Spritzer PM: Leptin and adiponectin in the female life course. Braz J Med Biol Res 2011;44:381-387.
19.
Sepilian VP, Crochet JR, Nagamani M: Serum soluble leptin receptor levels and free leptin index in women with polycystic ovary syndrome: relationship to insulin resistance and androgens. Fertil Steril 2006;85:1441-1447.
20.
Argente J, Barrios V, Chowen JA, Sinha MK, Considine RV: Leptin plasma levels in healthy Spanish children and adolescents, children with obesity, and adolescents with anorexia nervosa and bulimia nervosa. J Pediatr 1997;131:833-838.
21.
Jasik CB, Lustig RH: Adolescent obesity and puberty: the ‘perfect storm'. Ann NY Acad Sci 2008;1135:265-279.
22.
Tanner JM: Growth at Adolescence. Oxford, Blackwell Scientific Publications Ltd, 1962.
23.
Hernández M, Sánchez E, Sobradillo B: Curvas y tablas de crecimiento; in Argente J, Carrascosa A, Gracia R, Rodríguez F (eds): Curvas y Tablas de Crecimiento, Instituto de Investigación sobre Crecimiento y Desarrollo. Madrid, Fundación Faustino Orbegozo, Editorial Garsi, 1988.
24.
Greulich WW, Pyle SI: Radiographic Atlas of Skeletal Development of Hand and Wrist, ed 2. Stanford, CA, Stanford University Press, 1959.
25.
Moreno LA, Fleta J, Mur L, Rodríguez G, Sarría A, Bueno M: Waist circumference values in Spanish children. Gender related differences. Eur J Clin Nutr 1999;53:429-433.
26.
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;114:555-576.
27.
Birkebaek NH, Lange A, Holland-Fischer P, Kristensen K, Rittig S, Vilstrup H, Handberg A, Gronbaek H: Effect of weight reduction on insulin sensitivity, sex hormone-binding globulin, sex hormones and gonadotropins in obese children. Eur J Endocrinol 2010;163:895-900.
28.
Martos-Moreno GA, Barrios V, Argente J: Normative data for adiponectin, resistin, interleukin 6, and leptin/receptor ratio in a healthy Spanish pediatric population: relationship with sex steroids. Eur J Endocrinol 2006;155:429-434.
29.
García Cuartero B, García Lacalle C, Jiménez Lobo C, González Vergaz A, Calvo Rey C, Alcázar Villar MJ, Díaz Martínez E: Índice HOMA y QUICKI, insulina y péptido C en niños sanos. Puntos de corte de riesgo cardiovascular. An Pediatr (Barcelona) 2007;66:481-490.
30.
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. Arch Pediatr Adolesc Med 2003;157:821-827.
31.
Eyzaguirre F, Mericq V: Insulin resistance markers in children. Horm Res 2009;71:65-74.
32.
American Diabetes Association: Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2011;34:562-569.
33.
Denzer C, Weibel A, Muche R, Karges B, Sorgo W, Wabitsch M: Pubertal development in obese children and adolescents. Int J Obes (London) 2007;31:1509-1519.
34.
Kaplowitz PB: Link between body fat and the timing of puberty. Pediatrics 2008;121:208-217.
35.
Donoso MA, Muñoz-Calvo MT, Barrios V, Garrido G, Hawkins F, Argente J: Increased circulating adiponectin levels and decreased leptin/soluble leptin receptor ratio throughout puberty in female ballet dancers: association with body composition and the delay in puberty. Eur J Endocrinol 2010;162:905-911.
36.
Carlsoon B, Ankarberg C, Rosberg S, Norjavaara E, Albertsson-Wikland K, Carlsoon LM: Serum leptin concentration in relation to pubertal development. Arch Dis Child 1997;77:396-400.
37.
Matkovic V, Illich JZ, Skugor M: Leptin is inversely related to age at menarche in human females. J Clin Endocrinol Metab 1997;82:3239-3245.
38.
Moschos S, Chan JL, Mantzoros CS: Leptin and reproduction: a review. Fertil Steril 2002;77:433-444.
39.
Grinspoon S, Gulick T, Askari H, et al: Serum leptin levels in women with anorexia nervosa. J Clin Endocrinol Metab 1996;81:3861-3863.
40.
Mann DR, Johnson AO, Gimpel T, Castracane VD: Changes in circulating leptin, leptin receptor, and gonadal hormones from infancy until advanced age in humans. J Clin Endocrinol Metab 2003;88:3339-3345.
41.
Reinehr T, Kratzsch J, Kiess W, Andler W: Circulating soluble leptin receptor, leptin, and insulin resistance before and after weight loss in obese children. Int J Obes (London) 2005;29:1230-1235.
42.
Cinaz P, Bideci A, Camurdan MO, Güven A, Gönen S: Leptin and soluble leptin receptor levels in obese children in fasting and satiety states. J Clin Endocrinol Metab 2005;18:303-307.
43.
Mann DR, Johnson AO, Gimpel T, Castracane VD: Changes in circulating leptin, leptin receptor, and gonadal hormones from infancy until advanced age in humans. J Clin Endocrinol Metab 2003;88:3339-3345.
44.
Ogier V, Ziegler O, Méjean L, Nicolas JP, Stricker-Krongrad A: Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans. Int J Obesity Rel Metab Dis 2002;26:496-503.
45.
B Hahn S, Haselhorst U, Quadbeck B, Tan S, Kimmig R, Mann K, Janssen OE: Decreased soluble leptin receptor levels in women with polycystic ovary syndrome. Eur J Endocrinol 2006;154:287-294.
46.
Blum WF, Englaro P, Hanitsch S, Juul A, Hertel NT, Müller J, 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;82:2904-2910.
47.
Muñoz MT, De la Piedra C, Barrios V, Garrido G, Argente J: Changes in bone density and bone markers in rhythmic gymnasts and ballet dancers: implications for puberty and leptin levels. Eur J Endocrinol 2004;151:491-496.
48.
Kratzsch J, Lammert A, Bottner A, Seidel B, Mueller G, Thiery J, et al: Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence. J Clin Endocrinol Metab 2002;87:4587-4594.
49.
Chan JL, Blüher S, Yiannakouris N, Suchard MA, Kratzsch J, Mantzoros CS: Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin: observational and interventional studies in humans. Diabetes 2002;51:2105-2112.
50.
Sinha MK, Opentanova I, Ohannesian JP, Kolaczynski JW, Heiman ML, Hale J, Becker GW, Bowsher RR, Stephens TW, Caro JF: Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest 1996;98:1277-1282.
51.
Misra M, Miller KK, Almazan C, Ramaswamy K, Aggarwal A, Herzog DB, Neubauer G, Breu J, Klibanski A: Hormonal and body composition predictors of soluble leptin receptor, leptin, and free leptin index in adolescent girls with anorexia nervosa and controls and relation to insulin sensitivity. J Clin Endocrinol Metab 2004;89:3486-3495.
52.
Sakurai T, Ogasawara J, Kizaki T, Ishibashi Y, Sumitani Y, Takahashi K, Ishida H, Miyazaki H, Saitoh D, Haga S, Izawa T, Ohno H: Preventive and improvement effects of exercise training and supplement intake in white adipose tissues on obesity and lifestyle-related diseases. Environ Health Prev Med 2012;17:348-356.
53.
Schoppen S, Riestra P, García-Anguita A, López-Simón L, Cano B, de Oya I, de Oya M, Garcés C: Leptin and adiponectin levels in pubertal children: relationship with anthropometric variables and body composition. Clin Chem Lab Med 2010;48:707-711.
54.
Diamond FB Jr, Cuthbertson D, Hanna S, Eichler D: Correlates of adiponectin and the leptin/adiponectin ratio in obese and non-obese children. J Pediatr Endocrinol Metab 2004;17:1069-1075.
55.
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;20:187-195.
56.
Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, Druet C, Loredana M, Chiarielli F: Insulin resistance in children: consensus, perspective and future directions. J Clin Endocrinol Metab 2010;95:1-10.
57.
Vigouroux C, Maachi M, Nguyên TH, Coussieu C, Gharakhanian S, Funahashi T, Matsuzawa Y, Shimomura I, Rozenbaum W, Capeau J, Bastard JP: Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy. AIDS 2003;17:1503-1511.
58.
Finucane FM, Luan J, Wareham NJ, Sharp SJ, O'Rahilly S, Balkau B, Flyvbjerg A, Walker M, Højlund K, Nolan JJ, European Group for the Study of Insulin Resistance: Relationship between Insulin Sensitivity and Cardiovascular Disease Risk Study Group, Savage DB: Correlation of the leptin:adiponectin ratio with measures of insulin resistance in non-diabetic individuals. Diabetologia 2009;52:2345-2349.
59.
Wang Q, Yin J, Xu L, Cheng H, Zhao X, Xiang H, Lam HS, Mi J, Li M: 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.
60.
Reinehr T, Kiess W, Kapellen T, Andler W: Insulin sensitivity among obese children and adolescents, according to degree of weight loss. Pediatrics 2004;114:1569-1573.
61.
Tybor DJ, Lichtenstein AH, Dallal GE, Daniels SR, Must A: Independent effects of age-related changes in waist circumference and BMI z scores in predicting cardiovascular disease risk factors in a prospective cohort of adolescent females. Am J Clin Nutr 2011;93:392-401.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.