DOI QR코드

DOI QR Code

The relationship between leptin adiponectin ratio and insulin resistance in healthy children

건강한 소아에서 렙틴 아디포넥틴 비와 인슐린 저항성의 관계

  • Ahn, Gae-Hyun (Department of Pediatrics, College of Medicine, Pochon CHA University) ;
  • Kim, Shin-Hye (Department of Pediatrics, College of Medicine, Pochon CHA University) ;
  • Yoo, Eun-Gyong (Department of Pediatrics, College of Medicine, Pochon CHA University)
  • 안계현 (포천중문의과대학 소아과학교실) ;
  • 김신혜 (포천중문의과대학 소아과학교실) ;
  • 유은경 (포천중문의과대학 소아과학교실)
  • Received : 2007.10.10
  • Accepted : 2007.09.10
  • Published : 2008.03.15

Abstract

Purpose : Leptin and adiponectin are two representative adipocytokines. Leptin increases, but adiponectin decreases, with obesity and insulin resistance. We aimed to study the relationship between the leptin/adiponectin ratio and insulin resistance in healthy children. Methods : Seventy-seven healthy children (36 boys and 41 girls) were enrolled in this study. Anthropometric measurements were performed, and the percentage of weight for height (%WFH) was calculated in each subject. Fasting plasma levels of glucose, insulin, leptin, adiponectin, testosterone, estradiol, and sex-hormone binding globulin (SHBG) were measured. The free androgen index (FAI) was used as a representative of testosterone bioactivity. The homeostasis model assessment was used to estimate the degree of insulin resistance (HOMA-IR). Results : In the boys, HOMA-IR was significantly correlated with age, pubertal stage, free androgen index (FAI), leptin, and the leptin/adiponectin ratio. HOMA-IR was also significantly related to age, percentage of weight for height (%WFH), pubertal stage, estradiol, leptin, and the leptin/adiponectin ratio in girls. The leptin/adiponectin ratio was independently related to HOMA-IR after adjusting for age, %WFH, and FAI in the boys (P<0.05). The leptin/adiponectin ratio was not independently related to HOMA-IR after adjusting for age, %WFH, and estradiol in girls. Conclusion : In non-obese healthy children, the leptin/adiponectin ratio was significantly correlated with insulin resistance. The leptin/adiponectin ratio was independently related to insulin resistance even after adjusting for age, degree of obesity, and androgen levels in healthy boys.

목 적 : 렙틴과 아디포넥틴은 대표적인 adipocytokine으로 비만도 및 인슐린 저항성이 증가함에 따라 혈중 렙틴은 증가하고 아디포넥틴은 감소하는 것으로 알려져 있다. 본 연구에서는 건강한 소아에서 렙틴/아디포넥틴 비와 인슐린 저항성 사이에 어떠한 연관성이 있는지 알아보고자 하였다. 방 법 : 7-15세의 건강한 소아 77명(남아 36명, 여아 41명)을 대상으로 하여 신체계측을 하고 공복 후 채혈하여 혈당, 인슐린, 렙틴, 아디포넥틴, 총 테스토스테론, 에스트라디올 및 SHBG를 측정하였다. 활성 남성호르몬 농도로는 FAI를, 인슐린 저항성의 척도로는 HOMA-IR을 사용하였다. 결 과 : 남아에서 HOMA-IR은 연령, 사춘기 단계, FAI, 렙틴 및 렙틴/아디포넥틴 비와 의미있는 양의 상관관계를 보였다. 여아에서는 HOMA-IR과 연령, %WFH, 사춘기 단계, 에스트라디올, 렙틴, 그리고 렙틴/아디포넥틴 비 사이에 의미있는 양의 상관성이 관찰되었다. 다중회귀분석 결과, 남아에서 렙틴/아디포넥틴 비는 연령, %WFH, 및 FAI로 보정한 후에도 HOMA-IR과 독립적인 연관성을 보였다(P=0.010). 여아에서는 렙틴/아디포넥틴 비와 HOMA-IR 사이에 독립적인 연관성을 보이지 못하였다. 결 론 : 비만하지 않은 건강한 소아에서도 렙틴/아디포넥틴 비는 인슐린 저항성과 의미있는 연관성을 보였으며, 남아에서는 연령, 비만도 및 남성호르몬 농도로 보정한 후에도 렙틴/아디포넥틴 비와 인슐린 저항성 사이에 독립적인 연관성이 있었다.

Keywords

Acknowledgement

Supported by : 대한소아내분비학회

References

  1. Buse JB, Polonsky KS, Burant CF. Type 2 Diabetes mellitus In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, editors. Williams textbook of endocrinology, 10th ed. Philadelphia: WB Saunders Co, 2003:1433-6
  2. Paolisso G, Tagliamonte MR, Rizzo MR, Giugliano D. Advancing age and insulin resistance: new facts about an ancient history. Eur J Clin Invest 1999;29:758-69 https://doi.org/10.1046/j.1365-2362.1999.00522.x
  3. Mayer EJ, Newman B, Austin MA, Zhang D, Quesenberry CP, Edwards K, et al. Genetic and environmental influences on insulin levels and the insulin resistance syndrome: an analysis of women twins. Am J Epidemiol 1996;143:323-32 https://doi.org/10.1093/oxfordjournals.aje.a008746
  4. Vaag A, Henriksen JE, Beck-Nielsen H. Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1992; 89:782-8 https://doi.org/10.1172/JCI115656
  5. Kriketos AD, Greenfield JR, Peake DW, Furler SM, Denyer GS, Charlesworth JA, et al. Inflammation, insulin resistance, and adiposity. Diabetes Care 2004;27:2033-40 https://doi.org/10.2337/diacare.27.8.2033
  6. Lillioja S, Mott DM, Howard BV, Bennett PH, Yki-Jarvinen H, Freymond D, et al. Impaired glucose tolerance as a disorder of insulin action: longitudinal and cross-sectional studies in Pima Indians. N Engl J Med 1988;318:1217-25 https://doi.org/10.1056/NEJM198805123181901
  7. Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med 1990;113:909-15 https://doi.org/10.7326/0003-4819-113-12-909
  8. Park JM, Yoo EG, Kim DH. Type 2 Diabetes mellitus in children. J Korean Pediatr Soc 2002:45:646-53
  9. Lee SY, Shin CH, Yang SW. Clinical characteristics of type 2 diabetes in children and adolescents. J Korean Pediatr Soc 2002:45:754-63
  10. Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, et al. Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. Nat Med 1996;2:800-3 https://doi.org/10.1038/nm0796-800
  11. Spiegelman BM, Flier JS. Adipogenesis and obesity: rounding out the big picture. Cell 1996;87:377-89 https://doi.org/10.1016/S0092-8674(00)81359-8
  12. Mukherjee R, Villarreal D, Reams GP, Freeman RH, Tchoukina I, Sprea RM. Leptin as a common link to obesity and hypertension. Drugs Today (Bare) 2005:41:687-95 https://doi.org/10.1358/dot.2005.41.10.899612
  13. Waelput W, Brouckaert P, Broekaert D, Tavernier J. A role for leptin in the systemic inflammatory response (SIRS) and in immune response, an update. Curr Med Chem 2006; 13:465-75 https://doi.org/10.2174/092986706775527929
  14. Blum WF. Leptin: the voice of the adipose tissue. Horm Res 1997:48 Suppl 4:S2-8
  15. Tschritter O, Fritsche A, Thamer C, Haap M, Shirkavand F, Rahe S, et al. Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. Diabetes 2003;52:239-43 https://doi.org/10.2337/diabetes.52.2.239
  16. Chandran M, Phillips SA, Ciaraldi T, Henry RR. Adiponectin: more than just another fat cell hormone? Diabetes Care 2003;26:2442-50 https://doi.org/10.2337/diacare.26.8.2442
  17. Weiss R, Dufour S, Groszmann A, Petersen K, Dziura J, Taksali SE, et al. Low adiponectin levels in adolescent obesity: A marker of increased intramyocellular lipid accumulation. J Clin Endocrinol Metab 2003;88:2014-8 https://doi.org/10.1210/jc.2002-021711
  18. Kotani K, Sakane N, Saiga K, Kurozawa Y. Leptin : adiponectin ratio as an atherogenic index in patients with type 2 diabetes: relationship of the index to carotid intima-media thickness. Diabetologia 2005:48:2684-6 https://doi.org/10.1007/s00125-005-0015-4
  19. Inoue M, Yano M, Yamakado M, Maehata E, Suzuki S. Relationship between the adiponectin-leptin ratio and parameters of insulin resistance in subjects without hyperglycemia. Metabolism 2006;55:1248-54 https://doi.org/10.1016/j.metabol.2006.05.010
  20. Morales A, Wasserfall C, Brusko T, Carter C, Schatz D, Silverstein J, et al. Adiponectin and leptin concentrations may aid in discriminating disease forms in children and adolescents with type 1 and type 2 diabetes. Diabetes Care 2004;27:2010-4 https://doi.org/10.2337/diacare.27.8.2010
  21. 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;17:1069-75
  22. Yoo EG, Nam HY, Kim DH. Puberty and gender differences of plasma leptin, adiponectin levels, and leptin/adiponectin ratio. J Korean Soc Pediatr Endocrinol 2006;11:170-6
  23. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9 https://doi.org/10.1007/BF00280883
  24. Kim MR, Gupta MK, Travers SH, Rogers DG, Van Lente F, Faiman C. Serum prostate specific antigen, sex hormone binding globulin and free androgen index as markers of pubertal development in boys. Clin Endocrinol (Oxf) 1999;50:203-10 https://doi.org/10.1046/j.1365-2265.1999.00636.x
  25. Cunningham SK, Loughlin T, Culliton M, McKenna TJ. The relationship between sex steroids and sex hormone binding globulin in plasma in physiological and pathological conditions. Ann Clin Biochem 1985;22:489-97 https://doi.org/10.1177/000456328502200504
  26. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548-56 https://doi.org/10.1210/jc.2004-0395
  27. Taniguchi A, Fukushima M, Nakai Y, Kuroe A, Yamano G, Yanagawa T, et al. Soluble E-selectin, leptin, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients. Metabolism 2005;54:376-80 https://doi.org/10.1016/j.metabol.2004.10.006
  28. Gil-Campos M, Canete RR, Gil A. Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr 2004;23:963-74 https://doi.org/10.1016/j.clnu.2004.04.010
  29. Kim MJ, Lee Y, Lee BJ, Yoen JH, Shin SY, Shin YG, et al. Plasma adiponectin concentration and insulin resistance in type 2 diabetes. Korean J Diabetes Assoc 2003;27:260-71
  30. Matsuhisa M, Yamasaki Y, Emoto M, Shimabukuro M, Funahashi T, Matsuzawa Y. A novel index of insulin resistance determined from the homeostasis model assessment index and adiponectin levels in Japanese subjects. Diabetes Res Clin Pract 2007;77:151-4 https://doi.org/10.1016/j.diabres.2006.10.005
  31. Garcia-Mayor RV, Andrade MA, Rios M, Lage M, Dieguez C, Casanueva FF. 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 https://doi.org/10.1210/jc.82.9.2849
  32. Ahmed ML, Ong KK, Morrell DJ, Cox L, Drayer N, Perry L, et al. Longitudinal study of leptin concentrations during puberty: sex differences and relationship to changes in body composition. J Clin Endocrinol Metab 1999;84:899-905 https://doi.org/10.1210/jc.84.3.899
  33. Bottner A, Kratzsch J. Muller G, Kapellen TM, Bluher S, Keller E, et al. Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 2004;89: 4053-61 https://doi.org/10.1210/jc.2004-0303
  34. Tsou PL, Jiang YD, Chang CC, Wei IN, Sung FC, Lin CC, et al. Sex-related differences between adiponectin and insulin resistance in schoolchildren. Diabetes Care 2004;27:308-13 https://doi.org/10.2337/diacare.27.2.308
  35. Lee JM. Insulin resistance in children and adolescents. Rev Endocrinol Metab Disord 2006;7:141-7
  36. Krekoukia M, Nassis GP, Psarra G, Skenderi K, Chrousos GP, Sidossis LS. Elevated total and central adiposity and low physical activity are associated with insulin resistance in children. Metabolism 2007;56:206-13 https://doi.org/10.1016/j.metabol.2006.09.014
  37. De Lorenzo A, Del Gobbo V, Premrov MG, Bigioni M, Galvano F, Di Renzo L. Normal-weight obese syndrome: early inflammation? Am J Clin Nutr 2007;85:40-5 https://doi.org/10.1093/ajcn/85.1.40
  38. De Lorenzo A, Martinoli R, Vaia F, Di Renzo L. Normal weight obese (NWO) women: an evaluation of a candidate new syndrome. Nutr Metab Cardiovasc Dis 2006;16:513-23 https://doi.org/10.1016/j.numecd.2005.10.010
  39. Conwell LS, Trost SG, Brown WJ, Batch JA. Indexes of insulin resistance and secretion in obese children and adolescents: a validation study. Diabetes Care 2004;27:314-9 https://doi.org/10.2337/diacare.27.2.314
  40. Cutfield WS, Jefferies CA, Jackson WE, Robinson EM, Hofman PL. Evaluation of HOMA and QUICKI as measures of insulin sensitivity in prepubertal children. Pediatr Diabetes 2003;4:115-8 https://doi.org/10.1034/j.1399-5448.2003.00024.x

Cited by

  1. 비만 아동에서 leptin, adiponectin 및 resistin의 혈중농도와 인슐린 저항성과의 관계 vol.52, pp.7, 2009, https://doi.org/10.3345/kjp.2009.52.7.766
  2. 비만도에 따른 성인 여성의 혈청 인슐린, 렙틴, 아디포넥틴 및 hs-CRP 농도 비교와 상호 관련성 vol.16, pp.1, 2008, https://doi.org/10.5720/kjcn.2011.16.1.126