Diabetes and Metabolism Journal

Korean Diabetes Association (대한당뇨병학회)
권호 표지

Adiponectin Concentrations in Type 2 Diabetic Patients with or without Metabolic Syndrome

제2형 당뇨병환자에서 대사증후군 동반 여부에 따른 아디포넥틴의 특징

Park, Ja-Young;Kim, Ja-Won;Kim, Ji-Min;Han, Ying;Park, Soo-Kyung;Mok, Ji-Young;Park, Mi-Kyoung;Lee, Hye-Jeong;Kim, Duk-Kyu
박자영;김자원;김지민;한영;박수경;목지영;박미경;이혜정;김덕규

  • Published : 2008.06.01
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Abstract

Background: Adipocytes produce several adipokines that modulate insulin action as well as glucose and lipid metabolism. The aim of this study was to evaluate the relationship between serum adiponectin concentrations and metabolic syndrome(MS) in patients with type 2 diabetes mellitus. Methods: This study included 127 type 2 diabetic patients(males 63, females 64). The subjects were divided into two groups as with or without metabolic syndrome(MS(+) or MS(-)). The MS was diagnosed by International Diabetes Federation. Serum adiponectin, leptin, fasting plasma insulin, glucose, glycated hemoglobin, lipid profile, white blood corpuscle(WBC), aspartate aminotransferase(AST), alanine aminotransferase(ALT), uric acid and C-reactive protein(CRP) were examined.Results: Serum adiponectin concentrations were significantly lower in MS(+) than MS(-)(4.8 ± 2.4 μg/mL vs 7.6 ± 5.8 μg/mL, 7.6 ± 3.7 μg/mL vs 11.5 ± 7.2 μg/mL, P < 0.05 in males and females). After adjustment for age and body mass index(BMI), in MS(+), the serum levels of adiponectin correlated positively with high density lipoprotein - cholesterol(HDL-C) and negatively with height, body weight, ALT and CRP. In MS(-), the serum levels of adiponectin correlated positively with HDL-C and negatively with diastolic blood pressure(DBP), triglyceride and CRP. By multiple regression analysis, no parameters were independently correlated with serum adiponectin concentrations in MS(+), while DBP and HDL-C were independently related to serum adiponectin concentrations in MS(-). Conclusion: Serum adiponectin concentrations were lower in type 2 diabetic patients with MS than without MS. There were no significant parameters related to decrease serum adiponectin concentrations in MS. But further study is needed to confirm this result.(KOREAN DIABETES J 32:224-235, 2008)

연구배경: 지방세포에서 분비되는 아디포넥틴은 인슐린감수성을 조절하고 당과 지질대사에 관여하며, 심혈관질환에 중요한 역할을 한다. 제2형 당뇨병환자에서 대사증후군의 동반 유무에 따라서 혈청 아디포넥틴의 농도 변화를 관찰하고 아울러 혈청 아디포넥틴의 농도에 영향을 주는 인자가 있는 지를 살펴보고자 하였다. 방법: 내분비내과 외래를 방문한 127명의 제2형 당뇨병환자 중에서 대사증후군을 동반한 군이 80명(남자 40명, 여자 40명)이었고, 대사증후군을 동반하지 않은 군이 47명(남자 23명, 여자 24명)으로, 2005 년 IDF 진단 기준에 따른 대사증후군 유무와 성별에 따라서 나누어 단면적 연구를 시행하였다. 모든 연구대상자 중에서 혈청 아디포넥틴과 렙틴, 공복 혈장 혈당과 인슐린, 당화혈색소, 혈중 지질, 백혈구, 간기능 검사, 요산, CRP, 체질량지수, 허리둘레, 혈압측정을 실시하였다. 결과: 혈청 아디포넥틴의 농도는 성별에 상관없이 MS(-)군에 비해 MS(+)군이 통계적으로 유의하게 더 낮았다(남자환자에서 4.8 ± 2.4 μg/mL vs 7.6 ± 5.8 μg/mL, P < 0.05, 여자환자에서 7.6 ± 3.7 μg/mL vs 11.5 ± 7.2 μg/mL, P < 0.05). MS(+)군에서 혈청 아디포넥틴의 농도는 고밀도 지단백 콜레스테롤과 유의한 양의 상관관계가 있었고(r = 0.27, P < 0.05), 체중(r = -0.47, P < 0.05), 키(r = -0.44, P < 0.05), ALT(r = - 0.3, P < 0.05), CRP(r = - 0.37, P < 0.05)와는 유의한 음의 상관관계가 있었다. 한편 MS(-)군에서 혈청 아디포넥틴의 농도는 고밀도 지단백 콜레스테롤과 유의한 양의 상관관계를 보였고(r = 0.48, P < 0.01), 또한 이완기 혈압(r = -0.35, P < 0.05), 중성지방(r = -0.49, P < 0.01), CRP(r = -0.64, P < 0.05)와는 음의 상관관계를 보였다. 회귀분석 결과 MS(+)군에서는 어느 인자도 혈청 아디포넥틴의 농도에 독립적인 영향을 주지 않는 것으로 나타났으나 MS(-)군이 이완기 혈압과 고밀도 지단백 콜레스테롤가 독립적으로 관여하는 것으로 나타났다.

Keywords

References

  1. Ahima RS, Flier JS: Adipose tissue as an endocrine organ. Trends Endocrinol Metab 11:327-32, 2000 https://doi.org/10.1016/S1043-2760(00)00301-5
  2. Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, Yamashita S, Miura M, Fukuda Y, Takemura K, Tokunaga K, Matsuzawa Y: Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. Nat Med 2:800-3, 1996 https://doi.org/10.1038/nm0796-800
  3. Spiegelman BM, Flier JS: Adipogenesis and obesity: rounding out the big picture. Cell 87:377-89, 1996 https://doi.org/10.1016/S0092-8674(00)81359-8
  4. Tsao TS, Murrey HE, Hug C, Lee DH, Lodish HF: Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30). J Biol Chem 277:29359-62, 2002 https://doi.org/10.1074/jbc.C200312200
  5. Krakoff J, Funahashi T, Stehouwer CD, Schalkwijk CG, Tanaka S, Matsuzawa Y, Kobes S, Tataranni PA, Hanson RL, Knowler WC, Lindsay RS: Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diabetes Care 26:1745-51, 2003 https://doi.org/10.2337/diacare.26.6.1745
  6. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930-5, 2001 https://doi.org/10.1210/jc.86.5.1930
  7. Cnop M, Havel PJ, Utzschneider KM, Sinha MK, Boyko EJ, Retzlaff BM, Knopp RH, Brunzell JD, Kahn SE: Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 46:459-69, 2003 https://doi.org/10.1007/s00125-003-1074-z
  8. 유성태, 박석오, 김세화: 혈중 아디포넥틴 및 레지스틴 농도와 대사성 위험인자와의 상관관계. 대한내분비학회지 20:444-51, 2005 https://doi.org/10.3803/jkes.2005.20.5.444
  9. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y: Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595-9, 2000 https://doi.org/10.1161/01.ATV.20.6.1595
  10. 박상수, 최경묵, 권순범, 류옥현, 류혜진, 박수연, 김희영, 서지아 이계원, 김신곤, 김난희, 최동섭, 백세현: 혈청 아디포넥틴 농도와 대사증후군 발병의 연관성. 대한내분비학회지 19:492-500, 2004
  11. Choi KM, Ryu OH, Lee KW, Kim HY, Seo JA, Kim SG, Kim NH, Choi DS, Baik SH: Serum adiponectin, interleukin-10 levels and inflammatory markers in the metabolic syndrome. Diabetes Res Clin Pract 75:235-40, 2007 https://doi.org/10.1016/j.diabres.2006.06.019
  12. Kim SM, Cho KH, Park HS: Relationship between plasma adiponectin levels and the metabolic syndrome: Endocr J 53:247-54, 2006 https://doi.org/10.1507/endocrj.53.247
  13. Jang Y, Lee JH, Kim OY, Koh SJ, Chae JS, Woo JH, Cho H, Lee JE, Ordovas JM: The SNP276G>T polymorphism in the adiponectin (ACDC) gene is more strongly associated with insulin resistance and cardiovascular disease risk than SNP45T>G in nonobese/nondiabetic Korean men independent of abdominal adiposity and circulating plasma adiponectin. Metabolism 55:59-6, 2006 https://doi.org/10.1016/j.metabol.2005.07.007
  14. Choi KM, Lee J, Lee KW, Seo JA, Oh JH, Kim SG, Kim NH, Choi DS, Baik SH: Serum adiponectin concentrations predict the developments of type 2 diabetes and the metabolic syndrome in elderly Koreans. Clin Endocrinol 61:75-80, 2004 https://doi.org/10.1111/j.1365-2265.2004.02063.x
  15. Cruz M, Garcia-Macedo R, Garcia-Valerio Y, Gutierrez M, Medina-Navarro R, Duran G, Wacher N, Kumate J: Low adiponectin levels predict type 2 diabetes in Mexican children. Diabetes Care 27:1451-3, 2004 https://doi.org/10.2337/diacare.27.6.1451
  16. Yamamoto Y, Hirose H, Saito I, Nishikai K, Saruta T: Adiponectin, an adipocyte-derived protein, predicts future insulin resistance: two year follow-up study in Japanese population. J Clin Endocrinol Metab 89:87-90, 2004 https://doi.org/10.1210/jc.2003-031163
  17. Diabetes Trials Unit, Oxford, URL (2004). HOMA Calculator v2.2: http://www.dtu.ox.ac.uk/index.html/maindoc/publications/(accessed March 22 2005)
  18. Friedewald WT, Levy RT, Fredrickson DS: Estimation of the concentration of low density lipoprotein cholesterol in plasma without use of the ultracentrifuge. Clin Chem 18:449502, 1972
  19. International Diabetes Federation. The IDF consensus worldwide definition of the metabolic syndrome. April 14, 2005: http://www.idf.org/webdata/docs/IDF_ Metasyndrome_definition.pdf (accessed June 10, 2005)
  20. Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y: PPARg ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50:20949, 2001
  21. Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R: Hormonal regulation of adiponectin gene expression in 3T3-L1adipocytes. Biochem Biophys Res Commun 290:10849, 2002
  22. Halleux CM, Takahashi M, Delporte ML, Detry R, Funahashi T, Matsuzawa Y, Brichard SM: Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue. Biochem Biophys Res Commun 288:11027, 2001
  23. Motoshima H, Wu X, Sinha MK, HardyVE, Rosato EL, Barbot DJ, Rosato FE, Goldstein BJ: Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone. J Clin Endocrinol Metab 87:56627, 2002
  24. Yu JG, Javorschi S, Hevener AL, Kruszynska YT, Norman RA, Sinha M, Olefsky JM: The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 51:296874, 2002
  25. Hulver MW, Zheng D, Tanner CJ, Houmard JA, Kraus WE, Slentz CA, Sinha MK, Pories, WJ, MacDonald KG, Dohm GL: Adiponectin is not altered with exercise training despite enhanced insulin action. Am J Physiol, Endocrinol Metab 283:8615, 2002
  26. Abbasi F, Lamendola C, McLaughlin T, Hayden J, Reaven GM, Reaven PD: Plasma adiponectin concentrations do not increase in association with moderate weight loss in insulin resistant, obese women. Metabolism 53:2803, 2004
  27. Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R: Adiponectin gene expression is inhibited by beta-adrenergic stimulation via protein kinase A in 3T3-L1 adipocytes. FEBS Lett 507: 1426, 2001
  28. Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, Paschke R: Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 301:104550, 2003
  29. Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y; Osaka CAD Study Group, Coronary artery disease: Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 23:85-9, 2003 https://doi.org/10.1161/01.ATV.0000048856.22331.50
  30. Mallamaci F, Zoccali C, Cuzzola F, Tripepi G, Cutrupi S, Parlongo S, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y: Adiponectin in essential hypertension. J Nephrol 15:507-11, 2002
  31. Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y: Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 13:134-41, 2002
  32. Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, Maeda K, Nagaretani H, Kishida K, Maeda N, Nagasawa A, Funahashi T, Matsuzawa Y: Adiponectin specifically increased tissue inhibitor ofmetalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 109: 2046-9, 2004 https://doi.org/10.1161/01.CIR.0000127953.98131.ED
  33. Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, Kumada M, Hotta K, Nishida M, Takahashi M, Nakamura T, Shimomura I, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y: Adipocyte derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation 105:2893-8, 2002 https://doi.org/10.1161/01.CIR.0000018622.84402.FF
  34. Matsubara M, Maruoka S, Katayose S: Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 87:2764-9, 2002 https://doi.org/10.1210/jc.87.6.2764
  35. Nishzawa T, Shimomura I, Kishida K,Maeda N, Kuriyama H, Nagaretani H, Matsuda M, Kondo H, Furuyama N, Kihara S, Nakamura T, Tochino Y, Furuyama N, Matsuzawa Y: Androgen decrease plasma adiponectin, an insulin sensitizing adipocyte derived protein. Diabetes 51:2734-41, 2002 https://doi.org/10.2337/diabetes.51.9.2734
  36. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y: Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79-83,1999 https://doi.org/10.1006/bbrc.1999.0255
  37. 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 31:213-20, 2007 https://doi.org/10.1038/sj.ijo.0803355