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Changes in C-reactive protein predict insulin sensitivity in severely obese individuals after weight loss surgery

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

The production of inflammatory mediators by abdominal adipose tissue may link obesity and insulin resistance. We determined the influence of systemic levels of interleukin-6 and C-reactive protein on insulin sensitivity after weight loss via Roux-en-Y gastric bypass surgery. Severely obese individuals (n 5 15) were evaluated at baseline and at 6 months after surgery. Insulin sensitivity was determined by frequently sampled intravenous glucose tolerance testing at the same time points. Visceral and subcutaneous adipose tissue volumes were quantified by computed tomography. Interleukin-6 and C-reactive protein were measured by enzyme-linked immunoassay in plasma and in adipose tissue biopsies. Correlation analysis was used to determine associations between insulin sensitivity and other outcome variables. Significance was set at P < 0.05. Plasma interleukin-6 concentrations were significantly correlated to the IL-6 content of subcutaneous adipose tissue (r = 0.71). At 6 months postsurgery, subcutaneous and visceral adipose tissue volumes were significantly reduced (34.7% and 44.1%, respectively) and insulin sensitivity had improved by 160.9%. Significant longitudinal correlations were found between insulin sensitivity and plasma C-reactive protein (r = 20.61), but not plasma interleukin-6 at 6 months. These findings offer insights that link obesity and insulin resistance via the activity of inflammatory mediators.

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References

  1. Grimble RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care 2002;5:551–559.

    Article  PubMed  CAS  Google Scholar 

  2. Akira S, Hirano T, Taga T, Kishimoto T. Biology of multifunctional cytokines: IL-6 and related molecules (IL-1 and TNF). FASEB J 1990;4:2860–2867.

    PubMed  CAS  Google Scholar 

  3. Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 373-L1 adipocytes and is, like IL-18 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin resistant subjects. J Biol Chem 2003; 278:45777–45784.

    Article  PubMed  CAS  Google Scholar 

  4. Bastard JP, Maachi M, Van Nhieu JT, et al. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 2002;87:2084–2089.

    Article  PubMed  CAS  Google Scholar 

  5. Kern PA, Ranganathan S, Li C, Wood L, Ranganthan G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001;280:E745-E751.

    PubMed  CAS  Google Scholar 

  6. Fernandez-Real J-M, Vayreda M, Richart C, Gutierrez BM, Vendrell J, Ricart W. Circulating interleukin-6 levels, blood pressure and insulin sensitivity in apparently healthy men and women. J Clin Endocrinol Metab 2001;86:1154–1159.

    Article  PubMed  CAS  Google Scholar 

  7. Ziccardi P, Nappo F, Giugliano G, et al. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 2002;105:804–809.

    Article  PubMed  CAS  Google Scholar 

  8. Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 2003;285:E527-E533.

    PubMed  CAS  Google Scholar 

  9. Esposito K, Pontillo A, Ciotola M, et al. Weight loss reduces interleukin-18 concentrations in obese women. J Clin Endocrinol Metab 2002;87:3864–3866.

    Article  PubMed  CAS  Google Scholar 

  10. Kopp HP, Kopp CW, Festa A, et al. Schernthaner G. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vase Biol 2003;23:1042–1047.

    Article  CAS  Google Scholar 

  11. Vicennati V, Vottero A, Friedman C, Papanicolaou DA. Hormonal regulation of interleukin-6 production in human adipocytes. Int J Obes 2002;26:1–7.

    Article  Google Scholar 

  12. Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: Depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998;83:847–850.

    Article  PubMed  CAS  Google Scholar 

  13. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004;145:2273–2282.

    Article  PubMed  CAS  Google Scholar 

  14. Mohamed-Ali V, Goodrick S, Rawesh A, et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-a, in vivo. J Clin Endocrinol Metab 1997;82:4196–4200.

    Article  PubMed  CAS  Google Scholar 

  15. Gletsu N, Lin E, Li J-L, et al. Surgery; in press.

  16. Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Sleep apnea and daytime sleepiness and fatigue: Relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab 2000;85:1151.

    Article  PubMed  CAS  Google Scholar 

  17. Lin E, Gletsu N, Fugate K, et al. The effects of gastric surgery on systemic ghrelin levels in the morbidly obese. Arch Surg 2004;139:780–784.

    Article  PubMed  Google Scholar 

  18. Brochu M, R.D.S., Tchernof A, Matthews DE, Garcia-Rubi E, Poehlman ET. Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women. J Clin Endocrinol Metab 2000;85:2378–2384.

    Article  PubMed  CAS  Google Scholar 

  19. Bastard J-P, Jardel C, Bruckert E, et al. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tisse of obese women after weight loss. J Clin Endocrinol Metab 2000;85:3338–3342.

    Article  PubMed  CAS  Google Scholar 

  20. Kvist H, Chowdhury B, Sjostrom L, Tylen U, Cederblad A. Adipose tissue volume determination in males by computed tomography and 40K. Int J Obes 1988;12:249–266.

    PubMed  CAS  Google Scholar 

  21. Kahn HS, Austin H, Williamson DF, Arensberg D. A simple anthropometric indices associated with ischemic heart disease. J Clin Epidemiol 1996;49:1017–1024.

    Article  PubMed  CAS  Google Scholar 

  22. Bergman RN. Toward physiological understanding of glucose tolerance. Minimal-model approach. Diabetes 1989; 38:1512–1527.

    Article  PubMed  CAS  Google Scholar 

  23. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112:1796–1808.

    Article  PubMed  CAS  Google Scholar 

  24. Sakamoto K, Arakawa H, Mita S, et al. Elevation of circulating interleukin-6 after surgery: Factors influencing the serum level. Cytokine 1994;6:181–186.

    Article  PubMed  CAS  Google Scholar 

  25. Wlaszczyk A, Adamik B, Durek G, Kubler A, Zimecki M. Immunological status of patients subjected to cardiac surgery: serum levels of interleukin-6 and tumor necrosis factor alpha and the ability of peripheral blood mononuclear cells to proliferate and produce these cytokines in vitro. Arch Immunol Ther Exp (Warsz) 1996;44:225–234.

    CAS  Google Scholar 

  26. Hierholzer C, Kalff JC, Bednarski B, et al. Rapid and simultaneous activation of Stat3 and production of interleukin 6 in resuscitated hemorrhagic shock. Arch Orthop Trauma Surg 1999;119:332–336.

    Article  PubMed  CAS  Google Scholar 

  27. Ramos EJB, Xu Y, Romanova I, et al. Is obesity an inflammatory disease? Surgery 2003;134:329–335.

    Article  PubMed  Google Scholar 

  28. Csete M, Walikonis J, Slawny N, et al. Oxygen-mediated regulation of skeletal muscle satellite cell proliferation and adipogenesis in culture. J Cell Physiol 2001;189:189–196.

    Article  PubMed  CAS  Google Scholar 

  29. Yudkin JS, Stehouwer CDA, Emeis JJ, Coppack SW. Creactive protein in healthy subjects: Associations with obesity, insulin resistance and endothelial dysfunction: a potential role for cytokines orginating from adipose tissue. Arterioscler Thromb Vasc Biol 1999;19:972–978.

    PubMed  CAS  Google Scholar 

  30. McLaughlin T, Abbasi F, Lamendola C, et al. Differentiation between obesity and insulin resistance in the association with C-Reactive protein. Circulation 2002;106:2908–2912.

    Article  PubMed  CAS  Google Scholar 

  31. Pradhan AD, Cook NR, Buring JE, Manson JE, Ridker PM. C-reative protein is independently associated with fasting insulin in non-diabetic women. Arterioscler Thromb Vasc Biol 2003;23:650–655.

    Article  PubMed  CAS  Google Scholar 

  32. Segal KR, Landt M, Klein S. Relationship between insulin sensitivity and plasma leptin concentrations in lean and obese men. Diabetes 1996;45:987–991.

    Article  Google Scholar 

  33. Degawa-Yamauchi M, Bevenkerk JE, Juliar BE, et al. Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 2003;88:5452–5455.

    Article  PubMed  CAS  Google Scholar 

  34. Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941–946.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Emory University School of Medicine, 1364 Clifton Road, Suite H130, 30322, Atlanta, GA

    Nana Gletsu Ph.D., Edward Lin D.O., Leena Khaitan M.D., M.P.H., Scott A. Lynch M.D., M.P.H., Bruce Ramshaw M.D. & C. Daniel Smith M.D.

  2. Departments of Radiology, Emory University School of Medicine, Atlanta, Georgia

    Randall Raziano M.D. & William E. Torres M.D.

  3. Departments of Medicine, Emory University School of Medicine, Atlanta, Georgia

    Thomas R. Ziegler M.D. & Dimitris A. Papanicolaou M.D.

Authors
  1. Nana Gletsu Ph.D.
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  2. Edward Lin D.O.
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  3. Leena Khaitan M.D., M.P.H.
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  4. Scott A. Lynch M.D., M.P.H.
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  5. Bruce Ramshaw M.D.
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  6. Randall Raziano M.D.
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  7. William E. Torres M.D.
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  8. Thomas R. Ziegler M.D.
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  9. Dimitris A. Papanicolaou M.D.
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  10. C. Daniel Smith M.D.
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Corresponding author

Correspondence to Nana Gletsu Ph.D..

Additional information

Supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases 1R03 DK067167-01A1 (N.G.), the Emory University Research Committee Grant (N.G.), and the National Institutes of Health/National Center for Research Resources General Clinical Research Center Grant M01 RR00039 (N.G., E.L.).

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Gletsu, N., Lin, E., Khaitan, L. et al. Changes in C-reactive protein predict insulin sensitivity in severely obese individuals after weight loss surgery. J Gastrointest Surg 9, 1119–1128 (2005). https://doi.org/10.1016/j.gassur.2005.07.035

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  • DOI: https://doi.org/10.1016/j.gassur.2005.07.035

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