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Association Between C-Reactive Protein and Type 2 Diabetes in a Tunisian Population

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Abstract

The aim of this study was to investigate the association of CRP levels with type 2 diabetes (T2D) and its related variables in a sample of the Tunisian population. Our sample included 129 patients with T2D and 187 control subjects. Body mass index (BMI), plasma lipids, glucose, insulin, and CRP concentrations were measured for each participant. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. T2D was defined as a fasting plasma glucose (FPG) level ≥ 7.0 mmol/L, the use of anti-diabetic drugs, or both. Statistical analyses were performed using SPSS 11.5. A significant difference in mean values of BMI, plasma lipids, FPG, insulin, and HOMA-IR was observed between subjects with and without T2D. CRP level was significantly higher in subjects with T2D than those without (p = 0.023), and this result persisted even after adjustment for age, gender, BMI, smoking, and alcohol consumption. In both diabetes statuses, log CRP was significantly associated with FPG, insulin, and HOMA-IR. Subjects with elevated CRP levels (>5 mg/L) had an increased risk of T2D (OR = 2.02, 95% CI 1.18–3.46, p = 0.010) than those whose CRP levels were less or equal to 5 mg/L. Even after adjustment for potentially confounding factors, the risk of T2D was still increased in subjects with elevated CRP levels (OR = 1.91, 95% CI 1.08–3.36, p = 0.025). These results suggest that elevated CRP levels are independently associated with T2D.

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REFERENCES

  1. Lyra, R., M. Oliveira, D. Lins, and N. Cavalcanti. 2006. Prevention of type 2 diabetes mellitus. Arq Bras Endocrinol Metab 50: 239–249.

    Article  Google Scholar 

  2. Bogaert, Y.E., and R.W. Schrier. 2011. Into the future: prevention of diabetes. Contributions to Nephrology 170: 256–263.

    Article  PubMed  Google Scholar 

  3. Wong, T.Y., N. Cheung, W.T. Tay, J.J. Wang, T. Aung, S.M. Saw, S.C. Lim, E.S. Tai, and P. Mitchell. 2008. Prevalence and risk factors for diabetic retinopathy: the Singapore Malay Eye Study. Ophthalmology 115: 1869–1875.

    Article  PubMed  Google Scholar 

  4. Howard, B.V., B.L. Rodriguez, P.H. Bennett, M.I. Harris, R. Hammam, L.H. Kuller, T.A. Pearson, and J. Wylie-Rosett. 2002. Prevention Conference VI: Diabetes and cardiovascular disease: writing group I: epidemiology. Circulation 105: 132–137.

    Article  Google Scholar 

  5. Nabipour, I., K. Vahdat, S.M. Jafari Seyed, S. Beigi, M. Assadi, F. Azizi, and Z. Sanjdideh. 2008. Elevated high sensitivity c-reactive protein is associated with type 2 diabetes mellitus: the Persian Gulf healthy heart study. Endocrine Journal 55: 717–722.

    Article  PubMed  CAS  Google Scholar 

  6. Pickup, J.C., M.B. Mattock, G.D. Chusney, and D. Burt. 1997. NIDDM as disease of the immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 40: 1286–1292.

    Article  PubMed  CAS  Google Scholar 

  7. Pickup, J.C., and M.A. Crook. 1998. Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 41: 1241–1248.

    Article  PubMed  CAS  Google Scholar 

  8. Morohoshi, M., K. Fujisawa, I. Uchimura, and F. Numano. 1996. Glucose-dependent interleukin 6 and tumor necrosis factor production by human peripheral blood monocytes in vitro. Diabetes 45: 954–959.

    Article  PubMed  Google Scholar 

  9. Guha, M., W. Bai, J.L. Nadler, and R. Natarajan. 2000. Molecular mechanisms of tumor necrosis factor α gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways. Journal of Biological Chemistry 275: 17728–17739.

    Article  PubMed  CAS  Google Scholar 

  10. Hirschfield, G., and M. Pepys. 2003. C-reactive protein and cardiovascular disease: new insights from an old molecule. QJM 96: 793.

    Article  PubMed  CAS  Google Scholar 

  11. Pearson, T.A., G.A. Mensah, R.W. Alexander, J.L. Anderson, R.O. Cannon 3rd, M. Criqui, Y.Y. Fadl, S.P. Fortmann, Y. Hong, G.L. Myers, N. Rifai, S.C. Smith Jr., K. Taubert, R.P. Tracy, and F. Vinicor. 2003. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107: 499–511.

    Article  PubMed  Google Scholar 

  12. Ridker, P.M., M. Cushman, M.J. Stampfer, R.P. Tracy, and C.H. Hennekens. 1997. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. The New England Journal of Medicine 336: 973–979.

    Article  PubMed  CAS  Google Scholar 

  13. Yeh, E.T., and J.T. Willerson. 2003. Coming of age of C-reactive protein: using inflammation markers in cardiology. Circulation 107: 370–371.

    Article  PubMed  Google Scholar 

  14. Ridker, P.M. 2003. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107: 363–369.

    Article  PubMed  Google Scholar 

  15. Liuzzo, G., L.M. Biasucci, J.R. Gallimore, R.L. Grillo, A.G. Rebuzzi, M.B. Pepys, and A. Maseri. 1994. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. New Engl J Med 331: 417–424.

    Article  PubMed  CAS  Google Scholar 

  16. Ridker, P.M., C.H. Hennekens, J.E. Buring, and N. Rifai. 2000. C-Reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New Engl J Med 342: 836–843.

    Article  PubMed  CAS  Google Scholar 

  17. Festa, A., R. D'Agostino Jr., G. Howard, L. Mykkänen, R.P. Tracy, and S.M. Haffner. 2000. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102: 42–47.

    PubMed  CAS  Google Scholar 

  18. Pradhan, A.D., J.E. Manson, N. Rifai, J.E. Buring, and P.M. Ridker. 2001. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286: 327–334.

    Article  PubMed  CAS  Google Scholar 

  19. Nakanishi, S., K. Yamane, N. Kamei, M. Okubo, and N. Kohno. 2003. Elevated C-reactive protein is a risk factor for the development of type 2 diabetes in Japanese Americans. Diabetes Care 26: 2754–2757.

    Article  PubMed  CAS  Google Scholar 

  20. Thorand, B., J. Baumert, H. Kolb, C. Meisinger, L. Chambless, W. Koenig, and C. Herder. 2007. Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Diabetes Care 30: 854–860.

    Article  PubMed  CAS  Google Scholar 

  21. Hu, G., P. Jousilahti, J. Tuomilehto, R. Antikainen, J. Sundvall, and V. Salomaa. 2009. Association of serum C-reactive protein level with sex-specific type 2 diabetes risk: a prospective Finnish study. Journal of Clinical Endocrinology and Metabolism 94: 2099–2105.

    Article  PubMed  CAS  Google Scholar 

  22. Krakoff, J., T. Funahashi, C.D. Stehouwer, C.G. Schalkwijk, S. Tanaka, Y. Matsuzawa, S. Kobes, P.A. Tataranni, R.L. Hanson, W.C. Knowler, and R.S. Lindsay. 2003. Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diabetes Care 26: 1745–1751.

    Article  PubMed  CAS  Google Scholar 

  23. Dehghan, A., I. Kardys, M.P. de Maat, A.G. Uitterlinden, E.J. Sijbrands, A.H. Bootsma, T. Stijnen, A. Hofman, M.T. Schram, and J.C. Witteman. 2007. Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 56: 872–878.

    Article  PubMed  CAS  Google Scholar 

  24. Lee, C.C., A.I. Adler, M.S. Sandhu, S.J. Sharp, N.G. Forouhi, S. Erqou, R. Luben, S. Bingham, K.T. Khaw, and N.J. Wareham. 2009. Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis. Diabetologia 52: 1040–1047.

    Article  PubMed  CAS  Google Scholar 

  25. Friedewald, W.T., R.T. Levy, and D.S. Fredrickson. 1972. Estimation of the concentration of low density lipoprotein cholesterol in plasma without use of the ultracentrifuge. Clinical Chemistry 18: 449–502.

    Google Scholar 

  26. Matthews, D.R., J.P. Hosker, A.S. Rudenski, B.A. Naylor, D.F. Treacher, and R.C. Turner. 1985. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412–419.

    Article  PubMed  CAS  Google Scholar 

  27. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. 1997. Diabetes Care 20:1183–1197.

    Google Scholar 

  28. Dandona, P., A. Aljada, A. Chaudhuri, and A. Bandyopadhyay. 2003. The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complication in type 2 diabetes. Journal of Clinical Endocrinology and Metabolism 88: 2422–2429.

    Article  PubMed  CAS  Google Scholar 

  29. Doi, Y., Y. Kiyohara, M. Kubo, T. Ninomiya, Y. Wakugawa, K. Yonemoto, M. Iwase, and M. Iida. 2005. Elevated C-reactive protein is a predictor of the development of diabetes in a general Japanese population: the Hisayama Study. Diabetes Care 28: 2497–2500.

    Article  PubMed  CAS  Google Scholar 

  30. Freeman, D.J., J. Norrie, M.J. Caslake, A. Gaw, I. Ford, G.D. Lowe, D.S. O'Reilly, C.J. Packard, N. Sattar, and West of Scotland Coronary Prevention Study. 2002. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 51: 1596–1600.

    Article  PubMed  CAS  Google Scholar 

  31. Huffman, F.G., S. Whisner, G.G. Zarini, and S. Nath. 2010. Waist circumference and BMI in relation to serum high sensitivity C-reactive protein (hs-CRP) in Cuban Americans with and without type 2 diabetes. International Journal of Environmental Research and Public Health 7: 842–852.

    Article  PubMed  CAS  Google Scholar 

  32. Shemesh, T., K.G. Rowley, A. Jenkins, J. Brimblecombe, J.D. Best, and K. O'Dea. 2007. Differential association of C-reactive protein with adiposity in men and women in an Aboriginal community in northeast Arnhem Land of Australia. International Journal of Obesity 31: 103–108.

    Article  PubMed  CAS  Google Scholar 

  33. Baumann, H., and J. Gauldie. 1990. Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation. Molecular Biology & Medicine 7: 147–159.

    CAS  Google Scholar 

  34. Hotamisligil, G.S., P. Arner, J.F. Caro, R.L. Atkinson, and B.M. Spiegelman. 1995. Increased adipose tissue expression of tumor necrosis factor alpha in human obesity and insulin resistance. The Journal of Clinical Investigation 95: 2409–2415.

    Article  PubMed  CAS  Google Scholar 

  35. Warren, R.S., H.F. Starnes Jr., J.L. Gabrilove, H.F. Oettgen, and M.F. Brennan. 1987. The acute metabolic effects of tumor necrosis factor administration in humans. Archives of Surgery 122: 1396–1400.

    Article  PubMed  CAS  Google Scholar 

  36. Vgontzas, A.N., D.A. Papanicolaou, E.O. Bixler, A. Kales, K. Tyson, and G.P. Chrousos. 1997. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. Journal of Clinical Endocrinology and Metabolism 82: 1313–1316.

    Article  PubMed  CAS  Google Scholar 

  37. Yamada, S., T. Gotoh, Y. Nakashima, K. Kayaba, S. Ishikawa, N. Nago, Y. Nakamura, Y. Itoh, and E. Kajii. 2001. Distribution of serum C-reactive protein and its association with atherosclerotic risk factors in a Japanese population. Jichi Med School Cohort Study. Am J Epidemiol 153: 1183–1190.

    CAS  Google Scholar 

  38. Saijo, Y., N. Kiyota, Y. Kawasaki, Y. Miyazaki, J. Kashimura, M. Fukuda, and R. Kishi. 2004. Relationship between C-reactive protein and visceral adipose tissue in healthy Japanese subjects. Diabetes, Obesity & Metabolism 6: 249–258.

    Article  CAS  Google Scholar 

  39. Pickup, J.C. 2004. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27: 813–823.

    Article  PubMed  Google Scholar 

  40. Grunfeld, C., and K.R. Feingold. 1996. Regulation of lipid metabolism by cytokines during host defense. Nutrition 12: S24–S26.

    PubMed  CAS  Google Scholar 

  41. Nishikawa, T., D. Edelstein, X.L. Du, S. Yamaguchi, T. Matsumura, Y. Kaneda, M.A. Yorek, D. Beebe, P.J. Oates, H.P. Hammes, I. Giardino, and M. Brownlee. 2000. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycemic damage. Nature 404: 787–790.

    Article  PubMed  CAS  Google Scholar 

  42. Ceriello, A., and E. Motz. 2004. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arteriosclerosis, Thrombosis, and Vascular Biology 24: 816–823.

    Article  PubMed  CAS  Google Scholar 

  43. Cleland, S.J., N. Sattar, J.R. Petrie, N.G. Forouhi, H.L. Elliott, and J.M. Connell. 2000. Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. Clin Science 98: 531–535.

    Article  CAS  Google Scholar 

  44. Tooke, J. 1999. The association between insulin resistance and endotheliopathy. Diabetes, Obesity & Metabolism 1: S17–S22.

    Article  Google Scholar 

  45. Stewart, M.W., D.T. Cirkel, K. Furuseth, J. Donaldson, N. Biswas, M.G. Starkie, C. Phenekos, and A. Hamann. 2006. Effect of metformin plus rosiglitazone compared with metformin alone on glycaemic control in well-controlled type 2 diabetes. Diabetic Medicine 23: 1069–1078.

    Article  PubMed  CAS  Google Scholar 

  46. Ridker, P.M., C.P. Cannon, D. Morrow, N. Rifai, L.M. Rose, C.H. McCabe, M.A. Pfeffer, and E. Raunwald. 2005. C-reactive protein levels and outcomes after statin therapy. N Eng J Med 352: 20–28.

    Article  CAS  Google Scholar 

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ACKNOWLEDGMENTS

This work was supported by a grant from The “Ministry of Higher Education, Scientific Research and Technology” of Tunisia.

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Correspondence to Hanen Belfki.

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Belfki, H., Ben Ali, S., Bougatef, S. et al. Association Between C-Reactive Protein and Type 2 Diabetes in a Tunisian Population. Inflammation 35, 684–689 (2012). https://doi.org/10.1007/s10753-011-9361-1

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