, Volume 35, Issue 2, pp 684–689 | Cite as

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

  • Hanen Belfki
  • Samir Ben Ali
  • Souha Bougatef
  • Decy Ben Ahmed
  • Najet Haddad
  • Awatef Jmal
  • Monia Abdennebi
  • Habiba Ben Romdhane


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.


C-reactive protein inflammation type 2 diabetes insulin resistance 



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


  1. 1.
    Lyra, R., M. Oliveira, D. Lins, and N. Cavalcanti. 2006. Prevention of type 2 diabetes mellitus. Arq Bras Endocrinol Metab 50: 239–249.CrossRefGoogle Scholar
  2. 2.
    Bogaert, Y.E., and R.W. Schrier. 2011. Into the future: prevention of diabetes. Contributions to Nephrology 170: 256–263.PubMedCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 10.
    Hirschfield, G., and M. Pepys. 2003. C-reactive protein and cardiovascular disease: new insights from an old molecule. QJM 96: 793.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 14.
    Ridker, P.M. 2003. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107: 363–369.PubMedCrossRefGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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. 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.PubMedCrossRefGoogle Scholar
  27. 27.
    Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. 1997. Diabetes Care 20:1183–1197.Google Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.Google Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.Google Scholar
  38. 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.CrossRefGoogle Scholar
  39. 39.
    Pickup, J.C. 2004. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27: 813–823.PubMedCrossRefGoogle Scholar
  40. 40.
    Grunfeld, C., and K.R. Feingold. 1996. Regulation of lipid metabolism by cytokines during host defense. Nutrition 12: S24–S26.PubMedGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.CrossRefGoogle Scholar
  44. 44.
    Tooke, J. 1999. The association between insulin resistance and endotheliopathy. Diabetes, Obesity & Metabolism 1: S17–S22.CrossRefGoogle Scholar
  45. 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.PubMedCrossRefGoogle Scholar
  46. 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.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Hanen Belfki
    • 1
  • Samir Ben Ali
    • 1
  • Souha Bougatef
    • 1
  • Decy Ben Ahmed
    • 3
  • Najet Haddad
    • 3
  • Awatef Jmal
    • 2
  • Monia Abdennebi
    • 2
  • Habiba Ben Romdhane
    • 1
  1. 1.Laboratory of Epidemiology and Prevention of Cardiovascular Disease, Faculty of MedicineUniversity of Tunis El-ManarTunisTunisia
  2. 2.Laboratory of Medical BiologyMahmoud El-Matri Hospital of ArianaTunisTunisia
  3. 3.Center of Basic Health Care of Ariana EssoghraTunisTunisia

Personalised recommendations