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International Journal of Endocrinology
Volume 2013 (2013), Article ID 678159, 11 pages
http://dx.doi.org/10.1155/2013/678159
Review Article

Obesity and Inflammation: Epidemiology, Risk Factors, and Markers of Inflammation

1Biomedical Research Unit of the Mexican Social Security Institute at Durango, Predio Canoas 100, Los Angeles, 34067 Durango, DGO, Mexico
2Faculty of Medicine and Nutrition, Juárez University of Durango State, Av. Universidad and Fanny Anitúa s/n, Zona Centro, 34000 Durango, DGO, Mexico

Received 14 January 2013; Accepted 27 March 2013

Academic Editor: Abdelfattah El Ouaamari

Copyright © 2013 Heriberto Rodríguez-Hernández et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. M. Finucane, G. A. Stevens, M. J. Cowan et al., “National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants,” The Lancet, vol. 377, no. 9765, pp. 557–567, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. E. S. Ford and A. H. Mokdad, “Epidemiology of obesity in the Western Hemisphere,” The Journal of Clinical Endocrinology and Metabolism, vol. 93, pp. S1–S8, 2008.
  3. National Institutes of Health, Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults, U.S. Department of Health and Human Services, Bethesda, Md, USA, 1998.
  4. R. J. Kuczmarski, K. M. Flegal, S. M. Campbell, and C. L. Johnson, “Increasing prevalence of overweight among US adults: the National Health and Nutrition Examination Surveys, 1960 to 1991,” Journal of the American Medical Association, vol. 272, no. 3, pp. 205–211, 1994. View at Publisher · View at Google Scholar · View at Scopus
  5. R. P. Troiano, K. M. Flegal, R. J. Kuczmarski, S. M. Campbell, and C. L. Johnson, “Overweight prevalence and trends for children and adolescents: the National Health and Nutrition Examination Surveys, 1963 to 1991,” Archives of Pediatrics and Adolescent Medicine, vol. 149, no. 10, pp. 1085–1091, 1995. View at Scopus
  6. D. S. Freedman, L. K. Khan, M. K. Serdula, D. A. Galuska, and W. H. Dietz, “Trends and correlates of class 3 obesity in the United States from 1990 through 2000,” Journal of the American Medical Association, vol. 288, no. 14, pp. 1758–1761, 2002. View at Scopus
  7. H. M. Orpana, J. M. Berthelot, M. S. Kaplan, D. H. Feeny, B. McFarland, and N. A. Ross, “BMI and mortality: results from a national longitudinal study of canadian adults,” Obesity, vol. 18, no. 1, pp. 214–218, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. G. S. Hotamisligil, “Inflammation and metabolic disorders,” Nature, vol. 444, no. 7121, pp. 860–867, 2006. View at Publisher · View at Google Scholar · View at Scopus
  9. P. M. Ridker, J. E. Buring, J. Shih, M. Matias, and C. H. Hennekens, “Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women,” Circulation, vol. 98, no. 8, pp. 731–733, 1998. View at Scopus
  10. M. S. Kaplan, N. Huguet, J. T. Newsom, B. H. McFarland, and J. Lindsay, “Prevalence and correlates of overweight and obesity among older adults: findings from the Canadian National Population Health Survey,” Journals of Gerontology A, vol. 58, no. 11, pp. 1018–1030, 2003. View at Scopus
  11. L. A. Adams, J. F. Lymp, J. S. Sauver et al., “The natural history of nonalcoholic fatty liver disease: a population-based cohort study,” Gastroenterology, vol. 129, no. 1, pp. 113–121, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. P. Angulo, “Medical progress: nonalcoholic fatty liver disease,” The New England Journal of Medicine, vol. 346, no. 16, pp. 1221–1231, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Bellentani and M. Marino, “Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD),” Annals of Hepatology, vol. 8, supplement 1, pp. S4–S8, 2009. View at Scopus
  14. C. E. Ruhl and J. E. Everhart, “Trunk fat is associated with increased serum levels of alanine aminotransferase in the United States,” Gastroenterology, vol. 138, no. 4, pp. 1346.e3–1356.e3, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. H. Rodriguez-Hernandez, M. Cervantes-Alvarez, M. Rodriguez- Moran, and F. Guerrero-Romero, “Decrease of aminotransferase levels in obese women is related to body weight reduction, irrespective of type of diet,” Annals of Hepatology, vol. 10, pp. 486–492, 2011.
  16. H. Rodriguez-Hernandez, U. A. Morales-Amaya, R. Rosales-Valdéz, F. Rivera-Hinojosa, M. Rodriguez-Moran, and F. Guerrero-Romero, “Adding cognitive behavioural treatment to either low-carbohydrate or low-fat diets: differential short-term effects,” British Journal of Nutrition, vol. 102, no. 12, pp. 1847–1853, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Stepanova and Z. M. Younoussi, “Independent association between nonalcoholic fatty liver disease and cardiovascular disease in US population,” Clinical Gastroenterology and Hepatology, vol. 10, pp. 646–650, 2012.
  18. H. Kuper, A. Tzonou, and E. Kakalamani, “Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocelular carcinoma,” International Journal of Cancer, vol. 85, pp. 498–502, 2000.
  19. D. Trichopoulos, C. Bamia, and P. Lagiou, “Hepatocelular carcinoma risk factors and disease burden in a European cohort: a nested case-control study,” Journal of the National Cancer Institute, vol. 103, pp. 1686–1695, 2011.
  20. N. D. Freedman and J. A. Marrero, “Can dietary fish intake prevent liver cancer?” Gastroenterology, vol. 142, pp. 1411–1413, 2012.
  21. L. J. Su, S. Mahabir, G. L. Ellison, L. A. McGuinn, and B. C. Reid, “Epigenetic contributions to the relationship between cancer and dietary intake of nutrients, bioactive food, components, and environmental toxicants,” Nutrigenomics, vol. 2, pp. 1–12, 2012.
  22. M. F. Gregor and G. S. Hotamisligil, “Inflammatory mechanisms in obesity,” Annual Review of Immunology, vol. 29, pp. 415–445, 2011.
  23. E. Faloia, G. Michetti, M. de Robertis, M. P. Luconi, G. Furlani, and M. Boscaro, “Inflammation as a link between obesity and metabolic syndrome,” Journal of Nutrition and Metabolism, vol. 2012, Article ID 476380, 7 pages, 2012. View at Publisher · View at Google Scholar
  24. R. Stienstra, C. J. Tack, T. D. Kanneganti, L. A. Joosten, and M. G. Netea, “The inflammasome puts obesity in the danger zone,” Cell Metabolism, vol. 15, pp. 10–18, 2012.
  25. G. Solinas and M. Karin, “JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction,” The FASEB Journal, vol. 24, no. 8, pp. 2596–2611, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Boura-Halfon and Y. Zick, “Phosphorylation of IRS proteins, insulin action, and insulin resistance,” American Journal of Physiology, vol. 296, no. 4, pp. E581–E591, 2009. View at Publisher · View at Google Scholar · View at Scopus
  27. K. Schroder, R. Zhou, and J. Tschopp, “The NLRP3 inflammasome: a sensor for metabolic danger?” Science, vol. 327, no. 5963, pp. 296–300, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. H. Shi, M. V. Kokoeva, K. Inouye, I. Tzameli, H. Yin, and J. S. Flier, “TLR4 links innate immunity and fatty acid-induced insulin resistance,” The Journal of Clinical Investigation, vol. 116, no. 11, pp. 3015–3025, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Lamkanfi and T. D. Kanneganti, “The inflammasome: a remote control for metabolic syndrome,” Cell Research, vol. 22, pp. 1095–1098, 2012.
  30. L. D. Church, G. P. Cook, and M. F. McDermott, “Primer: inflammasomes and interleukin 1β in inflammatory disorders,” Nature Clinical Practice Rheumatology, vol. 4, no. 1, pp. 34–42, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Dagenais, J. Dupaul-Chicoine, and M. Saleh, “Function of NOD-like receptors in immunity and disease,” Current Opinion in Investigational Drugs, vol. 11, no. 11, pp. 1246–1255, 2010. View at Scopus
  32. M. Dagenais, A. Skeldon, and M. Saleh, “The inflammasome: in memory of Dr. Jurg Tschopp,” Cell Death and Differentiation, vol. 19, pp. 5–12, 2012.
  33. B. Vandanmagsar, Y. H. Youm, A. Ravussin et al., “The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance,” Cell Death and Differentiation, vol. 17, pp. 179–188, 2011.
  34. C. M. Larsen, M. Faulenbach, A. Vaag et al., “Interleukin-1-receptor antagonist in type 2 diabetes mellitus,” The New England Journal of Medicine, vol. 356, no. 15, pp. 1517–1526, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. R. Zhou, A. Tardivel, B. Thorens, I. Choi, and J. Tschopp, “Thioredoxin-interacting protein links oxidative stress to inflammasome activation,” Nature Immunology, vol. 11, no. 2, pp. 136–140, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. G. S. Hotamisligil, P. Peraldi, A. Budavari, R. Ellis, M. F. White, and B. M. Spiegelman, “IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance,” Science, vol. 271, no. 5249, pp. 665–668, 1996. View at Scopus
  37. B. Wang and P. Trayhurn, “Acute and prolonged effects of TNF-α on the expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture,” Pflugers Archiv European Journal of Physiology, vol. 452, no. 4, pp. 418–427, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. K. Stenlöf, I. Wernstedt, T. Fjällman, V. Wallenius, K. Wallenius, and J. O. Jansson, “Interleukin-6 levels in the central nervous system are negatively correlated with fat mass in overweight/obese subjects,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 9, pp. 4379–4383, 2003. View at Publisher · View at Google Scholar · View at Scopus
  39. W. E. Naugler and M. Karin, “The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer,” Trends in Molecular Medicine, vol. 14, no. 3, pp. 109–119, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. J. C. Pickup, “Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes,” Diabetes Care, vol. 27, no. 3, pp. 813–823, 2004. View at Publisher · View at Google Scholar · View at Scopus
  41. H. Baumann and J. Gauldie, “The acute phase response,” Immunology Today, vol. 15, no. 2, pp. 74–80, 1994. View at Publisher · View at Google Scholar · View at Scopus
  42. C. Gabay and I. Kushner, “Acute-phase proteins and other systemic responses to inflammation,” The New England Journal of Medicine, vol. 340, no. 6, pp. 448–454, 1999. View at Publisher · View at Google Scholar · View at Scopus
  43. J. S. Yudkin, M. Kumari, S. E. Humphries, and V. Mohamed-Ali, “Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link?” Atherosclerosis, vol. 148, no. 2, pp. 209–214, 2000. View at Publisher · View at Google Scholar · View at Scopus
  44. J. S. Yudkin, “Adipose tissue, insulin action and vascular disease: inflammatory signals,” International Journal of Obesity, vol. 27, supplement 3, pp. S25–S28, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. T. A. Pearson, G. A. Mensah, R. W. Alexander et al., “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, vol. 107, no. 3, pp. 499–511, 2003. View at Publisher · View at Google Scholar · View at Scopus
  46. M. B. Pepys and G. M. Hirschfield, “C-reactive protein: a critical update,” The Journal of Clinical Investigation, vol. 111, no. 12, pp. 1805–1812, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Jacobs, M. M. J. van Greevenbroek, C. J. H. van der Kallen et al., “Low-grade inflammation can partly explain the association between the metabolic syndrome and either coronary artery disease or severity of peripheral arterial disease: the CODAM study,” European Journal of Clinical Investigation, vol. 39, no. 6, pp. 437–444, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. P. A. Kern, M. Saghizadeh, J. M. Ong, R. J. Bosch, R. Deem, and R. B. Simsolo, “The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase,” The Journal of Clinical Investigation, vol. 95, no. 5, pp. 2111–2119, 1995. View at Scopus
  49. E. Lapice, S. Maione, L. Patti et al., “Abdominal adiposity is associated with elevated C-reactive protein independent of BMI in healthy nonobese people,” Diabetes Care, vol. 32, no. 9, pp. 1734–1736, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. D. E. Laaksonen, L. Niskanen, K. Nyyssönen et al., “C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men,” Diabetologia, vol. 47, no. 8, pp. 1402–1410, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. K. R. Feingold and C. Grunfeld, “Role of cytokines in inducing hyperlipidemia,” Diabetes, vol. 41, supplement 2, pp. 97–101, 1992. View at Scopus
  52. G. S. Hotamisligil and B. M. Spiegelman, “Tumor necrosis factor α: a key component of the obesity-diabetes link,” Diabetes, vol. 43, no. 11, pp. 1271–1278, 1994. View at Scopus
  53. F. X. Pi-Sunyer, “The obesity epidemic: pathophysiology and consequences of obesity,” Obesity Research, vol. 10, supplement 10, pp. 97S–104S, 2002. View at Scopus
  54. A. E. Caballero, “Endothelial dysfunction in obesity and insulin resistance: a road to diabetes and heart disease,” Obesity Research, vol. 11, no. 11, pp. 1278–1289, 2003. View at Scopus
  55. A. H. Berg and P. E. Scherer, “Adipose tissue, inflammation, and cardiovascular disease,” Circulation Research, vol. 96, no. 9, pp. 939–949, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. D. C. W. Lau, B. Dhillon, H. Yan, P. E. Szmitko, and S. Verma, “Adipokines: molecular links between obesity and atheroslcerosis,” American Journal of Physiology, vol. 288, no. 5, pp. H2031–H2041, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Visser, L. M. Bouter, G. M. McQuillan, M. H. Wener, and T. B. Harris, “Low-grade systemic inflammation in overweight children,” Pediatrics, vol. 107, no. 1, pp. 1–6, 2001. View at Scopus
  58. G. Nicoletti, G. Giugliano, A. Pontillo et al., “Effect of a multidisciplinary program of weight reduction on endothelial functions in obese women,” Journal of Endocrinological Investigation, vol. 26, no. 3, pp. RC5–RC8, 2003. View at Scopus
  59. L. K. Heilbronn, M. Noakes, and P. M. Clifton, “Energy restriction and weight loss on very-low-fat diets reduce C-reactive protein concentrations in obese, healthy women,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 21, no. 6, pp. 968–970, 2001. View at Scopus
  60. H. P. Kopp, C. W. Kopp, A. Festa et al., “Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 6, pp. 1042–1047, 2003. View at Publisher · View at Google Scholar · View at Scopus
  61. G. M. Reaven, “Role of insulin resistance in human disease,” Diabetes, vol. 37, no. 12, pp. 1595–1607, 1988. View at Scopus
  62. E. Ferrannini, S. M. Haffner, B. D. Mitchell, and M. P. Stern, “Hyperinsulinaemia: the key feature of cardiovascular and metabolic syndrome,” Diabetologia, vol. 34, no. 6, pp. 416–422, 1991. View at Scopus
  63. R. S. Gray, R. R. Fabsitz, L. D. Cowan, E. T. Lee, B. V. Howard, and P. J. Savage, “Risk factor clustering in the insulin resistance syndrome. The strong heart study,” American Journal of Epidemiology, vol. 148, no. 9, pp. 869–878, 1998. View at Scopus
  64. M. Carantoni, G. Zuliani, S. Volpato et al., “Relationships between fasting plasma insulin, anthropometrics, and metabolic parameters in a very old healthy population,” Metabolism, vol. 47, no. 5, pp. 535–540, 1998. View at Publisher · View at Google Scholar · View at Scopus
  65. G. S. Hotamisligil, N. S. Shargill, and B. M. Spiegelman, “Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance,” Science, vol. 259, no. 5091, pp. 87–91, 1993. View at Scopus
  66. V. Mohamed-Ali, S. Goodrick, A. Rawesh et al., “Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-α, in vivo,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 12, pp. 4196–4200, 1997. View at Scopus
  67. R. Anty, S. Bekri, N. Luciani et al., “The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, type 2 diabetes, and NASH,” American Journal of Gastroenterology, vol. 101, no. 8, pp. 1824–1833, 2006. View at Publisher · View at Google Scholar · View at Scopus
  68. P. Calabro, D. W. Chang, J. T. Willerson, and E. T. H. Yeh, “Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: linking obesity to vascular inflammation,” Journal of the American College of Cardiology, vol. 46, no. 6, pp. 1112–1113, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. H. Florez, S. Castillo-Florez, A. Mendez et al., “C-reactive protein is elevated in obese patients with the metabolic syndrome,” Diabetes Research and Clinical Practice, vol. 71, no. 1, pp. 92–100, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. A. S. González, D. B. Guerrero, M. B. Soto, S. P. Díaz, M. Martinez-Olmos, and O. Vidal, “Metabolic syndrome, insulin resistance and the inflammation markers C-reactive protein and ferritin,” European Journal of Clinical Nutrition, vol. 60, no. 6, pp. 802–809, 2006. View at Publisher · View at Google Scholar · View at Scopus
  71. N. Ouchi, S. Kihara, T. Funahashi et al., “Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue,” Circulation, vol. 107, no. 5, pp. 671–674, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. G. P. van Guilder, G. L. Hoetzer, J. J. Greiner, B. L. Stauffer, and C. A. DeSouza, “Influence of metabolic syndrome on biomarkers of oxidative stress and inflammation in obese adults,” Obesity, vol. 14, no. 12, pp. 2127–2131, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. E. Ingelsson, J. Hulthe, and L. Lind, “Inflammatory markers in relation to insulin resistance and the metabolic syndrome,” European Journal of Clinical Investigation, vol. 38, no. 7, pp. 502–509, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. Y. Matsuo, T. Hashizume, S. Shioji, and T. Akasaka, “Metabolic syndrome is strongly associated with chronic subclinical inflammation in patients achieving optimal low-density lipoprotein-cholesterol levels in secondary prevention of cardiovascular disease,” Circulation Journal, vol. 72, no. 12, pp. 2046–2050, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. G. Kressel, B. Trunz, A. Bub et al., “Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk,” Atherosclerosis, vol. 202, no. 1, pp. 263–271, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. R. Bataille, B. Klein, and I. Kushner, “C-reactive protein levels as a direct indicator of interleukin-6 levels in humans in vivo,” Arthritis and Rheumatism, vol. 35, no. 8, pp. 982–984, 1992. View at Publisher · View at Google Scholar · View at Scopus
  77. P. C. Heinrich, J. V. Castell, and T. Andus, “Interleukin-6 and the acute phase response,” Biochemical Journal, vol. 265, no. 3, pp. 621–636, 1990. View at Scopus
  78. J. V. Castell, M. J. Gomez-Lechon, M. David et al., “Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes,” FEBS Letters, vol. 242, no. 2, pp. 237–239, 1989. View at Publisher · View at Google Scholar · View at Scopus
  79. J. V. Castell, M. J. Gomes-Lechon, M. David, T. Hirano, T. Kishimoto, and P. C. Heinrich, “Recombinant human interleukin-6 (IL-6/BSF-2/HSF) regulates the synthesis of acute phase proteins in human hepatocytes,” FEBS Letters, vol. 232, no. 2, pp. 347–350, 1988. View at Publisher · View at Google Scholar · View at Scopus
  80. K. K. Koh, S. H. Han, and M. J. Quon, “Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions,” Journal of the American College of Cardiology, vol. 46, no. 11, pp. 1978–1985, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. W. H. Haught, M. Mansour, R. Rothlein et al., “Alterations in circulating intercellular adhesion molecule-1 and L-selectin: further evidence for chronic inflammation in ischemic heart disease,” American Heart Journal, vol. 132, no. 1 I, pp. 1–8, 1996. View at Publisher · View at Google Scholar · View at Scopus
  82. D. E. Laaksonen, L. Niskanen, K. Punnonen et al., “Sex hormones, inflammation and the metabolic syndrome: a population-based study,” European Journal of Endocrinology, vol. 149, no. 6, pp. 601–608, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. J. M. Fernández-Real and W. Ricart, “Insulin resistance and chronic cardiovascular inflammatory syndrome,” Endocrine Reviews, vol. 24, no. 3, pp. 278–301, 2003. View at Scopus
  84. J. S. Yudkin, C. D. A. Stehouwer, J. J. Emeis, and S. W. Coppack, “C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 19, no. 4, pp. 972–978, 1999. View at Scopus
  85. A. Festa, R. D'Agostino, G. Howard, L. Mykkänen, R. P. Tracy, and S. M. Haffner, “Chronic subclinical inflammation as part of the insulin resistance syndrome: the insulin resistance atherosclerosis study (IRAS),” Circulation, vol. 101, no. 1, pp. 42–47, 2000. View at Scopus
  86. T. S. Han, N. Sattar, K. Williams, C. Gonzalez-Villalpando, M. E. J. Lean, and S. M. Haffner, “Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City diabetes study,” Diabetes Care, vol. 25, no. 11, pp. 2016–2021, 2002. View at Publisher · View at Google Scholar · View at Scopus
  87. P. M. Ridker, J. E. Buring, N. R. Cook, and N. Rifai, “C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women,” Circulation, vol. 107, no. 3, pp. 391–397, 2003. View at Scopus
  88. N. Sattar, A. Gaw, O. Scherbakova et al., “Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study,” Circulation, vol. 108, no. 4, pp. 414–419, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. D. E. M. Williams, A. T. Prevost, M. J. Whichelow, B. D. Cox, N. E. Day, and N. J. Wareham, “A cross-sectional study of dietary patterns with glucose intolerance and other features of the metabolic syndrome,” British Journal of Nutrition, vol. 83, no. 3, pp. 257–266, 2000. View at Scopus
  90. N. M. McKeown, J. B. Meigs, S. Liu, E. Saltzman, P. W. F. Wilson, and P. F. Jacques, “Carbohydrate nutrition, insulin resistance, and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort,” Diabetes Care, vol. 27, no. 2, pp. 538–546, 2004. View at Publisher · View at Google Scholar · View at Scopus
  91. D. B. Panagiotakos, C. Pitsavos, C. Chrysohoou et al., “Impact of lifestyle habits on the prevalence of the metabolic syndrome among Greek adults from the ATTICA study,” American Heart Journal, vol. 147, no. 1, pp. 106–112, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. K. Esposito, R. Marfella, M. Ciotola et al., “Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial,” Journal of the American Medical Association, vol. 292, no. 12, pp. 1440–1446, 2004. View at Publisher · View at Google Scholar · View at Scopus
  93. N. Ahluwalia, V. A. Andreeva, E. Kesse-Guyot, and S. Hercberg, “Dietary patterns, inflammation and the metabolic syndrome,” Diabetes & Metabolism, 2012. View at Publisher · View at Google Scholar
  94. I. Lazich, P. Sarafidis, E. de Guzman, A. Patel, R. Oliva, and G. Bakris, “Effects of combining simvastatin with rosiglitazone on inflammation, oxidant stress and ambulatory blood pressure in patients with the metabolic syndrome: the SIROCO study,” Diabetes, Obesity and Metabolism, vol. 14, no. 2, pp. 181–186, 2012. View at Publisher · View at Google Scholar
  95. S. Devaraj, E. Chan, and I. Jialal, “Direct demonstration of an antiinflammatory effect of simvastatin in subjects with the metabolic syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 11, pp. 4489–4496, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. P. M. Ridker, N. Rifai, L. Rose, J. E. Buring, and N. R. Cook, “Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events,” The New England Journal of Medicine, vol. 347, no. 20, pp. 1557–1565, 2002. View at Publisher · View at Google Scholar · View at Scopus
  97. P. M. Ridker, M. Cushman, M. J. Stampfer, R. P. Tracy, and C. H. Hennekens, “Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men,” The New England Journal of Medicine, vol. 336, no. 14, pp. 973–979, 1997. View at Publisher · View at Google Scholar · View at Scopus
  98. R. P. Tracy, R. N. Lemaitre, B. M. Psaty et al., “Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 6, pp. 1121–1127, 1997. View at Scopus
  99. W. Koenig, M. Sund, M. Fröhlich et al., “C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (monitoring trends and determinants in cardiovascular disease) Augsburg cohort study, 1984 to 1992,” Circulation, vol. 99, no. 2, pp. 237–242, 1999. View at Scopus
  100. M. Cesari, B. W. J. H. Penninx, A. B. Newman et al., “Inflammatory markers and onset of cardiovascular events: results from the Health ABC Study,” Circulation, vol. 108, no. 19, pp. 2317–2322, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. P. M. Ridker, N. Rifai, M. J. Stampfer, and C. H. Hennekens, “Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men,” Circulation, vol. 101, no. 15, pp. 1767–1772, 2000. View at Scopus
  102. P. M. Ridker, N. Rifai, M. Pfeffer, F. Sacks, S. Lepage, and E. Braunwald, “Elevation of tumor necrosis factor-α and increased risk of recurrent coronary events after myocardial infarction,” Circulation, vol. 101, no. 18, pp. 2149–2153, 2000. View at Scopus
  103. D. C. W. Lau, B. Dhillon, H. Yan, P. E. Szmitko, and S. Verma, “Adipokines: molecular links between obesity and atheroslcerosis,” American Journal of Physiology, vol. 288, no. 5, pp. H2031–H2041, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. P. M. Ridker, C. H. Hennekens, J. E. Buring, and N. Rifai, “C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women,” The New England Journal of Medicine, vol. 342, no. 12, pp. 836–843, 2000. View at Publisher · View at Google Scholar · View at Scopus
  105. L. H. Kuller, J. E. Eichner, T. J. Orchard, G. A. Grandits, L. McCallum, and R. P. Tracy, “The relation between serum albumin levels and risk of coronary heart disease in the multiple risk factor intervention trial,” American Journal of Epidemiology, vol. 134, no. 11, pp. 1266–1277, 1991. View at Scopus
  106. G. Liuzzo, L. M. Biasucci, J. R. Gallimore et al., “The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina,” The New England Journal of Medicine, vol. 331, no. 7, pp. 417–424, 1994. View at Publisher · View at Google Scholar · View at Scopus
  107. S. G. Thompson, J. Kienast, S. D. M. Pyke et al., “Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris,” The New England Journal of Medicine, vol. 332, no. 10, pp. 635–641, 1995. View at Publisher · View at Google Scholar · View at Scopus
  108. P. M. Ridker, N. Rifai, M. A. Pfeffer et al., “Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels,” Circulation, vol. 98, no. 9, pp. 839–844, 1998. View at Scopus
  109. P. M. Ridker, R. J. Glynn, and C. H. Hennekens, “C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction,” Circulation, vol. 97, no. 20, pp. 2007–2011, 1998. View at Scopus
  110. J. Danesh, P. Whincup, M. Walker et al., “Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses,” British Medical Journal, vol. 321, no. 7255, pp. 199–204, 2000. View at Scopus
  111. C. M. Albert, J. Ma, N. Rifai, M. J. Stampfer, and P. M. Ridker, “Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death,” Circulation, vol. 105, no. 22, pp. 2595–2599, 2002. View at Publisher · View at Google Scholar · View at Scopus
  112. L. H. Kuller, R. P. Tracy, J. Shaten, and E. N. Meilahn, “Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study,” American Journal of Epidemiology, vol. 144, no. 6, pp. 537–547, 1996. View at Scopus
  113. M. A. Mendall, D. P. Strachan, B. K. Butland et al., “C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men,” European Heart Journal, vol. 21, no. 19, pp. 1584–1590, 2000. View at Publisher · View at Google Scholar · View at Scopus
  114. T. B. Harris, L. Ferrucci, R. P. Tracy et al., “Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly,” American Journal of Medicine, vol. 106, no. 5, pp. 506–512, 1999. View at Publisher · View at Google Scholar · View at Scopus
  115. W. L. Roberts, “CDC/AHA workshop on markers of inflammation and cardiovascular disease: application to clinical and public health practice: laboratory tests available to asses inflammation-performance and standardization: a background paper,” Circulation, vol. 110, no. 25, pp. e572–e576, 2004. View at Scopus
  116. R. J. Bisoendial, S. M. Boekholdt, M. Vergeer, E. S. G. Stroes, and J. J. P. Kastelein, “C-reactive protein is a mediator of cardiovascular disease,” European Heart Journal, vol. 31, no. 17, pp. 2087–2091, 2010. View at Scopus
  117. P. W. Wilson, M. Pencina, P. Jacques, J. Selhub, R. D'Agostino, and C. J. O'Donnell, “C-reactive protein and reclassification of cardiovascular risk in the Framingham Heart Study,” Circulation, vol. 1, no. 2, pp. 92–97, 2008. View at Scopus
  118. B. Keavney, “C reactive protein and the risk of cardiovascular disease,” British Medical Journal, vol. 342, article d144, 2011. View at Publisher · View at Google Scholar · View at Scopus
  119. S. P. Fortmann, E. Ford, M. H. Criqui et al., “CDC/AHA workshop on markers of inflammation and cardiovascular disease: application to clinical and public health practice: report from the population science discussion group,” Circulation, vol. 110, no. 25, pp. e554–e559, 2004. View at Scopus
  120. M. de Lorgeril, P. Salen, J. L. Martin, I. Monjaud, J. Delaye, and N. Mamelle, “Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study,” Circulation, vol. 99, no. 6, pp. 779–785, 1999. View at Scopus
  121. R. B. Singh, G. Dubnov, M. A. Niaz et al., “Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial,” The Lancet, vol. 360, no. 9344, pp. 1455–1461, 2002. View at Publisher · View at Google Scholar · View at Scopus
  122. T. Pischon, S. E. Hankinson, G. S. Hotamisligil, N. Rifai, W. C. Willett, and E. B. Rimm, “Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women,” Circulation, vol. 108, no. 2, pp. 155–160, 2003. View at Publisher · View at Google Scholar · View at Scopus
  123. L. Djoussé, J. S. Pankow, J. H. Eckfeldt et al., “Relation between dietary linolenic acid and coronary artery disease in the National Heart, Lung, and Blood Institute Family Heart study,” American Journal of Clinical Nutrition, vol. 74, no. 5, pp. 612–619, 2001. View at Scopus
  124. E. Lopez-Garcia, M. B. Schulze, J. E. Manson et al., “Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women,” Journal of Nutrition, vol. 134, no. 7, pp. 1806–1811, 2004. View at Scopus
  125. T. Madsen, H. A. Skou, V. E. Hansen et al., “C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease,” American Journal of Cardiology, vol. 88, no. 10, pp. 1139–1142, 2001. View at Publisher · View at Google Scholar · View at Scopus
  126. G. Zhao, T. D. Etherton, K. R. Martin, S. G. West, P. J. Gillies, and P. M. Kris-Etherton, “Dietary α-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women,” Journal of Nutrition, vol. 134, no. 11, pp. 2991–2997, 2004. View at Scopus
  127. L. S. Rallidis, G. Paschos, G. K. Liakos, A. H. Velissaridou, G. Anastasiadis, and A. Zampelas, “Dietary α-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients,” Atherosclerosis, vol. 167, no. 2, pp. 237–242, 2003. View at Publisher · View at Google Scholar · View at Scopus
  128. W. J. E. Bemelmans, J. D. Lefrandt, E. J. M. Feskens et al., “Increased α-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis,” European Journal of Clinical Nutrition, vol. 58, no. 7, pp. 1083–1089, 2004. View at Publisher · View at Google Scholar · View at Scopus
  129. P. M. Ridker, E. Danielson, F. A. H. Fonseca et al., “Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein,” The New England Journal of Medicine, vol. 359, no. 21, pp. 2195–2207, 2008. View at Publisher · View at Google Scholar · View at Scopus
  130. J. Shepherd, S. M. Cobbe, I. Ford et al., “Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia,” The New England Journal of Medicine, vol. 333, no. 20, pp. 1301–1307, 1995. View at Publisher · View at Google Scholar · View at Scopus
  131. J. R. Downs, M. Clearfield, S. Weis et al., “Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS,” Journal of the American Medical Association, vol. 279, no. 20, pp. 1615–1622, 1998. View at Publisher · View at Google Scholar · View at Scopus
  132. P. M. Ridker, C. P. Cannon, D. Morrow et al., “C-reactive protein levels and outcomes after statin therapy,” The New England Journal of Medicine, vol. 352, no. 1, pp. 20–28, 2005. View at Publisher · View at Google Scholar · View at Scopus
  133. D. A. Morrow, J. A. de Lemos, M. S. Sabatine et al., “Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial,” Circulation, vol. 114, no. 4, pp. 281–288, 2006. View at Publisher · View at Google Scholar · View at Scopus
  134. S. E. Nissen, E. M. Tuzcu, P. Schoenhagen et al., “Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease,” The New England Journal of Medicine, vol. 352, no. 1, pp. 29–38, 2005. View at Publisher · View at Google Scholar · View at Scopus
  135. P. M. Ridker, E. Danielson, F. A. Fonseca et al., “Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial,” The Lancet, vol. 373, no. 9670, pp. 1175–1182, 2009. View at Publisher · View at Google Scholar · View at Scopus
  136. J. K. Liao, “Role of statin pleiotropism in acute coronary syndromes and stroke,” International Journal of Clinical Practice, Supplement, no. 134, pp. 51–57, 2003. View at Scopus
  137. R. S. Rosenson and C. C. Tangney, “Antiatherothrombotic properties of statins: implications for cardiovascular event reduction,” Journal of the American Medical Association, vol. 279, no. 20, pp. 1643–1650, 1998. View at Publisher · View at Google Scholar · View at Scopus
  138. J. J. Li and X. J. Chen, “Simvastatin inhibits interleukin-6 release in human monocytes stimulated by C-reactive protein and lipopolysaccharide,” Coronary Artery Disease, vol. 14, no. 4, pp. 329–334, 2003. View at Publisher · View at Google Scholar · View at Scopus
  139. J. Musial, A. Undas, P. Gajewski, M. Jankowski, W. Sydor, and A. Szczeklik, “Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia,” International Journal of Cardiology, vol. 77, no. 2-3, pp. 247–253, 2001. View at Publisher · View at Google Scholar · View at Scopus
  140. T. Wæhre, J. K. Damås, L. Gullestad et al., “Hydroxymethylglutaryl coenzyme A reductase inhibitors down-regulate chemokines and chemokine receptors in patients with coronary artery disease,” Journal of the American College of Cardiology, vol. 41, no. 9, pp. 1460–1467, 2003. View at Publisher · View at Google Scholar · View at Scopus
  141. T. Wæhre, A. Yndestad, C. Smith et al., “Increased expression of interleukin-1 in coronary artery disease with downregulatory effects of HMG-CoA reductase inhibitors,” Circulation, vol. 109, no. 16, pp. 1966–1972, 2004. View at Publisher · View at Google Scholar · View at Scopus
  142. A. D. Pradhan, J. E. Manson, N. Rifai, J. E. Buring, and P. M. Ridker, “C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus,” Journal of the American Medical Association, vol. 286, no. 3, pp. 327–334, 2001. View at Scopus
  143. A. Festa, R. D'Agostino Jr., R. P. Tracy, and S. M. Haffner, “Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study,” Diabetes, vol. 51, no. 4, pp. 1131–1137, 2002. View at Scopus
  144. S. Nakanishi, K. Yamane, N. Kamei, M. Okubo, and N. Kohno, “Elevated C-reactive protein is a risk factor for the development of type 2 diabetes in Japanese Americans,” Diabetes Care, vol. 26, no. 10, pp. 2754–2757, 2003. View at Publisher · View at Google Scholar · View at Scopus
  145. K. C. B. Tan, N. M. S. Wat, S. C. F. Tam, E. D. Janus, T. H. Lam, and K. S. L. Lam, “C-reactive protein predicts the deterioration of glycemia in Chinese subjects with impaired glucose tolerance,” Diabetes Care, vol. 26, no. 8, pp. 2323–2328, 2003. View at Publisher · View at Google Scholar · View at Scopus
  146. B. Thorand, H. Löwel, A. Schneider et al., “C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg Cohort Study, 1984–1998,” Archives of Internal Medicine, vol. 163, no. 1, pp. 93–99, 2003. View at Publisher · View at Google Scholar · View at Scopus
  147. J. I. Barzilay, L. Abraham, S. R. Heckbert et al., “The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study,” Diabetes, vol. 50, no. 10, pp. 2384–2389, 2001. View at Scopus
  148. D. J. Freeman, J. Norrie, M. J. Caslake et al., “C-reactive protein is an independent predictor of risk for the development of diabetes in the west of Scotland coronary prevention study,” Diabetes, vol. 51, no. 5, pp. 1596–1600, 2002. View at Scopus
  149. M. B. Snijder, J. M. Dekker, M. Visser et al., “C-reactive protein and diabetes mellitus type 2,” Diabetologia, vol. 44, Supplement 1, article 115A, 2001.
  150. J. J. Senn, P. J. Klover, I. A. Nowak et al., “Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes,” The Journal of Biological Chemistry, vol. 278, no. 16, pp. 13740–13746, 2003. View at Publisher · View at Google Scholar · View at Scopus
  151. J. C. Pickup and M. A. Crook, “Is type II diabetes mellitus a disease of the innate immune system?” Diabetologia, vol. 41, no. 10, pp. 1241–1248, 1998. View at Publisher · View at Google Scholar · View at Scopus
  152. W. K. Lagrand, C. A. Visser, W. T. Hermens et al., “C-reactive protein as a cardiovascular risk factor more than an epiphenomenon?” Circulation, vol. 100, no. 1, pp. 96–102, 1999. View at Scopus
  153. P. A. Sakkinen, P. Wahl, M. Cushman, M. R. Lewis, and R. P. Tracy, “Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome,” American Journal of Epidemiology, vol. 152, no. 10, pp. 897–907, 2000. View at Publisher · View at Google Scholar · View at Scopus
  154. A. E. Hak, H. A. P. Pols, C. D. A. Stehouwer et al., “Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam Study,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 9, pp. 4398–4405, 2001. View at Publisher · View at Google Scholar · View at Scopus
  155. T. Temelkova-Kurktschiev, G. Siegert, S. Bergmann et al., “Subclinical inflammation is strongly related to insulin resistance but not to impaired insulin secretion in a high risk population for diabetes,” Metabolism, vol. 51, no. 6, pp. 743–749, 2002. View at Publisher · View at Google Scholar · View at Scopus
  156. S. Müller, S. Martin, W. Koenig et al., “Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors,” Diabetologia, vol. 45, no. 6, pp. 805–812, 2002. View at Scopus
  157. T. Temelkova-Kurktschiev, “Subclinical inflammation in newly detected type II diabetes and impaired glucose tolerance,” Diabetologia, vol. 45, no. 1, article 151, 2002. View at Publisher · View at Google Scholar · View at Scopus
  158. G. S. Hotamisligil, P. Arner, J. F. Caro, R. L. Atkinson, and B. M. Spiegelman, “Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance,” The Journal of Clinical Investigation, vol. 95, no. 5, pp. 2409–2415, 1995. View at Scopus
  159. M. Saghizadeh, J. M. Ong, W. T. Garvey, R. R. Henry, and P. A. Kern, “The expression of TNFα by human muscle: relationship to insulin resistance,” The Journal of Clinical Investigation, vol. 97, no. 4, pp. 1111–1116, 1996. View at Scopus
  160. P. Peraldi and B. Spiegelman, “TNF-α and insulin resistance: summary and future prospects,” Molecular and Cellular Biochemistry, vol. 182, no. 1-2, pp. 169–175, 1998. View at Publisher · View at Google Scholar · View at Scopus
  161. A. Katsuki, Y. Sumida, S. Murashima et al., “Serum levels of tumor necrosis factor-α are increased in obese patients with noninsulin-dependent diabetes mellitus,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 3, pp. 859–862, 1998. View at Publisher · View at Google Scholar · View at Scopus
  162. G. Winkler, F. Salamon, D. Salamon, G. Speer, K. Simon, and K. Cseh, “Elevated serum tumour necrosis factor. alpha levels can contribute to the insulin resistance in Type II (non-insulin-dependent) diabetes and in obesity,” Diabetologia, vol. 41, no. 7, pp. 860–862, 1998. View at Publisher · View at Google Scholar · View at Scopus
  163. J. C. Pickup, G. D. Chusney, S. M. Thomas, and D. Burt, “Plasma interleukin-6, tumour necrosis factor α and blood cytokine production in type 2 diabetes,” Life Sciences, vol. 67, no. 3, pp. 291–300, 2000. View at Publisher · View at Google Scholar · View at Scopus
  164. B. Vozarova, C. Weyer, R. S. Lindsay, R. E. Pratley, C. Bogardus, and P. A. Tataranni, “High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes,” Diabetes, vol. 51, no. 2, pp. 455–461, 2002. View at Scopus
  165. D. M. Steel and A. S. Whitehead, “The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein,” Immunology Today, vol. 15, no. 2, pp. 81–87, 1994. View at Publisher · View at Google Scholar · View at Scopus
  166. G. R. Steinberg, “Inflammation in obesity is the common link between defects in fatty acid metabolism and insulin resistance,” Cell Cycle, vol. 6, no. 8, pp. 888–894, 2007. View at Scopus
  167. F. Kim, K. A. Tysseling, J. Rice et al., “Free fatty acid impairment of nitric oxide production in endothelial cells is mediated by IKKβ,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 5, pp. 989–994, 2005. View at Publisher · View at Google Scholar · View at Scopus
  168. M. Roden, T. B. Price, G. Perseghin et al., “Mechanism of free fatty acid-induced insulin resistance in humans,” The Journal of Clinical Investigation, vol. 97, no. 12, pp. 2859–2865, 1996. View at Scopus
  169. S. E. Shoelson, J. Lee, and M. Yuan, “Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance,” International Journal of Obesity and Related Metabolic Disorders, vol. 27, Supplement 3, pp. S49–S52, 2003.
  170. G. S. Hotamisligil, “Inflammatory pathways and insulin action,” International Journal of Obesity, vol. 27, no. 3, pp. S53–S55, 2003. View at Publisher · View at Google Scholar · View at Scopus
  171. D. Cai, M. Yuan, D. F. Frantz et al., “Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB,” Nature Medicine, vol. 11, no. 2, pp. 183–190, 2005. View at Publisher · View at Google Scholar · View at Scopus
  172. S. E. Shoelson, J. Lee, and A. B. Goldfine, “Inflammation and insulin resistance,” The Journal of Clinical Investigation, vol. 116, no. 7, pp. 1793–1801, 2006. View at Publisher · View at Google Scholar · View at Scopus
  173. G. Bruno, P. Fornengo, G. Novelli et al., “C-reactive protein and 5-year survival in type 2 diabetes: the casale monferrato study,” Diabetes, vol. 58, no. 4, pp. 926–933, 2009. View at Publisher · View at Google Scholar · View at Scopus
  174. K. E. Wellen and G. S. Hotamisligil, “Inflammation, stress, and diabetes,” The Journal of Clinical Investigation, vol. 115, no. 5, pp. 1111–1119, 2005. View at Publisher · View at Google Scholar · View at Scopus
  175. H. Kaneto, Y. Nakatani, T. Miyatsuka et al., “Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide,” Nature Medicine, vol. 10, no. 10, pp. 1128–1132, 2004. View at Publisher · View at Google Scholar · View at Scopus
  176. G. Liu and C. M. Rondinone, “JNK: bridging the insulin signaling and inflammatory pathway,” Current Opinion in Investigational Drugs, vol. 6, no. 10, pp. 979–987, 2005. View at Scopus
  177. K. Maeda, H. Cao, K. Kono et al., “Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes,” Cell Metabolism, vol. 1, no. 2, pp. 107–119, 2005. View at Publisher · View at Google Scholar · View at Scopus
  178. R. S. Hundal, K. F. Petersen, A. B. Mayerson et al., “Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes,” The Journal of Clinical Investigation, vol. 109, no. 10, pp. 1321–1326, 2002. View at Publisher · View at Google Scholar · View at Scopus
  179. A. B. Goldfine, R. Silver, W. Aldhahi et al., “Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes,” Clinical and Translational Science, vol. 1, no. 1, pp. 36–43, 2008. View at Publisher · View at Google Scholar · View at Scopus
  180. A. B. Goldfine, V. Fonseca, K. A. Jablonski, L. Pyle, M. A. Staten, and S. E. Shoelson, “The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial,” Annals of Internal Medicine, vol. 152, no. 6, pp. 346–357, 2010. View at Scopus
  181. A. Fleischman, S. E. Shoelson, R. Bernier, and A. B. Goldfine, “Salsalate improves glycemia and inflammatory parameters in obese young adults,” Diabetes Care, vol. 31, no. 2, pp. 289–294, 2008. View at Publisher · View at Google Scholar · View at Scopus
  182. J. Koska, E. Ortega, J. C. Bunt et al., “The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study,” Diabetologia, vol. 52, no. 3, pp. 385–393, 2009. View at Publisher · View at Google Scholar · View at Scopus
  183. T. Sathyapalan, J. Shepherd, S. L. Atkin, and E. S. Kilpatrick, “The effect of atorvastatin and simvastatin on vitamin D, oxidative stress and inflammatory marker concentrations in patients with type 2 diabetes: a crossover study,” Diabetes, Obesity and Metabolism, 2013. View at Publisher · View at Google Scholar
  184. D. M. Cummings, D. E. King, and A. G. Mainous III, “C-reactive protein, antiinflammatory drugs, and quality of life in diabetes,” Annals of Pharmacotherapy, vol. 37, no. 11, pp. 1593–1597, 2003. View at Publisher · View at Google Scholar · View at Scopus
  185. S. W. Rabkin, A. Langer, E. Ur, C. D. Calciu, and L. A. Leiter, “Inflammatory biomarkers CRP, MCP-1, serum amyloid alpha and interleukin-18 in patients with HTN and dyslipidemia: impact of diabetes mellitus on metabolic syndrome and the effect of statin therapy,” Hypertension Research, 2013. View at Publisher · View at Google Scholar
  186. A. M. Wägner, J. L. Sánchez-Quesada, S. Benítez, C. Bancells, J. Ordóñez-Llanos, and A. Pérez, “Effect of statin and fibrate treatment on inflammation in type 2 diabetes. A randomized, cross-over study,” Diabetes Research and Clinical Practice, vol. 93, no. 1, pp. e25–e28, 2011. View at Publisher · View at Google Scholar
  187. J. D. Colbert and J. A. Stone, “Statin use and the risk of incident diabetes mellitus: a review of the literature,” Canadian Journal of Cardiology, vol. 28, no. 5, pp. 581–589, 2012. View at Publisher · View at Google Scholar