(Circulation. 2000;102:42.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome
The Insulin Resistance Atherosclerosis Study (IRAS)
From the Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio (A.F., L.M., S.M.H.); Department of Public Health Sciences, Wake Forest University School of Medicine, Winston Salem, NC (R.D’A., G.H.); and Laboratory for Clinical Biochemistry Research, Department of Pathology, University of Vermont College of Medicine, Burlington (R.P.T.).
Correspondence to Andreas Festa, MD, University of Texas Health Science Center at San Antonio, Mail Code 7873, 7703 Floyd Curl Dr, San Antonio, TX 78228-3900. E-mail festa{at}magnet.at
Background—Inflammation has been suggested as a risk factor for the development of atherosclerosis. Recently, some components of the insulin resistance syndrome (IRS) have been related to inflammatory markers. We hypothesized that insulin insensitivity, as directly measured, may be associated with inflammation in nondiabetic subjects.
Methods and Results—We studied the relation of C-reactive protein (CRP), fibrinogen, and white cell count to components of IRS in the nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS) (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), a multicenter, population-based study. None of the subjects had clinical coronary artery disease. Insulin sensitivity (SI) was measured by a frequently sampled intravenous glucose tolerance test, and CRP was measured by a highly sensitive competitive immunoassay. All 3 inflammatory markers were correlated with several components of the IRS. Strong associations were found between CRP and measures of body fat (body mass index, waist circumference), SI, and fasting insulin and proinsulin (all correlation coefficients >0.3, P<0.0001). The associations were consistent among the 3 ethnic groups of the IRAS. There was a linear increase in CRP levels with an increase in the number of metabolic disorders. Body mass index, systolic blood pressure, and SI were related to CRP levels in a multivariate linear regression model.
Conclusions—We suggest that chronic subclinical inflammation is part of IRS. CRP, a predictor of cardiovascular events in previous reports, was independently related to SI. These findings suggest potential benefits of anti-inflammatory or insulin-sensitizing treatment strategies in healthy individuals with features of IRS.
Key Words: inflammation • proteins • insulin resistance syndrome • insulin • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  R. L. Pande, T. S. Perlstein, J. A. Beckman, and M. A. Creager Association of Insulin Resistance and Inflammation With Peripheral Arterial Disease: The National Health and Nutrition Examination Survey, 1999 to 2004 Circulation, July 1, 2008; 118(1): 33 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Amar, R. Burcelin, J. B. Ruidavets, P. D Cani, J. Fauvel, M. C. Alessi, B. Chamontin, and J. Ferrieres Energy intake is associated with endotoxemia in apparently healthy men Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1219 - 1223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cartier, I. Lemieux, N. Almeras, A. Tremblay, J. Bergeron, and J.-P. Despres Visceral Obesity and Plasma Glucose-Insulin Homeostasis: Contributions of Interleukin-6 and Tumor Necrosis Factor-{alpha} in Men J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1931 - 1938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Greco, A. Kotronen, J. Westerbacka, O. Puig, P. Arkkila, T. Kiviluoto, S. Laitinen, M. Kolak, R. M. Fisher, A. Hamsten, et al. Gene expression in human NAFLD Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1281 - G1287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Romeo and A. Kazlauskas Oxysterol and Diabetes Activate STAT3 and Control Endothelial Expression of Profilin-1 via OSBP1 J. Biol. Chem., April 11, 2008; 283(15): 9595 - 9605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Joaquin, E Aguilera, M L Granada, M C Pastor, I Salinas, N Alonso, and A Sanmarti Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A. Eur. J. Endocrinol., April 1, 2008; 158(4): 483 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kaartinen, J. Syrjanen, I. Porsti, M. Hurme, A. Harmoinen, A. Pasternack, H. Huhtala, and J. Mustonen Inflammatory markers and the progression of IgA glomerulonephritis Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1285 - 1290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.E. Naschitz and R. Lenger Why traumatic leg amputees are at increased risk for cardiovascular diseases QJM, April 1, 2008; 101(4): 251 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Subramanian, C. Y. Han, T. Chiba, T. S. McMillen, S. A. Wang, A. Haw III, E. A. Kirk, K. D. O'Brien, and A. Chait Dietary Cholesterol Worsens Adipose Tissue Macrophage Accumulation and Atherosclerosis in Obese LDL Receptor-Deficient Mice Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 685 - 691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Moreno-Navarrete, F. J. Ortega, J. Bassols, A. Castro, W. Ricart, and J. M. Fernandez-Real Association of Circulating Lactoferrin Concentration and 2 Nonsynonymous LTF Gene Polymorphisms with Dyslipidemia in Men Depends on Glucose-Tolerance Status Clin. Chem., February 1, 2008; 54(2): 301 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N.-H. Pan, H.-M. Tsao, N.-C. Chang, Y.-J. Chen, and S.-A. Chen Aging Dilates Atrium and Pulmonary Veins: Implications for the Genesis of Atrial Fibrillation Chest, January 1, 2008; 133(1): 190 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Otter, M. Winter, W. Doering, E. Standl, and O. Schnell C-Reactive Protein in Diabetic and Nondiabetic Patients With Acute Myocardial Infarction Diabetes Care, December 1, 2007; 30(12): 3080 - 3082. [Full Text] [PDF]
|
|
|
|
|
|
J. Evans, M. Collins, C. Jennings, L. van der Merwe, I. Soderstrom, T. Olsson, N. S Levitt, E. V Lambert, and J. H Goedecke The association of interleukin-18 genotype and serum levels with metabolic risk factors for cardiovascular disease Eur. J. Endocrinol., November 1, 2007; 157(5): 633 - 640. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Westerbacka, M. Kolak, T. Kiviluoto, P. Arkkila, J. Siren, A. Hamsten, R. M. Fisher, and H. Yki-Jarvinen Genes Involved in Fatty Acid Partitioning and Binding, Lipolysis, Monocyte/Macrophage Recruitment, and Inflammation Are Overexpressed in the Human Fatty Liver of Insulin-Resistant Subjects Diabetes, November 1, 2007; 56(11): 2759 - 2765. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Nelson, N. Sattar, D. J. Freeman, J. D. Walker, and R. S. Lindsay Inflammation and Endothelial Activation Is Evident at Birth in Offspring of Mothers With Type 1 Diabetes Diabetes, November 1, 2007; 56(11): 2697 - 2704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Schindler Review: The metabolic syndrome as an endocrine disease: is there an effective pharmacotherapeutic strategy optimally targeting the pathogenesis? Therapeutic Advances in Cardiovascular Disease, October 1, 2007; 1(1): 7 - 26. [Abstract] [PDF]
|
|
|
|
|
|
F. Anan, T. Masaki, Y. Umeno, T. Iwao, H. Yonemochi, N. Eshima, T. Saikawa, and H. Yoshimatsu Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients Eur. J. Endocrinol., September 1, 2007; 157(3): 311 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ingelsson, M. J. Pencina, G. H. Tofler, E. J. Benjamin, K. J. Lanier, P. F. Jacques, C. S. Fox, J. B. Meigs, D. Levy, M. G. Larson, et al. Multimarker Approach to Evaluate the Incidence of the Metabolic Syndrome and Longitudinal Changes in Metabolic Risk Factors: The Framingham Offspring Study Circulation, August 28, 2007; 116(9): 984 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Liu, L. Tinker, Y. Song, N. Rifai, D. E. Bonds, N. R. Cook, G. Heiss, B. V. Howard, G. S. Hotamisligil, F. B. Hu, et al. A Prospective Study of Inflammatory Cytokines and Diabetes Mellitus in a Multiethnic Cohort of Postmenopausal Women Arch Intern Med, August 13, 2007; 167(15): 1676 - 1685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. Rosenson, D. A. Wolff, A. L. Huskin, I. B. Helenowski, and A. W. Rademaker Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome Diabetes Care, August 1, 2007; 30(8): 1945 - 1951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-T. Lin-Tan, J.-L. Lin, L.-H. Wang, L.-M. Wang, L.-M. Huang, L. Liu, J.-Y. Huang, and Y.-L. Huang Fasting Glucose Levels in Predicting 1-Year All-Cause Mortality in Patients Who Do Not Have Diabetes and Are on Maintenance Hemodialysis J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2385 - 2391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Orio, F. Manguso, S. Di Biase, A. Falbo, F. Giallauria, D. Labella, A. Tolino, G. Lombardi, A. Colao, and S. Palomba Metformin administration improves leukocyte count in women with polycystic ovary syndrome: a 6-month prospective study Eur. J. Endocrinol., July 1, 2007; 157(1): 69 - 73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Porrini, M. D. Gomez, A. Alvarez, M. Cobo, J. M. Gonzalez-Posada, L. Perez, L. Hortal, J. J. Garcia, M. Dolores Checa, A. Morales, et al. Glycated haemoglobin levels are related to chronic subclinical inflammation in renal transplant recipients without pre-existing or new onset diabetes Nephrol. Dial. Transplant., July 1, 2007; 22(7): 1994 - 1999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takebayashi, M. Suetsugu, S. Wakabayashi, Y. Aso, and T. Inukai Retinol Binding Protein-4 Levels and Clinical Features of Type 2 Diabetes Patients J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2712 - 2719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Fardet, J. Cabane, A. Kettaneh, C. Lebbe, and A. Flahault Corticosteroid-induced lipodystrophy is associated with features of the metabolic syndrome Rheumatology, July 1, 2007; 46(7): 1102 - 1106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. R. Celli and P. J. Barnes Exacerbations of chronic obstructive pulmonary disease Eur. Respir. J., June 1, 2007; 29(6): 1224 - 1238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Authors/Task Force Members, L. Ryden, E. Standl, M. Bartnik, G. V. d. Berghe, J. Betteridge, M.-J. de Boer, F. Cosentino, B. Jonsson, M. Laakso, et al. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: full text: The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD) Eur. Heart J. Suppl., June 1, 2007; 9(suppl_C): C3 - C74. [Full Text] [PDF]
|
|
|
|
|
|
A. G. Niehoff, T. W. van Haeften, N. C. Onland-Moret, C. C. Elbers, C. Wijmenga, and Y. T. van der Schouw C-Reactive Protein Is Independently Associated With Glucose but Not With Insulin Resistance in Healthy Men Diabetes Care, June 1, 2007; 30(6): 1627 - 1629. [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Flynn, B. K. McFarlin, and M. M. Markofski State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training American Journal of Lifestyle Medicine, May 1, 2007; 1(3): 220 - 235. [Abstract] [PDF]
|
|
|
|
 |
|
 X. Ye, Z. Yu, H. Li, O. H. Franco, Y. Liu, and X. Lin Distributions of C-Reactive Protein and its Association With Metabolic Syndrome in Middle-Aged and Older Chinese People J. Am. Coll. Cardiol., May 1, 2007; 49(17): 1798 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. M. Wahba and R. H. Mak Obesity and Obesity-Initiated Metabolic Syndrome: Mechanistic Links to Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., May 1, 2007; 2(3): 550 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hirayama, T. Miida, O. Miyazaki, and Y. Aizawa Pre{beta}1-HDL Concentration Is a Predictor of Carotid Atherosclerosis in Type 2 Diabetic Patients Diabetes Care, May 1, 2007; 30(5): 1289 - 1291. [Full Text] [PDF]
|
|
|
|
|
|
A. Lopez-Bermejo, B. Chico-Julia, A. Castro, M. Recasens, E. Esteve, J. Biarnes, R. Casamitjana, W. Ricart, and J.-M. Fernandez-Real Alpha Defensins 1, 2, and 3: Potential Roles in Dyslipidemia and Vascular Dysfunction in Humans Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1166 - 1171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Kakafika, D. P. Mikhailidis, A. Karagiannis, and V. G. Athyros The Role of Endocannabinoid System Blockade in the Treatment of the Metabolic Syndrome J. Clin. Pharmacol., May 1, 2007; 47(5): 642 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Tahara, H. Kai, S.-i. Yamagishi, M. Mizoguchi, H. Nakaura, M. Ishibashi, H. Kaida, K. Baba, N. Hayabuchi, and T. Imaizumi Vascular Inflammation Evaluated by [18F]-Fluorodeoxyglucose Positron Emission Tomography Is Associated With the Metabolic Syndrome J. Am. Coll. Cardiol., April 10, 2007; 49(14): 1533 - 1539. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Slattery, K. Curtin, R. Baumgartner, C. Sweeney, T. Byers, A. R. Giuliano, K. B. Baumgartner, and R. R. Wolff IL6, Aspirin, Nonsteroidal Anti-inflammatory Drugs, and Breast Cancer Risk in Women Living in the Southwestern United States Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 747 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kelishadi, M. Sharifi, A. Khosravi, and K. Adeli Relationship Between C-Reactive Protein and Atherosclerotic Risk Factors and Oxidative Stress Markers Among Young Persons 10-18 Years Old Clin. Chem., March 1, 2007; 53(3): 456 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ranjit, A. V. Diez-Roux, S. Shea, M. Cushman, T. Seeman, S. A. Jackson, and H. Ni Psychosocial Factors and Inflammation in the Multi-Ethnic Study of Atherosclerosis Arch Intern Med, January 22, 2007; 167(2): 174 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Koyama, T. Shoji, S. Fukumoto, K. Shinohara, T. Shoji, M. Emoto, K. Mori, H. Tahara, E. Ishimura, R. Kakiya, et al. Low Circulating Endogenous Secretory Receptor for AGEs Predicts Cardiovascular Mortality in Patients With End-Stage Renal Disease Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 147 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Lakka, T. Rankinen, T. Rice, A. S. Leon, D. C. Rao, J. S. Skinner, and C. Bouchard Quantitative trait locus on chromosome 20q13 for plasma levels of C-reactive protein in healthy whites: the HERITAGE Family Study Physiol Genomics, October 11, 2006; 27(2): 103 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Aeberli, L. Molinari, G. Spinas, R. Lehmann, D. l'Allemand, and M. B Zimmermann Dietary intakes of fat and antioxidant vitamins are predictors of subclinical inflammation in overweight Swiss children. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 748 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Irwin, M. Wang, C. O. Campomayor, A. Collado-Hidalgo, and S. Cole Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med, September 18, 2006; 166(16): 1756 - 1762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Markus, R. Labrum, S. Bevan, M. Reindl, G. Egger, C. J. Wiedermann, Q. Xu, S. Kiechl, and J. Willeit Genetic and Acquired Inflammatory Conditions Are Synergistically Associated With Early Carotid Atherosclerosis Stroke, September 1, 2006; 37(9): 2253 - 2259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G Leichman, D. Aguilar, T. M King, A. Vlada, M. Reyes, and H. Taegtmeyer Association of plasma free fatty acids and left ventricular diastolic function in patients with clinically severe obesity. Am. J. Clinical Nutrition, August 1, 2006; 84(2): 336 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. de Rekeneire, R. Peila, J. Ding, L. H. Colbert, M. Visser, R. I. Shorr, S. B. Kritchevsky, L. H. Kuller, E. S. Strotmeyer, A. V. Schwartz, et al. Diabetes, Hyperglycemia, and Inflammation in Older Individuals: The Health, Aging and Body Composition study Diabetes Care, August 1, 2006; 29(8): 1902 - 1908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Meigs, P. W. F. Wilson, C. S. Fox, R. S. Vasan, D. M. Nathan, L. M. Sullivan, and R. B. D'Agostino Body Mass Index, Metabolic Syndrome, and Risk of Type 2 Diabetes or Cardiovascular Disease J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2906 - 2912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Kahn, B. Zinman, S. M. Haffner, M. C. O'Neill, B. G. Kravitz, D. Yu, M. I. Freed, W. H. Herman, R. R. Holman, N. P. Jones, et al. Obesity is a major determinant of the association of C-reactive protein levels and the metabolic syndrome in type 2 diabetes. Diabetes, August 1, 2006; 55(8): 2357 - 2364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Somani, P. J. Grant, K. Kain, A. J. Catto, and A. M. Carter Complement C3 and C-Reactive Protein Are Elevated in South Asians Independent of a Family History of Stroke Stroke, August 1, 2006; 37(8): 2001 - 2006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Cook, J. E. Buring, and P. M Ridker The Effect of Including C-Reactive Protein in Cardiovascular Risk Prediction Models for Women Ann Intern Med, July 4, 2006; 145(1): 21 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Paternoster, S. Fantinato, A. Stella, K. N. Nanhorngue, M. Milani, M. Plebani, U. Nicolini, and A. Girolami C-reactive protein in hypertensive disorders in pregnancy. Clinical and Applied Thrombosis/Hemostasis, July 1, 2006; 12(3): 330 - 337. [Abstract] [PDF]
|
|
|
|
|
|
A. B. Goldfine, J. A. Beckman, R. A. Betensky, H. Devlin, S. Hurley, N. Varo, U. Schonbeck, M. E. Patti, and M. A. Creager Family History of Diabetes Is a Major Determinant of Endothelial Function J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2456 - 2461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Langenberg, J. Bergstrom, C. Scheidt-Nave, J. Pfeilschifter, and E. Barrett-Connor Cardiovascular Death and the Metabolic Syndrome: Role of adiposity-signaling hormones and inflammatory markers. Diabetes Care, June 1, 2006; 29(6): 1363 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Su, Y. Li, J. C. James, A. H. Matsumoto, G. A. Helm, A. J. Lusis, and W. Shi Genetic linkage of hyperglycemia, body weight and serum amyloid-P in an intercross between C57BL/6 and C3H apolipoprotein E-deficient mice Hum. Mol. Genet., May 15, 2006; 15(10): 1650 - 1658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Guven, A. Cetinkaya, M. Aral, G. Sokmen, M. A. Buyukbese, A. Guven, and N. Koksal High-Sensitivity C-Reactive Protein in Patients with Metabolic Syndrome Angiology, May 1, 2006; 57(3): 295 - 302. [Abstract] [PDF]
|
|
|
|
|
|
K. Esposito, M. Ciotola, D. Carleo, B. Schisano, F. Saccomanno, F. C. Sasso, D. Cozzolino, R. Assaloni, D. Merante, A. Ceriello, et al. Effect of Rosiglitazone on Endothelial Function and Inflammatory Markers in Patients With the Metabolic Syndrome Diabetes Care, May 1, 2006; 29(5): 1071 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Starkey |