(Circulation. 1996;93:1809-1817.)
© 1996 American Heart Association, Inc.
Articles |
Insulin Sensitivity and Atherosclerosis
From the Department of Public Health Sciences, Bowman Gray School of Medicine of Wake Forest University (G.H., D.Z.), Winston-Salem, NC; Department of Radiology, Tufts-New England Medical Center (D.H.O.), Boston, Mass; Division of Clinical Epidemiology, University of Texas at San Antonio (S.H.); Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center (M.R., R.H.), Denver; Division of Research, Kaiser Permanente (J.V.S.), Oakland, Calif; Division of Diabetes, Hypertension, and Nutrition, Department of Medicine, University of Southern California Medical Center (M.F.S.), Los Angeles; Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute (P.S.), Bethesda, Md; and Department of Physiology and Biophysics, University of Southern California School of Medicine (R.B.), Los Angeles.
Correspondence to George Howard, DrPH, Department of Public Health Sciences, Bowman Gray School of Medicine of Wake Forest University, Medical Center Blvd, Winston Salem, NC 27157-1063. E-mail howard@phs.bgsm.wfu.edu.
Background Reduced insulin sensitivity has been proposed as an important risk factor in the development of atherosclerosis. However, insulin sensitivity is related to many other cardiovascular risk factors, including plasma insulin levels, and it is unclear whether an independent role of insulin sensitivity exists. Large epidemiological studies that measure insulin sensitivity directly have not been conducted.
Methods and Results The Insulin Resistance Atherosclerosis Study (IRAS) evaluated insulin sensitivity (SI) by the frequently sampled intravenous glucose tolerance test with analysis by the minimal model of Bergman. IRAS measured intimal-medial thickness (IMT) of the carotid artery as an index of atherosclerosis by use of noninvasive B-mode ultrasonography. These measures, as well as factors that may potentially confound or mediate the relationship between insulin sensitivity and atherosclerosis, were available in relation to 398 black, 457 Hispanic, and 542 non-Hispanic white IRAS participants. There was a significant negative association between SI and the IMT of the carotid artery both in Hispanics and in non-Hispanic whites. This effect was reduced but not totally explained by adjustment for traditional cardiovascular disease risk factors, glucose tolerance, measures of adiposity, and fasting insulin levels. There was no association between SI and the IMT of the carotid artery in blacks. The association between SI and the IMT was stronger for the internal carotid artery than for the common carotid artery in all ethnic groups.
Conclusions Higher levels of insulin sensitivity are associated with less atherosclerosis in Hispanics and non-Hispanic whites but not in blacks. This effect is partially mediated by traditional cardiovascular risk factors.
Key Words: atherosclerosis • diabetes mellitus • insulin • carotid arteries
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 M. J. Davies, D. J. Baer, J. T. Judd, E. D. Brown, W. S. Campbell, and P. R. Taylor Effects of Moderate Alcohol Intake on Fasting Insulin and Glucose Concentrations and Insulin Sensitivity in Postmenopausal Women: A Randomized Controlled Trial JAMA, May 15, 2002; 287(19): 2559 - 2562. [Abstract] [Full Text] [PDF]
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R. S. Surwit, R. B. Williams, I. C. Siegler, J. D. Lane, M. Helms, K. L. Applegate, N. Zucker, M. N. Feinglos, C. M. McCaskill, and J. C. Barefoot Hostility, Race, and Glucose Metabolism in Nondiabetic Individuals Diabetes Care, May 1, 2002; 25(5): 835 - 839. [Abstract] [Full Text] [PDF]
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S. H. Golden, A. Maguire, J. Ding, J. R. Crouse, J. A. Cauley, H. Zacur, and M. Szklo Endogenous Postmenopausal Hormones and Carotid Atherosclerosis: A Case-Control Study of the Atherosclerosis Risk in Communities Cohort Am. J. Epidemiol., March 1, 2002; 155(5): 437 - 445. [Abstract] [Full Text] [PDF]
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E. D. Motley, S. M. Kabir, C. D. Gardner, K. Eguchi, G. D. Frank, T. Kuroki, M. Ohba, T. Yamakawa, and S. Eguchi Lysophosphatidylcholine Inhibits Insulin-Induced Akt Activation Through Protein Kinase C-{alpha} in Vascular Smooth Muscle Cells Hypertension, February 1, 2002; 39(2): 508 - 512. [Abstract] [Full Text] [PDF]
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G. Perseghin, A. Caumo, M. Caloni, G. Testolin, and L. Luzi Incorporation of the Fasting Plasma FFA Concentration into QUICKI Improves Its Association with Insulin Sensitivity in Nonobese Individuals J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4776 - 4781. [Abstract] [Full Text] [PDF]
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 A. W. Miller, C. Dimitropoulou, G. Han, R. E. White, D. W. Busija, and G. O. Carrier Epoxyeicosatrienoic acid-induced relaxation is impaired in insulin resistance Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1524 - H1531. [Abstract] [Full Text] [PDF]
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F. S. Facchini, N. Hua, F. Abbasi, and G. M. Reaven Insulin Resistance as a Predictor of Age-Related Diseases J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3574 - 3578. [Abstract] [Full Text] [PDF]
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N. M. Wedick, E. J. Mayer-Davis, D. L. Wingard, C. L. Addy, and E. Barrett-Connor Insulin Resistance Precedes Weight Loss in Adults without Diabetes : The Rancho Bernardo Study Am. J. Epidemiol., June 15, 2001; 153(12): 1199 - 1205. [Abstract] [Full Text] [PDF]
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U. Lindblad, R. D. Langer, D. L. Wingard, R. G. Thomas, and E. L. Barrett-Connor Metabolic Syndrome and Ischemic Heart Disease in Elderly Men and Women Am. J. Epidemiol., March 1, 2001; 153(5): 481 - 489. [Abstract] [Full Text] [PDF]
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P. V. G. Katakam, J. S. Pollock, D. M. Pollock, M. R. Ujhelyi, and A. W. Miller Enhanced endothelin-1 response and receptor expression in small mesenteric arteries of insulin-resistant rats Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H522 - H527. [Abstract] [Full Text] [PDF]
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 W. T. Cefalu Insulin Resistance: Cellular and Clinical Concepts Experimental Biology and Medicine, January 1, 2001; 226(1): 13 - 26. [Abstract] [Full Text]
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 Y Otsuka, S Miyazaki, H Okumura, S Yasuda, S Daikoku, I Morii, Y Sutani, Y Goto, and H Nonogi Abnormal glucose tolerance, not small vessel diameter, is a determinant of long-term prognosis in patients treated with balloon coronary angioplasty Eur. Heart J., November 1, 2000; 21(21): 1790 - 1796. [Abstract] [PDF]
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A. Caumo, R. N. Bergman, and C. Cobelli Insulin Sensitivity from Meal Tolerance Tests in Normal Subjects: A Minimal Model Index J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4396 - 4402. [Abstract] [Full Text]
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K. Takeda, T. Ichiki, T. Tokunou, Y. Funakoshi, N. Iino, K. Hirano, H. Kanaide, and A. Takeshita Peroxisome Proliferator-Activated Receptor {gamma} Activators Downregulate Angiotensin II Type 1 Receptor in Vascular Smooth Muscle Cells Circulation, October 10, 2000; 102(15): 1834 - 1839. [Abstract] [Full Text] [PDF]
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 T. J. Tegos, E. Kalodiki, S.-S. Daskalopoulou, and A. N. Nicolaides Stroke: Epidemiology, Clinical Picture, and Risk Factors: Part I of III Angiology, October 1, 2000; 51(10): 793 - 808. [Abstract] [PDF]
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T. Takagi, K. Yoshida, T. Akasaka, S. Kaji, T. Kawamoto, Y. Honda, A. Yamamuro, T. Hozumi, and S. Morioka Hyperinsulinemia during oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients: A serial intravascular ultrasound study J. Am. Coll. Cardiol., September 1, 2000; 36(3): 731 - 738. [Abstract] [Full Text] [PDF]
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N. Hirai, H. Kawano, O. Hirashima, T. Motoyama, Y. Moriyama, T. Sakamoto, K. Kugiyama, H. Ogawa, K. Nakao, and H. Yasue Insulin resistance and endothelial dysfunction in smokers: effects of vitamin C Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1172 - H1178. [Abstract] [Full Text] [PDF]
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T. Hammoud, J.-F. Tanguay, and M. G. Bourassa Management of coronary artery disease: therapeutic options in patients with diabetes J. Am. Coll. Cardiol., August 1, 2000; 36(2): 355 - 365. [Abstract] [Full Text] [PDF]
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T Inoue, R Matsunaga, Y Sakai, I Yaguchi, K Takayanagi, and S Morooka Insulin resistance affects endothelium-dependent acetylcholine-induced coronary artery response Eur. Heart J., June 1, 2000; 21(11): 895 - 900. [Abstract] [PDF]
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M. Pyorala, H. Miettinen, P. Halonen, M. Laakso, and K. Pyorala Insulin Resistance Syndrome Predicts the Risk of Coronary Heart Disease and Stroke in Healthy Middle-Aged Men : The 22-Year Follow-Up Results of the Helsinki Policemen Study Arterioscler Thromb Vasc Biol, February 1, 2000; 20(2): 538 - 544. [Abstract] [Full Text] [PDF]
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 P. Dylewicz, S. Bienkowska, L. Szczesniak, T. Rychlewski, I. Przywarska, M. Wilk, and A. Jastrzebski Beneficial Effect of Short-term Endurance Training on Glucose Metabolism During Rehabilitation After Coronary Bypass Surgery* Chest, January 1, 2000; 117(1): 47 - 51. [Abstract] [Full Text] [PDF]
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K. Saku, B. Zhang, K. Shirai, S. Jimi, K. Yoshinaga, and K. Arakawa Hyperinsulinemic hypoalphalipoproteinemia as a new indicator for coronary heart disease J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1443 - 1451. [Abstract] [Full Text] [PDF]
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E. J. G. Sijbrands, M. J. V. Hoffer, A. E. Meinders, L. M. Havekes, R. R. Frants, A. H. M. Smelt, and P. De Knijff Severe Hyperlipidemia in Apolipoprotein E2 Homozygotes Due to a Combined Effect of Hyperinsulinemia and an SstI Polymorphism Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2722 - 2729. [Abstract] [Full Text] [PDF]
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S. M. Haffner, R. D'Agostino Jr, D. Goff, B. Howard, A. Festa, M. F. Saad, and L. Mykkanen LDL Size in African Americans, Hispanics, and Non-Hispanic Whites : The Insulin Resistance Atherosclerosis Study Arterioscler Thromb Vasc Biol, September 1, 1999; 19(9): 2234 - 2240. [Abstract] [Full Text] [PDF]
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A. Festa, R. D'Agostino Jr, P. Rautaharju, D. H. O'Leary, M. Rewers, L. Mykkanen, and S. M. Haffner Is QT Interval a Marker of Subclinical Atherosclerosis in Nondiabetic Subjects? : The Insulin Resistance Atherosclerosis Study (IRAS) Stroke, August 1, 1999; 30(8): 1566 - 1571. [Abstract] [Full Text] [PDF]
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P. Lempiainen, L. Mykkanen, K. Pyorala, M. Laakso, and J. Kuusisto Insulin Resistance Syndrome Predicts Coronary Heart Disease Events in Elderly Nondiabetic Men Circulation, July 13, 1999; 100(2): 123 - 128. [Abstract] [Full Text] [PDF]
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E. Bonora, G. Targher, M. Alberiche, R. C. Bonadonna, F. Saggiani, M. B. Zenere, S. Uleri, and M. Muggeo Effect of Chronic Treatment with Lacidipine or Lisinopril on Intracellular Partitioning of Glucose Metabolism in Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1544 - 1550. [Abstract] [Full Text]
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A. Festa, R. D'Agostino Jr, L. Mykkanen, R. P. Tracy, D. J. Zaccaro, C. N. Hales, and S. M. Haffner Relative Contribution of Insulin and Its Precursors to Fibrinogen and PAI-1 in a Large Population With Different States of Glucose Tolerance : The Insulin Resistance Atherosclerosis Study (IRAS) Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 562 - 568. [Abstract] [Full Text] [PDF]
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S. Soderberg, B. Ahren, B. Stegmayr, O. Johnson, P.-G. Wiklund, L. Weinehall, G. Hallmans, and T. Olsson Leptin Is a Risk Marker for First-Ever Hemorrhagic Stroke in a Population-Based Cohort Stroke, February 1, 1999; 30(2): 328 - 337. [Abstract] [Full Text] [PDF]
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Y. Hong, T. Rice, J. Gagnon, J.-P. Després, A. Nadeau, L. Pérusse, C. Bouchard, A. S. Leon, J. S. Skinner, J. H. Wilmore, et al. Familial Clustering of Insulin and Abdominal Visceral Fat: The HERITAGE Family Study J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4239 - 4245. [Abstract] [Full Text]
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R. A. Phillips, L. R. Krakoff, A. Dunaif, D. T. Finegood, R. Gorlin, and S. Shimabukuro Relation among Left Ventricular Mass, Insulin Resistance, and Blood Pressure in Nonobese Subjects J. Clin. Endocrinol. Metab., December 1, 1998; 83(12): 4284 - 4288. [Abstract] [Full Text]
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