(Circulation. 1995;91:1432-1443.)
© 1995 American Heart Association, Inc.
Articles |
Non–Insulin-Dependent Diabetes Mellitus and Fasting Glucose and Insulin Concentrations Are Associated With Arterial Stiffness Indexes
The ARIC Study
From the National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland (V.S.); the Department of Neurology, Bowman Gray School of Medicine, Winston-Salem, NC (W.R.); the Department of Social Medicine, Hadassah Medical Organization and Hebrew University, Hadassah School of Public Health, Jerusalem, Israel (J.D.K.); the Department of Epidemiology, University of North Carolina, Chapel Hill (C.N.); and the Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis (A.R.F).
Correspondence to Dr Veikko Salomaa, National Public Health Institute, Department of Epidemiology and Health Promotion, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
Background Cardiovascular diseases are the most common cause of disability and death among subjects with non–insulin-dependent diabetes mellitus (NIDDM). The atherosclerotic process begins during the prediabetic phase characterized by impaired glucose tolerance, hyperinsulinemia, and insulin resistance. In vitro studies have suggested that glucose and insulin can substantially alter the structure and function of the arterial wall and affect the development of atherosclerosis.
Methods and Results We performed a cross-sectional study of the relation of arterial stiffness indexes with glucose tolerance and serum insulin concentrations. Several indexes of common carotid artery stiffness were assessed with noninvasive ultrasound methods in a biracial sample of 4701 men and women 45 to 64 years of age in the Atherosclerosis Risk in Communities (ARIC) Study. Arterial compliance (AC), stiffness index (SI), pressure-strain elastic modulus (Ep), and Young's elastic modulus (YEM) were calculated. YEM includes wall (intima-media) thickness and thus gives an estimate of arterial stiffness controlling for wall thickness. All indexes of arterial stiffness were higher with increasing concentrations of fasting glucose. This finding was consistent in both black and white examinees and in both sexes. A 25% increase in fasting glucose (approximately 1 SD) was associated in nondiabetic white men with a 5.8% (95% CI, -9.6% to -1.9%; P=.004) decrease in AC and increases of 5.8% (95% CI, 2.0% to 9.7%; P=.002) in SI, 11.3% (95% CI, 6.9% to 15.9%; P<.001) in Ep, and 11.2% (95% CI, 6.2% to 16.6%; P<.001) in YEM. In nondiabetic white women, the corresponding predicted changes were a decrease of 15.0% (95% CI, -18.2% to -11.7%; P<.001) in AC and increases of 16.6% (95% CI, 12.5% to 20.8%; P<.001) in SI, 23.2% (95% CI, 18.4% to 28.2%; P<.001) in Ep, and 19.2% (95% CI, 14.0% to 24.7%; P<.001) in YEM. Glucose and insulin contributed synergistically to the increase in stiffness indexes. Insulin and triglycerides also had a synergistic association with stiffness indexes.
Conclusions Our findings are compatible with the view that persons with NIDDM or borderline glucose intolerance have stiffer arteries than their counterparts with normal glucose tolerance and that the decreased elasticity is independent of artery wall thickness. The joint effect of elevated glucose, insulin, and triglycerides can have a considerable impact on arterial stiffness and play an important role in the early pathophysiology of macrovascular disease in NIDDM.
Key Words: glucose • insulin • diabetes mellitus • arteries • ultrasonics
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 K. J. Stewart Exercise Training and the Cardiovascular Consequences of Type 2 Diabetes and Hypertension: Plausible Mechanisms for Improving Cardiovascular Health JAMA, October 2, 2002; 288(13): 1622 - 1631. [Abstract] [Full Text] [PDF]
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P. Henry, F. Thomas, A. Benetos, and L. Guize Impaired Fasting Glucose, Blood Pressure and Cardiovascular Disease Mortality Hypertension, October 1, 2002; 40(4): 458 - 463. [Abstract] [Full Text] [PDF]
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 P. Nestel, H. Shige, S. Pomeroy, M. Cehun, M. Abbey, and D. Raederstorff The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans Am. J. Clinical Nutrition, August 1, 2002; 76(2): 326 - 330. [Abstract] [Full Text] [PDF]
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E. Suzuki, A. Kashiwagi, Y. Nishio, K. Egawa, S. Shimizu, H. Maegawa, M. Haneda, H. Yasuda, S. Morikawa, T. Inubushi, et al. Increased Arterial Wall Stiffness Limits Flow Volume in the Lower Extremities in Type 2 Diabetic Patients Diabetes Care, December 1, 2001; 24(12): 2107 - 2114. [Abstract] [Full Text] [PDF]
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J. Westerbacka, A. Seppala-Lindroos, and H. Yki-Jarvinen Resistance to Acute Insulin Induced Decreases in Large Artery Stiffness Accompanies the Insulin Resistance Syndrome J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5262 - 5268. [Abstract] [Full Text] [PDF]
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M. Domanski, J. Norman, M. Wolz, G. Mitchell, and M. Pfeffer Cardiovascular Risk Assessment Using Pulse Pressure in the First National Health and Nutrition Examination Survey (NHANES I) Hypertension, October 1, 2001; 38(4): 793 - 797. [Abstract] [Full Text] [PDF]
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K. Sutton-Tyrrell, A. Newman, E. M. Simonsick, R. Havlik, M. Pahor, E. Lakatta, H. Spurgeon, and P. Vaitkevicius Aortic Stiffness Is Associated With Visceral Adiposity in Older Adults Enrolled in the Study of Health, Aging, and Body Composition Hypertension, September 1, 2001; 38(3): 429 - 433. [Abstract] [Full Text] [PDF]
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N. Hosomi, K. Mizushige, H. Ohyama, T. Takahashi, M. Kitadai, Y. Hatanaka, H. Matsuo, M. Kohno, and J. A. Koziol Angiotensin-Converting Enzyme Inhibition With Enalapril Slows Progressive Intima-Media Thickening of the Common Carotid Artery in Patients With Non-Insulin-Dependent Diabetes Mellitus Stroke, July 1, 2001; 32(7): 1539 - 1545. [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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S. I. McFarlane, M. Banerji, and J. R. Sowers Insulin Resistance and Cardiovascular Disease J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 713 - 718. [Full Text]
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Shonni J. Silverberg; Cardiovascular Disease in Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3513 - 3514. [Full Text]
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R. Din-Dzietham, D. Liao, A. Diez-Roux, F. J. Nieto, C. Paton, G. Howard, A. Brown, M. Carnethon, and H. A. Tyroler Association of Educational Achievement with Pulsatile Arterial Diameter Change of the Common Crotid Artery The Atherosclerosis Risk in Communities (ARIC) Study, 1987-1992 Am. J. Epidemiol., October 1, 2000; 152(7): 617 - 627. [Abstract] [Full Text] [PDF]
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C. Espinola-Klein, H.-J. Rupprecht, S. Blankenberg, C. Bickel, H. Kopp, G. Rippin, G. Hafner, U. Pfeifer, and J. Meyer Are Morphological or Functional Changes in the Carotid Artery Wall Associated With Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus, or Herpes Simplex Virus Infection? Stroke, September 1, 2000; 31(9): 2127 - 2133. [Abstract] [Full Text] [PDF]
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E. Jeanclos, N. J. Schork, K. O. Kyvik, M. Kimura, J. H. Skurnick, and A. Aviv Telomere Length Inversely Correlates With Pulse Pressure and Is Highly Familial Hypertension, August 1, 2000; 36(2): 195 - 200. [Abstract] [Full Text] [PDF]
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H. F. Kuecherer, A. Just, and H. Kirchheim Evaluation of aortic compliance in humans Am J Physiol Heart Circ Physiol, May 1, 2000; 278(5): H1411 - H1413. [Full Text] [PDF]
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H.-M. Lakka, T. A. Lakka, J. Tuomilehto, J. Sivenius, and J. T. Salonen Hyperinsulinemia and the Risk of Cardiovascular Death and Acute Coronary and Cerebrovascular Events in Men: The Kuopio Ischaemic Heart Disease Risk Factor Study Arch Intern Med, April 24, 2000; 160(8): 1160 - 1168. [Abstract] [Full Text] [PDF]
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S Manzi, L H Kuller, D Edmundowicz, and K Sutton-Tyrrell Vascular imaging: changing the face of cardiovascular research Lupus, March 1, 2000; 9(3): 176 - 182. [Abstract] [PDF]
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E. J. Giltay, J. Lambert, L. J. G. Gooren, J. M. H. Elbers, M. Steyn, and C. D. A. Stehouwer Sex Steroids, Insulin, and Arterial Stiffness in Women and Men Hypertension, October 1, 1999; 34(4): 590 - 597. [Abstract] [Full Text] [PDF]
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M. J. Domanski, B. R. Davis, M. A. Pfeffer, M. Kastantin, and G. F. Mitchell Isolated Systolic Hypertension : Prognostic Information Provided by Pulse Pressure Hypertension, September 1, 1999; 34(3): 375 - 380. [Abstract] [Full Text] [PDF]
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P. C. G. Simons, A. Algra, M. L. Bots, D. E. Grobbee, and Y. van der Graaf Common Carotid Intima-Media Thickness and Arterial Stiffness : Indicators of Cardiovascular Risk in High-Risk PatientsThe SMART Study (Second Manifestations of ARTerial disease) Circulation, August 31, 1999; 100(9): 951 - 957. [Abstract] [Full Text] [PDF]
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D. Liao, D. K. Arnett, H. A. Tyroler, W. A. Riley, L. E. Chambless, M. Szklo, and G. Heiss Arterial Stiffness and the Development of Hypertension : The ARIC Study Hypertension, August 1, 1999; 34(2): 201 - 206. [Abstract] [Full Text] [PDF]
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K. L. Berry, R. A. P. Skyrme-Jones, J. D. Cameron, R. C. O'Brien, and I. T. Meredith Systemic arterial compliance is reduced in young patients with IDDM Am J Physiol Heart Circ Physiol, June 1, 1999; 276(6): H1839 - H1845. [Abstract] [Full Text] [PDF]
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M. J. Domanski, G. F. Mitchell, J. E. Norman, D. V. Exner, B. Pitt, and M. A. Pfeffer Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction J. Am. Coll. Cardiol., March 15, 1999; 33(4): 951 - 958. [Abstract] [Full Text] [PDF]
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J. N. Bella, M. J. Roman, R. Pini, J. E. Schwartz, T. G. Pickering, and R. B. Devereux Assessment of Arterial Compliance by Carotid Midwall Strain-Stress Relation in Normotensive Adults Hypertension, March 1, 1999; 33(3): 787 - 792. [Abstract] [Full Text] [PDF]
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J. N. Bella, M. J. Roman, R. Pini, J. E. Schwartz, T. G. Pickering, and R. B. Devereux Assessment of Arterial Compliance by Carotid Midwall Strain-Stress Relation in Hypertension Hypertension, March 1, 1999; 33(3): 793 - 799. [Abstract] [Full Text] [PDF]
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J. O. Toikka, P. Niemi, M. Ahotupa, H. Niinikoski, J. S. A. Viikari, T. Ronnemaa, J. J. Hartiala, and O. T. Raitakari Large-Artery Elastic Properties in Young Men : Relationships to Serum Lipoproteins and Oxidized Low-Density Lipoproteins Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 436 - 441. [Abstract] [Full Text] [PDF]
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Y. Nagai, C. J. Earley, M. K. Kemper, C. S. Bacal, and E.J. Metter Influence of age and postmenopausal estrogen replacement therapy on carotid arterial stiffness in women Cardiovasc Res, January 1, 1999; 41(1): 307 - 311. [Abstract] [Full Text] [PDF]
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 D. A. Towler, M. Bidder, T. Latifi, T. Coleman, and C. F. Semenkovich Diet-induced Diabetes Activates an Osteogenic Gene Regulatory Program in the Aortas of Low Density Lipoprotein Receptor-deficient Mice J. Biol. Chem., November 13, 1998; 273(46): 30427 - 30434. [Abstract] [Full Text] [PDF]
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 M. L. Goalstone, R. Natarajan, P. R. Standley, M. F. Walsh, J. W. Leitner, K. Carel, S. Scott, J. Nadler, J. R. Sowers, and B. Draznin Insulin Potentiates Platelet-Derived Growth Factor Action in Vascular Smooth Muscle Cells Endocrinology, October 1, 1998; 139(10): 4067 - 4072. [Abstract] [Full Text] [PDF]
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 J. R. Sowers Obesity and cardiovascular disease Clin. Chem., August 1, 1998; 44(8): 1821 - 1825. [Abstract] [Full Text] [PDF]
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B. P. McGrath, Y.-L. Liang, H. Teede, L. M. Shiel, J. D. Cameron, and A. Dart Age-Related Deterioration in Arterial Structure and Function in Postmenopausal Women : Impact of Hormone Replacement Therapy Arterioscler Thromb Vasc Biol, July 1, 1998; 18(7): 1149 - 1156. [Abstract] [Full Text] [PDF]
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C. M. Burchfiel, D. S. Sharp, J. D. Curb, B. L. Rodriguez, R. D. Abbott, R. Arakaki, and K. Yano Hyperinsulinemia and Cardiovascular Disease in Elderly Men : The Honolulu Heart Program Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 450 - 457. [Abstract] [Full Text] [PDF]
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G. F. Mitchell, L. A. Moye, E. Braunwald, J.-L. Rouleau, V. Bernstein, E. M. Geltman, G. C. Flaker, M. A. Pfeffer, and f. t. S. Investigators Sphygmomanometrically Determined Pulse Pressure Is a Powerful Independent Predictor of Recurrent Events After Myocardial Infarction in Patients With Impaired Left Ventricular Function Circulation, December 16, 1997; 96(12): 4254 - 4260. [Abstract] [Full Text]
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