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Semin Vasc Med 2002; 2(2): 157-164
DOI: 10.1055/s-2002-32039
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Arterial Stiffness and Insulin Resistance

Jukka Westerbacka, Hannele Yki-Järvinen
  • Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland
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Publication History

Publication Date:
06 June 2002 (online)

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ABSTRACT

Insulin resistance is associated with increased cardiovascular morbidity and mortality. The mechanism(s) underlying this association are poorly understood. Increased arterial stiffness is the main cause of the most prevalent form of hypertension, systolic hypertension. Hypertension is also commonly observed in individuals with insulin resistance. In cross-sectional epidemiological studies such as the Atherosclerosis Risk in Communities study, hyperinsulinemia was independently associated with increased arterial stiffness. Recent mechanistic studies performed in humans in vivo have suggested that increased stiffness could be yet another facet of insulin resistance. Insulin, at physiological concentrations, acutely diminishes wave reflection in the aorta in vivo. This action of insulin precedes any changes in peripheral blood flow, vascular resistance, ejection duration or heart rate, and therefore implies that insulin acutely diminishes stiffness in arteries greater than those controlling peripheral vascular resistance. This effect is blunted in insulin-resistant conditions such as obesity and type 1 diabetes. These data suggest that the inability of insulin to normally diminish arterial stiffness could provide a mechanistic link between insulin resistance and systolic hypertension.

KEYWORDS

Blood pressure - large arteries - obesity - diabetes

REFERENCES

  • 1 Lillioja S, Mott D M, Spraul M. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus.  N Engl J Med . 1993;  329 1988-1992
    CrossrefPubMedSearch in Google Scholar
  • 2 Stamler J, Vaccaro O, Neaton J D, Wentworth D. Diabetes, other risk factors, and 12-year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.  Diabetes Care . 1993;  16 434-444
    CrossrefPubMedSearch in Google Scholar
  • 3 Fuller J H, Shipley M J, Rose G, Jarrett R J, Keen H. Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study.  BMJ . 1983;  287 867-870
    PubMedSearch in Google Scholar
  • 4 Pyörälä K. Relationship of glucose tolerance and plasma insulin in the incidence of coronary heart disease. Results from two population studies in Finland.  Diabetes Care . 1979;  2 131-141
    CrossrefPubMedSearch in Google Scholar
  • 5 Yki-Järvinen H, Helve E, Koivisto V A. Hyperglycemia decreases glucose uptake in type 1 diabetes.  Diabetes . 1987;  36 892-896
    PubMedSearch in Google Scholar
  • 6 Yki-Järvinen H. Glucose toxicity.  Endocr Rev . 1992;  13 415-431
    CrossrefPubMedSearch in Google Scholar
  • 7 Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Poor glycemic control predicts coronary heart disease events in patients with type 1 diabetes without nephropathy.  Arterioscler Thromb Vasc Biol . 1999;  19 1014-1019
    PubMedSearch in Google Scholar
  • 8 Welborn T A, Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations.  Diabetes Care . 1979;  2 154-160
    PubMedSearch in Google Scholar
  • 9 Fontbonne A, Charles M A, Thibult N. Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up.  Diabetologia . 1991;  34 356-361
    CrossrefPubMedSearch in Google Scholar
  • 10 Laakso M, Rönnemaa T, Pyörälä K, Kallio V, Puukka P, Penttilä I. Atherosclerotic vascular disease and its risk factors in non-insulin-dependent diabetic and nondiabetic subjects in Finland.  Diabetes Care . 1988;  11 449-463
    PubMedSearch in Google Scholar
  • 11 Brand F N, McGee D L, Kannel W B, Stokes J, Castelli W P. Hyperuricemia as a risk factor of coronary heart disease: the Framingham Study.  Am J Epidemiol . 1985;  121 11-18
    PubMedSearch in Google Scholar
  • 12 Paolisso G, Tataranni P A, Foley J E, Bogardus C, Howard B V, Ravussin E. A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM.  Diabetologia . 1995;  38 1213-1217
    PubMedSearch in Google Scholar
  • 13 Lamarche B, Tchernof A, Moorjani S. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study.  Circulation . 1997;  95 69-75
    PubMedSearch in Google Scholar
  • 14 Ferrannini E, Buzzigoli G, Bonadonna R. Insulin resistance in essential hypertension.  N Engl J Med . 1987;  317 350-357
    CrossrefPubMedSearch in Google Scholar
  • 15 Pollare T, Lithell H, Berne C. Insulin resistance is a characteristic feature of primary hypertension independent of obesity.  Metabolism . 1990;  39 167-174
    PubMedSearch in Google Scholar
  • 16 Shen D C, Shieh S M, Fuh M M, Wu D A, Chen Y D, Reaven G M. Resistance to insulin-stimulated-glucose uptake in patients with hypertension.  J Clin Endocrinol Metab . 1988;  66 580-583
    PubMedSearch in Google Scholar
  • 17 Feskens E J, Tuomilehto J, Stengard J H, Pekkanen J, Nissinen A, Kromhout D. Hypertension and overweight associated with hyperinsulinaemia and glucose tolerance: a longitudinal study of the Finnish and Dutch cohorts of the Seven Countries Study.  Diabetologia . 1995;  38 839-847
    CrossrefPubMedSearch in Google Scholar
  • 18 Modan M, Halkin H, Almog S. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance.  J Clin Invest . 1985;  75 809-817
    PubMedSearch in Google Scholar
  • 19 Dowse G K, Collins V R, Alberti K G. Insulin and blood pressure levels are not independently related in Mauritians of Asian Indian, Creole or Chinese origin. The Mauritius Non-communicable Disease Study Group.  J Hypertens . 1993;  11 297-307
    PubMedSearch in Google Scholar
  • 20 Quinones G A, Natali A, Baldi S. Effect of insulin on uric acid excretion in humans.  Am J Physiol . 1995;  268 E1-E5
    PubMedSearch in Google Scholar
  • 21 Franklin S S, Jacobs M J, Wong N D, L'Italien G J, Lapuerta P. Predominance of isolated systolic hypertension among middle-aged and elderly U.S. hypertensives: analysis based on National Health and Nutrition Examination Survey (NHANES) III.  Hypertension . 2001;  37 869-874
    CrossrefPubMedSearch in Google Scholar
  • 22 Benetos A, Safar M, Rudnichi A. Pulse pressure: a predictor of long-term cardiovascular mortality in a French male population.  Hypertension . 1997;  30 1410-1415
    PubMedSearch in Google Scholar
  • 23 Franklin S S, Larson M G, Khan S A. Does the relation of blood pressure to coronary heart disease risk change with aging?.  <~>The Framingham Heart Study. Circulation . 2001;  103 1245-1249
    PubMedSearch in Google Scholar
  • 24 Sesso H D, Stampfer M J, Rosner B. Systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure as predictors of cardiovascular disease risk in men.  Hypertension . 2000;  36 801-807
    PubMedSearch in Google Scholar
  • 25 Domanski M, Norman J, Wolz M, Mitchell G, Pfeffer M. Cardiovascular risk assessment using pulse pressure in the first national health and nutrition examination survey (NHANES I).  Hypertension . 2001;  38 793-797
    CrossrefPubMedSearch in Google Scholar
  • 26 Madhavan S, Ooi W L, Cohen H, Alderman M H. Relation of pulse pressure and blood pressure reduction to the incidence of myocardial infarction.  Hypertension . 1994;  23 395-401
    CrossrefPubMedSearch in Google Scholar
  • 27 Franklin S S, Gustin W, Wong N D. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study.  Circulation . 1997;  96 308-315
    CrossrefPubMedSearch in Google Scholar
  • 28 Alderman M H, Cohen H, Madhavan S. Distribution and determinants of cardiovascular events during 20 years of successful antihypertensive treatment.  J Hypertens . 1998;  16 761-769
    CrossrefPubMedSearch in Google Scholar
  • 29 Franklin S S, Khan S A, Wong N D, Larson M G, Levy D. Is pulse pressure useful in predicting risk for coronary heart disease?.  <~>The Framingham Heart Study. Circulation . 1999;  100 354-360
    PubMedSearch in Google Scholar
  • 30 Verdecchia P, Schillaci G, Reboldi G, Franklin S S, Porcellati C. Different prognostic impact of 24-hour mean blood pressure and pulse pressure on stroke and coronary artery disease in essential hypertension.  Circulation . 2001;  103 2579-2584
    PubMedSearch in Google Scholar
  • 31 O'Rourke M F, Kelly R P. Wave reflection in the systemic circulation and its implications in ventricular function.  J Hypertens . 1993;  11 327-337
    PubMedSearch in Google Scholar
  • 32 Hirai T, Sasayama S, Kawasaki T, Yagi S. Stiffness of systemic arteries in patients with myocardial infarction. A noninvasive method to predict severity of coronary atherosclerosis.  Circulation . 1989;  80 78-86
    CrossrefPubMedSearch in Google Scholar
  • 33 Dart A M, Lacombe F, Yeoh J K. Aortic distensibility in patients with isolated hypercholesterolaemia, coronary artery disease, or cardiac transplant.  Lancet . 1991;  338 270-273
    CrossrefPubMedSearch in Google Scholar
  • 34 Gatzka C D, Cameron J D, Kingwell B A, Dart A M. Relation between coronary artery disease, aortic stiffness, and left ventricular structure in a population sample.  Hypertension . 1998;  32 575-578
    PubMedSearch in Google Scholar
  • 35 Laurent S, Boutouyrie P, Asmar R. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients.  Hypertension . 2001;  37 1236-1241
    CrossrefPubMedSearch in Google Scholar
  • 36 van Popele M N, Grobbee D E, Bots M L. Association between arterial stiffness and atherosclerosis: the Rotterdam Study.  Stroke . 2001;  32 454-460
    CrossrefPubMedSearch in Google Scholar
  • 37 London G M, Blacher J, Pannier B, Guerin A P, Marchais S J, Safar M E. Arterial wave reflections and survival in end-stage renal failure.  Hypertension . 2001;  38 434-438
    PubMedSearch in Google Scholar
  • 38 Nichols W W, O'Rourke M F. McDonalds's Blood Flow in Arteries. Theoretical, Experimental and Clinical Principles London: Arnold; 1998
    Search in Google Scholar
  • 39 Salomaa V, Riley W, Kark J D, Nardo C, Folsom A R. Non-insulin-dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes-The ARIC Study.  Circulation . 1995;  91 1432-1443
    CrossrefPubMedSearch in Google Scholar
  • 40 McVeigh G E, Brennan G, Hayes R, Cohn J, Finkelstein S, Johnston D. Vascular abnormalities in non-insulin-dependent diabetes mellitus identified by arterial waveform analysis.  Am J Med . 1993;  95 424-430
    CrossrefPubMedSearch in Google Scholar
  • 41 Lehmann E D, Riley W A, Clarkson P, Gosling R G. Non-invasive assessment of cardiovascular disease in diabetes mellitus.  Lancet . 1999;  350 14-19
    PubMedSearch in Google Scholar
  • 42 Glasser S P, Arnett D K, McVeigh G E. Vascular compliance and cardiovascular disease: a risk factor or a marker?.  Am J Hypertens . 1997;  10 1175-1189
    CrossrefPubMedSearch in Google Scholar
  • 43 Devereux R B, Roman M J, Paranicas M. Impact of diabetes on cardiac structure and function: the Strong Heart Study.  Circulation . 2000;  101 2271-2276
    PubMedSearch in Google Scholar
  • 44 Taddei S, Virdis A, Ghiadoni L, Salvetti A. Endothelial dysfunction in hypertension: fact or fancy?.  J Cardiovasc Pharmacol . 1998;  S41-S47 (S41-S47)
    PubMedSearch in Google Scholar
  • 45 Taniwaki H, Kawagishi T, Emoto M. Correlation between the intima-media thickness of the carotid artery and aortic pulse-wave velocity in patients with type 2 diabetes. Vessel wall properties in type 2 diabetes.  Diabetes Care . 1999;  22 1851-1857
    PubMedSearch in Google Scholar
  • 46 Berry K L, Skyrme-Jones R A, Cameron J D, O'Brien R C, Meredith I T. Systemic arterial compliance is reduced in young patients with IDDM.  Am J Physiol . 1999;  276 H1839-H1845
    PubMedSearch in Google Scholar
  • 47 Hu J, Wallensteen M, Gennser G. Increased stiffness of the aorta in children and adolescents with insulin-dependent diabetes mellitus.  Ultrasound Med Biol . 1996;  22 537-543
    CrossrefPubMedSearch in Google Scholar
  • 48 Oxlund H, Rasmussen L M, Andreassen T T, Heickendorff L. Increased aortic stiffness in patients with type 1 (insulin-dependent) diabetes mellitus.  Diabetologia . 1989;  32 748-752
    CrossrefPubMedSearch in Google Scholar
  • 49 Christensen T, Neubauer B. Increased arterial wall stiffness and thickness in medium-sized arteries in patients with insulin-dependent diabetes mellitus.  Acta Radiol . 1988;  29 299-302
    PubMedSearch in Google Scholar
  • 50 Ryden-Ahlgren A, Länne T, Wollmer P, Sonesson B, Hansen F, Sundkvist G. Increased arterial stiffness in woman, but not in men, with IDDM.  Diabetologia . 1995;  38 1082-1089
    PubMedSearch in Google Scholar
  • 51 Giannattasio C, Failla M, Piperno A. Early impairment of large artery structure and function in type I diabetes mellitus.  Diabetologia . 1999;  42 987-994
    CrossrefPubMedSearch in Google Scholar
  • 52 Kool M J, Lambert J, Stehouwer C D, Hoeks A P, Struijker Boudier A H, Van Bortel M L. Vessel wall properties of large arteries in uncomplicated IDDM.  Diabetes Care . 1995;  18 618-624
    PubMedSearch in Google Scholar
  • 53 Lehmann E D, Gosling R G, Sonksen P H. Arterial wall compliance in diabetes.  Diabet Med . 1992;  9 114-119
    CrossrefPubMedSearch in Google Scholar
  • 54 Brooks B, Molyneaux L, Yue D K. Augmentation of central arterial pressure in type 1 diabetes.  Diabetes Care . 1999;  22 1722-1727
    PubMedSearch in Google Scholar
  • 55 Wilkinson I B, MacCallum H, Rooijmans D F. Increased augmentation index and systolic stress in type 1 diabetes mellitus.  QJM . 2000;  93 441-448
    CrossrefPubMedSearch in Google Scholar
  • 56 Jensen-Urstad K J, Reichard P G, Rosfors J S, Lindblad L E, Jensen-Urstad M T. Early atherosclerosis is retarded by improved long-term blood glucose control in patients with IDDM.  Diabetes . 1996;  45 1253-1258
    PubMedSearch in Google Scholar
  • 57 Westerbacka J, Wilkinson I, Cockcroft J, Utriainen T, Vehkavaara S, Yki-Järvinen H. Diminished wave reflection in the aorta: a novel physiological action of insulin on large blood vessels.  Hypertension . 1999;  33 1118-1122
    CrossrefPubMedSearch in Google Scholar
  • 58 Malmström R, Packard C J, Watson T DG. Metabolic basis of hypotriglyceridemic effects of insulin in normal men.  Arterioscler Thromb Vasc Biol . 1997;  17 1454-1464
    PubMedSearch in Google Scholar
  • 59 Yki-Järvinen H. Action of insulin on glucose metabolism in vivo.  Baillieres Clin Endocrinol Metab . 1993;  7 903-927
    CrossrefPubMedSearch in Google Scholar
  • 60 Westerbacka J, Yki-Järvinen H, Turpeinen A. Inhibition of platelet-collagen interaction: an in vivo action of insulin abolished by insulin resistance in obesity.  Arterioscler Thromb Vasc Biol . 2002;  22 167-172
    CrossrefPubMedSearch in Google Scholar
  • 61 Taddei S, Virdis A, Mattei P, Natali A, Ferrannini E, Salvetti A. Effect of insulin on acetylcholine-induced vasodilatation in normotensive subjects and patients with essential hypertension.  Circulation . 1995;  92 2911-2918
    PubMedSearch in Google Scholar
  • 62 Westerbacka J, Vehkavaara S, Bergholm R, Wilkinson I, Cockcroft J, Yki-Järvinen H. Marked resistance of the ability of insulin to decrease arterial stiffness characterizes human obesity.  Diabetes . 1999;  48 821-827
    PubMedSearch in Google Scholar
  • 63 Westerbacka J, Uosukainen A, Mäkimattila S, Schlenzka A, Yki-Järvinen H. Insulin-induced decrease in large artery stiffness is impaired in uncomplicated type 1 diabetes mellitus.  Hypertension . 2000;  35 1043-1048
    PubMedSearch in Google Scholar
  • 64 Westerbacka J, Seppälä-Lindroos A, Yki-Järvinen H. Resistance to acute insulin-induced decreases in large artery stiffness accompanies the insulin resistance syndrome.  J Clin Endocrinol Metab . 2001;  86 5262-5268
    CrossrefPubMedSearch in Google Scholar
  • 65 Jiang Z Y, Lin Y W, Clemont A. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats.  J Clin Invest . 1999;  104 447-457
    CrossrefPubMedSearch in Google Scholar
  • 66 Steinberg H O, Tarshoby M, Monestel R. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.  J Clin Invest . 1997;  100 1230-1239
    CrossrefPubMedSearch in Google Scholar
  • 67 Lundman P, Eriksson M, Schenck-Gustafsson K, Karpe F, Tornvall P. Transient triglyceridemia decreases vascular reactivity in young, healthy men without risk factors for coronary heart disease.  Circulation . 1997;  96 3266-3268
    PubMedSearch in Google Scholar
  • 68 Yokoyama I, Ohtake T, Momomura S. Altered myocardial vasodilatation in patients with hypertriglyceridemia in anatomically normal coronary arteries.  Arterioscler Thromb Vasc Biol . 1998;  18 294-299
    PubMedSearch in Google Scholar
  • 69 Zeng G, Nystrom F H, Ravichandran L V. Roles for insulin receptor, PI 3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells.  Circulation . 2000;  101 1539-1545
    CrossrefPubMedSearch in Google Scholar
  • 70 Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin's vascular effects in humans.  J Clin Invest . 1994;  94 2511-2515
    CrossrefPubMedSearch in Google Scholar
  • 71 Steinberg H O, Brechtel G, Johnson A, Fireberg N, Baron A D. Insulin-mediated skeletal muscle vasodilatation is nitric oxide-dependent. A novel action of insulin to increase nitric oxide release.  J Clin Invest . 1994;  94 1172-1179
    CrossrefPubMedSearch in Google Scholar
  • 72 Rees D D, Palmer R MJ, Hodson H F, Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent dilatation.  Br J Pharmacol . 1989;  996 418-424
    PubMedSearch in Google Scholar
  • 73 Rask-Madsen C, Ihlemann N, Krarup T. Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.  Diabetes . 2001;  50 2611-2618
    CrossrefPubMedSearch in Google Scholar
  • 74 Vehkavaara S, Mäkimattila S, Schlenzka A, Vakkilainen J, Westerbacka J, Yki-Järvinen H. Insulin therapy improves endothelial function in type 2 diabetes.  Arterioscler Thromb Vasc Biol . 2000;  20 545-550
    PubMedSearch in Google Scholar
  • 75 Wilkinson I B, Qasem A, McEniery C M, Webb D J, Avolio A P, Cockcroft J R. Nitric oxide regulates local arterial distensibility in vivo.  Circulation . 2002;  105 213-217
    CrossrefPubMedSearch in Google Scholar
  • 76 Cushman W C, Materson B J, Williams D W, Reda D J. Pulse pressure changes with six classes of antihypertensive agents in a randomized, controlled trial.  Hypertension . 2001;  38 953-957
    PubMedSearch in Google Scholar
  • 77 Franklin S S. Ageing and hypertension: the assessment of blood pressure indices in predicting coronary heart disease.  J Hypertens . 1999;  S29-S36 (S29-S36)
    PubMedSearch in Google Scholar
  • 78 Burt V L, Cutler J A, Higgins M. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult U.S. population. Data from the Health Examination Surveys, 1960 to 1991.  Hypertension . 1995;  26 60-69
    CrossrefPubMedSearch in Google Scholar
  • 79 Pauca A L, O'Rourke M F, Kon N D. Prospective evaluation of a method for estimating ascending aortic pressure from the radial artery pressure waveform.  Hypertension . 2001;  38 932-937
    CrossrefPubMedSearch in Google Scholar
  • 80 O'Rourke M F, Gallagher D E. Pulse wave analysis.  J Hypertens . 1996;  14 S147-S157
    PubMedSearch in Google Scholar