Hypertension and Insulin Resistance

  • Andrea Natali
  • Stefano Taddei
  • Ele Ferrannini
Part of the Contemporary Biomedicine book series (CB, volume 15)


The demonstration of a defect in insulin-mediated glucose metabolism in essential hypertension has raised the interest of both the “metabolists,” who have gained new insight into the pathogenesis of insulin resistance, and the “hypertensionologists,” who have focused attention on the cardiovascular actions of insulin. Although the metabolic consequences of insulin resistance are well established, there are differing views regarding the pathogenesis of the defect and its impact on blood pressure (BP) homeostasis. Whether high BP and insulin resistance have a common genetic basis, or whether they share common pathogenetic links (in this case, whether one affects the other or both stem from a common abnormality) is still debated. These possibilities are under active investigation, and although a comprehensive explanation for the observed association is not yet available, the effort has rapidly led to the accumulation of physiologically relevant information. In the present chapter, we shall try to separate facts from opinions with full cognizance that this scope will not be entirely met. Particularly with a complex issue, some degree of bias is inevitable.


Insulin Resistance Insulin Sensitivity Essential Hypertension Clin Invest Plasma Insulin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Modan M, Halkin H, Almog S, Lusky A, Eshokol A, Shefi M. Hyperinsulinemia: a link between hypertension obesity and glucose intolerance. J Clin Invest 1985; 75: 809–817.PubMedCrossRefGoogle Scholar
  2. 2.
    Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S. Insulin resistance in essential hypertension. New Engl J Med 1987; 317: 350–357.PubMedCrossRefGoogle Scholar
  3. 3.
    Shen D-C, Shieh S-M, Fuh MM-T, Wu D-A, Chen Y-DI, Reaven GM. Resistance to insulin-stimulated glucose uptake in patients with hypertension. J Clin Endocrinol Metab 1988; 66: 580–583.PubMedCrossRefGoogle Scholar
  4. 4.
    Pollare T, Lithell H, Berne C. Insulin resistance is a characteristic feature of primary hypertension independent of obesity. Metabolism 1990; 39: 167–174.PubMedCrossRefGoogle Scholar
  5. 5.
    Salvatore T, Cozzolino D, Giunta R, Giugliano D, Torella R, D’Onoffrio F. Decreased insulin clearance as a feature of essential hypertension. J Clin Endocrinol Metab 1992; 74: 144–149.PubMedCrossRefGoogle Scholar
  6. 6.
    Natali A, Santoro D, Palombo C, Cerri M, Ghione S, Ferrannini E. Impaired insulin action on skeletal muscle metabolism in essential hypertension. Hypertension 1991; 17: 170–178.PubMedCrossRefGoogle Scholar
  7. 7.
    Lind L, Lithell H, Pollare T. Is it hyperinsulinmia or insulin resistance that is related to hypertension and other metabolic cardiovascular risk factors? J Hypertension 1993; 11 (Suppl 4): S11–516.CrossRefGoogle Scholar
  8. 8.
    Natali A, Quinones A, Arzilli F, Taddei S, Pecori N, Frascerra S, Salvetti A, Ferrannini E. Insulin sensitivity and renovascular hypertension. Clin Sci 1995; 85: 327–335.Google Scholar
  9. 9.
    Laakso M, Sarlund H, Mykkänen I. Essential hypertension and insulin resistance in noninsulin-dependent diabetes. Eur J Clin Invest 1989; 19: 518–526.PubMedCrossRefGoogle Scholar
  10. 10.
    Maheux P, Jeppens J, Sheu WH-H, Hollembeck CB, Clinkingbeard C, Greenfield MS, Chen YI, Reaven GN. Additive effects of obesity, hypertension, and type 2 diabetes on insulin resistance. Hypertension 1994; 24: 695–698.PubMedCrossRefGoogle Scholar
  11. 11.
    Doria A, Fioretto P, Avogaro A, Carraro A, Morocutti A, Trevisan R, Frigato F, Crepaldi G, Viberti G, Nosadini R. Insulin resistance is associated with high sodium-lithium countertransport in essential hypertension. Am J Physiol 1991; 261: E694 - E691.Google Scholar
  12. 12.
    Sharma AM, Ruland K, Spies KP, et al. Salt sensitivity in young normotensive subjects is associated with a hyperinsulinemic response to oral glucose. J Hypertension 1991; 9: 329–335.CrossRefGoogle Scholar
  13. 13.
    Egan BM, Stepniakowski K, Nazzaro P. Insulin levels are similar in obese salt-sensitive and salt-resistant hypertensive subjects. Hypertension 1994; 23 (Suppl I): Il-17.Google Scholar
  14. 14.
    Bianchi S, Bigazzi R, Valtriani C, Chiapponi I, Sgherri S, Baldari G, Natali A, Ferrannini E, Campese VM. Hyperinsulinemia in patients with essential hypertension and microalbuminuria. Hypertension 1994; 23: 681–687.PubMedCrossRefGoogle Scholar
  15. 15.
    Bianchi S, Bigazzi R, Quinones A, Muscelli E, Baldari E, Pecori N, Ciociaro D, Ferrannini E, Natali A. Insulin resistance in microalbuminuric patients: sites and mechanism. Hypertension, 1995; 26: 789–795.PubMedCrossRefGoogle Scholar
  16. 16.
    Ferrari P, Weidmann P, Shaw S, Giachino D, Riesen W, Allemann Y, Heynen G. Altered insulin sensitivity, hyperinsulinemia, and dyslipidemia in individuals with a hypertensive parent. Am J Med 1991; 91: 589–596.PubMedCrossRefGoogle Scholar
  17. 17.
    Nosadini R, Solini A, Velussi M, Muollo B, Frigato F, Sambataro M, Cipollina MR, DeRiva F, Brocco E, Crepaldi G. Impaired insulin-induced glucose uptake by extrahepatic tissue is hallmark of NIDDM patients who have or will develop hypertension and microalbuminuria. Diabetes 1994; 43: 491–499.PubMedCrossRefGoogle Scholar
  18. 18.
    Ferrannini E, Haffner SM, Stern MP, Mitchell BD, Natali A, Hazuda HP, Patterson JK. High blood pressure and insulin resistance: influence of genetic background. Eur J Clin Invest 1991; 21: 280–286.PubMedCrossRefGoogle Scholar
  19. 19.
    Haffner SM, Stern MP, Hazuda HP, Mitchell BD, Patterson JK, Ferrannini E. Parental history of diabetes is associated with increased cardiovascular risk factors. Arteriosclerosis 1989; 9: 928–933.PubMedCrossRefGoogle Scholar
  20. 20.
    Haffner SM, Ferrannini E, Hazuda HP, Stern MP. Clustering of cardiovascular risk factors in confirmed prehypertensive individuals. Hypertension 1992; 20: 38–45.PubMedCrossRefGoogle Scholar
  21. 21.
    Manolio TA, Savage PJ, Burke GK, Liu KL, Wagenknecht LE, Sidney S, Jacobs DR, Roseman JM, Donahue RP, Oberman A. Association of fasting insulin with blood pressure and lipids in young adults. The CARDIA study. Arteriosclerosis 1990; 10: 430–436.CrossRefGoogle Scholar
  22. 22.
    Bjorntorp P. “Portal” adipose tissue as a generator of risk factor for cardiovascular disease and diabetes. Arteriosclerosis 1990; 10: 493–496.Google Scholar
  23. 23.
    Bjorntorp P. Visceral fat accumulation: the missing link between psychosocial factors and cardiovascular disease. J Int Med 1991; 230: 195–201.CrossRefGoogle Scholar
  24. 24.
    Ferrannini E. The haemodynamics of obesity: a theoretical analysis. J Hypertension 1992; 10: 1417–1423.CrossRefGoogle Scholar
  25. 25.
    Bonadonna RC, Groop LC, Simonson DC, DeFronzo RA. Free fatty acid and glucose metabolism in human aging: evidence for operation of the Randle cycle. Am J Physiol 1994; 266: E501 - E509.PubMedGoogle Scholar
  26. 26.
    Ferrannini E, Vichi S, Beck-Nielsen H, Laakso M, Paolisso G, Smith U, on behalf of the European Group for the Study of Insulin Resistance. Insulin sensitivity and age, 1996; 45: 947–953.Google Scholar
  27. 27.
    Greene AS, Tonellato PJ, Lui J, Lombard JH, Cowley AW Jr. Microvascular rarefaction and tissue vascular resistance in hypertension. Am J Physiol 1989; 256: H126 - H131.PubMedGoogle Scholar
  28. 28.
    Edgerton VR, Smith JL, Simpson DR. Muscle fiber type populations of human leg muscles. Histochem J 1975; 7: 259–266.Google Scholar
  29. 29.
    Weinsier RL, Norris DJ, Birch R, Bernstein RS, Wang J, Yang M-U, Pierson RN Jr, Van Itallie TB. The relative contribution of body fat and fat pattern to blood pressure level. Hypertension 1985; 7: 578–585.PubMedCrossRefGoogle Scholar
  30. 30.
    Ferrannini E. Insulin and blood pressure: possible role of hemodynamics. Clin Exp Hypertension 1992; A14 (1and2): 271–284.CrossRefGoogle Scholar
  31. 31.
    Raison JM, Safar ME, Cambien F, London GM. Forearm haemodynamics in obese normotensive and hypertensive subjects. J Hypertension 1988; 6: 299–303.CrossRefGoogle Scholar
  32. 32.
    Castillo C, Bogardus C, Bergman R, Thuillez P, Lillioja S. Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men. J Clin Invest 1994; 93: 10–16.PubMedCrossRefGoogle Scholar
  33. 33.
    Juhlin-Dannfelt A, Frisk-Holmberg M, Karlsson J, Tesch P. Central and peripheral circulation in relation to muscle-fibre composition in normo-and hyper-tensive man. Clin Sci 1979; 56: 335–340.PubMedGoogle Scholar
  34. 34.
    Lillioja S, Young AA, Cutter CL, Ivy JL, Abbott WGH, Zawadski JK, Yki-Jarvinen H, Christin L, Secomb TW, Bogardus C. Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man. J Clin Invest 1987; 80: 415–424.PubMedCrossRefGoogle Scholar
  35. 35.
    Julius S, Jamerson K. Sympathetics, insulin resistance and coronary risk in hypertension: the “chicken-and-egg” question. J Hypertension 1994; 12: 495–502.CrossRefGoogle Scholar
  36. 36.
    Lever AF. Slow pressor mechanisms in hypertension: a role for hypertrophy of resistance vessels? J Hypertension 1986; 7: 259–266.Google Scholar
  37. 37.
    Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man: a novel mechanism for insulin resistance. J Clin Invest 1990; 85: 1844–1852.PubMedCrossRefGoogle Scholar
  38. 38.
    Baron AD, Laakso M, Brechtel G, Edelman SV. Mechanism of insulin resistance in insulin-dependent diabetes mellitus: a major role for reduced skeletal muscle blood flow. J Clin Endocrinol Metab 1991; 73: 637–643.PubMedCrossRefGoogle Scholar
  39. 39.
    Laakso M, Edelman S, Brechtel G, Baron AD. Impaired insulin mediated skeletal muscle blood flow in patients with NIDDM. Diabetes 1992; 41: 1076–1083.PubMedCrossRefGoogle Scholar
  40. 40.
    Baron AD. Cardiovascular actions of insulin in humans. Implications for insulin sensitivity and vascular tone. In: Insulin Resistance and Disease. Baillière’s Clinical Endocrinology and Metabolism Ferrannini E, ed. vol 7, no. 4. London: Baillière Tindall, pp 961–988, 1993.Google Scholar
  41. 41.
    Utriainen T, Malmstrom R, Makimattila S, Yki-Jarvinen H. Methodological aspects, dose response characteristics and causes of interindividual variation in insulin stimulation of limb blood flow in normal subjects. Diabetologia 1995; 38: 555–564.PubMedCrossRefGoogle Scholar
  42. 42.
    Hulten UL, Endre T, Matiasson I, Berglund G. Insulin and forearm vasodilatation in hypertension-prone men. Hypertension 1955; 25: 214–218.CrossRefGoogle Scholar
  43. 43.
    Vollenweider L, Tappy L, Owlya R, Jequier E, Nicod P, Scherrer U. Insulin induced sympathetic activation and vasodilation in skeletal muscle. Effects of insulin resistance in lean subjects. Diabetes 1995; 44: 641–645.PubMedCrossRefGoogle Scholar
  44. 44.
    Sherrer U, Randin D, Volleinweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin’s vascular effects in humans. J Clin Invest 1994; 94: 2511–2515.CrossRefGoogle Scholar
  45. 45.
    Natali A, Bonadonna R, Santoro D, Quinones Galvan A, Baldi S, Frascerra S, Palombo C, Ghione S, Ferrannini E. Insulin resistance and vasodilation in essential hypertension: studies with adenosine. J Clin Invest 1994; 94: 1570–1576.PubMedCrossRefGoogle Scholar
  46. 46.
    Rowe JR, Young JB, Minaker KL, Stenes AL, Pallotta J, Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 1981; 30: 219–225.PubMedGoogle Scholar
  47. 47.
    Gans ROB, Toorn LVD, Bilo HJG, et al. Renal and cardiovascular effects of exogenous insulin in healthy volunteers. Clin Sci 1991; 80: 219–225.PubMedGoogle Scholar
  48. 48.
    Anderson EA, Hoffman RP, Balon TW, Sinkley CA, Mark AL. Hyperinsulinemia produces both sympathetic neuronal activation and vasodilation in normal humans. J Clin Invest 1991; 87: 2246–2252.PubMedCrossRefGoogle Scholar
  49. 49.
    Landsberg L. Insulin as a regulator of sympathetic nervous system activity. In: Hypertension as an Insulin-Resistant Disorder. Excerpta Medica International Congress Series 980, Amsterdam: Smith U, Bruun NE, Hedner T, Hökfelt B, ed. pp. 133–146, 1991.Google Scholar
  50. 50.
    Julius S, Krause L, Schork N, et al. Hyperkinetic borderline hypertension in Tecumseh, Michigan. J Hypertension 1991; 9: 77–84.Google Scholar
  51. 51.
    Julius S. The interconnection between sympathetics, microcirculation, and insulin resistance in hypertension. Blood Pressure 1992; 1: 9–19.PubMedCrossRefGoogle Scholar
  52. 52.
    Anderson EA, Christine AS, Lawton WJ, Mark AL. Elevated sympathetic nerve activity in borderline hypertensive humans. Hypertension 1989; 14: 177–183.PubMedCrossRefGoogle Scholar
  53. 53.
    Yamada Y, Miyajima E, Tochikubo O, Matsukawa T, Ishii M. Age-related changes in muscle sympathetic nerve activity in essential hypertension. Hypertension 1989; 13: 870–877.PubMedCrossRefGoogle Scholar
  54. 54.
    Matsukawa T, Mano T, Ishii M. Elevated sympathetic nerve activity in patients with accelerated essential hypertension. J Clin Invest 1993; 92: 25–28.PubMedCrossRefGoogle Scholar
  55. 55.
    Lembo G, Napoli R, Capaldo B, Redina V, Iaccarino G, Volpe M, Trimarco B, Saccà L. Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension. J Clin Invest 1992; 90: 24–29.PubMedCrossRefGoogle Scholar
  56. 56.
    Lembo G, Capaldo B, Rendina V, Iaccarino G, Napoli R, Guida R, Trimarco B, Sacca L. Acute noradrenergic activation induces insulin resistance in human skeletal muscle. A J Physiol 1994; 266: E242–247.Google Scholar
  57. 57.
    Wollenweider L, Randin D, Tappy L, Jequier E, Nicod P, Sherrer U. Impaired insulin induced sympathetic neural activation and vasodilation in skeletal muscle in obese individuals. J Clin Invest 1995; 93: 2365–2371.CrossRefGoogle Scholar
  58. 58.
    Anderson EA, Wallin BG, Mark AL. Dissociation of sympathetic nerve activity in arm and leg muscle during mental stress. Hypertension 1987; 9 (Suppl III): 111114–111119.Google Scholar
  59. 59.
    Deibert DC, DeFronzo RA. Epinephrine-induced insulin resistance in man. J Clin Invest 1980; 65: 717–721.PubMedCrossRefGoogle Scholar
  60. 60.
    Marango AG, Alford FP, Ward G, Liskaser F, Aitken PM, Weber KM, Boston RC, Best JD. Hormonal effects of norepinephrine on acute glucose disposam in humans: a minimal model analysis. Metabolism 1988; 37: 855–891.Google Scholar
  61. 61.
    Baron AD, Brechtel G, Jhonson A, Fineberg N, Henry DP, Steinberg HO. Interactions between insulin and norepinephrine on blood pressure and insulin sensitivity. J Clin Invest 1994; 93: 2453–2462.PubMedCrossRefGoogle Scholar
  62. 62.
    DeFronzo R, Thorin D, Felber JP, Simonson DC, Thiebaud D, Jequier E, Golay A. Effect of beta and adrenergic blockade on glucose induced thermogenesis in man. J Clin Invest 1984; 73: 633–639.PubMedCrossRefGoogle Scholar
  63. 63.
    Fliser D, Arnold U, Kohl B, Hartung R, Ritz E. Angiotensin II enhances insulin sensitivity in healthy volunteers under euglycemic condition. J Hypertension 1993; 11: 983–988.CrossRefGoogle Scholar
  64. 64.
    Ferrannini E, Taddei S, Santoro D, Natali A, Boni C, Del Chiaro D, Buzzigoli G. Independent stimulation of glucose metabolism and Na+-K+ exchange by insulin in the human forearm. Am J Physiol 1988; 255: E953 - E958.PubMedGoogle Scholar
  65. 65.
    Natali A, Buzzigoli G, Taddei S, Santoro D, Cerri M, Pedrinelli R, Ferrannini E. Effects of insulin on hemodynamics and metabolism in human forearm. Diabetes 1990; 39: 490–500.PubMedCrossRefGoogle Scholar
  66. 66.
    Lembo G, Rendina V, Jaccarino G, Lamenza F, Volpe M, Trimarco B. Insulin reduces reflex forearm sympathetic vasoconstriction in healthy humans. Hypertension 1993; 21: 1015–1019.PubMedCrossRefGoogle Scholar
  67. 67.
    Sakai K, Imaizumi T, Masaki H, Takeschita A. Infra-arterial infusion of insulin attenuates vasoreactivity in human forearm. Hypertension 1993; 22: 67–73.PubMedCrossRefGoogle Scholar
  68. 68.
    Alexander WD, Oake RJ. The effect of insulin on vascular reactivity to norepinephrine. Diabetes 1977; 26: 611–614.PubMedCrossRefGoogle Scholar
  69. 69.
    Yagi S, Takata S, Kiyokawa H, Yamamoto M, Noto Y, Ikeda T, Hattori N. Effects of insulin on vasoconstrictive responses to norepinephrine and angiotensin II in rabbit femoral artery and vein. Diabetes 1988; 37: 1064–1067.PubMedCrossRefGoogle Scholar
  70. 70.
    Zemel MB, Reddy S, Sowers JR. Insulin attenuation of vasoconstrictor responses to phenylephrine in Zucker lean and obese rats. Am J Hypertension 1991; 4: 537–539.Google Scholar
  71. 71.
    Stainberg HO, Brechtel G, Jhonson A, Fineberg N, Baron AD. Insulin mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest 1994; 94: 1172–1179.CrossRefGoogle Scholar
  72. 72.
    Taddei S, Virdis A, Mattei P, Natali A, Ferrannini E, Salvetti A. Effect of insulin on acetylcholine induced vasodilation in normotensive subjects and patients with essential hypertension. Circulation, 1995; 92: 2911–2918.PubMedCrossRefGoogle Scholar
  73. 73.
    Utriainen T, Malmstrom R, Makimattila S, Yki-Jarvinen H. Methodological aspects, dose response characteristics and causes of interindividual variation in insulin stimulation of limb blood flow in normal subjects. Diabetologia 1995; 38: 555–564.PubMedCrossRefGoogle Scholar
  74. 74.
    Vollenweider P, Tappy L, Randin D, Schneiter P, Jéquier E, Nicod P, Scherrer U. Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans. J Clin Invest 1993; 92: 147–154.PubMedCrossRefGoogle Scholar
  75. 75.
    Wollenweider L, Tappy L, Owlya R, Jequier E, Nicod P, Sherrer U. Insulin induced sympathetic activation and vasodilation in skeletal muscle. Diabetes 1995; 44: 641–645.CrossRefGoogle Scholar
  76. 76.
    DeFronzo RA, Cooke CR, Andres R, Faloona GR, Davis PJ. The effect of insulin on renal sodium, potassium, calcium, and phosphate in man. J Clin Invest 1975; 55: 845–855.PubMedCrossRefGoogle Scholar
  77. 77.
    Skott P, Hother-Nielsen O, Bruun NE, et al. Effects of insulin on kidney function and sodium excretion, in healthy subjects. Diabetologia 1989; 32: 694–699.PubMedCrossRefGoogle Scholar
  78. 78.
    Rowe JR, Young JB, Minaker KL, Stevens AL, Pallotta J, Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 1981; 30: 219–225.PubMedGoogle Scholar
  79. 79.
    Anderson EA, Hoffman RP, Balon TW, Sinkley CA, Mark AL. Hyperinsulinemia produces both sympathetic neuronal activation and vasodilation in normal humans. J Clin Invest 1991; 87: 2246–2252.PubMedCrossRefGoogle Scholar
  80. 80.
    Scherrer U, Randin D, Vollenweider P, Vollenweider L, Nicod P. Nitric oxide release accounts for insulin vascular effects in humans. J Clin Invest 1994; 94: 2511–2515.PubMedCrossRefGoogle Scholar
  81. 81.
    Muscelli E, Natali A, Bianchi S, Bigazzi R, Quinones AG, Sironi A, Frascerra S, Ciociaro D, Ferrannini E. Effect of insulin on renal sodium and uric acid handling in patients with essential hypertension. Am J Hypertens 1996; 9: 746–752.PubMedCrossRefGoogle Scholar
  82. 82.
    Natali A, Galvan QA, Santoro D, Taddei S, Salvetti A, Ferrannini E. Relationship between insulin release, antinatriuresis, and hypokalemia following glucose ingestion in normal and hypertensive man. Clin Sci 1993; 85: 327–335.PubMedGoogle Scholar
  83. 83.
    Weidmann P, Ferrari P. Central role of sodium in hypertension in diabetic subjects. Diabetes Care 1991; 14 (3): 220–232.PubMedCrossRefGoogle Scholar
  84. 84.
    DeFronzo RA, Felig P, Ferrannini E, Wahren J. Effect of graded doses of insulin on splanchnic and peripheral potassium metabolism in man. Am J Physiol 1980; 238: E421 - E427.PubMedGoogle Scholar
  85. 85.
    Andres R, Baltzan M, Cader G, Zierler K. Effects of insulin on carbohydrate metabolism and on potassium in the forearm of man. J Clin Invest 1962; 41: 108–115.PubMedCrossRefGoogle Scholar
  86. 86.
    Zierler K. Effect of insulin on membrane potential and potassium content of rat muscle. Am J Physio11959; 197: 515–523.Google Scholar
  87. 87.
    Trovati M, Massucco P, Anfossi G, Cavalot F, Mularoni E, Mattiello L, Rocca G, Emanuelli G. Insulin influences the renin-angiotensin-aldosterone system in humans. Metabolism 1989; 38: 501–503.PubMedCrossRefGoogle Scholar
  88. 88.
    Rocchini AP, Moorehead C, DeRemer S, Goodfriend TL, Ball DL. Hyperinsulinemia and the aldosterone and pressor responses to angiotensin II. Hypertension 1990; 15: 861–866.PubMedCrossRefGoogle Scholar
  89. 89.
    Zavaroni I, Bonora E, Pagliara M, Dall’aglio E, Luchetti L, Buonanno G, Bonati PA, Bergonzani M, Gnudi L, Passeri M, Reaven GM. Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. New Engl J Med 1989; 320: 702–706.PubMedCrossRefGoogle Scholar
  90. 90.
    Tobey TA, Greenfield M, Kraemer F, Reaven GM. Relationship between insulin resistance, insulin secretion, very-low density lipoprotein kinetics and plasma trigliceride levels in normotrygliceridemic man. Metabolism 1981; 30: 165–171.PubMedCrossRefGoogle Scholar
  91. 91.
    Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest 1995; 95: 158–166.PubMedCrossRefGoogle Scholar
  92. 92.
    Pollare T, Vessby B, Lithell H. Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. Atherosclerosis 1991; 11: 1192–1203.Google Scholar
  93. 93.
    Ide Chen Y-D, Sheu WH-H, Swislocki ALM, Reaven GM. High density lipoprotein turnover in patients with hypertension. Hypertension 1991; 17: 386–393.PubMedCrossRefGoogle Scholar
  94. 94.
    Reaven GM, Chen IY-D, Jeppesen J, Maheux P, Krauss RM. Insulin resistance and hyperinsulinemia in individuals with small, dense, low density lipoprotein particles. J Clin Invest 1993; 92: 141–146.PubMedCrossRefGoogle Scholar
  95. 95.
    Juhan-Vague I, Alessi MC, Vague P. Increased plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia 1991; 34: 457–462.PubMedCrossRefGoogle Scholar
  96. 96.
    Ducimetiere P, Eschwege E, Papox L, Richard JL, Claude JR, Rosselin G. Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 1980; 19: 205–210.PubMedCrossRefGoogle Scholar
  97. 97.
    Pyöräla K. Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease: results from two population studies in Finland. Diabetes Care 1979; 2: 131–141.PubMedCrossRefGoogle Scholar
  98. 98.
    Welborn TA, Wearne K. Coronary disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care 1979; 2: 154–160.PubMedCrossRefGoogle Scholar
  99. 99.
    Kuusisto J, Mykkanen L, Pyorala K, Laakso M. Hyperinsulinemic microalbuminuria: a new risk indicator for coronary artery disease. Circulation 1995; 91: 831–837.PubMedCrossRefGoogle Scholar
  100. 100.
    Modan M, Almog S, Fuchs Z, Chetrit A, Lusky A, Halkin H. Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs. Hypertension 1991; 17: 565–573.PubMedCrossRefGoogle Scholar
  101. 101.
    Isaksson H, Cederholm T, Jansson E, Nygren A, Östergren J. Therapy-resistant hypertension associated with central obesity, insulin resistance, and large muscle fibre area. Blood Pressure 1993; 2: 46–52.PubMedCrossRefGoogle Scholar
  102. 102.
    Krotkiewsky M, Mandroukas K, Sjöstrom L, Sullivan L, Weterqvist P, Björntorp P. Effect of long-term physical training on body fat, metabolism, and blood pressure in obesity. Metabolism 1979; 28: 650–658.CrossRefGoogle Scholar
  103. 103.
    Stein PP, Black HR. Drug treatment of hypertension in patients with diabetes mellitus. Diabetes Care 1991; 14: 425–448.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Andrea Natali
  • Stefano Taddei
  • Ele Ferrannini

There are no affiliations available

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