Diabetes Mellitus and Vascular Disease Risk

  • Ira J. Goldberg
  • Clay F. Semenkovich
  • Henry N. Ginsberg


Diabetes mellitus is a complex, multifactorial disorder that has an overall prevalence of about 5% in the United States. Whereas approximately 90% of diabetics have type II,or non-insulin-dependent diabetes mellitus (NIDDM), the remainder have type I, or insulin-dependent diabetes mellitus (IDDM). The prevalence of diabetes varies greatly among different ethnic groups, with rates as high as 20% in some Asian-Indian and American-Indian populations. These wide variations in prevalence are accounted for mainly by NIDDM. Although the cause or causes of NIDDM are not known, the environment is clearly very important. The molecular basis for IDDM is better defined, but the primary cause remains unclear. Despite the etiologic and pathogenic differences between NIDDM and IDDM, the chronic sequelae of both forms of diabetes are the same, and vascular disease, particularly coronary heart disease (CHD), is the major cause of morbidity and mortality in diabetic patients.


Coronary Heart Disease Vascular Calcification Multiple Risk Factor Intervention Trial Amadori Product Bezafibrate Infarction Prevention 
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  1. 1.
    American Diabetes Association: Managing Diabetes in the 1990s. Alexandria, VA: American Diabetes Association; 1989.Google Scholar
  2. 2.
    Krolewski AS, Kosinski EJ, Warram JH, et al.: Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus. Am J Cardiol 1987, 59: 750–755.PubMedCrossRefGoogle Scholar
  3. 3.
    Krolewski AS, Warram JH, Valsania P, et al.:Evolving natural history of coronary artery disease in diabetes mellitus. Am J Med 1991, 90(suppl 2A):565–615.CrossRefGoogle Scholar
  4. 4.
    Wilson PWF, Kannel WB: Epidemiology of hyperglycemia and atherosclerosis. In Hyperglycemia, Diabetes, and Vascular Disease. Edited by Ruderuran N, Williamson J, Brownlee M. New York: Oxford; 1992: 21–29.Google Scholar
  5. 5.
    Stolar MW: Atherosclerosis in diabetes: the role of hyperinsulinemia. Metabolism 1988, 38 (suppl 1): 1–9.CrossRefGoogle Scholar
  6. 6.
    Assmann G, Schulte H: The Prospective Cardiovascular Munster (PROCAM) Study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease. Am Heart J 1988, 116: 1713–1724.PubMedCrossRefGoogle Scholar
  7. 7.
    Stamler J, Wentworth D, Neaton J, et al.: Diabetes and risk of coronary, cardiovascular, and all causes mortality: findings for 356,000 men screened by the Multiple Risk Factor Intervention Trial (MRFIT). Circulation 1984, 70 (suppl 2): 161.Google Scholar
  8. 8.
    American Diabetes Association: Consensus statement. Diabetes Care 1989, 12: 573–579.Google Scholar
  9. 9.
    Ledet T, Heickendorff L, Rasmussen LM: Cellular mechanisms of diabetic large vessel disease. In International Textbook of Diabetes Mellitus. Edited by Alverti KGMM, DeFronzo RA, Keen H, Zimmet P. City: John Wiley & Sons Ltd; 1992: 1435–1446.Google Scholar
  10. 10.
    Detrano RC, Wong ND, French WJ, et al.: Prevalence of fluoroscopic coronary calcific deposits in high-risk asymptomatic persons. Am Heart J 1994, 127: 1526–1532.PubMedCrossRefGoogle Scholar
  11. 11.
    Lehto S, Niskanen L, Suhonen M et al.: Medical artery calcification: a neglected harbinger of cardiovascular complications in non-insulindependent diabetes mellitus. Arterioscl Thromb Vasc Bio11996, 16: 978–983.Google Scholar
  12. 12.
    Yokoyama I, Momomura S-I, Ohtake T, et al.: Reduced myocardial flow reserve in non-insulin dependent diabetes mellitus. J Am Coll Cardiol 1997, 30: 1472–1477.PubMedCrossRefGoogle Scholar
  13. 13.
    Abbott RD, Donahue PR, Kannel WB, et al.: The impact of diabetes survival following myocardial infarction in men vs women: the Framingham Study. JAMA 1988, 260: 3456–3460.PubMedCrossRefGoogle Scholar
  14. 14.
    Sprafka JM, Burke GL, McGovern PG, Halm LP: Trends in prevalence of diabetes mellitus in patients with myocardial infarction and effect of diabetes on survival. Diabet Care 1991, 537–543.Google Scholar
  15. 15.
    Woodfield SL, Lundergan CF, Reiner JS, et al.: Angiographic findings and outcomes in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-I experience. J Am Coll Cardiol 1996, 28: 1661–1669.PubMedCrossRefGoogle Scholar
  16. 16.
    Haffner SM, Lehto S, Ronnemaa T, et al.: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. New Engl J Med 1998, 339: 229–234.PubMedCrossRefGoogle Scholar
  17. 17.
    BARI Investigators: Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med 1996, 335: 217–225.CrossRefGoogle Scholar
  18. 18.
    Nordestgaard BG, et al.: Effect of exogenous hyperinsulinemia on atherogenesis in cholesterol-fed rabbits. Diabetologia 1997, 40: 512–520.PubMedCrossRefGoogle Scholar
  19. 19.
    Bierman EL: Arterioscler Throm 1992, 12: 647–656.CrossRefGoogle Scholar
  20. 19a.
    Duff G, Mar Millan G: The effect of all oxan diabetes on experimental atherosclerosis in the rabbit. JEXP Med 1949, 89: 611–612.CrossRefGoogle Scholar
  21. 20.
    Kunjathoor VV, Wilson DL, LeBoeuf RC: Increased atherosclerosis in streptozotocin-induced diabetic mice. J Clin Invest 1996, 97: 1767–1773.PubMedCrossRefGoogle Scholar
  22. 21.
    Matsumoto T, Ohashi Y, Yamada N, Kikuchi M: Coronary heart disease mortality is actually low in diabetic Japanese by direct comparison with the Joslin cohort. Diabetes Care 1994, 17: 1062–1063.PubMedCrossRefGoogle Scholar
  23. 22.
    Taskinen M-R, Beltz WF, Harper I, et al.: Effects of NIDDM on very-low-density lipoprotein triglyceride and apolipoprotein B metabolism: studies before and after sulfonylurea therapy. Diabetes 1986, 35: 1268–1277.PubMedCrossRefGoogle Scholar
  24. 23.
    Garg A, Grundy SM: Management of dyslipidemia in NIDDM. Diabetes Care 1990, 13: 153–164.PubMedCrossRefGoogle Scholar
  25. 24.
    DeFronzo RA, Goodman AM: Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus: the Multicenter Metformin Study Group. N Engl J Med 1995, 333: 541–549.PubMedCrossRefGoogle Scholar
  26. 25.
    Ghazzi MN, Perez JE, Antonucci TK, et al.: Cardiac and glycemic benefits of troglitazone treatment in NIDDM: the Troglitazone Study Group. Diabetes 1997, 46: 433–439.PubMedCrossRefGoogle Scholar
  27. 26.
    Dunn FL, Pietri A, Raskin P, et al.: Plasma lipid and lipoprotein levels with continuous subcutaneous insulin infusion in type I diabetes mellitus. Ann Intern Med 1981, 95: 426–431.PubMedCrossRefGoogle Scholar
  28. 27.
    Manson JE, Colditz GA, Stampfer MJ, et al.: A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med 1991, 151: 1141–1147.PubMedCrossRefGoogle Scholar
  29. 28.
    Pyórälä K, Pedersen JR, Kjekshus J, et al.: Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. Diabet Care 1997, 20: 614–620.CrossRefGoogle Scholar
  30. 29.
    Goldberg R, et al [abstract].: Circulation 1996, 94:1–540.CrossRefGoogle Scholar
  31. 30.
    Koskinen P, Mannttari M, Manninen V, et al.: Coronary heart disease incidence in NIDDM patients in the Helsinki Heart Study. Diabet Care 1992, 15: 820–825.CrossRefGoogle Scholar
  32. 31.
    Yan SD, Schmidt, Anderson GM, et al.: Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem 1994, 269: 9889–9897.PubMedGoogle Scholar
  33. 32.
    Semenkovich CF, Heinecke JW: The mystery of diabetes and atherosclerosis: time for a new plot. Diabetes 1997, 46: 327–334.PubMedCrossRefGoogle Scholar
  34. 33.
    Meinert CL, Knatterud GL, Prout TE, Klimt CR: A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. Diabetes 1970, 19 (suppl 2): 789–830.PubMedGoogle Scholar
  35. 34.
    Knatterud GL, Klimt CR, Levin, et al.: Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VII. Mortality and selected nonfatal events with insulin treatment. JAMA 1978, 240: 37–42.PubMedCrossRefGoogle Scholar
  36. 35.
    Turner R: Intensive blood-glucose control with sulfonylureas or insuline compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998, 352: 837–853.CrossRefGoogle Scholar
  37. 36.
    DCCT Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993, 329: 977–986.CrossRefGoogle Scholar
  38. 37.
    Malmberg K, Ryden L, Efendic S, et al.: Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol 1995, 26: 57–65.PubMedCrossRefGoogle Scholar
  39. 38.
    Pyórälä K Savolainen E, Kaukola S, Haapakoski J: Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive during 91/2 year follow-up of the Helsinki Policeman Study population. Acta Med Scan 1985, 701 (suppl): 38–52.Google Scholar
  40. 39.
    Welborn TA, Wearne K: Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentration. Diabet Care 1979, 2: 154–160.CrossRefGoogle Scholar
  41. 40.
    Eschwege E, Richard JL, Thibult N, et al.: Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels: the Paris Prospective Study 10 years later. Hormone Metab Res 1985, 15 (suppl): 41–46.Google Scholar
  42. 41.
    Welin L, Eriksson H, Larsson B, et al.: Hyperinsulinemia is not a major coronary risk factor in elderly men: the study of men born in 1913. Diabetologia 1992, 35: 766–770.PubMedGoogle Scholar
  43. 42.
    Orchard TJ, Eichner J, Kuller LH, et al.: Insulin as a predictor of coronary heart disease: interaction with Apolipoprotein E phenotype: a report from the Multiple Risk Factor Intervention Trial. Ann Epidemio11994, 4: 40–45.Google Scholar
  44. 43.
    Ferrara A, Barrett-Connor EL, Edelstein SL: Hyperinsulinemia does not increase the risk of fatal cardiovascular disease in elderly men or women without diabetes: the Rancho Bernardo Study, 1984–1991. Am J Epidemiol 1994, 140: 857–869.PubMedGoogle Scholar
  45. 44.
    DesprésJP, Lamarche B, Mauriege P, et al.: Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996, 334: 952–957.CrossRefGoogle Scholar
  46. 45.
    Haffner SM, Miettinen H: Insulin resistance implications for type II diabetes mellitus and coronary heart disease. Am J Med 1997, 103: 152–162.PubMedCrossRefGoogle Scholar
  47. 46.
    Schneider DJ, et al.: Coronary Artery Dis 1992, 3: 26–32.CrossRefGoogle Scholar
  48. 47.
    Antiplatelet Trialists’ Collaboration: Collaborative overview of randomized trials of antiplatelet therapy. I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Br Med J 1994, 308: 81–106.CrossRefGoogle Scholar
  49. 48.
    McVeigh GE, Brennan GM, Johnston BJ, et al.: Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1992, 35: 771–776.PubMedGoogle Scholar
  50. 49.
    Cunningham JJ, Ellis SL, McVeigh GE, et al.: Reduced mononuclear leukocyte ascorbic acid content in adults with insulin-dependent diabetes mellitus consuming adequate dietary vitamin C. Metabolism 1991, 40: 146–149.PubMedCrossRefGoogle Scholar
  51. 50.
    Ting HH, Timimi FK, Boles KS, et al.: Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1996, 97: 22–28.PubMedCrossRefGoogle Scholar
  52. 51.
    Zuanetti G, Latini R, Maggioni AP, et al.: Effect of the ACE inhibitor lisinopril on mortality in diabetic patients with acute myocardial infarction: data from the GISSI-3 study. Circulation 1997, 96: 4239–4245.PubMedCrossRefGoogle Scholar
  53. 52.
    Estacio RO, Jeffers BW, Hiatt WR, et al.: The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med 1998, 338: 645–652.PubMedCrossRefGoogle Scholar
  54. 53.
    Hansson L, Zanchett A, Carruthers SG, et al.: Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet 1998, 351: 1755–1762.PubMedCrossRefGoogle Scholar
  55. 54.
    Jonas M, Reicher-Reiss H, Boyko V, et al.: Usefulness of beta-blocker therapy in patients with non-insulin-dependent diabetes mellitus and coronary artery disease: Bezafibrate Infarction Prevention (BIP) Study Group. Am J Cardiol 1996, 77: 1273–1277.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Ira J. Goldberg
  • Clay F. Semenkovich
  • Henry N. Ginsberg

There are no affiliations available

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