Drugs & Aging

, Volume 17, Issue 6, pp 463–476 | Cite as

Beneficial and Detrimental Effects of Intensive Glycaemic Control, with Emphasis on Type 2 Diabetes Mellitus

Review Article

Abstract

Diabetes mellitus is a major health problem in the world. Several clinical trials have shown that some of the major complications of diabetes mellitus can be partially prevented or delayed by intensive glycaemic control. However, there are benefits and risks in aiming for near normal blood glucose levels.

Intensive glycaemic control delays the onset and progression of retinopathy, nephropathy and neuropathy. Epidemiological and observational studies have shown that cardiovascular events may be correlated with the severity and duration of diabetes mellitus, but major randomised trials have only shown weak and nonsignificant benefits of intensive glycaemic management in decreasing event rates. A modest improvement in lipid profile results from blood glucose control although, in the majority of cases, not enough to reach current targets.

Detrimental effects of intensive glycaemic control include bodyweight gain and hypoglycaemia. Controversial issues in the management of patients with diabetes mellitus include the unproven increase in cardiovascular morbidity from sulphonylureas and hyperinsulinaemia, and the still unknown long term effects of newer oral antihyperglycaemic agents alone or in combination with traditional therapies (such as sulphonylureas and metformin).

It is important to individualise management in setting glycaemic goals. Control of cardiovascular risk factors through blood pressure and lipid control and treatment with aspirin (acetylsalicylic acid) and ACE inhibitors have consistently shown benefits in the prevention of both macro- and micro vascular complications in patients with diabetes mellitus; these measures deserve priority.

References

  1. 1.
    King H, Aubert R, Herman W. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 1998; 21(9): 1414–31PubMedCrossRefGoogle Scholar
  2. 2.
    Geiss LS, Herman WH, Smith PJ. Mortality in non-insulin-dependent diabetes. In: Harris M. editor. Diabetes in America, 2nd ed. Bethesda (MD): National Institutes of Health, 1995. Publication no. 95-1468: 133–55Google Scholar
  3. 3.
    Kannel WB, McGee DL. Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham Study. Diabetes Care 1979; 2: 120–6PubMedCrossRefGoogle Scholar
  4. 4.
    Wilson P, Cupples LA, Kannel W. Is hyperglycemia associated with cardiovascular disease? The Framingham Study. Am Heart J 1991; 121: 586–90PubMedCrossRefGoogle Scholar
  5. 5.
    Krowelski AS, Czyzyk A, Janeczko D, et al. Mortality from cardiovascular disease among diabetics. Diabetologia 1977; 13: 345–50CrossRefGoogle Scholar
  6. 6.
    Kessler J. Mortality experience of diabetic patients: a twenty-six year follow-up study. Am J Med 1971; 51: 715–34PubMedCrossRefGoogle Scholar
  7. 7.
    Ford ES, DeStefano F. Risk factors for mortality from all causes and from coronary heart disease among persons with diabetes. Am J Epidemiol 1991; 133: 1220–30PubMedGoogle Scholar
  8. 8.
    Sasaki A, Uehara M, Horiuchi N, et al. A long term follow-up study of Japanese diabetic patients: mortality and causes of death. Diabetologia 1983; 25: 309–12PubMedCrossRefGoogle Scholar
  9. 9.
    Manson JA, 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: 1141–7PubMedCrossRefGoogle Scholar
  10. 10.
    Rubin RJ, Alrman WM, Mendelson DM. Health care expenditures for people with diabetes mellitus, 1992. J Clin Endocrinol Metab 1994; 78: 809A–809FPubMedCrossRefGoogle Scholar
  11. 11.
    Diabetes Control and Complications Trial 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: 977–86CrossRefGoogle Scholar
  12. 12.
    DCCT Research Group. Reliability and validity of a diabetes quality-of-life measure for the Diabetes Control and Complications Trial (DCCT). Diabetes Care 1988: 11: 725–32CrossRefGoogle Scholar
  13. 13.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837–53CrossRefGoogle Scholar
  14. 14.
    University Group Diabetes Program II: Mortality results. Diabetes 1970; 19 Suppl. 2: 789–830Google Scholar
  15. 15.
    Abraira C, Colwell J, Nuttal F, et al. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VACSDM) Group. Cardiovascular events and correlates in the Veterans Affairs diabetes feasibility trial. Arch Intern Med 1997; 157: 181–8PubMedCrossRefGoogle Scholar
  16. 16.
    American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care 2000; 23 Suppl. 1Google Scholar
  17. 17.
    Hayward RA, Manning WG, Kaplan SH, et al. Starting insulin therapy in patients with type 2 diabetes: effectiveness, complications, and resource utilization JAMA 1997; 278: 1663–9PubMedCrossRefGoogle Scholar
  18. 18.
    Peters AL, McCulloch DK, Hayward RA, et al. Case one: too little too late–delayed diagnosis of NIDDM. J Clin Outcomes 1994; 1: 9–26Google Scholar
  19. 19.
    Pogach L, Weinstock R, Hawley G, et al. Diabetes cost and outcome report. Reports from the national Center for Cost Containment. Veterans Affairs Forum 1999 Nov: Washington, DC. Available from: URL: http://www.ahsr.org/publications/forum/forumnov99.htm [Accessed 2000 Dec 1]Google Scholar
  20. 20.
    Zinman B. Insulin regimens and strategies for IDDM. Diabetes Care 1993; 16 Suppl. 3: 24–8PubMedGoogle Scholar
  21. 21.
    DeFronzo R. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 1999: 131: 281–303PubMedGoogle Scholar
  22. 22.
    American Diabetes Association. Medical management of non-insulin-dependent (type 2) diabetes mellitus. 3rd ed. American Diabetes Association: Alexandria (VA, 1994–1995Google Scholar
  23. 23.
    Holleman F, Hoekstra JBL. Insulin lispro. N Engl J Med 1997; 337: 176–83PubMedCrossRefGoogle Scholar
  24. 24.
    Talaulicar M, Willms B, Rosskamp R. HOE 901, a new insulin analogue for substitution of basal insulin requirement in type 1 diabetes. Diabe Stoffw 1996: 5: 3–6Google Scholar
  25. 25.
    Dreyer M, Pein M, Schmidt Ch, et al. Comparison of the phar-macokinetics/dynamics of Gly (A21)-Arg (B31, B32)-hu-man-insulin (HOE71GT) with NPH-insulin following subcutaneous injection by using euglycemic clamp technique [abstract]. Diabetologia 1994; 37 Suppl. 1: A78Google Scholar
  26. 26.
    Heinemann L, Traut T, Heise T. Time-action profile of inhaled insulin. Diabet Med 1997: 14(1): 63–72PubMedCrossRefGoogle Scholar
  27. 27.
    Owens DR. Repaglinide: a new short-acting insulinotropic agent for the treatment of type 2 diabetes. Eur J Clin Invest 1999; 29 Suppl. 2: 30–7PubMedCrossRefGoogle Scholar
  28. 28.
    Grant PJ. The effects of metformin on the fibrinolytic system in diabetic and non-diabetic subjects. Diabetes Metab 1991; 17: 168–73Google Scholar
  29. 29.
    Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. Diabetes Care 1993; 16: 621–9PubMedCrossRefGoogle Scholar
  30. 30.
    Henry RR. Thiazolidinediones. Endocrinol Metab Clin North Am 1997; 26: 5553–74CrossRefGoogle Scholar
  31. 31.
    Lebovitz HE. Alpha-glucosidase inhibitors. Endocrinol Metab Clin North Am 1997; 26: 539–52PubMedCrossRefGoogle Scholar
  32. 32.
    Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995 May; 28(2): 103–17PubMedCrossRefGoogle Scholar
  33. 33.
    Levin S, Coburn JW, Abraira C, et al. The effect of intensive glycemic control on microalbuminuria in type 2 diabetes mellitus. Diabetes Care 2000; 23: 1478–85PubMedCrossRefGoogle Scholar
  34. 34.
    Vijan S, Hofer TP, Hayward RA. Estimated benefits of glycemic control in microvascular complications in type 2 diabetes. Ann Intern Med 1997; 127: 788–95PubMedGoogle Scholar
  35. 35.
    Dortimer A, Shenoy P, Shiroff R, et al. Diffuse coronary artery disease in diabetic patients. Circulation 1978; 55: 133–6CrossRefGoogle Scholar
  36. 36.
    Mueller HS, Cohen LS, Braunwald E, TIMI Investigators, et al.. Predictors of early mortality and morbidity after thrombolytic therapy of acute myocardial infarction: analyses of patient subgroups in the Thrombolysis in Myocardial Infarction (TIMI) trial, phase II. Circulation 1992; 85: 1254–64PubMedCrossRefGoogle Scholar
  37. 37.
    Stein B, Weintraub WS, Gebhart SP, et al. Influence of diabetes mellitus on early and late outcome after percutaneous trans-luminal coronary angiplasty. Circulation 1995; 91: 979–89PubMedCrossRefGoogle Scholar
  38. 38.
    Vigorito C, Betocchi S, Bonzani G, et al. Severity of coronary artery disease in diabetic patients mellitus: angiographic study of 34 diabetic and 120 non-diabetic patients. Am Heart J 1980; 100: 782–7PubMedCrossRefGoogle Scholar
  39. 39.
    Johnstone MT, Creager SJ, Scales KM, et al. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 1993; 88: 2510–6PubMedCrossRefGoogle Scholar
  40. 40.
    Cohen RA. Dysfunction of vascular endothelium in diabetes mellitus. Circulation 1993; 87 Suppl. 5: 67–76Google Scholar
  41. 41.
    Tesfamariam B. Free radicals in diabetic endothelial cell dysfunction. Free Radic Biol Med 1994; 16: 383–91PubMedCrossRefGoogle Scholar
  42. 42.
    Walmsley D, Hamptom K, Grant P. Contrasting fibrinolytic response in type 1 insulin-dependent) and type 2 (non-insulin-dependent) diabetes. Diabet Med 1991; 8: 954–9PubMedCrossRefGoogle Scholar
  43. 43.
    Gough SC, Grant PJ. The fibrinolytic system in diabetes mellitus. Diabet Med 1991; 8: 898–905PubMedCrossRefGoogle Scholar
  44. 44.
    Breddin H, Krzywanek H, Althoff P, et al. Platelet aggregation as a risk factor in diabetes: results of a prospective study. Horm Metab Res 1985; 15 Suppl.: 63–8Google Scholar
  45. 45.
    Osterman H, van der Loo J. Factors of the hemostatic system in the diabetic patient. Hemostasis 1986; 16: 386–416Google Scholar
  46. 46.
    Rosove MH, Frank HJ, Harwig SS. Plasma B-thromboglobulin, platelet factor 4, fibrinopeptide A and other hemostatic functions during improved short-term glycemic control in diabetes mellitus. Diabetes Care 1984; 7: 174–9PubMedCrossRefGoogle Scholar
  47. 47.
    Ganda O, Arkin C. Hyperfibrinogenemia: an important risk factor for vascular complications in diabetes. Diabetes Care 1992; 15: 1245–50PubMedCrossRefGoogle Scholar
  48. 48.
    Donohue RP, Orchard TJ. Diabetes mellitus and vascular complications: an epidemiological perspective. Diabetes Care 1992; 15: 1141–55CrossRefGoogle Scholar
  49. 49.
    Pyorala 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: 131–41PubMedCrossRefGoogle Scholar
  50. 50.
    Kuusisto J, Mykkanen L, Pyorala K, et al. NIDDM and its metabolic control predict coronary heart disease in elderly subjects. Diabetes 1994; 43: 960–7PubMedCrossRefGoogle Scholar
  51. 51.
    Lomuscio A, Castagnone M, Vergani D, et al. Clinical correlation between diabetic and non diabetic patients with myocardial infarction. Acta Cardiologica 1991; 46: 543–54PubMedGoogle Scholar
  52. 52.
    Karlson BW, Herlitz J, Hjalmarson A. Prognosis of acute myo-cardial infarction in diabetic and non-diabetic patients. Diabet Med 1993; 10: 449–54PubMedCrossRefGoogle Scholar
  53. 53.
    Granger CB, Califf RM, Young S, et al. Outcome of patients with diabetes mellitus and acute myocardial infarction treated with thrombolytic agents: the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. J Am Coll Cardiol 1993; 21: 920–5PubMedCrossRefGoogle Scholar
  54. 54.
    Barbash GI, White HD, Modan M, et al. Significance of diabetes mellitus in patients with acute myocardial infarction receiving thrombolysis therapy. J Am Coll Cardiol 1993: 22: 707–13PubMedCrossRefGoogle Scholar
  55. 55.
    Malmberg K, Ryden L. Myocardial infarction in patients with diabetes mellitus. Eur Heart J 1988; 9: 259–64PubMedGoogle Scholar
  56. 56.
    Soler NG, Pentecost BL, Bennett MA, et al. Coronary care for myocardial infarction in diabetics. Lancet 1974; II: 475–7CrossRefGoogle Scholar
  57. 57.
    Gwilt D, Petri M, Lamb P, et al. Effect of intravenous insulin infusion on mortality among diabetic patients after myocardial infarction. Br Heart J 1984; 51: 626–31PubMedCrossRefGoogle Scholar
  58. 58.
    Jaffe AS, Spadaro JJ, Schechtman K, et al. Increased congestive heart failure after myocardial infarction of modest extent in patients with diabetic mellitus. Am Heart J 1984; 108: 31–7PubMedCrossRefGoogle Scholar
  59. 59.
    Stone PH, Muller JE, Hartwell T, et al. The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and left ventricular dysfunction to the adverse prognosis: the MILIS Study Group. J Am Coll Cardiol 1989; 14: 49–57PubMedCrossRefGoogle Scholar
  60. 60.
    Savage MP, Krolewki AS, Kenien GG, et al. Acute myocardial infarction in diabetes mellitus and significance of congestive heart failure as a prognostic factor. Am J Cardiol 1988; 62: 665–9PubMedCrossRefGoogle Scholar
  61. 61.
    Czyzk A, Krolewski AS, Szablowska S, et al. Clinical course of myocardial infarction among diabetic patients. Diabetes Care 1980; 3: 526–9PubMedCrossRefGoogle Scholar
  62. 62.
    Tansey MJ, Opie LH, Kennelly BM. High mortality in obese women diabetics with acute myocardial infarction. BMJ 1977; 1: 1624–6PubMedCrossRefGoogle Scholar
  63. 63.
    Kouvaras G, Cokkinos D, Spyropoulou M. Increased mortality of diabetics after acute myocardial infarction attributed to diffusely impaired left ventricular performance as assessed by endocardiography. Jpn Heart J 1988; 29: 1–9PubMedCrossRefGoogle Scholar
  64. 64.
    Yudkin JS, Oswald GA. Determinants of hospital admission and case fatality in diabetic patients with myocardial infarction. Diabetes Care 1988; 11: 351–8PubMedCrossRefGoogle Scholar
  65. 65.
    Mak K-H, Moliterno DJ, Granger CB, et al. Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. J Am Coll Cardiol 1997; 30: 171–9PubMedCrossRefGoogle Scholar
  66. 66.
    Fava S, Azzopardi J, Agius-Muscat H. Outcome of unstable angina in patients with diabetes mellitus. Diabet Med 1997; 14: 209–13PubMedCrossRefGoogle Scholar
  67. 67.
    Lawson M, Gerstein H, Tsui E, et al. Effect of intensive therapy on early macrovascular disease in young individuals with type 1 diabetes: a systematic review and meta-analysis. Diabetes Care 1999: 22 Suppl. 2: B35–42PubMedGoogle Scholar
  68. 68.
    Malmberg K, Ryden L, Efendic S. A randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction: effects on mortality. J Am Coll Cardiol 1995; 26: 57–65PubMedCrossRefGoogle Scholar
  69. 69.
    Malmberg K, Ryden L, Hamsten A, et al. Effects of insulin treatment on cause-specific one year mortality and morbidity in diabetic patients with acute myocardial infarction. Eur Heart J 1996; 17: 1337–44PubMedCrossRefGoogle Scholar
  70. 70.
    Malmberg K. Prospective randomized study of insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ 1997; 314: 1512–5PubMedCrossRefGoogle Scholar
  71. 71.
    UK Prospective Diabetes Study Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998: 352: 854–65CrossRefGoogle Scholar
  72. 72.
    Antiplate let Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet treatment. I. Prevention of death, myocardial infarction, and stroke by prolonged anti-platelet therapy in various categories of patients. BMJ 1994; 308: 81–106CrossRefGoogle Scholar
  73. 73.
    American Diabetes Association. Management of dyslipidemia in adults with diabetes. Diabetes Care 199: 22 Suppl. 1: S56–9Google Scholar
  74. 74.
    Emanuele N, Azad N, Abraira C, et al. Effect of intensive glycemic control on fibrinogen, lipids, and lipoproteins: Veterans Affairs Cooperative Study in Type II Diabetes Mellitus. Arch Intern Med 1998; 158: 2485–90PubMedCrossRefGoogle Scholar
  75. 75.
    Abraira C, Colwell JA, Nuttall FQ, et al. Veterans Affairs Co-operative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM): results of the feasibility trial. Diabetes Care 1995; 18: 1113–23PubMedCrossRefGoogle Scholar
  76. 76.
    Bolli GB. Hypoglycemia unawareness. Diabetes Metab 1997; 23 Suppl. 3: 29–35PubMedGoogle Scholar
  77. 77.
    O’Keefe JH, Miles J, Harris W, et al. Improving the adverse cardiovascular prognosis of type 2 diabetes. Mayo Clin Proc 1999; 74: 171–80PubMedCrossRefGoogle Scholar
  78. 78.
    O’Keefe JH, Blackstone EH, Sergeant P, et al. The optimal mode of coronary revascularization for diabetics: a risk-adjusted long-term study comparing coronary angioplasty and coronary bypass surgery. Eur Heart J 1998; 19: 1696–703PubMedCrossRefGoogle Scholar
  79. 79.
    Abraira A, Maki K. Does insulin treatment increase cardiovascular risk in NIDDM? Clin Diabet March/April 1995; 13: 29–31Google Scholar
  80. 80.
    Laight DW, Carrier MJ, Anggard EE. Antioxidants, diabetes and endothelial dysfunction. Cardiovasc Res 2000; 18: 457–64CrossRefGoogle Scholar
  81. 81.
    Stout RW. The impact of insulin on atherosclerosis. Horm Metab Res 1994; 26: 125–8PubMedCrossRefGoogle Scholar
  82. 82.
    Durrington PN. Is insulin atherogenic? Diabet Med 1992; 9: 597–600PubMedCrossRefGoogle Scholar
  83. 83.
    Fontbonne A, Eschwege E, Cambien F, et al. Hypertriglyceri-daemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes: results from the 11-year follow-up of the Paris prospective Study. Diabetologia 1989; 32: 300–4PubMedCrossRefGoogle Scholar
  84. 84.
    Fontbonne A, Charles MA, Thibult N, et al. Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study: 15-year follow-up. Diabetologia 1991; 34: 356–61PubMedCrossRefGoogle Scholar
  85. 85.
    Welborn TA, Wearne K. Coronary heart disease incidence and cardiovascular mortality in Busselton with reference to glucose and insulin concentrations. Diabetes Care 1979: 2: 154–60PubMedCrossRefGoogle Scholar
  86. 86.
    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, ten years later. Horm Metab Res 1985: 15 Suppl.: 41–6Google Scholar
  87. 87.
    Yarnell JWG, Sweetnam PM, Marks V, et al. Insulin in ischaemic heart disease: are associations explained by triglyceride concentrations? The Caerphilly prospective study. Br Heart J 1994; 171: 293–6CrossRefGoogle Scholar
  88. 88.
    Despres JP, Lamarch B, Mauriege P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334: 952–7PubMedCrossRefGoogle Scholar
  89. 89.
    Ernest E, Resch KL. Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of literature. Ann Intern Med 1993; 118: 956–63Google Scholar
  90. 90.
    Anonymous. Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 1998; 116: 874–86Google Scholar
  91. 91.
    Ellis D, Avner ED, Transue D, et al. Diabetic nephropathy in adolescence: appearance during improved glycemic control. Pediatrics 1983; 71: 824–9PubMedGoogle Scholar
  92. 92.
    Henricsson M, Nilsson A, Janzon L, et al. The effect of glycaemic control and the introduction of insulin therapy on retinopathy in non-insulin-dependent diabetes mellitus. Diabet Med 1997; 14: 123–31PubMedCrossRefGoogle Scholar
  93. 93.
    Emanuele N, Klein R, Abraira C, et al. Evaluations of retinopathy in the VA Cooperative Study on Glycemic Control and complications in Type II Diabetes (VA CSDM): a feasibility study. Diabetes Care 1996; 19: 1375–81PubMedCrossRefGoogle Scholar
  94. 94.
    Chautelau E, Kohner EM. Why some cases of retinopathy worsen when diabetes control improves. BMJ 1997; 315: 1105–6CrossRefGoogle Scholar
  95. 95.
    Orchard TJ. Glycemic control and CAD risk: a heretical thought [letter]. Diabetes Care 1999; 22: 1220PubMedCrossRefGoogle Scholar
  96. 96.
    Purnell JQ, Hokanson JE, Marcovina SM, et al. Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure. JAMA 1998; 280: 140–6PubMedCrossRefGoogle Scholar
  97. 97.
    DCCT Research Group. Adverse events and their association with treatment regimens in the Diabetes Control and Complications Trial. Diabetes Care 1995; 18: 1415–27CrossRefGoogle Scholar
  98. 98.
    Williams K, Erbey J, Becker D, et al. Improved glycemic control reduces the impact of weight gain on cardiovascular risk factors in type 1 diabetes: the Epidemiology of Diabetes Complications study. Diabetes Care 199: 22: 1084–91Google Scholar
  99. 99.
    U.K. Prospective Diabetes Study Group. Quality of life in type 2 diabetic patients is affected by complications but not by intensive policies to improve blood glucose or blood pressure control (UKPDS 37). Diabetes Care 1999: 22: 1125–36CrossRefGoogle Scholar
  100. 100.
    Ferris FL III. How effective are treatments for diabetic retinopathy? JAMA 1993; 269: 1290–1PubMedCrossRefGoogle Scholar
  101. 101.
    United Kingdom Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and micro-vascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 703–12CrossRefGoogle Scholar
  102. 102.
    Sacks FM, Pfeffer MA, Moye LA, et al., Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996; 335: 1001–9PubMedCrossRefGoogle Scholar
  103. 103.
    Tentkanen L, Manttari M, Manninen V. Some coronary risk factors related to the insulin resistance syndrome and treatment with gemfibrozil: experience from the Helsinski Heart Study. Circulation 1995; 92: 1779–85CrossRefGoogle Scholar
  104. 104.
    Pyorala K, Pedersen TR, Kjekshus J, et al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S) [published erratum appears in Diabetes Care 1997; 20: 1048]. Diabetes Care 1997; 20: 614–20PubMedCrossRefGoogle Scholar
  105. 105.
    United Kingdom Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998; 317: 713–20CrossRefGoogle Scholar
  106. 106.
    Early Treatment Diabetic Retinopathy Study Investigators. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. Early Treatment Diabetic Retinopathy Study report 14. JAMA 1992; 268: 1292–300CrossRefGoogle Scholar
  107. 107.
    Epidemiology of Diabetes Interventions and Complication Research Group. Epidemiology of Diabetes Interventions and Complications. Design, implementation and preliminary results of a long term follow up of the Diabetes Control and Complications Trial cohort. Diabetes Care 1999; 22: 99–111CrossRefGoogle Scholar
  108. 108.
    Abraira C, Duckworth W, McCarren M: Seven year VA Cooperative Study on glycemic control and complications [abstract]. Diabetes 2000; 49 Suppl. 1: A1422Google Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Pauline Camacho
    • 1
  • Shailesh Pitale
    • 1
  • Carlos Abraira
    • 2
  1. 1.Loyola University Medical CenterMaywoodUSA
  2. 2.Miami Veterans Affairs Medical CenterMiamiUSA

Personalised recommendations