Prevention of Microvascular Complications of Diabetes

  • Zachary Bloomgarden
  • Alina Gouller


There are several approaches to the prevention of complications of diabetes. They include controlling hyperglycemia, controlling blood pressure, utilizing angiotensin converting enzyme (ACE)-inhibitors and angiotensin-receptor blockers (ARBs) and preventing formation of advanced glycosylation end products (AGEs).


Glycemic Control Diabetic Retinopathy Angiotensin Converting Enzyme Inhibitor Aldose Reductase Microvascular Complication 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Nathan DM. The pathophysiology of diabetic complications: how much does the glucose hypothesis explain? Ann Intern Med 124: 86–89, 1996.PubMedCrossRefGoogle Scholar
  2. 2.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352: 837–853, 1998.CrossRefGoogle Scholar
  3. 3.
    The 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 329: 977–986, 1993.CrossRefGoogle Scholar
  4. 4.
    The Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med 122: 561–568, 1995.CrossRefGoogle Scholar
  5. 5.
    The Diabetes Control and Complications Research Group. The relationship of glycemic exposure (HbAlc) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes 44: 968–983, 1995.CrossRefGoogle Scholar
  6. 6.
    The Diabetes Control and Complications Trial Research Group. Adverse events and their association with treatment regimens in the Diabetes Control and Complications Trial. Diabetes Care 18: 1415–1427, 1995.CrossRefGoogle Scholar
  7. 7.
    Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood glucose control on late complications of type 1 diabetes. Lancet 341: 1306–9, 1993.PubMedCrossRefGoogle Scholar
  8. 8.
    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 28: 103–117, 1995.PubMedCrossRefGoogle Scholar
  9. 9.
    Testa MA, Simonson DC. Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus. JAMA 280: 1490–1496, 1998.PubMedCrossRefGoogle Scholar
  10. 10.
    Knatterud GL, Klimt CR, Levin ME, Jacobson ME, Goldner MG. Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VII. Mortality and selected nonfatal events with insulin treatment. JAMA 240: 37–42, 1978.PubMedCrossRefGoogle Scholar
  11. 11.
    The University Group Diabetes Program. A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. V. Evaluation of phenformin therapy. Diabetes 24 (Suppl 1): 65–184, 1975.Google Scholar
  12. 12.
    Genuth S. Exogenous insulin administration and cardiovascular risk in non-insulin-dependent and insulin-dependent diabetes mellitus. Ann Intern Med 124: 104–109, 1996.PubMedCrossRefGoogle Scholar
  13. 13.
    Colwell JA. The feasibility of intensive insulin management in noninsulin-dependent diabetes mellitus: implications of the Veterans Affairs Cooperative Study on Glycemic Control and Complications in NIDDM. Ann Intern Med 124 (1, pt 2): 131–135, 1996.PubMedCrossRefGoogle Scholar
  14. 14.
    Klein R, Klein BE, Moss SE. Relation of glycemic control to diabetic microvascular complications in diabetes mellitus. Ann Intern Med 124 (1, pt 2): 90–96, 1996.PubMedCrossRefGoogle Scholar
  15. 15.
    Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy, XV: the long-term incidence of macular edema. Ophthalmology 102: 7–16, 1995.PubMedGoogle Scholar
  16. 16.
    Klein R, Klein BE, Moss SE. The Wisconsin Epidemiologic Study of Diabetic Retinopathy, XVI: the relationship of C-peptide to the incidence and progression of diabetic retinopathy. Diabetes 44: 796–801, 1995.PubMedCrossRefGoogle Scholar
  17. 17.
    Moss SE, Klein R, Klein BE. Long-term incidence of lower-extremity amputations in a diabetic population. Arch Fam Med 5: 391–398, 1996.PubMedCrossRefGoogle Scholar
  18. 18.
    Laakso M. Glycemic control and the risk for coronary heart disease in patients with non-insulin-dependent diabetes mellitus: the Finnish studies. Ann Intern Med 124: 127–130, 1996.PubMedCrossRefGoogle Scholar
  19. 19.
    Lehto S, Ronnemaa T, Pyorala K, Laakso M. Predictors of stroke in middle-aged patients with non-insulin-dependent diabetes. Stroke 27: 63–68, 1996.PubMedCrossRefGoogle Scholar
  20. 20.
    Anderson DK, Svardsudd K. Long-term glycemic control relates to mortality in type II diabetes. Diabetes Care 18: 1534–1543, 1995.CrossRefGoogle Scholar
  21. 21.
    Stratton IM, Adler AI, Neil HAW on behalf of the UKPDS group. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35). Br Med J 321: 405–412, 2000.CrossRefGoogle Scholar
  22. 22.
    The sixth report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure. Arch Internal Medicine 157: 2413–46, 1997.CrossRefGoogle Scholar
  23. 23.
    Hansson L, Zanchetti A, Carruthers SG, et al, for the HOT Study Group. 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 351: 1755–1762, 1998.PubMedCrossRefGoogle Scholar
  24. 24.
    UK Prospective Diabetes Study group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Brit Med Journal 317: 703–713, 1998.CrossRefGoogle Scholar
  25. 25.
    UK Prospective Diabetes Study group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. Brit Med Journal 317: 703–713, 1998.CrossRefGoogle Scholar
  26. 26.
    Vlassara H, Fuh H, Makita Z, Krungari S, Cerami A, Bucala R. Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc Nat Acad of Sci 89 (24): 12043–7, 1992.CrossRefGoogle Scholar
  27. 27.
    Vlassara H. Serum advanced glycosylation end products. A new class of uremic toxins ? Blood Purif 12 (1): 54–9, 1994.PubMedCrossRefGoogle Scholar
  28. 28.
    Yang CW, Vlassara H, Peten EP, et al. Advanced glycation end products up-regulate gene expression found in diabetic glomerular disease. Proc Nat Acad Sci USA 27: 9634–9640, 1994.Google Scholar
  29. 29.
    Ono Y, Aoki, et al. Increased serum level of advanced glycation end products and diabetic complications. Diabetes Res. Clinical Practice 41 (2), 131–137, 1998.CrossRefGoogle Scholar
  30. 30.
    Bucala R. What is the effect of hyperglycemia on atherogenesis and can it be reversed by aminoguanidine? Diabetes Research Clinical Practice Feb; 30 Suppl: 123–130, 1996.Google Scholar
  31. 31.
    Brownlee M, Vlassara H, Koonee T, et al. Aminoguanidine prevents diabetes induced arterial wall protein cross-linking. Science 232: 1629 1632, 1986.Google Scholar
  32. 32.
    Hammes HP, Martin S; Federlin K; Geisen K, Brownlee M. Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. Proc Natl Acad Sci 88 (24): 11555–11558, 1991.PubMedCrossRefGoogle Scholar
  33. 33.
    Soulis T, Cooper ME, Vranes D, et al. Effects of aminoguanidine in preventing experimental diabetic nephropathy are related to the duration of treatment. Kidney Intl 50: 627–634, 1996.CrossRefGoogle Scholar
  34. 34.
    Yagihashi S, Kamijo M, Baba, M, et al. Effect of aminoguanidine on functional and structural abnormalities in peripheral nerve of stz induced diabetic rats. Diabetes 41: 47, 1992.PubMedCrossRefGoogle Scholar
  35. 35.
    Clark CM, Lee DA, Prevention and treatment of the complications of diabetes mellitus. New England Journal of Medicine 332: 1210–1217, 1995.PubMedCrossRefGoogle Scholar
  36. 36.
    Al-Abed, et al. Inhibition of advanced glycation end product formation by acetaldehyde. Proc Natl Acad Sci 96: 2385–2390, 1999.PubMedCrossRefGoogle Scholar
  37. 37.
    Kassab J, Guillot, R et al. Renal and microvascular effects of an aldosereductase inhibitor in experimental diabetes. Biochem Pharmacology 48: 1003, 1994.CrossRefGoogle Scholar
  38. 38.
    Engerman R, Kern, Garment, M, et al. Capillary basement membrane in retina, kidney and muscle of diabetic dogs and galactosemic dogs and its response to 5 years of aldose-reductase inhibition. J Diabetes complications 7: 241–245, 1993.PubMedCrossRefGoogle Scholar
  39. 39.
    A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Sorbinil Retinopathy Trial Research Group Arch Ophthalmol 108: 1234–1244, 1990.Google Scholar
  40. 40.
    Passariello N, Sepe J, Marazzo, G, et al. Effect of aldose reductase inhibitor [tolrestat] on urinary albumin excretion rate and glomerular filtration rate in IDDM subjects with nephropathy. Diabetes care 16: 789795, 1993.Google Scholar
  41. 41.
    Mc-Auliffe A, Brooks, B, et al. Administration of ascorbic acid and aldose reductase inhibitor tolrestat in diabetes. Effect on urinary albumin excretion. Nephron 80: 277–284, 1998.CrossRefGoogle Scholar
  42. 42.
    Santiago J, Sonksen P, Boulton. Withdrawal of the aldose reductase inhibitor tolrestat in diabetic neuropathy. Effect on nerve function. J Diab Compl 7: 170–178, 1993.CrossRefGoogle Scholar
  43. 43.
    Boulton A, Levin S, et. al. A multicenter trial of aldose reductase inhibitor tolrestat in patients with symptomatic diabetic neuropathy. Diabetologia 33: 431–437, 1990.PubMedCrossRefGoogle Scholar
  44. 44.
    Christen WG, Manson JE, Bubes V, Glynn RJ. Risk factors for progression of distal symmetric polyneuropathy in type 1 diabetes mellitus. Sorbinil Retinopathy Trial Research Group. Am J Epidemiol 150 (11): 1142–51, 1999.PubMedCrossRefGoogle Scholar
  45. 45.
    Chaturvedi N, Sjolie AK, Stephenson JM, et al. And the EUCLID Study Group; Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes mellitus. Lancet 351: 28–31, 1998.PubMedCrossRefGoogle Scholar
  46. 46.
    Effects of Ramipril on cardiovascular and microvascular outcomes in patients with diabetes mellitus: results of the HOPE and MICRO-HOPE study. HOPE study investigators. Lancet 355:253–259, 2000.Google Scholar
  47. 47.
    Parving MD, Hendrik L, et al. For the Irbesartan in Patients with type 2 diabetes and microalbuminuria study group. The effect of Irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 345: 870–878, 2001.PubMedCrossRefGoogle Scholar
  48. 48.
    Brenner BM, Cooper ME, et al. for the RENAAL study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345: 861–869, 2001.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Zachary Bloomgarden
  • Alina Gouller

There are no affiliations available

Personalised recommendations