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Microvascular Changes in the Diabetic Foot

  • Chapter
The Diabetic Foot

Part of the book series: Contemporary Diabetes ((CDI))

Abstract

It has been nearly half a century since the concept of “small vessel disease”; was introduced as a unique entity in the microvasculature of the patient with diabetes. This misconception was arrived at through a retrospective histological study demonstrating the presence of periodic acid Schiff-positive material occluding the arterioles in amputated limb specimens of patients with diabetes (1). From these observations, Goldenberg and his colleagues deduced that the deposits in the small and medium-sized arterioles were the hallmark of vascular disease in the patient with diabetes. Perpetuation of this erroneous idea led to the belief that preferential occlusion of the small vessels in the patient with diabetes produced a poorer prognosis with limited revascularization options.

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References

  1. Goldenberg S, Joshi R. Nonatheromatous peripheral vascular disease of the lower extremity in diabetes mellitus. Diabetes 1959;8:261–273.

    PubMed  CAS  Google Scholar 

  2. Strandness D, Gibbons G. Combined clinical and pathological study of diabetic and nondi-abetic peripheral arterial disease. Diabetes 1964;13:366–372.

    PubMed  Google Scholar 

  3. Conrad M. Large and small artery occlusion in diabetics and nondiabetics with severe vascular disease. Circulation 1967;36:83–91.

    PubMed  CAS  Google Scholar 

  4. Barner H, Kaiser G, Willman V. Blood flow in the diabetic leg. Circulation 1971;43:391–394.

    PubMed  CAS  Google Scholar 

  5. LoGerfo F, Coffman J. Current concepts. Vascular and microvascular disease of the foot in diabetes. Implications for foot care. N Engl J Med 1984;311:1615–1619.

    Article  PubMed  CAS  Google Scholar 

  6. Jaap AJ, Shore AC, Stockman AJ, Tooke JE. Skin capillary density in subjects with impaired glucose tolerance and patients with type 2 diabetes. Diabetes Med 1996;13:160–167.

    Article  CAS  Google Scholar 

  7. Rayman G, Malik RA, Sharma AK, Day JL. Microvascular response to tissue injury and capillary ultrastructure in the foot skin of type I diabetic patients. Clin Sci 1995;89:467–474.

    PubMed  CAS  Google Scholar 

  8. Malik RA, Newrick PG, Sharma AK, et al. Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy. Diabetologia 1989;32:92–102.

    Article  PubMed  CAS  Google Scholar 

  9. Williamson JR, Kilo C. Basement membrane physiology and pathophysiology, in International Textbook of Diabetes Mellitus (Alberti KGMM, DeFronzo RA, Keen H, Zimmet P, eds.), Volume 2, John Wiley, Chichester, 1992, pp. 1245–1265.

    Google Scholar 

  10. Raskin P, Pietri A, Unger R, Shannon WA Jr. The effect of diabetic control on skeletal muscle capillary basement membrane width in patients with type 1 diabetes mellitus. N Engl J Med 1983;309:1546–1550.

    Article  PubMed  CAS  Google Scholar 

  11. Rayman G, Williams SA, Spencer PD, et al. Impaired microvascular hyperaemic response to minor skin trauma in type I diabetes. BMJ 1986;292:1295–1298.

    Article  PubMed  CAS  Google Scholar 

  12. Tilton RG, Faller Am, Burkhardt JK, et al. Pericyte degeneration and acellular capillaries are increased in the feet of human diabetes. Diabetologia 1985;28:895–900.

    Article  PubMed  CAS  Google Scholar 

  13. Tooke JE. Microvascular function in human diabetes: a physiological perspective. Diabetes 1995;44:721–726.

    Article  PubMed  CAS  Google Scholar 

  14. Parving H, Viberti G, Keen H, et al. Hemodynamic factors in the genesis of diabetic microangiopathy. Metabolism 1983;32:943–949.

    Article  PubMed  CAS  Google Scholar 

  15. Flynn MD, Tooke JE. Aetiology of diabetic foot ulceration: a role for the microcirculation? Diabet Med 1992;8:320–329.

    Article  Google Scholar 

  16. Jorneskog G, Brismar K, Fagrell B. Skin capillary circulation severely impaired in toes of patients with IDDM, with and without late diabetic complications. Diabetologia 1995;38:474–480.

    Article  PubMed  CAS  Google Scholar 

  17. Veves A, Akbari CM, Primavera J, et al. Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease and foot ulceration. Diabetes 1998;47:457–463.

    Article  PubMed  CAS  Google Scholar 

  18. Rendell M, Bergman T, O’Donnell G, et al. Microvascular blood flow, volume, and velocity measured by laser Doppler techniques in IDDM. Diabetes 1989;38:819–824.

    Article  PubMed  CAS  Google Scholar 

  19. Flynn MD, Williams SA, Tooke AE. Clinical television microscopy. J Med Eng Technol 1989;13:278–284.

    PubMed  CAS  Google Scholar 

  20. Boulton AJM, Scarpello JHB, Ward JD. Venous oxygenation in the diabetic neuropathic foot: evidence of arteriovenous shunting? Diabetologia 1981;22:6–8.

    Article  Google Scholar 

  21. Murray HJ, Boulton A. The pathophysiology of diabetic foot ulceration. Clin Pediatr Med Surg 1995;12:1–7.

    CAS  Google Scholar 

  22. Conrad MC. Functional Anatomy of the Circulation to the Lower Extremities, Year Book Medical Publishers, Chicago, 1971, pp. 60–75.

    Google Scholar 

  23. Flynn MD, Tooke JE. Diabetic neuropathy and the microcirculation. Diabetes Med 1995;12:298–301.

    CAS  Google Scholar 

  24. Edmonds ME, Roberts VC, Watkins PJ. Blood flow in the diabetic neuropathic foot. Diabetologia 1982;22:141–147.

    Article  Google Scholar 

  25. Palmer RMJ, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 1998;333:664–666.

    Article  Google Scholar 

  26. Williams SB, Cusco JA, Roddy M, Johnstone MY, Creager MA. Impaired nitric oxide-mediated vasodilation in patients with non-insulin-dependent diabetes mellitus. J Am Coll Cardio 1996;27:567–574.

    Article  CAS  Google Scholar 

  27. Johnstone MT, Creager SJ, Scales KM, et al. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 1993;88:2510–2516.

    PubMed  CAS  Google Scholar 

  28. Caballero AE, Arora S, Saouaf R, et al. Micro-and macro-vascular reactivity is impaired in subjects at risk for type 2 diabetes. Diabetes 1999;48:1863–1867.

    Article  Google Scholar 

  29. Morris SJ, Shore AC, Tooke JE. Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients with NIDDM. Diabetologia 1995;38:1337–1344.

    Article  PubMed  CAS  Google Scholar 

  30. Elhadd TA, Kennedy G, Hill A, et al. Abnormal markers of endothelial cell activation and oxidative stress in children, adolescents and young adults with type 1 diabetes with no clinical vascular disease. Diabetes Metab Res Rev 1999;15:405–411.

    Article  PubMed  CAS  Google Scholar 

  31. Sarman B, Farkas K, Toth M, Somogyi A, Tulassay Z. Circulating plasma endothelin-1, plasma lipids and complications in type 1 diabetes mellitus. Diabetes Nutr Metab 2000;13:142–148.

    PubMed  CAS  Google Scholar 

  32. Woo KS, Chook P, Lolin YI, Sanderson JE, Metreweli C, Celermajer DS. Folic acid improves arterial endothelial function in adults with hyperhomocystinemia. J Am Coll Cardiol 1999;34:2002–2006.

    Article  PubMed  CAS  Google Scholar 

  33. Karamanos B, Porta M, Songini M, et al. Different risk factors of microangiopathy in patients with type I diabetes mellitus of short versus long duration. The EURODIAB IDDM Complications Study. Diabetologia 2000;43:348–355.

    Article  PubMed  CAS  Google Scholar 

  34. Singh TP, Groehn H, Kazmers A. Vascular function and carotid intimal-medial thickness in children with insulin-dependent diabetes mellitus. J Am Coll Cardiol 2003;41:661–665.

    Article  PubMed  Google Scholar 

  35. Koitka A, Abraham P, Bouhanick B, Sigaudo-Roussel D, Demiot C, Saumet JL. Impaired pressure-induced vasodilation at the foot in young adults with type 1 diabetes. Diabetes 2004;53:721–725.

    Article  PubMed  CAS  Google Scholar 

  36. Lambert J, Aarsen M, Donker AJ, Stehouwer CD. Endothelium-dependent and-independent vasodilation of large arteries in normoalbuminuric insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 1996;16:705–711.

    PubMed  CAS  Google Scholar 

  37. Stehouwer CD, Fischer HR, van Kuijk AW, Polak BC, Donker AJ. Endothelial dysfunction precedes development of microalbuminuria in IDDM. Diabetes 1995;44:561–564.

    Article  PubMed  CAS  Google Scholar 

  38. Dogra G, Rich L, Stanton K, Watts GF. Endothelium-dependent and independent vasodilation studies at normoglycaemia in type I diabetes mellitus with and without microalbuminuria. Diabetologia 2001;44:593–601.

    Article  PubMed  CAS  Google Scholar 

  39. Meeking DR, Cummings MH, Thorne S, et al. Endothelial dysfunction in type 2 diabetic subjects with and without microalbuminuria. Diabet Med 1999;16:841–847.

    Article  PubMed  CAS  Google Scholar 

  40. McVeigh GE, Brennan GM, Johnston GD, et al. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1992;35:771–776.

    PubMed  CAS  Google Scholar 

  41. Watts GF, O’Brien SF, Silvester W, Millar JA. Impaired endothelium-dependent and independent dilatation of forearm resistance arteries in men with diet-treated non-insulin-dependent diabetes: role of dyslipidaemia. Clin Sci 1996;91:567–573.

    PubMed  CAS  Google Scholar 

  42. Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–376.

    Article  PubMed  CAS  Google Scholar 

  43. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biologic activity of endothelium-derived relaxing factor. Nature 1987;327:524–526.

    Article  PubMed  CAS  Google Scholar 

  44. 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.

    Article  PubMed  CAS  Google Scholar 

  45. Taddei S, Virdis A, Mattei P, et al. Effect of insulin on acetylcholine-induced vasodilation in normotensive subjects and patients with essential hypertension. Circulation 1995;92:2911–2918.

    PubMed  CAS  Google Scholar 

  46. Arora S, Smakowski P, Frykberg RG, et al. Differences in foot and forearm skin microcircu-lation in diabetic patients with and without neuropathy. Diabetes Care 1998;21:1339–1344.

    Article  PubMed  CAS  Google Scholar 

  47. Williamson JR, Chang K, Tilton RG, et al. Increased vascular permeability in spontaneously diabetic BB/W rats and in rats with mild versus severe streptozotocin-induced diabetes. Diabetes 1987;36:813–821.

    Article  PubMed  CAS  Google Scholar 

  48. Joannides R, Haefeli WE, Linder L, et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995;91:1314–1319.

    PubMed  CAS  Google Scholar 

  49. Szabo C, Zanchi A, Komjati K et al. Poly (ADP-Ribose) polymerase is activated in subjects at risk of developing type 2 diabetes and is associated with impaired vascular reactivity. Circulation 2002;106:2680–2686.

    Article  PubMed  CAS  Google Scholar 

  50. Wolff SP, Dean RT. Glucose autoxidation and protein modification: the role of oxidative glycosylation in diabetes. Biochem J 1987;245:234–250.

    Google Scholar 

  51. The Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000;342:154–160.

    Article  Google Scholar 

  52. Bursell SE, Clermont AC, Aiello LP, et al. High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Diabetes Care 1999;22:1245–1251.

    Article  PubMed  CAS  Google Scholar 

  53. Panayiotis A, Khaodhiar L, Caselli A, et al. The effect of vitamin E on endothelial function of micro-and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients. Diabetes 2005;54:204–211.

    Article  Google Scholar 

  54. Makita Z, Radoff S, Rayfield EJ. Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med 1991;325:836–842.

    Article  PubMed  CAS  Google Scholar 

  55. Schernthaner G. Cardiovascular mortality and morbidity in type-2 diabetes mellitus. Diabetes Res Clin Pract 1996;33:S3–S14.

    Article  Google Scholar 

  56. Verrotti A, Greco R, Basciani F, Morgese G, Chiarelli F. von Willebrand factor and its propeptide in children with diabetes. Relation between endothelial dysfunction and microalbuminuria. Pediatr Res 2003;53:382–386.

    Article  PubMed  CAS  Google Scholar 

  57. Ridker PM, Hennekens CH, Roitman-Johnson B, Stamofer MJ, Allen J. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 1998;351:88–92.

    Article  PubMed  CAS  Google Scholar 

  58. Ferri C, Desideri G, Baldoncini R, et al. Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities. Diabetes 1998;47:660–667.

    Article  PubMed  CAS  Google Scholar 

  59. Otosuki M, Hashimoto K, Morimoto Y, Kishimoto T, Kasayama S. Circulating vascular cell adhesion molecule-1 (V CAM-1) in atherosclerotic NIDDM patients. Diabetes 1997;46:2096–2101.

    Article  Google Scholar 

  60. Altannavch TS, Roubalova K, Kucera P, Andel M. Effect of high glucose concentrations on expression of ELAM-1, VCAM-1 and ICAM-1 in HUVEC with and without cytokine activation. Physiol Res 2004;53:77–82.

    PubMed  CAS  Google Scholar 

  61. Vinik AI, Erbas T, Park TS, Stansberry KB, Scanelli JA, Pittenger GL. Dermal neurovascular dysfunction in type 2 diabetes. Diabetes Care 2001;24:1468–1475.

    Article  PubMed  CAS  Google Scholar 

  62. Hernandez C, Burgos R, Canton A, Garcia-Arumi J, Segura RM, Simo R. Vitreous levels of vascular cell adhesion molecule and vascular endothelial growth factor in patients with proliferative diabetic retinopathy: a case-control study. Diabetes Care 2001;24:516–521.

    Article  PubMed  CAS  Google Scholar 

  63. Hamdy O, Abou-Elenin K, LoGerfo FW, Horton ES, Veves A. Contribution of nerve-axon reflex-related vasodilation to the total skin vasodilation in diabetic patients with and without neuropathy. Diabetes Care 2001;24:344–349.

    Article  PubMed  CAS  Google Scholar 

  64. Parkhouse N, LeQueen PM. Impaired neurogenic vascular response in patients with diabetes and neuropathic foot lesions. N Engl J Med 1988;318:1306–1309.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

    Thanh Dinh DPM (Clinical Instructor in Surgery)

  2. Microcirculation Lab and Joslin-Beth Israel Deaconess Foot Center, Boston, MA

    Aristidis Veves MD, DSc

  3. Harvard Medical School, Boston, MA

    Aristidis Veves MD, DSc

Authors
  1. Thanh Dinh DPM
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  2. Aristidis Veves MD, DSc
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Editor information

Editors and Affiliations

  1. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

    Aristidis Veves MD, DSc , John M. Giurini DPM  & Frank W. Logerfo MD ,  & 

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© 2006 Humana Press Inc., Totowa, NJ

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Dinh, T., Veves, A. (2006). Microvascular Changes in the Diabetic Foot. In: Veves, A., Giurini, J.M., Logerfo, F.W. (eds) The Diabetic Foot. Contemporary Diabetes. Humana Press. https://doi.org/10.1007/978-1-59745-075-1_7

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  • DOI: https://doi.org/10.1007/978-1-59745-075-1_7

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-610-8

  • Online ISBN: 978-1-59745-075-1

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