Biomed Res Int. 2013;2013:490964.

Hyperglycemia increases susceptibility to ischemic necrosis.

Lévigne D, Tobalem M, Modarressi A, Pittet-Cuénod B

Division of Plastic, Reconstructive & Aesthetic Surgery, University Hospitals of Geneva, University of Geneva, Faculty of Medicine, Geneva, Switzerland.


Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral and the saphenous artery. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, respectively). In this study we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia.

PMID: 23509730


Supplementary information

The progression from critical limb ischemia to necrosis and gangrene is reportedly more than four times higher in diabetic patients compared to non-diabetic patients.1 The most important factors favoring the development and progression of diabetic foot ulcers are believed to be peripheral neuropathy and arteriosclerosis. The role of hyperglycemia itself is poorly understood, and there is no consensus concerning the role of hyperglycemia per se in the progressive necrosis at the wound margins that leads to the characteristic extension of diabetic wounds.

In this study, we revealed that hyperglycemia increases the susceptibility to necrosis in ischemic limbs. At critical perfusion levels, the likelihood of major limb necrosis was 2.5 times higher in hyperglycemic animals, in comparison to normoglycemic rats. Accordingly, other studies have demonstrated that hyperglycemia is associated with impaired outcome and expanded infarct volume in patients with ischemic strokes and myocardial infarctions.2-4

Hyperglycemia per se is likely to sensitize to ischemic tissue necrosis by: 1) increasing blood viscosity and hypercoagulability,5 and 2) inducing cellular toxicity via increased oxidative stress6,7 and lactic acidosis8. As the mechanisms through which both ischemia and hyperglycemia induce cellular toxicity are similar, it is conceivable that they amplify each other. We advocate that strict glycemic control must be an inherent part of modern management of all pathologies associated with critical arterial perfusion, including peripheral acute ischemia, in order to limit ischemic necrosis.



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