Hyperglycemia Increases Susceptibility to Ischemic Necrosis

Abstract

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 arteries. 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%, resp.). 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.

The beneficial effects of probiotic administration on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

“…Various studies have demonstrated controversial results, of which some reported that probiotic supplementation significantly reduced lipid profiles, while some studies did not report any improvements in lipid profiles . Hyperglycaemia and hyperinsulinemia are associated with an acceleration of arteriosclerotic and atherosclerotic changes of the greater arteries resulting in the decreased blood flow, further contributing to a limb‐threatening ischemic condition . Therefore, improvement in glucose metabolism has been suggested as an effective means to delay vascular complications in DFU subjects.…”

Expression of Concern: The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

“…However, no significant change in glucose and insulin concentrations was seen after zinc supplementation (240 mg/day of zinc as zinc gluconate) among patients with T2DM with normal zinc levels for 3 months . Hyperglycemia and insulin resistance are associated with an acceleration of arteriosclerotic changes of the greater arteries resulting in decreased blood flow, further contributing to a limb threatening ischemic condition . The diabetic dyslipidemia is one of several factors that contribute to developing macrovascular disease in diabetic patients .…”

Hyperglycemia Interacts with Ischemia in a Synergistic Way on Wound Repair and Myofibroblast Differentiation

“…As described previously, 17 through a longitudinal incision in the inguinal region that has been shaved, the femoral artery was dissected down to popliteal artery and resected in the left limb (ischemic limb) while conserved in the control right limb (nonischemic limb). After the arterial lesion, wounds were created on both legs on the dorsal aspect of the both feet in all animals by removing a full-thickness skin area of 1.2 × 0.8 cm (Fig.…”

“… 9 , 10 By contrast, the role of hyperglycemia per se is not well elucidated and remains controversial. 3 , 11 , 12 Clinical studies reported that hyperglycemia may interfere with ischemia and adversely affect the outcome of ischemic insults, 13 – 17 but this interaction has not been investigated in wound repair yet.…”