The Relationship Between Blood Hypoxia-Inducible Factor-1α, Fetuin-A, Fibrinogen, Homocysteine, and Amputation Level

Reduced life expectancy has resulted from an increased incidence of chronic complications in patients with diabetes. The diabetic foot is one of these complications and generally presents together with diabetic neuropathy and vascular insufficiency. Hypoxia-inducible factor-1α (HIF-1α) is important in developing the adaptation response to hypoxia and facilitates healing through regulation of keratinocyte migration and epithelium restoration in wounds. Fetuin-A is a transporter protein that is synthesized in the liver and inhibits vascular and ectopic calcifications. It has been observed that altered fetuin-A is associated with peripheral artery disease through vascular calcification and is associated with inflammation and metabolic syndrome occurrence in diabetic patients. Fibrinogen is an acute-phase reactant and has a major role in homeostasis, tissue repair, and wound healing. Increased fibrinogen blood level is one of the factors that facilitates the hypercoagulability in diabetics. Homocysteine has atherogenic features and causes vascular toxicity by enhancing low-density lipoprotein oxidation. We evaluated the association of serum HIF-1α, fetuin-A, fibrinogen, and homocysteine levels with amputation in 31 patients diagnosed with diabetes mellitus. According to our evaluation, a negative correlation was determined between fetuin-A and amputation level (P = .012, r = -0.450), which was statistically significant. Unfortunately, there was no significant correlation between HIF-1α, fibrinogen, homocysteine, and amputation level (P > .05). As a result, it was suggested that vascular calcification due to fetuin-A deficiency may be important in the diabetic foot pathogenesis and that fetuin-A levels may be a predictor for amputation level.

Keywords: HIF-1α; amputation; diabetic foot; fetuin-A; fibrinogen; homocysteine.