Glycated Hemoglobin (HbA1c) as a Biomarker for Diabetic Foot Peripheral Neuropathy

Background: Diabetic peripheral neuropathy (DPN) is known to predict foot ulceration, lower-extremity amputation and mortality. Patients with diabetes mellitus have a predisposition toward developing chronic inflammatory demyelinating polyneuropathy, and this may also facilitate the formation of diabetic foot and cutaneous impairment, which are considered one of the most serious impairments of diabetes mellitus, with a prevalence of 4-10% in this population. Biomarkers research provides opportunities for the early diagnosis of these complications for specific treatments useful to prevent amputation and, therefore, physical inability and mental disturbance. The recent literature has suggested that glycemic levels may be a novel factor in the pathogenesis of diabetic foot complications and is an important mediator of axonal dysfunction. The aim of this systematic literary review is to determine whether hemoglobin A1c (HbA1c) is a positive predictor for diabetic foot peripheral neuropathy and its complications, such as foot cutaneous impairments. There is a lack of consensus regarding the effect of glycemic variability on diabetic foot peripheral neuropathy, unlike other complications such as retinopathy, nephropathy or micro/macrovascular pathology. Methods: Relevant articles were searched in the Medline database using PubMed and Scopus and relevant keywords. The primary search terms used were "glycated hemoglobin" OR "HbA1c" AND "diabetic neuropathies" AND "Foot". Results: A number of articles (336) were initially identified while searching the scientific literature regarding this topic, and 32 articles were selected and included in this review. Conclusions: This review highlights the role of HbA1c in diabetic foot peripheral neuropathy. Biomarkers play an important role in the decision-making process, and HbA1c levels are extensively used for diabetic foot clinical outcomes and settings, but biomarker research in diabetic foot peripheral neuropathy is in its infancy and will require careful attention to a number of factors and associations, since the consequences of DPN also include neurological alterations. HbA1c is an accurate and easy-to-administer test and can be an effective biomarker in establishing the diagnosis of diabetes, but future research should focus on standardizing the HbA1c level and selecting which DPN value and its correlated complications, such as foot cutaneous impairments, are the most informative.