Neuropeptide Y: a potential theranostic biomarker for diabetic peripheral neuropathy in patients with type-2 diabetes

Abstract

Background: Diabetic peripheral neuropathy (DPN), the most common microvascular complication of type-2 diabetes mellitus (T2DM), results in nontraumatic lower-limb amputations. When DPN is not detected early, disease progression is irreversible. Thus, biomarkers for diagnosing DPN are needed. Methods: We analyzed three data sets of T2DM DPN: two for mouse models (GSE70852 and GSE34889) and one for a human model (GSE24290). We found common differentially expressed genes (DEGs) in the two mouse data sets and validated them in the human data set. To identify the phenotypic function of the DEGs, we overexpressed them in zebrafish embryos. Clinical information and serum samples of T2DM patients with and without DPN were obtained from the Korea Biobank Network. To assess the plausibility of DEGs as biomarkers of DPN, we performed an enzyme-linked immunosorbent assay. Results: Among the DEGs, only NPY and SLPI were validated in the human data set. As npy is conserved in zebrafish, its mRNA was injected into zebrafish embryos, and it was observed that the branches of the central nervous system became thicker and the number of dendritic branches increased. Baseline characteristics between T2DM patients with and without DPN did not differ, except for the sex ratio. The mean serum NPY level was higher in T2DM patients with DPN than in those without DPN ( p = 0.0328), whereas serum SLPI levels did not differ ( p = 0.9651). Conclusion: In the pathogenesis of DPN, NPY may play a protective role in the peripheral nervous system and may be useful as a biomarker for detecting T2DM DPN.

The Role of Early Revascularization and Biomarkers in the Management of Diabetic Foot Ulcers: A Single Center Experience

“…The latest literature has revealed the role of interesting biomarkers, such as the Neuropeptide Y (NPY) and the Elabela Peptide. Cho et al showed that high levels of this marker are visible from the earlier times of diabetic disease, before early symptoms [ 10 ]. Elabela peptide is a product of the renin-angiotensin-aldosterone system; Kaplan et al showed significant growth of this marker in patients with high grades of Rutherford and WIfi scale, with an increase in cardiovascular disease risk [ 31 ].…”

“…The early identification of DPN and PAD is often challenging and these patients get the correct diagnosis and management when lesions are already irreversible. Thus, screening for early symptoms and signs of DPN and PAD is critical in the clinical practice, to improve patient prognosis and quality of life and reduce healthcare costs [ 10 ]. Despite the possibility to assess the main direct causes of aggressive DFU through different instrumental diagnostic methods, the difficulties related to their execution usually find a late application, when irreversible lesions are already present.…”

Formate Might Be a Novel Potential Serum Metabolic Biomarker for Type 2 Diabetic Peripheral Neuropathy

“…2 It is reported that approximately 50% of patients with T2DM would be accompanied by diabetic peripheral neuropathy (DPN), one of the most frequent chronic complications of diabetes mellitus. 3,4 DPN is characterized by neuropathic pain, numbness, and sensory abnormality on symmetrical, bilateral distal limbs, which not only increases the risks of foot ulceration and even lower-limb amputation but also results in a substantial effect on the patient's health and a heavy financial burden. 5 Up to now, the potential pathogenic mechanisms of DPN have not yet been completely elucidated, which limits the further exploration of useful prevention and treatment strategies for DPN.…”