Relationship between sarm1 and hif-1 alpha expression polyneuropathy development in patients with type-2 diabetes mellitus

Despite the existence of numerous studies on the subject, there is still no clear treatment protocol for distal symmetric polyneuropathy (DSPN), which is the most common microvascular complication caused by type-2 diabetes mellitus (T2DM). Consequently, while individuals experience neuropathic pain, autonomic dysfunction, foot ulcers, amputation, increased mortality risk and low quality of life, the financial burden on healthcare expenditure is significant due to increased treatment costs and prolonged hospitalisation. The objective of this doctoral thesis was to evaluate the gene and protein expression levels of sterile alpha and Toll/interleukin-1 receptor (TIR) motif-containing protein (SARM)-1 and hypoxia-inducible factor-1 alpha (HIF-1α) in patients diagnosed with DSPN who were also diagnosed with T2DM. The study was designed as a controlled, randomized block type, with the control group, designated as Group 1, comprising healthy individuals. The study groups were as follows: Group 2 consisted of cases with a T2DM diagnosis alone; Group 3 consisted of cases with a DSPN diagnosis in addition to T2DM; and Group 4 consisted of cases with impaired glucose tolerance (IGT). Subsequently, the expressions and protein levels of the SARM1 and HIF-1α genes, which are purported to be essential components in axonal degeneration, were quantified in the venous blood of individuals across all groups. During the statistical analysis of the obtained data, Tukey's Honestly Significant Test (HSD) was employed as a multiple comparison test following the Analysis of Variance in comparisons between groups. Additionally, the relationship between the variables was evaluated with the Pearson Correlation test. In intergroup comparisons, the effect of the groups on SARM1 gene expression was found to be statistically significant (P<0.05). However, although negative changes were detected on Hif-1α gene expression, these changes were statistically insignificant (P>0.05). When the changes in the protein levels of both SARM1 and Hif-1α were evaluated, it was understood that these changes in all protein levels were statistically significant (P <0.05). Furthermore, a weak negative correlation was observed between SARM1 and Hif-1α, although this relationship was not statistically significant (P>0.05). It is believed that the findings of this study may contribute to the development of targeted treatments for patients with DSPN associated with T2DM in the future. Furthermore, it is postulated that the prevention of DSPN development due to axon degeneration necessitates the use of neuropharmacological agents to inhibit SARM1 and protect Hif-1α. Key words: Axon degeneration, Distal Symmetric Polyneuropathy, Hif-1α, Impaired glucose tolerance, SARM1, Type-2 Diabetes Mellitus.