Abstract
The increasing prevalence of type 2 diabetes mellitus (T2DM), largely attributable to poor dietary habits and nutritional imbalances, highlights the need for novel diagnostic and therapeutic approaches. Emerging evidence emphasizes the critical role of trace elements in the pathogenesis and management of T2DM. However, the molecular mechanisms through which zinc and chromium deficiencies contribute to disease progression remain largely unexplored. This study aimed to investigate the role of zinc and chromium in T2DM pathogenesis through a combination of bioinformatics analysis, molecular docking, trace element profiling, and gene expression validation. Relevant genes identified from the literature were analyzed using a bioinformatics pipeline to uncover hub gene networks and regulatory pathways associated with trace element deficiencies. Molecular docking of HUB genes with zinc and chromium enriched compounds were employed to uncover the new therapeutic approach. For experimental validation, serum zinc and chromium levels were measured in fifty T2DM patients and fifteen healthy controls using atomic absorption spectrophotometry. Gene expression profiling of GCK (zinc associated) and GLUT4 (chromium associated) was performed using real time PCR. Bioinformatics analysis revealed that HUB genes affected due to zinc and chromium deficiency were linked to an elevated risk of T2DM. Crucial metabolic pathways was altered due to zinc and chromium deficiency in T2DM.The serum concentration of zinc and chromium were markedly lower in T2DM patients as compared to controls. Level of zinc was significantly lower in T2DM patients with nephropathy and chromium level was significantly were lower in T2DM patients with CVD. Expression of GCK and GLUT4 was reduced by approximately 4-6 folds and 3-4 folds, respectively, in T2DM and its associated complications. The study provide novel insights into the gene-environment interaction driving T2DM and highlight the therapeutic approach of zinc and chromium supplementation in mitigating diseases progression. This study paves the way for future research into personalized nutritional interventions targeting gene expression abnormalities in diabetes management.