The current study was designed to determine the role of the host genes involved in the development of chronic hepatitis C-associated type 2 diabetes mellitus. This study was carried out in patients in four different stages of chronic hepatitis C virus (HCV) infection, including treatment-naïve HCV patients, HCV-positive patients with type 2 diabetes mellitus (T2DM), non-responders and responders. The mRNA expression level of host genes, such as glucose-6-phosphatase (G6Pase), tumor necrosis factor α (TNF-α) and different adipokines including adiponectin, leptin and resistin, was quantified and compared to healthy controls. HCV infection was found to be associated with insulin resistance, a step towards type 2 diabetes mellitus (T2DM). The results also suggest the potential role of adipokines in chronic HCV (CHC)-associated T2DM. The upregulation of gluconeogenic genes, such as G6Pase and resistin, and a decreased mRNA expression level of adiponectin suggest the potential role of selected markers in the CHC-associated T2DM in Pakistani population. Based on these results, it is concluded that upregulation of TNF-α, G6Pase and resistin in chronic HCV patients leads to gluconeogenesis, eventually favoring T2DM. Collectively, these findings suggest that CHC patients are more prone to T2DM.