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Insulin resistance Several studies have noted a direct role of HCV in altering glucose metabolism, leading to insulin resistance and diabetes.[29, 30] Of interest is the observation that achieving SVR with therapy has resulted in improvement in insulin resistance and a reduced incidence of diabetes mellitus.[31] An epidemiological overlap between HCV and glucose metabolism impairment could explain the impact of metabolic abnormalities on SVR,[32] independent of HCV genotype[33, 34] or IL28B genotype.[35] HCV core protein promotes degradation of insulin receptor substrates 1 and 2 [by over-expressed tumour necrosis factor a (TNFa) and suppression of cytokine signalling-3 (SOCS)],[36] leading to defective downstream PI3K and Akt phosphorylation