['Hepatitis C virus (HCV) core protein can induce liver steatosis and glucose intolerance in transgenic mice. We aimed to clarify the association of HCV core region heterogeneity with the development of insulin resistance (IR) among patients with chronic hepatitis C (CHC).', 'A total of 56 non-diabetic CHC genotype-1b patients were enrolled. IR was evaluated by the homeostasis model assessment (HOMA). The amino acid (aa) sequences in the core region were determined by polymerase chain reaction and direct sequencing.', 'Patients with a higher HOMA-IR (≥3.5) had a higher ratio of aa substitutions in core 70 (p = 0.025), a higher body mass index (p = 0.021) and serum total cholesterol level (p = 0.044) and presence of hepatic steatosis (≥5%) as compared with those with a lower HOMA-IR (<3.5). Multivariate analysis showed that independent factors of higher HOMA-IR were mutated aa70 (odds ratio 3.80, p = 0.033) and body mass index (odds ratio 1.20, p = 0.042). Patients with mutated aa70 had a higher serum tumor necrosis factor-α level than those with wild-type (p = 0.014).'] Do amino acid substitutions in the core region associate with insulin resistance in chronic hepatitis C?