Background & aims: Cirrhosis is associated with insulin resistance and impaired glucose tolerance, which may be caused by impairments at different tissue levels (liver, skeletal muscle, and/or beta cell). Methods: Here, glucose kinetics at whole-body and skeletal muscle level in patients with cirrhosis (Child-Pugh A and B) were studied during parenteral nutrition using the isotope dilution technique and arteriovenous balance approach across the leg. As opposed to the euglycemic hyperinsulinemic clamp or glucose tolerance tests applied in previous studies, this approach provides a nutrient composition more similar to a normal meal while circumventing any possible portal-systemic shunting, impaired hepatic uptake and incretin effect. Results: We confirmed the presence of hepatic and peripheral insulin resistance in our patient population. Endogenous glucose production was less suppressed in response to parenteral nutrition. However, glucose uptake in skeletal muscle was increased. Conclusion: Our results suggests that in our study participants with cirrhosis, the hepatic and peripheral insulin resistance is compensated for by increased insulin secretion and thus, increased glucose uptake in muscle. Hereby, glucose homeostasis is maintained.