Acetate metabolism was studied in patients with insulin resistance. To evaluate the interaction between glucose and acetate metabolism, we measured acetate and glucose turnover with a hyperinsulinemic euglycemic clamp (hot clamp) in obese and diabetic patients with insulin resistance (n = 8) and in a group of controls with normal insulin sensitivity (n = 6). At baseline, acetate turnover and plasma concentrations were similar in the two groups (mean of the two groups: 4.3 ± 0.4 µmol.kg^-1.min^-1 and 128.2 ± 11.1 µmol/L). Acetate concentrations decreased in both groups with hyperinsulinemia but was significantly lower in the insulin resistant group (20% vs 12%, P < 0.05). After the hot clamp, acetate turnover increased for the two groups and was higher in the group with normal insulin sensitivity: 8.1 ± 0.7 vs 5.5 ± 0.5 µmol.kg^-1.min^-1 (P < 0.001). No change related to insulin action was observed in both groups in the percentage of acetate oxidation. This was 70% of overall utilization at baseline and during the clamp. No correlation between glucose and acetate utilization was observed. Our results support the hypothesis that like glucose metabolism, acetate metabolism is sensitive to insulin.