Patients with type 2 diabetes mellitus demonstrate inadequate insulin release, elevated gluconeogenesis, and diminished non-oxidative glucose disposal. Similar metabolic changes occur during systemic injury caused by infection, trauma, and cancer. Described here are metabolic changes occurring in 16 type 2 diabetics (DM), 11 lung cancer patients (CA)and 13 normal volunteers (NV). After a 10-hour overnight fast all subjects had fasting hormone and substrate concentrations determined, along with rates of glucose production, leucine appearance, and leucine oxidation. Fasting insulin (data not shown)and C-peptide concentrations were elevated in DM and CA compared to weight matched NV (0.72±0.09, 0.64±0.08 vs. 0.51±0.03 mg/l; p<0.05). C-Reactive Protein concentration was elevated in the CA compared to DM and NV (23.3±6.0 vs 4.2±1.4, and 2.1±0.5 mg/dl, p<0.01. All counter regulatory hormones were normal except for serum cortisol (11.4±1.0, 12.1±1.0 vs 8.9±0.7 ug/dl; DM, CA vs NL respectively, p<0.05). Glucose production was increased in DM and CA compared to NV (4.22±0.6, 3.53±0.3 vs 2.76±0.2 mg/kg lean body weight/min; p<0.01). Leucine oxidation (LO) and leucine appearance (LA) were increased in DM and CA compared to NV (LO: 27.3±1.5, 19.7±1.5 vs 12.5±1.1 mmol/kg/min, p<0.01; LA:91.9±6.6, 90.7±7.0 vs 79.1±6.0 mmol/kg lean body weith/min; p<0.01). Patients with type 2 diabetes mellitus share similar metabolic derangements with cancer patients. The increase in leucine appearance may be secondary to an increased glucose production where amino acids are mobilized to provide the liver with adequate substrate to make glucose. The increase in glucose production may also be part of the injury response or it may represent a form of insulin resistance that exists in both the diabetic patients and the non-diabetic patients with cancer.