In a randomized, crossover 5-wk study design, we recently reported that a weight-maintaining diet in which the percentage of total food energy as protein was increased from 15-30% resulted in a decrease in postprandial glucose and glycohemoglobin in people with untreated type 2 diabetes without a significant change in insulin. Protein was substituted for carbohydrate in the diet. The fat content remained unchanged. In this publication, we present data on other hormones and metabolites that were considered to potentially be affected by substitution of protein for carbohydrate in the diet. The mean fasting plasma GH and total IGF-I concentrations were elevated on the 30% protein diet. The urinary free cortisol also was increased. However, the urinary aldosterone was unchanged. Although urinary pH was decreased, calcium excretion was not significantly increased. The plasma post-prandial α-amino nitrogen concentrations were increased, but the 24-h integrated concentration was unchanged, indicating an accelerated amino acid removal rate. The plasma urea nitrogen was increased as expected. The urea production rate also was increased such that a new steady-state fasting value was present. The calculated urea production rate accounted for 97% of the protein ingested on the 15% protein diet, but only 80% on the 30% protein diet, suggesting net nitrogen retention on the high-protein diet. In conclusion, an increase in dietary protein results in a number of metabolic adaptations in addition to reducing the circulating glucose concentration. Serum TSH, total T3, free T4, B12, folate, homocysteine, uric acid, and creatinine concentrations were unchanged.