We recently reported that in subjects with untreated type 2 diabetes mellitus, a 5-week diet of 20:30:50 carbohydrate-protein-fat ratio resulted in a dramatic decrease in 24-hour integrated glucose and total glycohemoglobin compared with a control diet of 55:15:30. Body weight, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and serum ketones were unchanged; insulin and nonesterified fatty acids were decreased. We now present data on other hormones and metabolites considered to be affected by dietary macronutrient changes. The test diet resulted in an elevated fasting plasma total insulin-like growth factor 1, but not growth hormone. Urinary aldosterone was unchanged; free cortisol was increased, although not statistically. Urinary pH and calcium were unchanged. Blood pressure, creatinine clearance, serum vitamin B12, folate, homocysteine, thyroid hormones, and uric acid were unchanged. Serum creatinine was modestly increased. Plasma alpha-amino nitrogen and urea nitrogen were increased. Urea production rate was increased such that a new steady state was present. The calculated urea production rate accounted for 87% of protein ingested on the control diet, but only 67% on the test diet, suggesting net nitrogen retention on the latter. The lack of negative effects, improved glucose control, and a positive nitrogen balance suggest beneficial effects for subjects with type 2 diabetes mellitus at risk for loss of lean body mass.