Adult-onset insulin dependent diabetes mellitus (IDDM) is associated with significant residual insulin secretion. The process leading to the ultimate destruction of B cells may be influenced, among other factors, by the quality and amount of ingested protein. Using a standardized food questionnaire, we matched 13 individuals with normal protein (NP; 0.74 +/- 0.08 g/kg.day) and high protein (HP; 1.87 +/- 0.26 g/kg.day) intake from a sample of 117 newly diagnosed IDDM patients according to sex, age, body mass index, and energy intake. Nondiabetic control subjects were also selected. Dietary habits did not change significantly over an observation period of 1 yr. Glucagon-stimulated C peptide was significantly higher in the NP compared to the HP group (0.71 +/- 0.06 vs. 0.50 +/- 0.04 nmol/L; P < 0.002). NP food was associated with higher overall insulin sensitivity in both patients and nondiabetic subjects. Hepatic glucose output was significantly increased in individuals with HP intake [HP IDDM, 14.8 +/- 0.6 vs. NP IDDM, 12.7 +/- 0.7 (P < 0.01); HP control, 12.2 +/- 0.5 vs. NP control, 10.9 +/- 0.5 (P < 0.01 mumol/kg.min). Insulin-mediated suppression of hepatic glucose production was impaired in diabetic patients with high protein intake, but not in patients with normal protein diet. Gluconeogenesis estimated from 13C enrichment in breath and plasma was increased in individuals on a HP diet. We conclude that a NP diet is accompanied by delayed progression of the continuous loss of endogenous insulin in IDDM. This phenomenon is possibly due to decreased insulin demand on the B cells and/or reduced hepatic glucose production favoring enhanced insulin sensitivity.