The acute effect of increasing meal frequency as a model of slow absorption was studied for 1 d in 11 patients with non-insulin-dependent diabetes. On 1 d they took 13 snacks (the nibbling diet) and on another day the same diet was taken as three meals and one snack (the three-meal diet). The nibbling diet reduced mean blood glucose, serum insulin, and C peptide concentrations over the 9.5 h of observation and 24-h urinary C peptide output by 12.7 +/- 3.7% (mean +/- SE) (P = 0.0062), 20.1 +/- 5.8% (P = 0.0108), 9.2 +/- 2.6% (P = 0.0073), and 20.37 +/- 8.12% (P = 0.039), respectively, compared with the three-meal diet. Serum triglyceride concentrations were lower by 8.5 +/- 3.2% (P = 0.037). Despite lower insulin concentrations on the nibbling diet, the concentrations of free fatty acids, 3-hydroxybutyrate, and the insulin-sensitive branched-chain amino acids responded similarly on both treatments. Metabolic benefits seen with increased meal frequency may explain the success of similar agents that prolong absorption, including fiber and enzyme inhibitors.