OBJECTIVE - In normal subjects, ingestion of butter with potato resulted in considerably lower blood glucose levels but similar or higher insulin concentrations compared with those observed in the same subjects after potato ingestion alone. We determined whether butter ingested with potato would result in a greater stimulation in insulin secretion than ingestion of potato alone in subjects with NIDDM. RESEARCH DESIGN AND METHODS - Seven male subjects with untreated NIDDM ingested 50 g CHO alone or 50 g CHO with 5, 15, 30, or 50 g fat as a breakfast meal. Fat was ingested in the form of butter, and CHO was given in the form of potato. Subjects received 50 g glucose on two separate occasions for comparative purposes. The subjects also were given only water and were studied over the same time period (water control). Plasma glucose, glucagon, α-amino nitrogen, nonesterified fatty acids, serum insulin, C-peptide, and triglyceride concentrations were determined over 5 h. The integrated area responses were quantified over the 5-h period using the water control as a baseline. RESULTS - The mean plasma glucose area response after ingestion of potato with or without the various amounts of butter were all similar and were 82% of that observed after ingestion of 50 g glucose. The mean insulin area response to potato alone was 532 pmol · h · L-1. The mean insulin area responses to potato plus 5,15,30, and 50 g of fat meals were 660,774,750, and 756 pmol · h · L-1, respectively. Thus, the mean insulin areas were all greater than for ingestion of potato alone, and a maximal response was observed with addition of 15 g fat (1.4-fold). The C- peptide data did not confirm an increase in insulin secretion. Overall the area responses after ingestion of meals containing fat were not different from the response to potato ingestion alone, although the responses were erratic. The glucagon area response was positive after ingestion of all fat containing meals except for that containing only 5 g fat, and there was a dose-response relationship. The plasma α-amino nitrogen and nonesterified fatty acid area responses were negative after potato ingestion and were not significantly different when fat was added. The serum triglyceride concentration increase was greater after the ingestion of butter with the potato as expected. CONCLUSIONS - In contrast to the results in normal subjects after ingestion of butter with potato, the glucose response was not smaller in subjects with NIDDM. The insulin response was greater. The insulin area response data indicated the presence of a dose-response relationship. Whether similar responses will be observed with other dietary fat and CHO sources remains to be determined.