BACKGROUND/OBJECTIVES: Postprandial hyperglycemia increases the risks of development of type 2 diabetes and cardiovascular diseases. The purpose of this study was to determine whether a 3-day low-carbohydrate/high-fat diet (LC/HFD) alters postprandial plasma glucose and incretin levels during oral glucose tolerance test (OGTT) in healthy men. SUBJECTS/METHODS: Nine healthy young men (age (mean±s.e.), 27±1 years; body mass index, 22±1 kg/m 2 ) consumed either a normal diet (ND: energy from B22% fat) or a LC/HFD (energy from B69% fat) for 3 days each. The total energy intake from each diet was similar. An OGTT was performed after each 3-day dietary intervention. Postprandial plasma glucose, insulin, free fatty acid and glucagon-like peptide-1 (GLP-1) levels were determined at rest and during the OGTT. RESULTS: Plasma glucose levels and incremental area under the curve during the OGTT were significantly higher in the LC/HFD trial than in the ND trial (P ¼ 0.024). In addition, increase in GLP-1 levels was significantly higher in the LC/HFD trial than in the ND trial (P ¼ 0.025). The first-phase insulin secretion indexes were significantly lower in the LC/HFD trial than in the ND trial (Po0.041).CONCLUSIONS: These results demonstrate that even short-term LC/HFD increased postprandial plasma glucose and GLP-1 levels in healthy young men. A decrease in first-phase insulin secretion may partially contribute to the short-term LC/HFD-induced increase in postprandial plasma glucose levels. Keywords: postprandial hyperglycemia; incretin; impaired glucose tolerance; glucose-dependent insulinotropic polypeptide INTRODUCTION Postprandial hyperglycemia is a condition of high blood glucose level after eating a meal, and is an effective predictor of mortality from all causes and cardiovascular diseases (CVD) as well as the risk of developing type 2 diabetes.1-3 Furthermore, decreasing postprandial hyperglycemia with medications reduces the risks of developing CVD and type 2 diabetes. [4][5][6] One of the factors explaining the association between postprandial hyperglycemia and the development of CVD and type 2 diabetes is the resulting acute fluctuation in blood glucose levels. Interestingly, acute fluctuation in blood glucose levels suppresses endotheliumdependent vasodilation, 7 and increases levels of interleukin-6, tumor necrosis factor-a 8 and platelet hyperaggregability 9 in healthy men; all these parameters have been associated with the development of CVD. Therefore, it is important to elucidate the factors that elicit postprandial hyperglycemia for the prevention of both CVD and type 2 diabetes.A low-carbohydrate/high-fat diet (LC/HFD) has a key role in the development of postprandial hyperglycemia. Short-term exposure (1-11 days) to LC/HFD decreases carbohydrate oxidation 10-16 and increases endogenous glucose production. 10,17 In addition, shortterm LC/HFD (3-5 days) decreases insulin sensitivity, as measured using the hyperinsulinemic-euglycemic glucose clamp 18,19 and the intravenous glucose tolerance test. 20 However...