Ingestion of an Exogenous Ketone Monoester Improves the Glycemic Response during Oral Glucose Tolerance Test in Subjects with Impaired Glucose Tolerance: A Crossover Randomized Trial.

AIMS/INTRODUCTION Since a low-carbohydrate diet and the use of sodium glucose transporter-2 inhibitors are both known to increase D-beta-hydroxybutyrate (βHB) levels, the effect of these levels on glucose metabolism has attracted attention. We investigated the acute effects of ketone monoester (KM) ingestion on blood glucose levels during 75-g oral glucose tolerance testing (OGTT) in participants with impaired glucose tolerance (IGT). MATERIALS AND METHODS Nine Japanese adults aged 48-62 years (4 male, 5 female) with IGT participated in this study. After participants fasted overnight, we performed OGTT for 180 minutes with and without KM ingestion on 2 separated days in a randomized cross-over design. We compared the area under the curve (AUC) of βHB, glucose, insulin, C-peptide, glucagon, and free fatty acids (FFA) during OGTT. RESULTS The AUC-βHB during OGTT was significantly higher with KM than without KM (KM, 5995.3 ± 1257.1 mmo/L h; without KM, 116.1 ± 33.9 mmo/L·h , P<0.0001), and the AUC-glucose with KM was significantly lower than that without KM (KM, 406.6 ± 70.6 mg/dL h; without KM, 483.2 ± 74.3 mg/dL·h, P<0.0001). This improved glucose excursion was associated with enhanced AUC-insulin during the first half (0-90 minutes) of OGTT, even though the AUC-C-peptide during this period was unchanged. In contrast, AUC-insulin, C-peptide, glucagon, and FFA during 180 minutes of OGTT were similar in both conditions. CONCLUSION The ingestion of KM decreased AUC-glucose during 75-g OGTT in Japanese with IGT, and the mechanism may involve elevated levels of circulating early phase insulin.