Ingestion of an exogenous ketone monoester improves the glycemic response during oral glucose tolerance test in individuals with impaired glucose tolerance: A cross-over randomized trial

Abstract

Aims/introduction: As a low-carbohydrate diet and the use of sodium-glucose transporter-2 inhibitors are both known to increase D-beta-hydroxybutyrate 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 the 75-g oral glucose tolerance test (OGTT) in participants with impaired glucose tolerance.

Materials and methods: Nine Japanese adults aged 48-62 years (4 men, 5 women) with impaired glucose tolerance participated in this study. After participants fasted overnight, we carried out OGTT for 180 min with and without KM ingestion on two separate days in a randomized cross-over design. We compared the area under the curve (AUC) of D-beta-hydroxybutyrate, glucose, insulin, C-peptide, glucagon and free fatty acids during OGTT.

Results: The AUC of D-beta-hydroxybutyrate during OGTT was significantly higher with KM than without KM (KM 5995.3 ± 1257.1 mmol/L·h; without KM 116.1 ± 33.9 mmol/L·h, P < 0.0001), and the AUC of 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 of insulin during the first half (0-90 min) of OGTT, even though the AUC of C-peptide during this period was unchanged. In contrast, the AUC of insulin, C-peptide, glucagon and free fatty acids during 180 min of OGTT were similar in both conditions.

Conclusion: The ingestion of KM decreased the AUC of glucose during 75-g OGTT in Japanese individuals with impaired glucose tolerance, and the mechanism might involve elevated levels of circulating early phase insulin.

Keywords: Impaired glucose tolerance; Insulin secretion; Ketone.

Figure 1

CONSORT flow diagram for cross‐over randomized trials. OGTT, oral glucose tolerance test.

Figure 2

Temporal changes in blood parameters during a 75‐g oral glucose tolerance test. (a) D‐beta‐hydroxybutyrate (βHB), (b) plasma glucose, (c) insulin, (d) C‐peptide, (e) glucagon and (f) free fatty acids (FFA). The dotted lines indicate the control condition, and the solid lines indicate the ketone condition. Each datapoint indicates the mean value ± standard deviation with n = 9, except n = 8 for insulin at 180 min. *P < 0.05, significant difference between the conditions.