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

J Diabetes Investig. 2021 May;12(5):756-762. doi: 10.1111/jdi.13423. Epub 2020 Nov 1.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • 3-Hydroxybutyric Acid / blood
  • Area Under Curve
  • Blood Glucose / drug effects*
  • C-Peptide / blood
  • Cross-Over Studies
  • Eating
  • Fatty Acids, Nonesterified / blood
  • Female
  • Glucagon / blood
  • Glucose / administration & dosage
  • Glucose Intolerance / blood*
  • Glucose Intolerance / therapy*
  • Glucose Tolerance Test
  • Glycemic Control
  • Humans
  • Insulin / blood
  • Ketones / pharmacology*
  • Male
  • Middle Aged

Substances

  • Blood Glucose
  • C-Peptide
  • Fatty Acids, Nonesterified
  • Insulin
  • Ketones
  • Glucagon
  • Glucose
  • 3-Hydroxybutyric Acid