Pre-meals of 3-hydroxybutyrate in Type 2 Diabetes

NCT05581043 | Completed

• 1 other identifier: V4_03052022
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Hyperglycemia following meals in patients with type 2 diabetes mellitus (T2DM) is a common problem. Recently, our group found that oral consumption of the ketone metabolite, 3-hydroxybutyrate (3-OHB), effectively stimulates insulin secretion and delays gastric emptying.The aim of this study is to investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 20 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes)

Conditions

Ketosis; Postprandial Hyperglycemia; Glucose Metabolism Disorders (Including Diabetes Mellitus)

Outcome Measures

Primary Outcomes (1)

• Blood glucose following the OGTT

  Change in blood glucose following the OGTT and compared between the different visits. Incremental change (delta) from baseline to peak. Measured with laboratory kits.

  Blood samples will be obtained -60, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes from the OGTT

Secondary Outcomes (1)

• Plasma concentrations of 3-OHB, insulin, C-peptide, glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), acetaminophen, free fatty acids along others.

  Blood samples will be obtained -60, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes from the OGTT

Study Arms (6)

0 gram 3-OHB 30 minutes before an OGTT

PLACEBO COMPARATOR

0 gram 3-OHB 30 minutes before an OGTT

Dietary Supplement: 3-hydroxybutyrate (3-OHB)

10 gram 3-OHB 30 minutes before an OGTT

EXPERIMENTAL

10 gram 3-OHB 30 minutes before an OGTT

Dietary Supplement: 3-hydroxybutyrate (3-OHB)

20 gram 3-OHB 30 minutes before an OGTT

EXPERIMENTAL

20 gram 3-OHB 30 minutes before an OGTT

Dietary Supplement: 3-hydroxybutyrate (3-OHB)

40 gram 3-OHB 30 minutes before an OGTT

EXPERIMENTAL

40 gram 3-OHB 30 minutes before an OGTT

Dietary Supplement: 3-hydroxybutyrate (3-OHB)

20 gram 3-OHB 0 minutes before an OGTT

EXPERIMENTAL

20 gram 3-OHB 0 minutes before an OGTT

Dietary Supplement: 3-hydroxybutyrate (3-OHB)

20 gram 3-OHB 60 minutes before an OGTT

EXPERIMENTAL

20 gram 3-OHB 60 minutes before an OGTT

Dietary Supplement: 3-hydroxybutyrate (3-OHB)

Interventions

3-hydroxybutyrate (3-OHB) DIETARY_SUPPLEMENT

The aim of this study was therefore to i) investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 25 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes).

0 gram 3-OHB 30 minutes before an OGTT; 10 gram 3-OHB 30 minutes before an OGTT; 20 gram 3-OHB 0 minutes before an OGTT; 20 gram 3-OHB 30 minutes before an OGTT; 20 gram 3-OHB 60 minutes before an OGTT; 40 gram 3-OHB 30 minutes before an OGTT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Older than 18 years of age
• Type 2 diabetes diagnosis
• No antiglycemic treatment or monotherapy with metformin

You may not qualify if:

• Hba1c \> 70
• Severe liver disease (Child-Pugh score \>10) or kidney disease (eGFR\< 40 ml/min)
• Anemia (Hgb \< 6.5 mM)
• History with pancreatitis
• Practicing ketogenic diets (i.e., low-carb diet, fasting regime)
• Inability to understand Danish or English
• Ongoing cancer or other acute/chronic serious diseases (PI will determine)

Sponsors & Collaborators

• University of Aarhus: lead
• Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark: collaborator
• Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark: collaborator

Study Sites (1)

Department of Endocrinology and Internal Medicine

Aarhus, 8200, Denmark

Location

Related Publications (1)

• Bangshaab M, Bengtsen MB, Smedegaard S, Sondergaard E, Moller N, Svart MV, Rittig N. Ketone supplementation dose-dependently lowers postprandial blood glucose, lipid and ghrelin levels in individuals with type 2 diabetes: a randomised crossover study. Diabetologia. 2025 Nov 28. doi: 10.1007/s00125-025-06614-0. Online ahead of print.

  PMID: 41315088 DERIVED

MeSH Terms

Conditions

Ketosis; Hyperglycemia; Glucose Metabolism Disorders

Interventions

3-Hydroxybutyric Acid

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Hydroxybutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Ketone Bodies; Ketones; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Niels Møller, Professor

  Professor

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We will use a randomized cross-over design to investigate 10 volunteers with T2DM on six different occasions separated with at least one week.

Study Record Dates

• First Submitted: October 4, 2022
• First Posted: October 14, 2022
• Study Start: January 12, 2023
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: January 17, 2024

Record last verified: 2022-10

Locations

DK (1)