The Effect of a Ketone Drink on Liver Glucose Production in People With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
What is the effect of a ketone drink on liver glucose production, and postprandial glycemia, in people with type 2 diabetes.

Detailed Description
-----------------
Background: Ketones are molecules that are naturally produced by our body during fasting or diets low in carbohydrates. Ketones can affect how our liver produces and maintains our body's blood sugar levels, which could be important in the management of type 2 diabetes (T2D), where high blood sugar levels are partly because of excess sugar production by the liver. Objectives: To determine if, and how, a ketone drink can lower blood glucose in people with T2D following a meal. Methods: Twelve people with T2D will visit our laboratory in the morning on two occasions and ingest a drink containing ketones or placebo on each visit in a random order before ingesting a milkshake style drink containing sugar. Blood samples will then be taken at regular intervals over 4 hours to determine if the ketone drink has lowered blood sugar levels in response to the meal, and if this was due to reduced sugar production by the liver. Value: This research will provide new knowledge about the regulation of liver blood sugar production in response to ketone ingestion. This may also inform future clinical trials to establish if ketone drinks could be used as a treatment for T2D.

Official Title
-----------------
The Effect of a Ketone Drink on Liver Glucose Production in People With Type 2 Diabetes

Conditions
-----------------
Diabetes Mellitus, Ketosis

Intervention / Treatment
-----------------
* Dietary Supplement: Ketone - beta-hydroxybutyrate (β-OHB)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with type 2 diabetes by a physician, a current HbA1c of 6.5-8.5%, and receiving treatment with lifestyle advice or oral glucose-lowering medications. Non-smoking Blood pressure <160/100 mm/Hg Exclusion Criteria: Exogenous insulin or SGLT2 inhibitors for type 2 diabetes treatment. Following a low-carbohydrate ketogenic diet, periodic fasting diet, or consuming ketogenic supplements. Other diagnosed chronic metabolic, cardiovascular, respiratory, neurological, or gastrointestinal disease. Smoker Blood pressure >160/100 mm/Hg Lactose intolerant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Ketone vs placebo crossover
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketone<br>Ketone monester (beta-hydroxybutyrate (β-OHB) | Dietary Supplement: Ketone - beta-hydroxybutyrate (β-OHB)<br>* Ketone - beta-hydroxybutyrate (β-OHB)<br>|
| Placebo Comparator: Placebo<br>Non-caloric placebo | Dietary Supplement: Ketone - beta-hydroxybutyrate (β-OHB)<br>* Ketone - beta-hydroxybutyrate (β-OHB)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EGP | Endogenous glucose production | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial glycemia | Postprandial glucose concentrations | 4 hours | 
| Insulin | Serum insulin concentration | 6 hours | 
| Plasma β-OHB | Plasma β-OHB concentrations | 6 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes, Exogenous ketones, Postprandial glycemia, Endogenous glucose production