Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT04854330 |
Other study ID # |
007 |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
April 26, 2021 |
Est. completion date |
February 21, 2023 |
Study information
Verified date |
April 2021 |
Source |
University of Portsmouth |
Contact |
Maria Perissiou, PhD |
Phone |
+447762860432 |
Email |
maria.perissiou[@]port.ac.uk |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Type 2 diabetes mellitus (T2DM) reduces the ability of the body to use sugar as a fuel. As an
alternative people with T2DM can use fat from the blood stream instead. Fat is a good store
of energy, however, the body requires about 20% more oxygen to produce energy from fat
compared to sugar. People with T2DM often have heart disease as well. This can lead to
limited availability of oxygen in the heart muscle, which increases the workload of the heart
and will impact on the ability to perform everyday tasks, such as walking up a flight of
steps. Recently, it has been suggested that ketone esters (a sports drink that contains
ketones) may be used as an alternative source of energy for people with diabetes as they are
approximately 8% more efficient than fat. The investigators will assess whether these ketones
can be used as a more efficient source of energy and improve how the heart works in people
with T2DM. If successful, this is a relatively cheap treatment, which could be immediately
implemented in people with T2DM to improve heart function and the ability to perform everyday
tasks.
Description:
Type 2 diabetes mellitus (T2DM) is a chronic and progressive metabolic disease associated
with an increased prevalence of cardiovascular events, and therefore represents a significant
global health concern. The aetiology of the disease is complex and involves the interaction
of both non-modifiable (i.e., genetic predisposition) and modifiable (e.g., physical activity
levels, diet, body mass) risk factors. Individuals with T2DM have an impaired ability to
utilise glucose, the body's most efficient energy substrate (providing 2.58 ATP per molecule
of oxygen), due to a decreased capacity to produce and/or utilise insulin. Consequently,
there is an increased reliance on the metabolism of less efficient fuel sources,
predominantly the metabolism of the free fatty acid palmitate, which produces 2.33 ATP per
molecule of oxygen and thereby increases oxygen requirements by approximately 10% relative to
glucose metabolism. This increased oxygen cost that manifests at rest and during exercise,
increases the effort required to perform physical tasks which may discourage physical
activity, further exacerbating the disease state and the prevalence of associated
cardiovascular co-morbidities, and may ultimately reduce quality of life.
Whereas at high concentrations, ketone bodies are known to be toxic, at a low dose ß
hydroxybutyrate, one of the most common ketone bodies produced, can be used as a metabolic
substrate. Although not an efficient store of energy per se, the energy can be released at a
lower O2 cost than free fatty acids, generating 2.50 units of ATP per unit of O2 consumed.
Theoretically, this 7% improvement in efficiency would be of benefit to those with heart
disease and diabetes. Whilst there are several studies demonstrating the theoretical benefit
of this improvement in efficiency in vitro or in animal models, to date this has not been
demonstrated in humans.
Sodium glucose transporter 2 (SGLT-2) inhibitors, a class of anti-hyperglycaemic agents, have
been shown to suppress insulin production whilst stimulating glucagon, an action that
engenders mild hyperketonaemia. Interestingly, recent trials have suggested the use of SGLT-2
inhibitors have a cardio-protective effect indicated by a significant reduction in
cardiovascular related death in people with type 2 diabetes. It is hypothesised that this
benefit is mediated through alternate substrate utilisation. These medications, however
cannot be used for all individuals. They are not licensed for, nor are likely to be effective
for people with impaired renal function, which is common among people with heart failure and
diabetes. The associated risk of genital infections is over 10% even in those who have been
prescribed the SGLT-2 inhibitors medication.
Exogenous ketone supplements can be ingested in the form of ketone esters and have been
proven efficient in improving metabolic profile by decreasing circulating glucose and free
fatty acids. More specifically a ketone monoester (Kme) supplement has been shown to provide
a rapid increase in blood ß-hydroxybutyrate levels within 30 min in healthy humans.
Importantly, once ingested, Kme is metabolised into ß-hydroxybutyrate, which is the isoform
produced by endogenous ketogenesis. Therefore, the oral consumption of Kme may be an
interesting alternative for increasing ß hydroxybutyrate and therefore improving metabolic
efficiency and cardiovascular function in individuals with T2DM.