Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02624609 |
| Other study ID # |
MEEC 12-037c |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
December 4, 2015 |
| Last updated |
June 2, 2017 |
| Start date |
November 2015 |
| Est. completion date |
March 2016 |
Study information
| Verified date |
June 2017 |
| Source |
University of Leeds |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Consumption of carbohydrate containing foods or sugary drinks brings about changes to the
blood glucose levels. After a meal or drink, blood glucose rises until it reaches a peak
concentration usually after 30 minutes. When the body senses the increase in blood glucose,
a hormonal process involving insulin takes place to ensure that the glucose is taken up from
the blood for storage and where it is needed for energy in the body. This process then
brings about a decrease in the concentration of glucose until it reaches approximately the
starting concentration. The original concentration of glucose is attained approximately 2
hours after eating or drinking a carbohydrate food or sugary drink respectively in healthy
people.
Different carbohydrates and sugary drinks have different effects on blood glucose response
depending on the amount as well as the type of carbohydrate. Those that give rise to a high
glucose response compared to a reference carbohydrate (usually glucose) are said to be high
glycaemic index (GI) foods and those with a lower glucose response compared to a reference
carbohydrate (usually glucose) are said to be low glycaemic index (GI) foods.
Research has shown that diets that give rise to a high glucose response are associated with
a number of abnormalities like increased risk of metabolic syndrome. Metabolic syndrome
mostly comprises of insulin resistance and glucose intolerance which gives an increased risk
of type 2 diabetes. It also gives rise to other conditions like high blood pressure
(arterial hypertension), elevated blood insulin levels (hyper-insulinemia), elevated amounts
of fat in the liver (fatty hepatosis) and elevated amounts of lipids in the blood
(dyslipidemia). After type 2 diabetes become clinically apparent, the risk of cardiovascular
disease also rises. Research has also shown that foods/drinks which raise blood glucose
levels gradually (low GI) rather than rapidly (high GI) have health benefits which include
reducing the risk of metabolic syndrome. Laboratory studies have shown that polyphenols
found in fruits, vegetables and plant based foods have a positive effect on carbohydrate
metabolism and can lower the blood glucose levels.
This research will determine whether the presence of polyphenols in the diet has any
lowering effect on the blood glucose levels and hence the glycaemic index of foods. This
will be determined by asking volunteers to consume commercially available food supplements
together with white bread and then determining the glycaemic response. The blood glucose
response of bread will be determined initially as a control reference. All will be consumed
in random order.
Analysis will be done by measuring blood glucose response after consumption of the control
reference meal and the test meal containing polyphenols and then determining the incremental
area under the glucose curve.
Description:
The world health organisation has reported that over 220 million people suffer from diabetes
worldwide and that by the year 2030, this number will be doubled. The world health
organisation (WHO) also reports that in 2004, about 3.4 million people died from high blood
sugar. About 90% of all diabetes cases is due to type II diabetes. Type 2 diabetes is
largely due to overweight and lack of physical activity characterised by high glucose levels
(hyperglycaemia).
In the human diet, the source of blood glucose is carbohydrates. Dietary carbohydrate is
important to maintain glycaemic homeostasis and provides the most of the energy in the diets
of most people. The control of blood glucose is a hormonal process and it is very important
to human physiology. Hormonal processes involve the release of insulin from the β- cells of
the pancreatic cells which stimulates the uptake of glucose after a meal, to other tissues
either for utilisation (glycolysis) or to be stored in the liver as glycogen (glycogenesis).
When blood glucose falls below normal, glucagon is secreted from the pancreatic α-cells and
it promotes liver glucose production by inducing the generation of glucose from
non-carbohydrate substrates such as amino and fatty acids (gluconeogenesis) and the
generation of glucose from glycogen (glycogenolysis).
When the glucose homeostasis hormonal control fails, it entails high blood glucose levels
(postprandial hyperglycaemia) which can lead to metabolic syndrome which includes obesity,
impaired glucose tolerance (IGT), hypertension and dyslipidemia. Disturbance of glucose
homeostasis can also lead to other symptoms such as inflammation and oxidative stress at the
whole body level as well as disturbances of the functionality in several organs as well as
diabetes . Therefore, as much as carbohydrates are required in the human body as a major
source of energy, too much in the diet can have adverse health effects especially the one
with high glycaemic effect.
The proposed mechanism adapted from Aston, 2006 of how carbohydrates may affect human health
is that when there is a continual presence of high glycaemic index foods in the diet, this
gives rise to postprandial glucose rise as well as high insulin demand to act on the high
blood glucose levels in the blood. Postprandial glucose rise and high insulin demand may
lead to insulin resistance which is the major component of metabolic syndrome. High insulin
demand may also lead to β-cell failure which may also result in hyperglycaemia which is also
a cause of insulin resistance. Insulin resistance and hyperglycaemia are risk factors for
metabolic syndrome and diabetes type 2.
Scientific evidence suggest that postprandial hyperglycaemia in humans has a major role to
play in health priorities like type 2 diabetes and blood glucose control. It has been
reported that about 90% of all diabetes cases consist of type 2 diabetes. Apart from type I
and type 2 diabetes, there are other related conditions which include pre-diabetes (impaired
glucose tolerance (IGT) and impaired fasting glucose (IFG) as well as metabolic syndrome
(obesity, hypertension and insulin resistance). It has been reported that pre-diabetes and
metabolic syndrome increases the risk of developing cardiovascular disease and diabetes
mellitus. The glycaemic index was originally proposed with the aim of managing diabetes.
However, recent studies have shown that the GI has potential in the prevention of type 2
diabetes as well as in the treatment of metabolic syndrome. Research has shown that high GI
diets are associated with increased risk of developing type 2 diabetes . More research has
shown that high GI diet is associated with a number of abnormalities like increased
metabolic syndrome and insulin resistance. In the same way, a low GI diet is said to improve
insulin sensitivity but more research is needed to support this. A few studies have shown
this to be the case. However it was observed that it was difficult to know whether this was
as a result of improved insulin sensitivity, or improved insulin secretion or due to reduced
rate of glucose absorption.
Potential solution Having anything in the diet that can either slow down the digestion and
absorption of carbohydrates can help reduce the risk . Among others, two potential solutions
are that of consumption of low glycaemic index foods or having ingredients in the diet that
can reduce the glycaemic index of foods as well as postprandial blood glucose levels. The
presence of inhibiting components in the diet that can reduce postprandial glucose can also
be a solution to reducing the risk. Drugs like acarbose are currently used in some countries
for the management of type 2 diabetes which act by inhibiting carbohydrate digestive
enzymes. However, the use of acarbose has side effects such as nausea, flatulence and
diarrhoea. It has been reported that polyphenols also have the potential to inhibit the rise
in blood glucose by hindering the rapid absorption of glucose.
A recent review has reported that research using animal models as well as a limited number
of human studies, have shown that polyphenols and polyphenol rich foods or beverages have
the potential to affect postprandial glycaemic responses and fasting glycaemia as well as an
improvement of acute insulin secretion and sensitivity. Other possible mechanisms as
reported in the review include pancreatic β- cells stimulation to secrete insulin as well as
activation of insulin receptors, modulation of the release of glucose from the liver as well
as of intracellular signalling pathways and gene expression.
Another recent review concluded that it is very possible that the effects of polyphenols in
the diet will affect glycaemic index of foods as well as postprandial glucose responses in
humans. The two mechanisms highlighted by which this can be achieved being the inhibition of
sugar metabolising enzymes as well as transporters. This potential action of polyphenols can
thus be compared to that of acarbose which acts by the same mechanism and research in
chronic intervention studies has shown that it reduces diabetes risk.
This research will involve the use of pomegranate juice as a source of polyphenols. The
study was approved by the University of Leeds Mathematical and Physical Sciences (MAPs) and
Engineering joint Faculty Research Ethics Committee (MEEC) with application number
MEEC12-037 (amended). A total of 16 volunteers will be recruited. The volunteers will be
screened for their fasting blood glucose level. They will need to be healthy and their
fasting blood glucose levels should fall within the healthy range of 4.3-5.9mmol/L.
The volunteers are scheduled to attend 4 visits. During each visit, the volunteer comes
fasted in the morning and the fasting blood glucose is measured by the use of a glucometer.
The volunteer is then given a test meal which will be randomized and blood glucose will be
measured at 15, 30, 45, 60, 90, 120,150 and 180 minutes after the first bite of the test
meal. The results will be used to plot the area under the curve and results obtained after
consuming test meals will be compared to those obtained after consumption of control meals.
