Diabetes Mellitus Clinical Trial
Official title:
Dried Fruit as a Means for Lowering the Glycemic Response to High Glycemic Index-carbohydrate Foods
Dried fruits show promising potential for the management of blood glucose. Previous trials have reported beneficial effects of raisins on post-prandial glucose and insulin responses in healthy individuals when compared with white bread. However, to date there is limited data evaluating the potential beneficial effects of other dried fruits (i.e. sultanas, dates and apricots). It is also unclear whether dried fruits can be used to lower the postprandial glycemic responses to high-GI carbohydrate foods by either displacing available carbohydrate (displacement effect) or providing 'catalytic' doses of fructose ('catalytic' fructose effect). To address these questions, the investigators propose to assess the GI of 4 common types of dried fruit (raisins, sultanas, dates, apricots) (GI effect) and their ability to decrease the postprandial glycemic response to white bread by either partially displacing available carbohydrate (displacement effect) or by providing a 'catalytic' dose of fructose ('catalytic' fructose effect).
BACKGROUND:
All studies assessing the glycemic index (GI) of traditional dried fruit show that they are
low-to-moderate GI foods and that the insulin response is proportional to their GI. A recent
study compared the glycemic response of two doses of raisins (28 and 69g) versus white bread
showing that both doses of raisins significantly reduced post-prandial glucose and insulin
levels compared with white bread. However, the effect of combining dried fruits with high-GI
carbohydrate foods has never been addressed. The potential impact of combining nuts (i.e.
pistachios) and high-GI carbohydrate foods has already analyzed with positive results. The
investigators found that a dose of 56g of pistachios consumed alone had a minimal effect on
post-prandial glycemia, but when taken with a high-carbohydrate meal attenuated the relative
glycemic response. Although foods with high fibre content generally have a low-GI, other
factors also contribute to a food's glycemic response. Factors thought to contribute to the
glycemic response of dried fruits include the viscous texture when chewed; their whole food
matrix; the presence of phenolic compounds and organic acids and the type of sugar present.
In the case of dried fruit, about 50% fructose (low-GI) is present. Therefore, the
consumption of dried fruit with high-carbohydrate foods may lead to glycemic control
benefits by lowering the GI of a food. In addition to potentially lowering the GI of a food,
dried fruits may also affect glycemic control by providing 'catalytic' doses of fructose.
Fructose, through its metabolite fructose-1-P, has been shown to have "catalytic" effects on
hepatic glucose metabolism by inducing glucokinase activity in hepatocytes. In specific,
fructose-1-P displaces fructose-6-P from glucokinase's regulatory binding protein in the
nucleus causing the release of glucokinase from its regulatory protein, allowing it to
translocate to the cytosol, resulting in increased phosphorylation of glucose. Infusion
studies in humans have shown that this mechanism relates to a ~30% decrease in hepatic
glucose output under hyperglycemic conditions in participants with type 2 diabetes (T2D) and
a ~3-fold increase in glycogen synthesis by C13-nuclear magnetic resonance (NMR)
spectroscopy under euglycemic conditions in healthy people. Clinical translation of these
findings has proven promising. Catalytic doses of fructose at 7.5g and 10g have been shown
to decrease the postprandial glycemic responses to high GI meals (oral glucose,
maltodextrins, or mashed potatoes) from ~15-30% in healthy participants and those with
pre-diabetes or diabetes . These acute effects have been shown to be sustainable over the
longer term as well. Systematic reviews and meta-analyses of controlled feeding trials have
shown that small doses of fructose in exchange for other carbohydrates decreases HbA1c at a
level which exceeds the clinically meaningful threshold of 0.3% proposed by the Federal Drug
Administration (FDA) for the development of new oral anti-hyperglycemic agents. Therefore,
the consumption of dried fruit with high-carbohydrate foods may lead to glycemic control
benefits by acting as a vehicle for 'catalytic' doses of fructose.
OBJECTIVES:
To investigate the effect of using dried fruit to modify the glycemic response of high GI
foods, the investigators propose the following 3 objectives:
1. To assess the GI of 4 common types of dried fruit (raisins, sultanas, dates, apricots)
(GI effect)
2. To assess the ability of the 4 common types of dried fruit (raisins, sultanas, dates,
apricots) to decrease the postprandial glycemic response to white bread by displacing
half of the available carbohydrate (displacement effect)
3. To assess the ability of the 4 common types of dried fruit (raisins, sultanas, dates,
apricots) to decrease the postprandial glycemic response to white bread by providing a
'catalytic' dose (7.5g) of fructose ('catalytic' fructose effect)
PARTICIPANTS:
The investigators will include male or non-pregnant female participants aged 18-75 years and
who are otherwise healthy.
DESIGN:
The trial will use a randomized multiple crossover acute-feeding design in which each
participants acts as their own control.
PROTOCOL:
The protocol will follow ISO 26642:2010(en), "Food products — Determination of the glycaemic
index (GI) and recommendation for food classification". All participants will complete all
test and control foods in the study series. An individual participant will normally complete
1 to 3 tests per week with at least one day in between. Participants will be studied between
7:00 and 9:30am after an overnight fast of 10-14h. On each test occasion the subject will be
weighed, and two fasting blood samples will be obtained at -5 minute (min) intervals by
finger-prick. Then the subject will start to consume a test meal. At the first bite a timer
will be started and additional blood samples will be taken at 15, 30, 45, 60, 90 and 120 min
after the start of the meal. Before and during the test, a blood glucose test record will be
filled out with the subject's initials, ID number, date, body weight, test meal, time they
start to eat, time it took to eat, time and composition of last meal, and any unusual
activities. During the 2 hours the test subjects will remain seated.
BLOOD SAMPLES:
Each finger-prick sample consists of a total of 2-3 drops of blood obtained by finger prick
and will be divided into two separate vials. The 2 to 3 drops of capillary blood will be
collected into flat-bottomed 5ml plastic tubes with a push cap containing a small amount of
sodium fluoride and potassium oxalate as an anticoagulant and preservative. These samples
will be used for analyzing capillary blood glucose levels. The finger-prick samples for
glucose analysis will initially be placed in the refrigerator and at the end of two hours,
placed in a -20°C freezer until analysis which will be performed within a week. Glucose
analysis will be done using a YSI model 2300 STAT analyzer (Yellow Springs, OH). Each
subject will participate in a total of 15 separate test meals: 3 white bread control meals
and 3 dried fruit treatments (dried fruit - GI effect, dried fruit -displacement effect, and
dried fruit - 'catalytic' fructose effect) for each of the 4 dried fruits (raisins,
sultanas, dates and apricots) (Figure 1). The order of the test meals will be randomized by
a coordinator blinded to the treatment allocation. Test meals will be separated by a minimum
of a 1-day washout.
STATISTICAL ANALYSES:
Blood glucose areas will be calculated as the incremental area under the curve (iAUC) using
the trapezoidal rule with peak heights as maximal incremental rises in glucose. The glycemic
indices of the test meals will be calculated using the 3 bread meals as the reference food.
Pairwise differences in GI between the white bread control and the 3 dried fruit treatments
(dried fruit - GI effect, dried fruit - GI displacement effect, and dried fruit -
'catalytic' fructose effect) for each of the 4 dried fruits (raisins, sultanas, dates and
apricots) will be assessed by the Dunnett's test in SAS (SAS Inst. Version 8.2; Gary, NC).
EXPECTED RESULTS:
The investigators expect that dried fruit will have a low-to-moderate GI and will reduce
postprandial glycemic responses when consumed in combination with high-GI foods in
comparison to high-GI foods alone. The specific aims of our study are: (1) to quantify the
GI of 4 different types of dried fruit (raisins, sultanas, dates, apricots) (GI effect); and
(2) to assess the ability of these 4 dried fruits to decrease the postprandial glycemic
response to white bread by either partially displacing available carbohydrate (displacement
effect); or (3) by providing a 'catalytic' dose of fructose ('catalytic' fructose effect).
The proposed study will help to identify mechanisms by which dried fruits can improve
postprandial glycemia when consumed in combination with high-GI carbohydrate foods by
assessing a glucose displacement mechanism along with a 'catalytic' fructose mechanism. The
results will stimulate important industry innovation and improve the design of future
clinical investigations that will ultimately lead to the use of dried fruits as an effective
tool to modify the glycemic response of high carbohydrate foods and with it longer-term
glycemic control in people with or at risk for type 2 diabetes.
;
Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator)
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