Dried Fruit and Postprandial Glycemia Trial

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.