Dried Fruit and Postprandial Glycemia Trial

November 7, 2016 updated by: John Sievenpiper, University of Toronto

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).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Anticipated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5C 2N8
        • GI Labs

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult males and/or non-pregnant females aged 18-75 years and in good health

Exclusion Criteria:

  • Age less than 18 years or greater than 75 years
  • BMI<18.5kg/m2 or >30kg/m2
  • Known history of HIV, liver disease, kidney disease, thyroid disease, diabetes, heart disease or or any other major illnesses that may affect carbohydrate metabolism
  • Subjects using medications which might, either: 1) make participation dangerous to the subject or to others, or 2) affect the results
  • Subjects who cannot or will not comply with the experimental procedures or do not follow the clinic's safety guidelines.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: White Bread (Control)
Participants will consume a test meal containing white bread (dose: 50g available carbohydrate) at three study visits.
Other: White Bread (Control)
A randomized multiple-crossover acute-feeding trial design. Each participant will act as their own control receiving the treatments in random order, each separated by a 1 day washout period.
Experimental: Dried Fruit - Glycemic Index
Participants will consume a test meal containing one variety of dried fruit (dose: 50g available carbohydrate) per visit for four visits. Varieties include raisins, sultanas, dates, and apricots.
Other: Dried Fruit - Glycemic Index
A randomized multiple-crossover acute-feeding trial design. Each participant will act as their own control receiving the treatments in random order, each separated by a 1 day washout period.
Experimental: Catalytic Fructose Dose Effect
Participants will consume a test meal containing white bread (dose: 50g available carbohydrate) and one variety of dried fruit (dose: 7g fructose) per visit for four visits. Varieties of dried fruit include: raisins, sultanas, dates, and apricots.
Other: Catalytic Fructose Dose Effect
A randomized multiple-crossover acute-feeding trial design. Each participant will act as their own control receiving the treatments in random order, each separated by a 1 day washout period.
Experimental: High GI Displacement Effect
Participants will consume a test meal containing white bread (dose: 25g available carbohydrate) and one variety of dried fruit (dose: 25g available carbohydrate) per visit for four visits. Varieties of dried fruit include: raisins, sultanas, dates, and apricots.
Other: High GI Displacement Effect
A randomized multiple-crossover acute-feeding trial design. Each participant will act as their own control receiving the treatments in random order, each separated by a 1 day washout period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Glycemic index (GI)
Time Frame: Up to 120min
Up to 120min

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Toronto

Collaborators

International Nut and Dried Fruit Council (INC)
The National Dried Fruit Trade Association (NDFTA)
Glycemia Consulting Inc.

Investigators

  • Principal Investigator: John L Sievenpiper, MD PhD FRCPC, University of Toronto, St. Michael's Hospital
  • Principal Investigator: Cyril Kendall, PhD, University of Toronto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2016

Primary Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

November 1, 2016

First Submitted That Met QC Criteria

November 7, 2016

First Posted (Estimate)

November 9, 2016

Study Record Updates

Last Update Posted (Estimate)

November 9, 2016

Last Update Submitted That Met QC Criteria

November 7, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INC-Dried Fruit Trial 2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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