Effects of an Apple Extract on Glycaemia: The GLU-Pomme Study

Dose-response Effect of an Apple Extract on Postprandial Glycaemia: a Randomised Controlled Trial. The GLU-POMME Study.

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02940249

Acronym

GLU-Pomme

Enrollment

Registered

2016-10-20

Start date

2017-01-31

Completion date

2018-02-28

Last updated

2020-06-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prevention of Hyperglycaemia

Keywords

Polyphenol, Apple, Fruit, Hyperglycaemia, Metabolic

Brief summary

Postprandial hyperglycaemia can lead to adverse modifications to functional proteins within the body and eventually lead to the development of type 2 diabetes. Previous research by this group has shown that an apple polyphenol extract reduced hyperglycaemia following a high-carbohydrate meal. The aim of this study is to investigate the effects of lower doses of the apple extract on postprandial glycaemia, insulinaemia and plasma gastric inhibitory polypeptide concentrations following a mixed carbohydrate test meal.

Detailed description

Introduction: Sharp peaks in blood glucose levels can lead to adverse modifications to functional proteins, oxidative stress and pancreatic beta cell dysfunction. It is therefore desirable to consume a diet that will allow more gradual rises in blood glucose levels after meals. Fruit polyphenols may help to limit the glucose excursion following a high carbohydrate meal. Previous research by this research group has demonstrated that 1200 mg of apple polyphenols (Appl'In™) inhibited the average incremental area under the curve (T+0 to T+30 min) of plasma glucose by 54% relative to placebo. Possible mechanisms include inhibition of intestinal enzymes and inhibition of intestinal glucose absorption by decreasing SGLT1/GLUT2 transport activity. The literature also suggests that foods rich in polyphenols exert beneficial effects on risk factors of cardiovascular disease such as hypertension, lipid metabolism and vascular function. Study design: A randomised, controlled, double-blind, cross-over study will be conducted. Four matched test drinks will be consumed in random order on separate study visits immediately before a mixed-carbohydrate test meal, containing either: 1) 1.2 g, 2) 0.9 g 3). 0.6 g of apple polyphenols, or 4). placebo. Postprandial changes in plasma glucose, insulin, NEFA, GIP, GLP-1 concentrations as well as changes in vascular function will be measured. Twenty-four hour urine samples will be collected for analysis of urinary polyphenol metabolites and glucose. In a sub sample of participants, a paracetamol absorption test will be incorporated via addition of 1.5 g paracetamol into the test drink.

Interventions

DIETARY_SUPPLEMENTApple polyphenols

Drinks will be delivered in random order at 4 separate study visits immediately before a high-carbohydrate meal. Seven days wash-out period will be required between study days.

DIETARY_SUPPLEMENTPlacebo

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

Yes

Inclusion criteria

* Age: 18-70 y * Male and female * Healthy (free of diagnosed diseases listed in the

Exclusion criteria

) * Body Mass Index 18-35 kg/m2 * Able to understand the information sheet and willing to comply with study protocol * Able to give informed written consent

Design outcomes

Primary

Measure	Time frame	Description
Postprandial Glycaemia	30 min following the test drink	Primary outcome: Area over baseline t+0-30 min for plasma glucose

Secondary

Measure	Time frame	Description
Postprandial Insulinaemia	baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink	Peak postprandial insulin concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Postprandial Glucose-dependent Insulinotropic Polypeptide (GIP) Concentrations	baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink	Peak postprandial GIP concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Postprandial Glucagon-like Peptide-1 (GLP-1) Concentrations	baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink	Peak postprandial GLP-1 concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Postprandial C-peptide Concentrations	baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink	Peak postprandial C-peptide concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Postprandial Non-esterified Fatty Acid (NEFA) Concentrations	baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink	Peak postprandial NEFA concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min
Postprandial Triglyceride (TAG) Concentrations	baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink	Peak postprandial TAG concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Postprandial Paracetamol Concentrations	baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink	Peak postprandial paracetamol concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min (1.5 g paracetamol will be added to all test drinks in a sub-group of participants).
Urinary Polyphenol Metabolites	0-4 h, 4-8 h, 8-24 h following the test drink	Change in urinary polyphenol metabolite concentration following the test drink.
Urinary Glucose	0-4 h, 4-8 h, 8-24 h following the test drink	Change in urinary glucose concentration following the test drink.
Postprandial Polyphenol Metabolite Concentrations	baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink	Peak postprandial polyphenol metabolites concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Vascular Endothelial Function by Flow-mediated Dilation (FMD)	baseline and 120, 240, 300 min following the test drink	Change in FMD after the consumption of test drink.
Vascular Function (Arteriograph Measurement)	Baseline and 60, 90, 120, 180, 240 min following the test drink	Change in augmentation index following the test drink.
Blood Pressure	Baseline and 60, 90, 120, 180, 240 min following the test drink	Change in blood pressure following the test drink.

Other

Measure	Time frame	Description
7-day Food Diary	Baseline	Habitual dietary intake analysis
Women's Health Questionnaire	Baseline	Questionnaire to identify menstrual phase

Countries

United Kingdom

Participant flow

Recruitment details

Healthy participants were recruited from King's College London (KCL) and the general public in London and surrounding counties.

Pre-assignment details

34 out of 64 screened were randomized. Of those not randomized, 8 did not meet inclusion criteria, 1 had a minor adverse event, and 21 declined to participate.

Participants by arm

Arm	Count
All Study Participants All participants completing all study interventions	30
Total	30

Baseline characteristics

Characteristic	All Study Participants	—
Age, Customized Males	30 years STANDARD_DEVIATION 12	—
Age, Customized Postmenopausal females	56 years STANDARD_DEVIATION 7	—
Age, Customized Premenopausal females	27 years STANDARD_DEVIATION 8	—
Fasting glucose	5.18 mmol/L STANDARD_DEVIATION 0.39	—
Race and Ethnicity Not Collected	—	— Participants
Region of Enrollment United Kingdom	30 participants	—
Sex: Female, Male Female	19 Participants	—
Sex: Female, Male Male	11 Participants	—

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 0	0 / 0	0 / 0	0 / 0
other Total, other adverse events	0 / 34	0 / 34	0 / 34	0 / 34
serious Total, serious adverse events	0 / 34	0 / 34	0 / 34	0 / 34

Outcome results

Primary

Postprandial Glycaemia

Primary outcome: Area over baseline t+0-30 min for plasma glucose

Time frame: 30 min following the test drink

Arm	Measure	Value (MEAN)	Dispersion
1.8 g Apple Extract	Postprandial Glycaemia	11.3 mmol/L*min	Standard Error 1.2
1.2 g Apple Extract	Postprandial Glycaemia	15.2 mmol/L*min	Standard Error 1.5
0.9 g Apple Extract	Postprandial Glycaemia	17.8 mmol/L*min	Standard Error 1.6
0 g Apple Extract	Postprandial Glycaemia	27.1 mmol/L*min	Standard Error 2.5

Secondary

Blood Pressure

Change in blood pressure following the test drink.

Time frame: Baseline and 60, 90, 120, 180, 240 min following the test drink

Secondary

Postprandial C-peptide Concentrations

Peak postprandial C-peptide concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.