Relationship between a low fructose consumption and insulin resistance

ISRCTN	ISRCTN41579277
DOI	https://doi.org/10.1186/ISRCTN41579277
Protocol serial number	ISCIII 012/00231 and OBE04/2013
Sponsor	Fundación Canaria de Investigación Sanitaria
Funders	Instituto de Salud Carlos III, Fundacion Caja Canarias , Fundación DISA: premios de investigación médica 2018

Submission date: 04/11/2016
Registration date: 15/11/2016
Last edited: 06/05/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Insulin resistance (IR) is a condition in which the cells of the body do not respond normally to the hormone insulin, leading to high blood sugar levels. IR is a strong predictor for the development of type 2 diabetes mellitus and cardiovascular disease (heart and blood vessel disease). Fructose (a natural sugar found in plants) has become a widely-used additive in many food industry products such as soft drinks and nonalcoholic beverages, generally in the form of fructose-enriched corn syrup. The aim of this study is to determine whether a low fructose diet supervised by a physician or nurse decreases IR compared to a standard diet.

Who can participate?
Overweight and obese adults aged between 29 and 66.

What does the study involve?
Health care zones are randomly allocated to one of two groups. Those in the first group are asked to follow a low fructose diet. Those in the second group are advised to eat a standard diet. The calories in diets in both groups contain around 30-40% less than each individual’s calorie requirements to help them to lose weight. Participants in both groups provide blood samples at the start of the study and then again after 24 and 48 weeks to assess insulin resistance. In addition, the cholesterol and fat levels in the blood and their BMI are measured at the same timepoints.

What are the possible benefits and risks of participating?
There are no direct benefits involved with participating. There is a small risk of pain, bruising or bleeding when blood samples are taken.

Where is the study run from?
Primary care centers in the island of Tenerife (Canary Islands, Spain)

When is the study starting and how long is it expected to run for?
May 2012 to December 2017

Who is funding the study?
1. Instituto de Salud Carlos III (Spain)
2. Fundacion Caja Canarias (Spain)

Who is the main contact?
Dr Santiago Domínguez-Coello
sdomcoe@gobiernodecanarias.org

Contact information

Dr Santiago Dominguez Coello
Scientific

Gerencia de Atención Primaria de Tenerife
Servicio Canario de Salud.
Calle Carmen Monteverde nº 45
Santa Cruz de Tenerife
38003
Spain

ORCID ID	0000-0003-1974-1936
Phone	+34 (0)922 581 900
Email	sdomcoe@gobiernodecanarias.org

Dr Jesus Gobierno Hernandez
Scientific

Consultorio el Escobonal
Plaza San Jose S/N
El Escohonal-Güimar
38591
Spain

Phone	+34 (0)822 171 816
Email	jgobierno@gmail.com

Study information

Primary study design	Interventional
Study design	Single-blind multi-centre randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effect of a diet low in fructose and sucrose on insulin resistance: clinical trial in primary care
Study acronym	DISFRUTE
Study objectives	A low fructose/sucrose diet reduces insulin resistance more than a standard diet.
Ethics approval(s)	CEIC Hospital Universitario Nuestra Señora de Candelaria-Tenerife-Canary Islands Spain, 23/05/2012, ref: 160
Health condition(s) or problem(s) studied	Insulin resistance
Intervention	Participants are randomized by health care zone to one of two groups. Low-fructose diet intervention (LFDI) group: Participants are assigned to health centers in the western zone of Tenerife island. They are advised to eat a low-fructose diet (1000, 1250, 1500, 1750, 2000, 2250, 2500 or 2750 kcal/day). Low-fructose diets are designed by calculating free and total (free + fructose associated with sucrose) fructose contents in standard diets. Foods with a fructose content in the highest quartile for the amounts corresponding to the standard diet are removed from the standard diet. Standard diet control (SDC) group: Participants are assigned to health centers in the eastern zone of the island. They are advised to eat a standard diet (recommended by the Canary Health Service). The kcal/day in the prescribed diets are calculated as 30% or 40% less than the kcal/day in the participant’s energy requirements for his or her ideal weight according to age, sex and physical activity. Follow up for all participants takes place at 4, 8, 12, 20, 24 and 48 weeks, and involves nutrition counseling and reinforcement, as well as the measure of weight, waist circumference and blood pressure.
Intervention type	Other
Primary outcome measure(s)	Insulin resistance is estimated from fasting serum glucose (measured with enzymatic methods) and insulin concentrations (measured with a chemiluminescence immunoassay method) with a computer-based Homeostasis Model Assessment system (HOMA2-IR) at baseline, 24 and 48 weeks.
Key secondary outcome measure(s)	1. Body mass index is determined using weight and height measurements at baseline, 4, 8, 12, 20, 24 and 48 weeks 2. Waist circumference is determined using a nonstretchable measuring tape at baseline, 4, 8, 12, 20, 24 and 48 weeks 3. Total Cholesterol, HDL cholesterol and triglycerides are measured using enzymatic methods at baseline, 24 and 48 weeks. LDL cholesterol is calculated using the Friedewald formula
Completion date	01/04/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	490
Total final enrolment	438
Key inclusion criteria	1. Age between 29-66 years 2. BMI between 29 and 40.99 kg/m2
Key exclusion criteria	1. Pregnancy (female participants only) 2. Behavioral eating disorders 3. Relevant gastrointestinal disease (ulcerating colitis, Crohn’s disease, celiac disease, digestive tract cancer) 4. Excessive alcohol consumption (>28 U or 280 g/week in men, > 17 U or 168 g/week in women 5. Severe cardiovascular disease 6. Diabetes, 7. Polycystic ovary disease 8. Treatment with any medication that could alter insulin sensitivity or body weight (corticosteroids, antipsychotics, antidepressants) 9. Pharmacological treatment for clinical or subclinical hypothyroidism 10. Hyperthyroidism 11. Depression 12. Psychosis 13. Microalbumin/creatinine ratio >100 mg/g or stage IIIB or higher chronic kidney disease (glomerular filtration rate < 45 mL/min) 14. Use of medication requiring frequent dose adjustments 15. Low intellectual or mental functioning that could interfere with the participant’s compliance with the recommendations 16. If the result of the glucose overload test is blood glucose ≥ 200 mg/dL the participant is excluded if the physician opts to add medication or insulin to the dietary and physical exercise regime.
Date of first enrolment	01/05/2014
Date of final enrolment	30/06/2017

Locations

Countries of recruitment

Spain

Study participating centres

Centro de Salud (CS) de La Victoria de Acentejo

C/Domingo Salazar 21
La Victoria de Acentejo
38380
Spain

CS La Matanza de Acentejo

Carretera General del Norte
Ermita
La Matanza de Acentejo
38370
Spain

CS Santa Úrsula

C/Calvo Sotelo s/n
Santa Ursula
38390
Spain

Consultorio La Perdoma

C/ Manuel Vega Santos, nº 7
La Orotava
38315
Spain

CS Los Realejos

C/San Isidro nº 10
Los Realejos
38410
Spain

CS Casco Botánico

Carretera Las Dehesas nº 8
Puerto de La Cruz
38400
Spain

CS Tacoronte

Carretera General del Norte nº 5
Tacoronte
38350
Spain

Consultorio La Esperanza

Carretera Sardinera s/n
La Laguna
38290
Spain

Consultorio Valle Guerra

C/Camino Las Toscas nº 4
La Laguna
38290
Spain

CS Taco

C/Moisés Alberto s/n
Santa Cruz de Tenerife
38108
Spain

CS Guimar

C/Poeta Hernández Mora s/n
Güimar
38500
Spain

CS Barranco Grande

Calle Ruiseñor, s/n
Santa Cruz de Tenerife
38107
Spain

CS Ofra Delicias

Avenida Príncipes de España 7A
Santa Cruz de Tenerife
38310
Spain

CS Toscal-Centro

C/Ruiz de Padrón 6
Santa Cruz de Tenerife
38002
Spain

CS Finca España

Carretera General Santa Cruz-Laguna nº 141
La Laguna
38201
Spain

Consultorio Igueste de Candelaria

C/ Ajoreña 0
Candelaria
38520
Spain

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated and analysed during the current study will be available upon request from Santiago Domínguez-Coello (sdomcoe@gobiernodecanarias.org; sdominguezc@telefonica.net) once this study has been published. These datasets will be available at any time and will be anonymous. All the requirements will have to be motivated on specific scientific reasons which must be detailed.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	19/04/2020	06/05/2020	Yes	No
Protocol article	protocol	07/08/2017		Yes	No
Basic results		14/01/2018	14/01/2019	No	No
Basic results		03/12/2019	03/12/2019	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN41579277_BasicResults_14Jan18.pdf: Uploaded 14/01/2019
ISRCTN41579277_BasicResults_03Dec19.pdf: Uploaded 03/12/2019

Editorial Notes

06/05/2020: Publication reference and total final enrolment number added.
03/12/2019: The updated basic results of this trial have been uploaded as an additional file.
21/06/2019: Internal review.
21/01/2019: IPD sharing statement added.
14/01/2019: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/12/2017 to 01/04/2018.
2. Fundación DISA: premios de investigación médica 2018 was added as a funder.
3. The basic results of this trial have been uploaded as an additional file.
09/08/2017: Publication reference added.