Plain English Summary
Background and study aims
Type 2 diabetes is a worldwide health burden leading to other diseases and death. It develops when our body is not responding well to the important actions of insulin. Insulin is a hormone that helps our body to function well and to make use of the food that we eat. If the body is not responding well to insulin, the sugar will accumulate in the blood leading to the diagnosis of diabetes. Having excess weight increases the chance of becoming diabetic. Type 2 diabetes can be prevented by weight-loss. However, there is a need to identify the overweight or obese patients who will most likely become diabetic in order to best prevent this disease. Having high numbers of particles that carry cholesterol in the blood (or apoB) could increase the chance for developing diabetes. This is because high blood apoB decreases the function of our tissues, like fat and muscle, which decreases their response to insulin. Accordingly, we believe that targeting subjects with high blood apoB with weight-loss programs would lead to maximal prevention of type 2 diabetes among a population of overweight and obese subjects. The aim of this study is to identify those who are high risks of developing type 2 diabetes based on certain markers in their blood samples.
Who can participate?
Adults aged 45 to 74 years old who are overweight
What does the study involve?
Participants are asked to follow a healthy weight-loss program for six month using a low-calorie diet, which is based on the Canadian Food Guide. To encourage this, participants meet with dieticians for one hour each month. Participants are encouraged to maintain their normal activity level during the six months. Participants are asked to keep a three day food intake record at the beginning and end of the study. Participants are followed up with blood tests to analyse their cholesterol levels in their blood.
What are the possible benefits and risks of participating?
Participants may benefit from being enrolled in a weight-loss program under close nutritional and medical supervision. They also may benefit from having access to in-depth medical examination using combinations of tests that are only accessible through medical research. There are no direct risks with participating.
Where is the study run from?
Montreal Clinical Research Institute (Institut de Recherches cliniques de Montréal (IRCM))
When is the study starting and how long is it expected to run for?
October 2007 to August 2014
Who is funding the study?
Canadian Institutes of Health Research (Canada)
Who is the main contact?
Dr May Faraj
Trial website
Contact information
Type
Scientific
Primary contact
Dr May Faraj
ORCID ID
http://orcid.org/0000-0002-3473-0031
Contact details
Institut de recherches cliniques de Montréal (IRCM)
Office 1770.2
110
Avenue des Pins Ouest
Montréal
Québec
H2W 1R7
Canada
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
IRCM research protocol # 2009-33
Study information
Scientific title
Targeting hyperapoB to reduce the risk of type 2 diabetes in obese subjects; mechanism of action
Acronym
Study hypothesis
The plasma concentration of apoB-lipoproteins (i.e. plasma apoB) associates positively with:
1. Baseline risk factors for type 2 diabetes (systemic insulin resistance, glucose-induced hyperinsulinemia, delayed postprandial fat metabolism, inflammation and ex vivo white adipose tissue dysfunction and inflammation) in overweight and obese subjects.
2. Amelioration of these risk factors for type 2 diabetes following a 6-month hypocaloric diet
Ethics approval
Montreal Clinical Research Institute (Institut de Recherches cliniques de Montréal (IRCM)) Human ethics board, 01/03/2010, ref: 2009-33
Study design
Single-centre interventional for 6-months
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Other
Trial type
Prevention
Patient information sheet
No participant information sheet available’
Condition
ApoB-lipoproteins and risk for type 2 diabetes
Intervention
Participants are asked to follow a hypocaloric diet for six months. The diet is administered during individual sessions by two registered dietitians. Daily energy needs are calculated as basal metabolic rate, measured by an indirect calorimetry, multiplied by a sedentary physical activity factor of 1.4, from which 500 kcal were subtracted.
Participants are counseled to follow a balanced diet based on the Canadian Food Guide and Health Canada (45-65% carbohydrate, 20-35% fat and 15-35% protein). To encourage compliance, subjects met monthly with the dietitians for one hour, during which body weight is also recorded.
Participants are encouraged to maintain their habitual (i.e. sedentary) activity level during the six month intervention. Prior to the baseline and post-intervention metabolic testing, subjects undergo a weight stability period of four weeks (± 2 kg), with their weight being verified weekly at the the study centre.
Intervention type
Behavioural
Phase
Drug names
Primary outcome measure
1. Plasma apoB-lipoprotein profile is measured using an automated analyzer at baseline and seven months
2. Body composition is measured using dual-energy X-ray absorptiometry (DXA) at baseline and seven months
3. Systemic glucose-induced insulin secretion and sensitivity is measured using a Botnia clamp at baseline and seven months
4. Plasma inflammatory markers are measured using commercial hsELISA kits on blood samples at baseline and seven months
5. Postprandial plasma clearance and oxidation rates of a 13C-labeled high fat meal is measured using isotope ratio mass spectrometry at baseline and seven months
6. Gynoid white adipose tissue function is measured ex vivo using in situ lipoprotein-lipase activity technique at baseline and seven months
7. Gynoid white adipose tissue genetic and protein expression of inflammatory markers is measured using RT-PCR and immunoblot, respectively at baseline and seven months
Secondary outcome measures
1. Blood pressure is measured using an automated machine at baseline and seven months
2. Waist and hip circumferences is measured using a measure tape at baseline and seven months
3. Metabolic rate and macronutrient oxidation rates are measured using indirect calimetry at baseline and seven months
4. Dietary intake is measured using 3-day food intake records at baseline and six months (directly at the end of the hypocaolic diet)
5. Plasma C-peptide is measured using a commercial RIA kit at baseline and seven months
6. Fatty acids are measured using a commercial kit at baseline and seven months
7. ApoB48 is measured using a commercial hsELISA kit at baseline and seven months
8. apoA-1 is measured using an automated analyzer at baseline and seven months
9. PCSK9 is measured using a commercial hsELISA kit at baseline and seven months
Overall trial start date
01/10/2007
Overall trial end date
01/08/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Having a body mass index (BMI) > 27 kg/m2
2. Aged between 45 and 74 years
3. Having confirmed menopausal status (FSH ≥ 30 U/l) for women
4. Non-smoker
5. Sedentary (less than 2 hours of structured physical exercise (ex: sports club) per week)
6. Low alcohol consumption: less than 2 alcoholic drinks/day
Participant type
Healthy volunteer
Age group
Mixed
Gender
Both
Target number of participants
82
Total final enrolment
59
Participant exclusion criteria
1. Abnormal physiological values necessitating rapid medical intervention:
1.1. Elevated risk of cardiovascular disease (>20% of calculated Framingham Risk Score)
1.2. Fasting glycaemia > 7.0 mmol/L
1.3. Blood pressure >160/100 mmHg
1.4. Hb < 100 g/L
1.5. Creatinin > 135 µmol/L
2. AST or ALT > 3 times upper normal level
3. Suffering from:
3.1. Claustrophobia
3.2. Type 1 or 2 diabetes
3.3. Un-treated thyroid disease
3.4. Cardiovascular or vascular disease with an event occurring less than 6 months ago
3.5. Event of cancer in the last 3 years
3.6. Chronic inflammatory disease such as rheumatoid arthritis or lupus
4. Abnormal blood coagulation
5. Presently following or have followed in the past 3 months :
5.1. Oestrogen treatment
5.2. Hormone replacement therapy (except thyroid hormone at a stable dose)
5.3. Corticosteroids, nerve sedatives
5.4. Hypertension treatment
5.5. Hyperlipidemia treatment
5.6. Anticoagulant treatment
5.7. Weight-loss, psycho-active or adrenergic agonist medications
6. Substance abuse
7. Have exceeded the annual total allowed radiation dose (like X-ray scans and/or tomography in the previous year or in the year to come) according to the physician’s judgement.
8. Lack of time to participate in the full length of the study (33 weeks)
9. All other medical or psychological conditions deemed inappropriate according to the physician
Recruitment start date
01/03/2010
Recruitment end date
01/11/2013
Locations
Countries of recruitment
Canada
Trial participating centre
Montreal Clinical Research Institute (Institut de Recherches cliniques de Montréal (IRCM))
110, Avenue des Pins Ouest
Montréal, Québec
H2W 1R7
Canada
Sponsor information
Organisation
Montreal Clinical Research Institute (Institut de Recherches cliniques de Montréal (IRCM))
Sponsor details
110 Avenue des Pins Ouest
Montréal
Québec
H2W 1R7
Canada
+1 514 987 5500
info@ircm.qc.ca
Sponsor type
Research organisation
Website
Organisation
University of Montréal
Sponsor details
Faculty of Medicine
Department of Nutrition
2405
Chemin de la Côte-Sainte-Catherine
Montréal
Québec
H3T 1A8
Canada
Sponsor type
University/education
Website
https://nutrition.umontreal.ca/
Organisation
University of Montreal
Sponsor details
Sponsor type
Not defined
Website
Funders
Funder type
Government
Funder name
Canadian Institutes of Health Research
Alternative name(s)
Instituts de Recherche en Santé du Canada, CIHR, IRSC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Canada
Results and Publications
Publication and dissemination plan
Baseline data are already published in peer reviewed journals and presented at national and international conferences.
IPD sharing statement:
The datasets generated during and/or analysed during the current study is not expected to be made available as we did not seek consent from participants to share their data publically. Additional sample and data analysis can be conducted in collaboration with Dr May Faraj
Intention to publish date
15/12/2017
Participant level data
Not expected to be available
Basic results (scientific)
Publication list
1. 2013 baseline data in https://www.ncbi.nlm.nih.gov/pubmed/23417739
2. 2015 baseline data in https://www.ncbi.nlm.nih.gov/pubmed/26350813
3. 2015 baseline data in https://www.ncbi.nlm.nih.gov/pubmed/26417659
4. 2017 baseline data in https://www.ncbi.nlm.nih.gov/pubmed/28391908
5. 2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/29917037 (added 05/08/2019)