Pre-diabetesPREVIEWNCT01777893
Effect of Diet and Physical Activity on Incidence of Type 2 Diabetes
A study testing High protein/ high intensity physical activity (HP-HI), High protein / moderate intensity physical activity (HP-MI) and Moderate protein/ high intensity physical activity (MP-HI) in people with Pre-diabetes and Obesity, run by Anne Birgitte Raben at 9 sites in 8 countries.
Trial summary
Type-2 diabetes is one of the fastest growing chronic diseases worldwide. This trend is mainly driven by a global increase in the prevalence of obesity. The PREVIEW study has been initiated to find out the most effective lifestyle-components (diet and physical activity) in the prevention of Type-2 diabetes. Read more about this study
- Who is it for?
- Ages 10 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Pre-diabetes, Obesity
- What is being tested?
- High protein/ high intensity physical activity (HP-HI), High protein / moderate intensity physical activity (HP-MI) and Moderate protein/ high intensity physical activity (MP-HI)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,500 participants
- Where
- 9 sitesin 8 countries
- Study dates
- Jun 2013to Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 70 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- For adults:
- Age 25 - 70 years:
- From mid 2013 - mid 2014, subjects aged 25-45 and 55-70 years were enrolled. From mid 2014, subjects aged 46-54 years were also enrolled.
- Overweight or obesity status BMI>25 kg/m2
- Pre-diabetes The criteria from WHO/IDF (International Diabetes Foundation) for assessing pre-diabetes will be used as the formal inclusion criteria (at screening), i.e. having:
- Impaired Fasting Glucose (IFG): Fasting venous plasma glucose concentration 5.6 - 6.9 mmol/l or Impaired Glucose Tolerance (IGT): Venous Plasma glucose concentration of 7.8 - 11.0 mmol/l at 2 h after oral administration of 75 g glucose (oral glucose tolerance test, OGTT), with fasting plasma glucose less than 7.0 mmol/l.
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- Due to potential between-lab variation (local assessments), HbA1c is not used as an inclusion criteria in the screening.
- Informed consent required
- Ethnic group - No restrictions
- Smoking - Smoking is allowed, provided subjects have not recently (within 1 month) changed habits. However, smoking status is monitored throughout the study and used as a confounding variable.
- Motivation - Motivation and willingness to be randomized to any of the groups and to do his/hers best to follow the given protocol
- Other - Able to participate at CID's during normal working hours.
- For children and adolescents:
- Age 10-18 years
- Age-adjusted value corresponding to BMI>25 kg/m2 (Cole et al. 2000)
- Since the prevalence of pre-diabetes among children with overweight or obesity is low, it is not feasible to include exclusively pre-diabetic children (according to criteria of the IDF).
- Therefore, insulin resistant over-weight/obese children will be included, defined as: HOMA-IR ≥ 2.0 for Tanner stage > 2. No HOMA criteria is used for Tanner stage 1 and 2.
- Informed consent required
- Ethnic group - No restrictions
- Smoking - Smoking is allowed, provided subjects have not recently (within 1 month) changed habits. However, smoking status is monitored throughout the study and used as a confounding variable.
- Motivation - Motivation and willingness to be randomized to any of the groups and to do his/hers best to follow the given protocol
- Other - Able to participate at CID's during normal school/working hours.
Who cannot join
- Based on interview and/or questionnaire, individuals with the following problems will be excluded:
- Medical conditions as known by the subjects:
- Diabetes mellitus (other than gestational diabetes mellitus);
- Significant cardiovascular disease including current angina; myocardial infarction or stroke within the past 6 months; heart failure; symptomatic peripheral vascular disease ;
- Systolic blood pressure above 160 mmHg and/or diastolic blood pressure above 100 mmHg whether on or off treatment for hypertension. If being treated, no change in drug treatment within last 3 months;
- Advanced chronic renal impairment;
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- Significant liver disease e.g. cirrhosis (fatty liver disease allowed);
- Malignancy which is currently active or in remission for less than five years after last treatment (local basal and squamous cell skin cancer allowed);
- Active inflammatory bowel disease, celiac disease, chronic pancreatitis or other disorder potentially causing malabsorption;
- Previous bariatric surgery;
- Chronic respiratory, neurological, musculoskeletal or other disorders where, in the judgement of the investigator, participants would have unacceptable risk or difficulty in complying with the protocol (e.g. physical activity program);
- A recent surgical procedure until after full convalescence (investigators judgement);
- Transmissible blood-borne diseases e.g. hepatitis B, HIV;
- Psychiatric illness (e.g. major depression, bipolar disorder).
- Medication:
- Use currently or within the previous 3 months of prescription medication that has the potential of affecting body weight or glucose metabolism such as glucocorticoids (but excluding inhaled and topical steroids; bronchodilators are allowed), psychoactive medication, epileptic medication, or weight loss medications (either prescription, over the counter or herbal). Low dose antidepressants are allowed if they, in the judgement of the investigator, do not affect weight or participation to the study protocol. Levothyroxine for treatment of hypothyroidism is allowed if the participant has been on a stable dose for at least 3 months.
- Personal/Other:
- Engagement in competitive sports;
- Self-reported weight change of >5 % (increase or decrease) within 2 months prior to screening;
- Special diets (e.g. vegan, Atkins) within 2 months prior to study start. A lacto-vegetarian diet is allowed;
- Severe food intolerance expected to interfere with the study;
- Regularly drinking > 21 alcoholic units/week (men), or > 14 alcoholic units/week (women);
- Use of drugs of abuse within the previous 12 months;
- Blood donation or transfusion within the past 1 month before baseline or CID's;
- Self-reported eating disorders;
- Pregnancy or lactation, including plans to become pregnant within the next 36 months.
- No access to either phone or Internet (this is necessary when being contacted by the instructor's during the maintenance phase);
- Adequate understanding of national language;
- Psychological or behavioral problems which, in the judgement of the investigator, would lead to difficulty in complying with the protocol.
- Laboratory screening:
- If all of the above criteria are satisfied, the participant is eligible for a glucose tolerance test (blood at 0 and 120 mins), and blood glucose concentrations are analyzed immediately (Haemocue). In addition full blood count, urea, and electrolytes may be analyzed as a further safety evaluation. Having normal (i.e. not prediabetic) glucose concentrations at 0 and 2h of OGTT at any stage of the study is not an exclusion criterion.
- ONLY IF the glucose tolerance test meets the entry criteria for the study, the remaining samples are sent to the local laboratory for a safety check, with the following exclusion criteria:
- Hemoglobin concentration below local laboratory reference values (i.e. anemia).
- Creatinine >1.5 times Upper Limit of Normal (local laboratory reference values).
- Alanine Transaminase (ALT) and/or Aspartate Transaminase (AST) >3 times the Upper Limit of Normal (local laboratory reference values) Or any other significant abnormality on these tests which in the investigators opinion may be clinically significant and require further assessment
- Electrocardiography (ECG). Any abnormality which in the opinion of the investigator might indicate undiagnosed cardiac disease requiring further assessment (e.g. significant conduction disorder, arrhythmia, pathological Q waves). This is done in adults 55-70 years of age.
- After LCD phase (in adults):
- Failure to reach at least 8% weight reduction during the LCD phase. This leads to exclusion from the intervention.
- Note:
- The listed inclusion and exclusion criteria are applied at screening;
- Having normal (i.e. not pre-diabetic) glucose concentrations at 0 and 2 h of OGTT at any stage of the study after screening is not an exclusion criterion
Trial locations and contacts
9 sites in 8 countries.
9 sites in 8 countries
United Kingdom2 sites
University of Nottingham Medical School
Nottingham, NG7 2UH
Swansea University
Swansea, SA1 8EN
About this study
Official title: PREVention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World
Type-2 diabetes is one of the fastest growing chronic diseases worldwide. This trend is mainly driven by a global increase in the prevalence of obesity. The PREVIEW study has been initiated to find out the most effective lifestyle-components (diet and physical activity) in the prevention of Type-2 diabetes. The project consists of a randomized lifestyle-intervention with the more specific aim to determine the preventative impact of a high-protein and low-GI diet in combination with moderate or high intensity physical activity compared with a moderate-protein and moderate GI diet in combination with the same activity levels on the incidence of Type-2 diabetes in predisposed, pre-diabetic children, young and older adults.
The trial will be performed in 6 EU countries (Bulgaria, Denmark, Finland, Spain, Netherlands, UK) and Australia and New Zealand.
Read more
A total of 2,500 overweight or obese adult participants (25-70 y) as well as 150 children and adolescents aged 10-18 y) will be recruited. All adult participants are first treated by a low-calorie diet for 8 weeks, with an aim to reach ≥ 8% weight reduction. Children and adolescents are treated separately with a conventional weight-reduction diet, with-out a specific aim for absolute weight loss.
The adult participants are randomized into two different diet interventions and two exercise interventions for a total of 148 weeks. This period aims at preventing Type-2 diabetes by weight-maintenance (prevention of relapse in reduced body weight) and by independent metabolic effects of diet and physical activity.
The primary endpoint of the study is the incidence of Type-2 diabetes in the adults during 3 years (156 weeks) according to diet (high protein/low-GI versus moderate protein/moderate-GI, adjusted for physical activity), based on a 75 g oral glucose tolerance test and/or HbA1c.
For children and adolescents:
Change in insulin resistance at 2 years after randomization to high protein versus moderate protein diet, measured by insulin resistance analyzed by the homeostatic model (HOMA-IR) as well as physiological improvement of health with respect to pre-diabetic characteristics.
Our hypothesis is that a high-protein, low-GI diet will be superior in preventing type-2 diabetes, compared with a moderate protein, moderate GI diet, and that high-intensity physical activity will be superior compared to moderate-intensity physical activity.
Read the detailed description
Type-2 diabetes is one of the fastest growing chronic diseases worldwide. This trend is mainly driven by a global increase in the prevalence of obesity. The PREVIEW study has been initialized to find the most effective lifestyle-components (diet and physical activity) in the prevention of T2D. The project is a randomized lifestyle-intervention. The main aim is to determine the preventative impact of a high-protein and low-GI diet in combination with moderate or high intensity physical activity on the incidence of T2D in predisposed, pre-diabetic children, younger and older adults (both gender). In substudies following will be assessed; changes in fat distribution (adults), risk of colon cancer by biomarkers (fecal samples in adults), change in physical fitness (VO2 max in adults), metabolomics profile (adults), food reward (children and adolescents) and sleep architecture (children and adolescents).
Objective: The project addresses prevention in individuals with high risk for T2D. The trial will be performed in 6 EU countries (Bulgaria, Denmark, Finland, Spain, Netherlands, United Kingdom), as well as in Australia and New Zealand.
Study design: The PREVIEW intervention study will be carried out as a 3-year randomized, clinical intervention consisting of an initial 8-week weight loss period and a 148 week randomized weight maintenance intervention.
Study population: A total of 2500 adult as well as 150 children and adolescent participants will participate in the intervention. All adult participants are first treated by a low-calorie diet for 8 weeks, with an aim to reach >8% weight reduction. In skeletal immature children weight loss is not desirable and the goal is to maintain weight (while gaining length) during the initial 8 weeks.
Intervention: The two diet interventions for participants are:
HP = high-protein: protein 25 E%, carbohydrates 45 E%, dietary glycaemic index (GI) <50.
MP = moderate-protein: protein intake 15% in total energy intake (E%), carbohydrates 55 E%, GI >56;
Both diets are composed by using healthy food items.
The two exercise interventions are:
MI = moderate-intensity: 60-75% of maximal heart rate (HRmax), e.g., brisk walking;
HI = high intensity: 76-90% HRmax, e.g., running.
The randomization for the adults is stratified by sex and age group, and by sex in children.
The participants are supervised in groups during the LCD (4 times) and throughout the weight-maintenance period. Children are being supervised separately. Meeting frequency is reduced towards the end of the study. The main assessment points (clinical investigation days, CID) are at week 0 (start of weight reduction), week 8 (end of weight reduction/start of randomized intervention), week 26 (6 months from baseline), week 52 (12 months from baseline), week 78 (18 months from baseline) week 104 (24 months from baseline) and week 156 (36 months from baseline / End of Trial, EOT). For the children and adolescents the last assessment point is at week 104 (24 months from baseline/ End of Trial, EOT).
Main study endpoints: The primary endpoint of the intervention study is for adults the incidence of Type-2 diabetes during 3 years (156 weeks) according to diet (high protein versus moderate protein, adjusted for physical activity), based on a 75 g oral glucose tolerance test (OGTT). The incidence of diabetes will be assessed annually by participant self-report of medication requiring diabetes, doctor informed (and confirmed) diabetes diagnosis or diabetes diagnosed by fasting plasma glucose (FPG) and/or OGTT according to IDF guidelines.
For children and adolescents: Change in insulin resistance at 2 years after randomization to high protein versus medium protein diet, measured by insulin resistance analyzed by the homeostatic model (HOMA-IR) as well as physiological improvement of health with respect to pre-diabetic characteristics.
Secondary endpoints are (tested against the four possible combinations of diet and physical activity if not stated otherwise) the effects of high intensity vs. moderate intensity physical activity on incidence of type 2 diabetes, based on WHO/IDF criteria (adjusted for diet); changes in HbA1c (a measure of average blood glucose levels), body weight and waist, hip and thigh circumference; change in body fat mass (kg, proportion of body weight); proportion of subjects maintaining at least 0, 5 or 10% weight loss (relative to initial body weight); insulin sensitivity (Matsuda Index based on the OGTT, glucose and insulin area under the curve (AUC) during OGTT, beta-cell disposition index)(only adults); risk factors for cardiovascular disease, with at least the following measures: blood pressure, lipids (triglycerides, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol), C-reactive protein, and liver enzymes; changes in perceived quality of life and workability, habitual well-being and chronic stress, sleep duration and quality (accelerometer and questionnaire), appetite sensations, and habitual (long-term) physical activity.
Substudies. Fat distribution: Assessment of fat distribution by MRI (Magnetic Resonance Imaging) and H-MRS (Hydrogen Magnetic Resonance Spectroscopy) is done in a sub-group of subjects at University of Maastricht: 20 from HPMI and 20 from MPMI group. MRI/H-MRS is a non-invasive and non-irradiant imaging technique, which will be used to determine abdominal fat and muscle mass of the upper part of the lower limbs (MRI), muscle and liver fat (H-MRS). MRI and H-MRS measurements take place at weeks 0, 26 and 104.
Sampling and analyses of DNA and RNA: The intended use of the samples is epi/genetic analyses in relation to obesity and associated diseases. Genetic sampling will take place at week 0, 52 and 156.
Metabolomics profile: In a sub-group of subjects, urine from baseline week 0 and week 52 will be analyzed for metabolomics profile.
Fecal samples: Full fecal samples from 3 consecutive days are collected from a sub-group. The samples are used for assessment of colon cancer risk markers, ie phenolic metabolites, short-chain fatty acids (SCFA), nitrogenous compounds. Subjects are recruited from all four groups on a consecutive invitation basis. Moreover, samples from the same subjects are stored for potential analysis of microbiota. Fecal samples will be collected during weeks 0 and 52.
Sleep architecture: In a sub-study we will identify the mediating role of sleeping patterns (sleep quality and duration), stress and brain plasticity on the protein/ activity intervention and the outcome parameters. The sub-study assessing the role of sleep and brain plasticity will be conducted as a repeated measures design embedded in the main intervention study. Measurements will be taken at 0, 26 and 104 weeks.
Food reward: A possible relationship of peripheral insulin sensitivity and brain reward activation will be assessed in a sub-group of pre-diabetic adults, consisting of 2 stratified intervention groups. The sub-study will take place in University of Maastricht and will use functional magnetic resonance imaging (fMRI) in a block design with high calorie/ low calorie food images and control images. Measurements of food reward will be done at weeks 0, 26, and 104.
Sub-group of elderly (+55 y): Serum creatinine and urinary albumine assessments for kidney safety measures.
Cost-effectiveness: All adult participants will fill in a short questionnaire on medicine use, days absent from work, "less than optimal" workability etc. These answers are used to estimate cost-effectiveness of the life-style programs in PREVIEW. Cost-effectiveness will be assessed in week 0, 52, 104, 156.
- Conditions
- Pre-diabetes, Obesity
- Being tested
- High protein/ high intensity physical activity (HP-HI), High protein / moderate intensity physical activity (HP-MI), Moderate protein/ high intensity physical activity (MP-HI), Moderate protein/ moderate intensity physical activity (MP-MI)
- Keywords
- Type-2 diabetes mellitus, Obesity, High protein diet, Low GI, Physical activity
- Medical subject headings
- Glucose Intolerance, Obesity, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High protein/ high intensity physical activity (HP-HI)Behavioural
Participants follow a high protein diet and a high intensity physical activity intervention
High protein / moderate intensity physical activity (HP-MI)Behavioural
Participants follow a high protein diet and moderate intensity physical activity intervention
Moderate protein/ high intensity physical activity (MP-HI)Behavioural
Participants follow a moderate protein diet and a high intensity physical activity intervention
Moderate protein/ moderate intensity physical activity (MP-MI)Behavioural
Participants follow a moderate protein diet and moderate intensity physical activity intervention
| Study group | Role | What they receive |
|---|---|---|
| HP-HI | Experimental | High protein/ high intensity physical activity Receives: Behavioral: High protein/ high intensity physical activity (HP-HI) |
| HP-MI | Experimental | High protein/ moderate intensity physical activity Receives: Behavioral: High protein / moderate intensity physical activity (HP-MI) |
| MP-HI | Experimental | Moderate protein/ high intensity physical activity Receives: Behavioral: Moderate protein/ high intensity physical activity (MP-HI) |
| MP-MI | Experimental | Moderate protein/ moderate intensity physical activity Receives: Behavioral: Moderate protein/ moderate intensity physical activity (MP-MI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of type 2 diabetes
For adults by OGTT
Incidence of type 2 diabetes, in high protein versus medium protein diet, measured during 3 years after baseline and based on WHO/IDF criteria:
Fasting plasma glucose (FPG) > 7.0 mmol/l (126 mg/dl) or, 75 g oral glucose tolerance test (OGTT) with FPG > 7.0 mmol/l (126 mg/dl) and/or 2 hour plasma glucose > 11.1 mmol/l (200 mg/dl) or, Glycated haemoglobin (HbA1c) > 6.5% (48 mmol/mol), or Random plasma glucose > 11.1 mmol/l (200 mg/dl) in the presence of classical diabetes symptoms.
For children and adolescents:
Change in insulin resistance at 2 years after randomization to high protein versus medium protein diet, measured by insulin resistance analysed by the homeostatic model (HOMA-IR).
Measured: 3 years
Secondary outcomes (25)
Incidence of type-2 diabetes
For children by HOMA-IR The effect of high intensity vs. moderate intensity physical activity on incidence of type 2 diabetes, based on WHO/IDF criteria (adjusted for diet).
Fasting plasma glucose (FPG) > 7.0 mmol/l (126 mg/dl) or, 75 g oral glucose tolerance test (OGTT) with FPG > 7.0 mmol/l (126 mg/dl) and/or 2 hour plasma glucose > 11.1 mmol/l (200 mg/dl) or, Glycated hemoglobin (HbA1c) > 6.5% (48 mmol/mol), or Random plasma glucose > 11.1 mmol/l (200 mg/dl) in the presence of classical diabetes symptoms.
For children and adolescents:
Change in insulin resistance at 2 years after randomization to high intensity vs. moderate intensity physical activity, analyzed by the homeostatic model (HOMA-IR).
Measured: 2 years
Change in HbA1c
A measure of average blood glucose levels
Measured: 3 years
Change in body weight (kg or percent) and waist 8cm), hip (cm) and thigh circumference (cm)
Measures of body composition
Measured: 3 years
Change in body composition - fat mass and fat-free mass (kg, proportion of body weight)
DXA, BodPod, or bio-impedance
Measured: 3 years
Proportion of subjects maintaining at least 0, 5 or 10% weight loss
Relative to initial body weight
Measured: 3 years
Insulin sensitivity (e.g Matsuda Index based on the OGTT, glucose area under the curve (AUC) during OGTT, beta-cell disposition index) (OGTT only adults)
Measures of insulin sensitivity and glucose tolerance
Measured: 3 years
Risk factors for cardiovascular disease, with at least the following measures: blood pressure, heart rate, lipids (triglycerides, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol), C-reactive protein, and liver enzymes
Risk factors for CVD
Measured: 3 years
Changes in dietary intake (4-d weighed food records)
Measured: 3 years
Changes in physical activity (accelerometers and questionnaires).
Measured: 3 years
Changes in perceived quality of life and workability, habitual well-being, sleep and chronic stress, subjective appetite sensations, dietary restraint, moderators, mediators, behavioral and social environment.
Measured: 3 years
The effects of stature (height; proportion leg-length/height) in adults and changes in stature in children and adolescents, on the changes in relationship between reduction in body weight, body fat and insulin sensitivity
Measured: 3 years
Safety parameters (blood samples).
Measured: Screening and during 3 years
Adverse events and concomitant medication.
Registration by questionnaires.
Measured: Screening and during 3 years
Compliance by urin samples for nitrogen analyses.
Measured: 3 years
In a sub-group: Metabolomic profiling.
Measured: 3 years
In a sub-group: DNA, RNA
Measured: 3 years
In a sub-group: Colon cancer risk markers
Measured: 3 years
In a sub-group: Kidney safety markers, body fat and liver-fat content.
Measured: 3 years
In a sub-group: Body and liver-fat content.
Measured: 3 years
In a sub-group: Changes in brain responses and cortical thickness
Measured: 2 years
In a sub-group: Changes in 48-h energy expenditure in a respiration chamber setting
Measured: 3 years
In a sub-group: Gut microbiome
Measured: 3 years
In a sub-group: Circulating amino acids
Measured: 8 wks
In a sub-group: Plasma mitochondrial peptides
Measured: 8 wks
In a sub-group: Insulin Growth factor 2 (IGF-II) and IGF-II receptor (IGF2R)
Measured: 8 wks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2013 (estimated)
- Study startJun 2013
- Primary completionMar 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Pre-diabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Anne Birgitte Raben
- Sponsor type
- University, hospital or other
- Collaborators
- University of Helsinki, Maastricht University, University of Nottingham, University of Navarra, Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria, University of Sydney, University of Auckland, New Zealand, University of Stuttgart, Swansea University, Cambridge Manufacturing Company Limited, European Union, Wageningen University, Meyers Madhus, NetUnion SARL, Terveyden Ja Hyvinvoinnin Laitos, Laval University
- Responsible party
- Sponsor-investigator, Anne Birgitte Raben, University of Copenhagen
- Investigators
- Thomas M Larsen, Ass. Prof., Principal investigator, University of CopenhagenMikael Fogelholm, Professor, Principal investigator, University of HelsinkiMargriet Westerterp-Plantenga, Professor, Principal investigator, Maastricht UniversityIan Macdonald, Professor, Principal investigator, University of Nottingham Medical SchoolJ. Alfredo Martinez, Professor, Principal investigator, University of NavarraSvetoslav Handjiev, Professor, Principal investigator, Medical University SofiaJennie Brand-Miller, Professor, Principal investigator, University of SydneySally D. Poppitt, Professor, Principal investigator, University of Auckland, New Zealand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01777893
- Sponsor's protocol ID
- B303
- Other IDs
- 312057
- Acronym
- PREVIEW
- Status last verified
- Mar 2019
- First submitted
- 24 Jan 2013
- Last updated
- 20 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Zhu R, Guo J, Stratton G, Macdonald IA, Handjieva-Darlenska T, Handjiev S, Navas-Carretero S, Poppitt SD, Silvestre MP, Fogelholm M, Adam T, Raben A, Martinez JA, Xie M, Brand-Miller J. Novel OGTT metrics do not provide incremental predictive value beyond conventional glycemic criteria for remission of prediabetes in individuals with impaired fasting glucose: results from the PREVIEW trial. Cardiovasc Diabetol. 2026 Apr 22;25(1):168. doi: 10.1186/s12933-026-03186-0.
PubMed 42021301Zhu R, Guo J, Huttunen-Lenz M, Silvestre M, Stratton G, Macdonald IA, Handjieva-Darlenska T, Handjiev S, Navas-Carretero S, Poppitt SD, Fogelholm M, Martinez-Urbistondo D, Martinez JA, Raben A, Brand-Miller J. Long-term effects of dietary protein and carbohydrate quality on prediabetes remission: results from the PREVIEW randomised multinational diabetes prevention trial. Diabetologia. 2026 Jan;69(1):81-92. doi: 10.1007/s00125-025-06560-x. Epub 2025 Oct 15.
PubMed 41094026Lim JJ, Prodhan UK, Silvestre MP, Liu AY, McLay J, Fogelholm M, Raben A, Poppitt SD, Cameron-Smith D. Low serum glycine strengthens the association between branched-chain amino acids and impaired insulin sensitivity assessed before and after weight loss in a population with pre-diabetes: The PREVIEW_NZ cohort. Clin Nutr. 2024 Dec;43(12):17-25. doi: 10.1016/j.clnu.2024.09.047. Epub 2024 Oct 2.
PubMed 39423758Jiang YC, Lai K, Muirhead RP, Chung LH, Huang Y, James E, Liu XT, Wu J, Atkinson FS, Yan S, Fogelholm M, Raben A, Don AS, Sun J, Brand-Miller JC, Qi Y. Deep serum lipidomics identifies evaluative and predictive biomarkers for individualized glycemic responses following low-energy diet-induced weight loss: a PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) substudy. Am J Clin Nutr. 2024 Oct;120(4):864-878. doi: 10.1016/j.ajcnut.2024.08.015. Epub 2024 Aug 23.
PubMed 39182617Huttunen-Lenz M, Hansen S, Raben A, Westerterp-Plantenga M, Adam T, Macdonald I, Stratton G, Swindell N, Martinez JA, Navas-Carretero S, Handjieva-Darlenska T, Handjiev S, Poppitt SD, Silvestre MP, Larsen TM, Vestentoft PS, Fogelholm M, Jalo E, Brand-Miller J, Muirhead R, Schlicht W. Hybrid Evaluation of a Lifestyle Change Program to Prevent the Development of Type 2 Diabetes Among Individuals With Prediabetes: Intended and Observed Changes in Intervening Mechanisms. J Prim Care Community Health. 2024 Jan-Dec;15:21501319241248223. doi: 10.1177/21501319241248223.
PubMed 38916158Huttunen-Lenz M, Raben A, Adam T, Macdonald I, Taylor MA, Stratton G, Mackintosh K, Martinez JA, Handjieva-Darlenska T, Bogdanov GA, Poppitt SD, Silvestre MP, Fogelholm M, Jalo E, Brand-Miller J, Muirhead R, Schlicht W. Socio-economic factors, mood, primary care utilization, and quality of life as predictors of intervention cessation and chronic stress in a type 2 diabetes prevention intervention (PREVIEW Study). BMC Public Health. 2023 Aug 30;23(1):1666. doi: 10.1186/s12889-023-16569-9.
PubMed 37649005Zhu R, Craciun I, Bernhards-Werge J, Jalo E, Poppitt SD, Silvestre MP, Huttunen-Lenz M, McNarry MA, Stratton G, Handjiev S, Handjieva-Darlenska T, Navas-Carretero S, Sundvall J, Adam TC, Drummen M, Simpson EJ, Macdonald IA, Brand-Miller J, Muirhead R, Lam T, Vestentoft PS, Faerch K, Martinez JA, Fogelholm M, Raben A. Age- and sex-specific effects of a long-term lifestyle intervention on body weight and cardiometabolic health markers in adults with prediabetes: results from the diabetes prevention study PREVIEW. Diabetologia. 2022 Aug;65(8):1262-1277. doi: 10.1007/s00125-022-05716-3. Epub 2022 May 25.
PubMed 35610522Jian C, Silvestre MP, Middleton D, Korpela K, Jalo E, Broderick D, de Vos WM, Fogelholm M, Taylor MW, Raben A, Poppitt S, Salonen A. Gut microbiota predicts body fat change following a low-energy diet: a PREVIEW intervention study. Genome Med. 2022 May 23;14(1):54. doi: 10.1186/s13073-022-01053-7.
PubMed 35599315Zhu R, Fogelholm M, Jalo E, Poppitt SD, Silvestre MP, Moller G, Huttunen-Lenz M, Stratton G, Sundvall J, Macdonald IA, Handjieva-Darlenska T, Handjiev S, Navas-Carretero S, Martinez JA, Muirhead R, Brand-Miller J, Raben A. Animal-based food choice and associations with long-term weight maintenance and metabolic health after a large and rapid weight loss: The PREVIEW study. Clin Nutr. 2022 Apr;41(4):817-828. doi: 10.1016/j.clnu.2022.02.002. Epub 2022 Feb 8.
PubMed 35263691Zhu R, Larsen TM, Poppitt SD, Silvestre MP, Fogelholm M, Jalo E, Hatonen KA, Huttunen-Lenz M, Taylor MA, Simpson L, Mackintosh KA, McNarry MA, Navas-Carretero S, Martinez JA, Handjieva-Darlenska T, Handjiev S, Drummen M, Westerterp-Plantenga MS, Lam T, Vestentoft PS, Muirhead R, Brand-Miller J, Raben A. Associations of quantity and quality of carbohydrate sources with subjective appetite sensations during 3-year weight-loss maintenance: Results from the PREVIEW intervention study. Clin Nutr. 2022 Jan;41(1):219-230. doi: 10.1016/j.clnu.2021.11.038. Epub 2021 Dec 3.
PubMed 34915273Navas-Carretero S, San-Cristobal R, Siig Vestentoft P, Brand-Miller JC, Jalo E, Westerterp-Plantenga M, Simpson EJ, Handjieva-Darlenska T, Stratton G, Huttunen-Lenz M, Lam T, Muirhead R, Poppitt S, Pietilainen KH, Adam T, Taylor MA, Handjiev S, McNarry MA, Hansen S, Brodie S, Silvestre MP, Macdonald IA, Boyadjieva N, Mackintosh KA, Schlicht W, Liu A, Larsen TM, Fogelholm M, Raben A, Martinez JA. Appraisal of Triglyceride-Related Markers as Early Predictors of Metabolic Outcomes in the PREVIEW Lifestyle Intervention: A Controlled Post-hoc Trial. Front Nutr. 2021 Nov 1;8:733697. doi: 10.3389/fnut.2021.733697. eCollection 2021.
PubMed 34790686Drummen M, Adam TC, Macdonald IA, Jalo E, Larssen TM, Martinez JA, Handjiev-Darlenska T, Brand-Miller J, Poppitt SD, Stratton G, Pietilainen KH, Taylor MA, Navas-Carretero S, Handjiev S, Muirhead R, Silvestre MP, Swindell N, Huttunen-Lenz M, Schlicht W, Lam T, Sundvall J, Raman L, Feskens E, Tremblay A, Raben A, Westerterp-Plantenga MS. Associations of changes in reported and estimated protein and energy intake with changes in insulin resistance, glycated hemoglobin, and BMI during the PREVIEW lifestyle intervention study. Am J Clin Nutr. 2021 Nov 8;114(5):1847-1858. doi: 10.1093/ajcn/nqab247.
PubMed 34375397Zhu R, Fogelholm M, Larsen TM, Poppitt SD, Silvestre MP, Vestentoft PS, Jalo E, Navas-Carretero S, Huttunen-Lenz M, Taylor MA, Stratton G, Swindell N, Kaartinen NE, Lam T, Handjieva-Darlenska T, Handjiev S, Schlicht W, Martinez JA, Seimon RV, Sainsbury A, Macdonald IA, Westerterp-Plantenga MS, Brand-Miller J, Raben A. A High-Protein, Low Glycemic Index Diet Suppresses Hunger but Not Weight Regain After Weight Loss: Results From a Large, 3-Years Randomized Trial (PREVIEW). Front Nutr. 2021 Jun 1;8:685648. doi: 10.3389/fnut.2021.685648. eCollection 2021.
PubMed 34141717Adam TC, Drummen M, Macdonald I, Jalo E, Siig-Vestentoft P, Martinez JA, Handjiev-Darlenska T, Brand-Miller J, Poppitt S, Stratton G, Fogelholm M, Pietilainen KH, Taylor M, Navas-Carretero S, Winkens B, Handjiev S, Muirhead R, Silvestre M, Swindell N, Huttunen-Lenz M, Schlicht W, Lam T, Sundvall J, Raman L, Feskens E, Larssen TM, Tremblay A, Raben A, Westerterp-Plantenga M. Association of Psychobehavioral Variables With HOMA-IR and BMI Differs for Men and Women With Prediabetes in the PREVIEW Lifestyle Intervention. Diabetes Care. 2021 Jul;44(7):1491-1498. doi: 10.2337/dc21-0059. Epub 2021 Jun 4.
PubMed 34088702Zhu R, Larsen TM, Fogelholm M, Poppitt SD, Vestentoft PS, Silvestre MP, Jalo E, Navas-Carretero S, Huttunen-Lenz M, Taylor MA, Stratton G, Swindell N, Drummen M, Adam TC, Ritz C, Sundvall J, Valsta LM, Muirhead R, Brodie S, Handjieva-Darlenska T, Handjiev S, Martinez JA, Macdonald IA, Westerterp-Plantenga MS, Brand-Miller J, Raben A. Dose-Dependent Associations of Dietary Glycemic Index, Glycemic Load, and Fiber With 3-Year Weight Loss Maintenance and Glycemic Status in a High-Risk Population: A Secondary Analysis of the Diabetes Prevention Study PREVIEW. Diabetes Care. 2021 Jul;44(7):1672-1681. doi: 10.2337/dc20-3092. Epub 2021 May 27.
PubMed 34045241
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PREVention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World
- ClinicalTrials.gov ID
- NCT01777893
- Acronym / sponsor ID
- PREVIEW / B303
- Conditions
- Pre-diabetes, Obesity
- Keywords
- Type-2 diabetes mellitus, Obesity, High protein diet, Low GI, Physical activity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,500 participants (estimated)
- Lead sponsor
- Anne Birgitte RabenUniversity, hospital or other
- Collaborators
- University of Helsinki, Maastricht University, University of Nottingham, University of Navarra, Clinical Center of Endocrinology, Medical University, Sofia, Bulgaria, University of Sydney, University of Auckland, New Zealand, University of Stuttgart, Swansea University, Cambridge Manufacturing Company Limited, European Union, Wageningen University, Meyers Madhus, NetUnion SARL, Terveyden Ja Hyvinvoinnin Laitos, Laval University
- Study start
- Jun 2013
- Primary completion
- Mar 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 29 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Type-2 diabetes is one of the fastest growing chronic diseases worldwide. This trend is mainly driven by a global increase in the prevalence of obesity. The PREVIEW study has been initiated to find out the most effective lifestyle-components (diet and physical activity) in the prevention of Type-2 diabetes. The project consists of a randomized lifestyle-intervention with the more specific aim to determine the preventative impact of a high-protein and low-GI diet in combination with moderate or high intensity physical activity compared with a moderate-protein and moderate GI diet in combination with the same activity levels on the incidence of Type-2 diabetes in predisposed, pre-diabetic children, young and older adults.
The trial will be performed in 6 EU countries (Bulgaria, Denmark, Finland, Spain, Netherlands, UK) and Australia and New Zealand.
A total of 2,500 overweight or obese adult participants (25-70 y) as well as 150 children and adolescents aged 10-18 y) will be recruited. All adult participants are first treated by a low-calorie diet for 8 weeks, with an aim to reach ≥ 8% weight reduction. Children and adolescents are treated separately with a conventional weight-reduction diet, with-out a specific aim for absolute weight loss.
The adult participants are randomized into two different diet interventions and two exercise interventions for a total of 148 weeks. This period aims at preventing Type-2 diabetes by weight-maintenance (prevention of relapse in reduced body weight) and by independent metabolic effects of diet and physical activity.
The primary endpoint of the study is the incidence of Type-2 diabetes in the adults during 3 years (156 weeks) according to diet (high protein/low-GI versus moderate protein/moderate-GI, adjusted for physical activity), based on a 75 g oral glucose tolerance test and/or HbA1c.
For children and adolescents:
Change in insulin resistance at 2 years after randomization to high protein versus moderate protein diet, measured by insulin resistance analyzed by the homeostatic model (HOMA-IR) as well as physiological improvement of health with respect to pre-diabetic characteristics.
Our hypothesis is that a high-protein, low-GI diet will be superior in preventing type-2 diabetes, compared with a moderate protein, moderate GI diet, and that high-intensity physical activity will be superior compared to moderate-intensity physical activity.
Detailed description
Type-2 diabetes is one of the fastest growing chronic diseases worldwide. This trend is mainly driven by a global increase in the prevalence of obesity. The PREVIEW study has been initialized to find the most effective lifestyle-components (diet and physical activity) in the prevention of T2D. The project is a randomized lifestyle-intervention. The main aim is to determine the preventative impact of a high-protein and low-GI diet in combination with moderate or high intensity physical activity on the incidence of T2D in predisposed, pre-diabetic children, younger and older adults (both gender). In substudies following will be assessed; changes in fat distribution (adults), risk of colon cancer by biomarkers (fecal samples in adults), change in physical fitness (VO2 max in adults), metabolomics profile (adults), food reward (children and adolescents) and sleep architecture (children and adolescents).
Objective: The project addresses prevention in individuals with high risk for T2D. The trial will be performed in 6 EU countries (Bulgaria, Denmark, Finland, Spain, Netherlands, United Kingdom), as well as in Australia and New Zealand.
Study design: The PREVIEW intervention study will be carried out as a 3-year randomized, clinical intervention consisting of an initial 8-week weight loss period and a 148 week randomized weight maintenance intervention.
Study population: A total of 2500 adult as well as 150 children and adolescent participants will participate in the intervention. All adult participants are first treated by a low-calorie diet for 8 weeks, with an aim to reach >8% weight reduction. In skeletal immature children weight loss is not desirable and the goal is to maintain weight (while gaining length) during the initial 8 weeks.
Intervention: The two diet interventions for participants are:
HP = high-protein: protein 25 E%, carbohydrates 45 E%, dietary glycaemic index (GI) <50.
MP = moderate-protein: protein intake 15% in total energy intake (E%), carbohydrates 55 E%, GI >56;
Both diets are composed by using healthy food items.
The two exercise interventions are:
MI = moderate-intensity: 60-75% of maximal heart rate (HRmax), e.g., brisk walking;
HI = high intensity: 76-90% HRmax, e.g., running.
The randomization for the adults is stratified by sex and age group, and by sex in children.
The participants are supervised in groups during the LCD (4 times) and throughout the weight-maintenance period. Children are being supervised separately. Meeting frequency is reduced towards the end of the study. The main assessment points (clinical investigation days, CID) are at week 0 (start of weight reduction), week 8 (end of weight reduction/start of randomized intervention), week 26 (6 months from baseline), week 52 (12 months from baseline), week 78 (18 months from baseline) week 104 (24 months from baseline) and week 156 (36 months from baseline / End of Trial, EOT). For the children and adolescents the last assessment point is at week 104 (24 months from baseline/ End of Trial, EOT).
Main study endpoints: The primary endpoint of the intervention study is for adults the incidence of Type-2 diabetes during 3 years (156 weeks) according to diet (high protein versus moderate protein, adjusted for physical activity), based on a 75 g oral glucose tolerance test (OGTT). The incidence of diabetes will be assessed annually by participant self-report of medication requiring diabetes, doctor informed (and confirmed) diabetes diagnosis or diabetes diagnosed by fasting plasma glucose (FPG) and/or OGTT according to IDF guidelines.
For children and adolescents: Change in insulin resistance at 2 years after randomization to high protein versus medium protein diet, measured by insulin resistance analyzed by the homeostatic model (HOMA-IR) as well as physiological improvement of health with respect to pre-diabetic characteristics.
Secondary endpoints are (tested against the four possible combinations of diet and physical activity if not stated otherwise) the effects of high intensity vs. moderate intensity physical activity on incidence of type 2 diabetes, based on WHO/IDF criteria (adjusted for diet); changes in HbA1c (a measure of average blood glucose levels), body weight and waist, hip and thigh circumference; change in body fat mass (kg, proportion of body weight); proportion of subjects maintaining at least 0, 5 or 10% weight loss (relative to initial body weight); insulin sensitivity (Matsuda Index based on the OGTT, glucose and insulin area under the curve (AUC) during OGTT, beta-cell disposition index)(only adults); risk factors for cardiovascular disease, with at least the following measures: blood pressure, lipids (triglycerides, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol), C-reactive protein, and liver enzymes; changes in perceived quality of life and workability, habitual well-being and chronic stress, sleep duration and quality (accelerometer and questionnaire), appetite sensations, and habitual (long-term) physical activity.
Substudies. Fat distribution: Assessment of fat distribution by MRI (Magnetic Resonance Imaging) and H-MRS (Hydrogen Magnetic Resonance Spectroscopy) is done in a sub-group of subjects at University of Maastricht: 20 from HPMI and 20 from MPMI group. MRI/H-MRS is a non-invasive and non-irradiant imaging technique, which will be used to determine abdominal fat and muscle mass of the upper part of the lower limbs (MRI), muscle and liver fat (H-MRS). MRI and H-MRS measurements take place at weeks 0, 26 and 104.
Sampling and analyses of DNA and RNA: The intended use of the samples is epi/genetic analyses in relation to obesity and associated diseases. Genetic sampling will take place at week 0, 52 and 156.
Metabolomics profile: In a sub-group of subjects, urine from baseline week 0 and week 52 will be analyzed for metabolomics profile.
Fecal samples: Full fecal samples from 3 consecutive days are collected from a sub-group. The samples are used for assessment of colon cancer risk markers, ie phenolic metabolites, short-chain fatty acids (SCFA), nitrogenous compounds. Subjects are recruited from all four groups on a consecutive invitation basis. Moreover, samples from the same subjects are stored for potential analysis of microbiota. Fecal samples will be collected during weeks 0 and 52.
Sleep architecture: In a sub-study we will identify the mediating role of sleeping patterns (sleep quality and duration), stress and brain plasticity on the protein/ activity intervention and the outcome parameters. The sub-study assessing the role of sleep and brain plasticity will be conducted as a repeated measures design embedded in the main intervention study. Measurements will be taken at 0, 26 and 104 weeks.
Food reward: A possible relationship of peripheral insulin sensitivity and brain reward activation will be assessed in a sub-group of pre-diabetic adults, consisting of 2 stratified intervention groups. The sub-study will take place in University of Maastricht and will use functional magnetic resonance imaging (fMRI) in a block design with high calorie/ low calorie food images and control images. Measurements of food reward will be done at weeks 0, 26, and 104.
Sub-group of elderly (+55 y): Serum creatinine and urinary albumine assessments for kidney safety measures.
Cost-effectiveness: All adult participants will fill in a short questionnaire on medicine use, days absent from work, "less than optimal" workability etc. These answers are used to estimate cost-effectiveness of the life-style programs in PREVIEW. Cost-effectiveness will be assessed in week 0, 52, 104, 156.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HP-HI | Experimental | Behavioral: High protein/ high intensity physical activity (HP-HI)High protein/ high intensity physical activity |
| HP-MI | Experimental | Behavioral: High protein / moderate intensity physical activity (HP-MI)High protein/ moderate intensity physical activity |
| MP-HI | Experimental | Behavioral: Moderate protein/ high intensity physical activity (MP-HI)Moderate protein/ high intensity physical activity |
| MP-MI | Experimental | Behavioral: Moderate protein/ moderate intensity physical activity (MP-MI)Moderate protein/ moderate intensity physical activity |
Who may qualify
- Ages
- 10 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (22 listed)
- Age 25 - 70 years:
- From mid 2013 - mid 2014, subjects aged 25-45 and 55-70 years were enrolled. From mid 2014, subjects aged 46-54 years were also enrolled.
- Overweight or obesity status BMI>25 kg/m2
- Pre-diabetes The criteria from WHO/IDF (International Diabetes Foundation) for assessing pre-diabetes will be used as the formal inclusion criteria (at screening), i.e. having:
- Impaired Fasting Glucose (IFG): Fasting venous plasma glucose concentration 5.6 - 6.9 mmol/l or Impaired Glucose Tolerance (IGT): Venous Plasma glucose concentration of 7.8 - 11.0 mmol/l at 2 h after oral administration of 75 g glucose (oral glucose tolerance test, OGTT), with fasting plasma glucose less than 7.0 mmol/l.
Key exclusion criteria (41 listed)
- Based on interview and/or questionnaire, individuals with the following problems will be excluded:
- Diabetes mellitus (other than gestational diabetes mellitus);
- Significant cardiovascular disease including current angina; myocardial infarction or stroke within the past 6 months; heart failure; symptomatic peripheral vascular disease ;
- Systolic blood pressure above 160 mmHg and/or diastolic blood pressure above 100 mmHg whether on or off treatment for hypertension. If being treated, no change in drug treatment within last 3 months;
- Advanced chronic renal impairment;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High protein/ high intensity physical activity (HP-HI)Participants follow a high protein diet and a high intensity physical activity intervention | Behavioural | HP-HI |
| High protein / moderate intensity physical activity (HP-MI)Participants follow a high protein diet and moderate intensity physical activity intervention | Behavioural | HP-MI |
| Moderate protein/ high intensity physical activity (MP-HI)Participants follow a moderate protein diet and a high intensity physical activity intervention | Behavioural | MP-HI |
| Moderate protein/ moderate intensity physical activity (MP-MI)Participants follow a moderate protein diet and moderate intensity physical activity intervention | Behavioural | MP-MI |
Primary outcome
Incidence of type 2 diabetes
Time frame: 3 years
For adults by OGTT Incidence of type 2 diabetes, in high protein versus medium protein diet, measured during 3 years after baseline and based on WHO/IDF criteria: Fasting plasma glucose (FPG) > 7.0 mmol/l (126 mg/dl) or, 75 g oral glucose tolerance test (OGTT) with FPG > 7.0 mmol/l (126 mg/dl) and/or 2 hour plasma glucose > 11.1 mmol/l (200 mg/dl) or, Glycated haemoglobin (HbA1c) > 6.5% (48 mmol/mol), or Random plasma glucose > 11.1 mmol/l (200 mg/dl) in the presence of classical diabetes symptoms. For children and adolescents: Change in insulin resistance at 2 years after randomization to high protein versus medium protein diet, measured by insulin resistance analysed by the homeostatic model (HOMA-IR).
25 secondary outcomes
Incidence of type-2 diabetes
Time frame: 2 years
Change in HbA1c
Time frame: 3 years
Change in body weight (kg or percent) and waist 8cm), hip (cm) and thigh circumference (cm)
Time frame: 3 years
Change in body composition - fat mass and fat-free mass (kg, proportion of body weight)
Time frame: 3 years
Proportion of subjects maintaining at least 0, 5 or 10% weight loss
Time frame: 3 years
Insulin sensitivity (e.g Matsuda Index based on the OGTT, glucose area under the curve (AUC) during OGTT, beta-cell disposition index) (OGTT only adults)
Time frame: 3 years
Risk factors for cardiovascular disease, with at least the following measures: blood pressure, heart rate, lipids (triglycerides, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol), C-reactive protein, and liver enzymes
Time frame: 3 years
Changes in dietary intake (4-d weighed food records)
Time frame: 3 years
Changes in physical activity (accelerometers and questionnaires).
Time frame: 3 years
Changes in perceived quality of life and workability, habitual well-being, sleep and chronic stress, subjective appetite sensations, dietary restraint, moderators, mediators, behavioral and social environment.
Time frame: 3 years
The effects of stature (height; proportion leg-length/height) in adults and changes in stature in children and adolescents, on the changes in relationship between reduction in body weight, body fat and insulin sensitivity
Time frame: 3 years
Safety parameters (blood samples).
Time frame: Screening and during 3 years
Adverse events and concomitant medication.
Time frame: Screening and during 3 years
Compliance by urin samples for nitrogen analyses.
Time frame: 3 years
In a sub-group: Metabolomic profiling.
Time frame: 3 years
In a sub-group: DNA, RNA
Time frame: 3 years
In a sub-group: Colon cancer risk markers
Time frame: 3 years
In a sub-group: Kidney safety markers, body fat and liver-fat content.
Time frame: 3 years
In a sub-group: Body and liver-fat content.
Time frame: 3 years
In a sub-group: Changes in brain responses and cortical thickness
Time frame: 2 years
In a sub-group: Changes in 48-h energy expenditure in a respiration chamber setting
Time frame: 3 years
In a sub-group: Gut microbiome
Time frame: 3 years
In a sub-group: Circulating amino acids
Time frame: 8 wks
In a sub-group: Plasma mitochondrial peptides
Time frame: 8 wks
In a sub-group: Insulin Growth factor 2 (IGF-II) and IGF-II receptor (IGF2R)
Time frame: 8 wks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2019.
- Derived from this study: PubMed 42021301Zhu R, Guo J, Stratton G, Macdonald IA, Handjieva-Darlenska T, Handjiev S, Navas-Carretero S, Poppitt SD, Silvestre MP, Fogelholm M, Adam T, Raben A, Martinez JA, Xie M, Brand-Miller J. Novel OGTT metrics do not provide incremental predictive value beyond conventional glycemic criteria for remission of prediabetes in individuals with impaired fasting glucose: results from the PREVIEW trial. Cardiovasc Diabetol. 2026 Apr 22;25(1):168. doi: 10.1186/s12933-026-03186-0.
- Derived from this study: PubMed 41094026Zhu R, Guo J, Huttunen-Lenz M, Silvestre M, Stratton G, Macdonald IA, Handjieva-Darlenska T, Handjiev S, Navas-Carretero S, Poppitt SD, Fogelholm M, Martinez-Urbistondo D, Martinez JA, Raben A, Brand-Miller J. Long-term effects of dietary protein and carbohydrate quality on prediabetes remission: results from the PREVIEW randomised multinational diabetes prevention trial. Diabetologia. 2026 Jan;69(1):81-92. doi: 10.1007/s00125-025-06560-x. Epub 2025 Oct 15.
- Derived from this study: PubMed 39423758Lim JJ, Prodhan UK, Silvestre MP, Liu AY, McLay J, Fogelholm M, Raben A, Poppitt SD, Cameron-Smith D. Low serum glycine strengthens the association between branched-chain amino acids and impaired insulin sensitivity assessed before and after weight loss in a population with pre-diabetes: The PREVIEW_NZ cohort. Clin Nutr. 2024 Dec;43(12):17-25. doi: 10.1016/j.clnu.2024.09.047. Epub 2024 Oct 2.
- Derived from this study: PubMed 39182617Jiang YC, Lai K, Muirhead RP, Chung LH, Huang Y, James E, Liu XT, Wu J, Atkinson FS, Yan S, Fogelholm M, Raben A, Don AS, Sun J, Brand-Miller JC, Qi Y. Deep serum lipidomics identifies evaluative and predictive biomarkers for individualized glycemic responses following low-energy diet-induced weight loss: a PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) substudy. Am J Clin Nutr. 2024 Oct;120(4):864-878. doi: 10.1016/j.ajcnut.2024.08.015. Epub 2024 Aug 23.
- Derived from this study: PubMed 38916158Huttunen-Lenz M, Hansen S, Raben A, Westerterp-Plantenga M, Adam T, Macdonald I, Stratton G, Swindell N, Martinez JA, Navas-Carretero S, Handjieva-Darlenska T, Handjiev S, Poppitt SD, Silvestre MP, Larsen TM, Vestentoft PS, Fogelholm M, Jalo E, Brand-Miller J, Muirhead R, Schlicht W. Hybrid Evaluation of a Lifestyle Change Program to Prevent the Development of Type 2 Diabetes Among Individuals With Prediabetes: Intended and Observed Changes in Intervening Mechanisms. J Prim Care Community Health. 2024 Jan-Dec;15:21501319241248223. doi: 10.1177/21501319241248223.
- Derived from this study: PubMed 37649005Huttunen-Lenz M, Raben A, Adam T, Macdonald I, Taylor MA, Stratton G, Mackintosh K, Martinez JA, Handjieva-Darlenska T, Bogdanov GA, Poppitt SD, Silvestre MP, Fogelholm M, Jalo E, Brand-Miller J, Muirhead R, Schlicht W. Socio-economic factors, mood, primary care utilization, and quality of life as predictors of intervention cessation and chronic stress in a type 2 diabetes prevention intervention (PREVIEW Study). BMC Public Health. 2023 Aug 30;23(1):1666. doi: 10.1186/s12889-023-16569-9.
- Derived from this study: PubMed 35610522Zhu R, Craciun I, Bernhards-Werge J, Jalo E, Poppitt SD, Silvestre MP, Huttunen-Lenz M, McNarry MA, Stratton G, Handjiev S, Handjieva-Darlenska T, Navas-Carretero S, Sundvall J, Adam TC, Drummen M, Simpson EJ, Macdonald IA, Brand-Miller J, Muirhead R, Lam T, Vestentoft PS, Faerch K, Martinez JA, Fogelholm M, Raben A. Age- and sex-specific effects of a long-term lifestyle intervention on body weight and cardiometabolic health markers in adults with prediabetes: results from the diabetes prevention study PREVIEW. Diabetologia. 2022 Aug;65(8):1262-1277. doi: 10.1007/s00125-022-05716-3. Epub 2022 May 25.
- Derived from this study: PubMed 35599315Jian C, Silvestre MP, Middleton D, Korpela K, Jalo E, Broderick D, de Vos WM, Fogelholm M, Taylor MW, Raben A, Poppitt S, Salonen A. Gut microbiota predicts body fat change following a low-energy diet: a PREVIEW intervention study. Genome Med. 2022 May 23;14(1):54. doi: 10.1186/s13073-022-01053-7.
- Derived from this study: PubMed 35263691Zhu R, Fogelholm M, Jalo E, Poppitt SD, Silvestre MP, Moller G, Huttunen-Lenz M, Stratton G, Sundvall J, Macdonald IA, Handjieva-Darlenska T, Handjiev S, Navas-Carretero S, Martinez JA, Muirhead R, Brand-Miller J, Raben A. Animal-based food choice and associations with long-term weight maintenance and metabolic health after a large and rapid weight loss: The PREVIEW study. Clin Nutr. 2022 Apr;41(4):817-828. doi: 10.1016/j.clnu.2022.02.002. Epub 2022 Feb 8.
- Derived from this study: PubMed 34915273Zhu R, Larsen TM, Poppitt SD, Silvestre MP, Fogelholm M, Jalo E, Hatonen KA, Huttunen-Lenz M, Taylor MA, Simpson L, Mackintosh KA, McNarry MA, Navas-Carretero S, Martinez JA, Handjieva-Darlenska T, Handjiev S, Drummen M, Westerterp-Plantenga MS, Lam T, Vestentoft PS, Muirhead R, Brand-Miller J, Raben A. Associations of quantity and quality of carbohydrate sources with subjective appetite sensations during 3-year weight-loss maintenance: Results from the PREVIEW intervention study. Clin Nutr. 2022 Jan;41(1):219-230. doi: 10.1016/j.clnu.2021.11.038. Epub 2021 Dec 3.
- Derived from this study: PubMed 34790686Navas-Carretero S, San-Cristobal R, Siig Vestentoft P, Brand-Miller JC, Jalo E, Westerterp-Plantenga M, Simpson EJ, Handjieva-Darlenska T, Stratton G, Huttunen-Lenz M, Lam T, Muirhead R, Poppitt S, Pietilainen KH, Adam T, Taylor MA, Handjiev S, McNarry MA, Hansen S, Brodie S, Silvestre MP, Macdonald IA, Boyadjieva N, Mackintosh KA, Schlicht W, Liu A, Larsen TM, Fogelholm M, Raben A, Martinez JA. Appraisal of Triglyceride-Related Markers as Early Predictors of Metabolic Outcomes in the PREVIEW Lifestyle Intervention: A Controlled Post-hoc Trial. Front Nutr. 2021 Nov 1;8:733697. doi: 10.3389/fnut.2021.733697. eCollection 2021.
- Derived from this study: PubMed 34375397Drummen M, Adam TC, Macdonald IA, Jalo E, Larssen TM, Martinez JA, Handjiev-Darlenska T, Brand-Miller J, Poppitt SD, Stratton G, Pietilainen KH, Taylor MA, Navas-Carretero S, Handjiev S, Muirhead R, Silvestre MP, Swindell N, Huttunen-Lenz M, Schlicht W, Lam T, Sundvall J, Raman L, Feskens E, Tremblay A, Raben A, Westerterp-Plantenga MS. Associations of changes in reported and estimated protein and energy intake with changes in insulin resistance, glycated hemoglobin, and BMI during the PREVIEW lifestyle intervention study. Am J Clin Nutr. 2021 Nov 8;114(5):1847-1858. doi: 10.1093/ajcn/nqab247.
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Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), Artificial Intelligence Mobile Application
RecruitingPhase 3
A Study of Orforglipron in Participants With Overweight at Risk of Development of Obesity-Related Complications or Progression to Class 1 Obesity
Overweight, Prediabetic State
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Enrolling by invitationEarly Phase 1
Truway Diagnostic Tools in Primary Care
Chronic Disease, Type 2 Diabetes Mellitus (T2DM), Obesity, Overweight
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas M Larsen, Ass. Prof. principal investigator
University of Copenhagen
Mikael Fogelholm, Professor principal investigator
University of Helsinki
Margriet Westerterp-Plantenga, Professor principal investigator
Maastricht University
9 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High protein/ high intensity physical activity (HP-HI), High protein / moderate intensity physical activity (HP-MI) and Moderate protein/ high intensity physical activity (MP-HI) in people with Pre-diabetes and Obesity, run by Anne Birgitte Raben at 9 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom, Australia, Bulgaria, Denmark, Finland and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of type 2 diabetes (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01777893, which also lists 25 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2019.