PREVention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 2,500
- 试验地点
- 18
- 主要终点
- Incidence of type 2 diabetes
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
- •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 >
- •No HOMA criteria is used for Tanner stage 1 and
- •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.
排除标准
- •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;
- •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.
- •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
研究组 & 干预措施
HP-HI
High protein/ high intensity physical activity
干预措施: High protein/ high intensity physical activity (HP-HI) (Behavioral)
HP-MI
High protein/ moderate intensity physical activity
干预措施: High protein / moderate intensity physical activity (HP-MI) (Behavioral)
MP-HI
Moderate protein/ high intensity physical activity
干预措施: Moderate protein/ high intensity physical activity (MP-HI) (Behavioral)
MP-MI
Moderate protein/ moderate intensity physical activity
干预措施: Moderate protein/ moderate intensity physical activity (MP-MI) (Behavioral)
结局指标
主要结局
Incidence of type 2 diabetes
时间窗: 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).
次要结局
- Change in body composition - fat mass and fat-free mass (kg, proportion of body weight)(3 years)
- In a sub-group: Kidney safety markers, body fat and liver-fat content.(3 years)
- Changes in dietary intake (4-d weighed food records)(3 years)
- In a sub-group: Metabolomic profiling.(3 years)
- In a sub-group: Body and liver-fat content.(3 years)
- In a sub-group: Changes in 48-h energy expenditure in a respiration chamber setting(3 years)
- Proportion of subjects maintaining at least 0, 5 or 10% weight loss(3 years)
- Change in HbA1c(3 years)
- Changes in physical activity (accelerometers and questionnaires).(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.(3 years)
- Adverse events and concomitant medication.(Screening and during 3 years)
- Compliance by urin samples for nitrogen analyses.(3 years)
- Incidence of type-2 diabetes(2 years)
- Change in body weight (kg or percent) and waist 8cm), hip (cm) and thigh circumference (cm)(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)(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(3 years)
- Safety parameters (blood samples).(Screening and during 3 years)
- In a sub-group: Colon cancer risk markers(3 years)
- In a sub-group: Changes in brain responses and cortical thickness(2 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(3 years)
- In a sub-group: DNA, RNA(3 years)
- In a sub-group: Gut microbiome(3 years)
- In a sub-group: Plasma mitochondrial peptides(8 wks)
- In a sub-group: Circulating amino acids(8 wks)
- In a sub-group: Insulin Growth factor 2 (IGF-II) and IGF-II receptor (IGF2R)(8 wks)
研究者
Anne Birgitte Raben
Professor
University of Copenhagen