Effect of Diet and Physical Activity on Incidence of Type 2 Diabetes — PREVIEW  

Obesity Clinical Trial

Official title: PREVention of Diabetes Through Lifestyle Intervention and Population Studies in Europe and Around the World

Status Completed

Clinical 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. 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Diabetes Mellitus
• Glucose Intolerance
• Obesity
• Pre-diabetes
• Prediabetic State

• NCT number: NCT01777893
• Study type: Interventional
• Source: University of Copenhagen
• Status: Completed
• Phase: N/A
• Start date: June 2013
• Completion date: December 2018