PREMIER: PREvention of Metabolic Illness Through prEcision nutRition

Study Overview
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Brief Summary
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Dietary intake is a major driving force behind the escalating obesity and type 2 diabetes epidemics. Large, high-quality clinical trials have shown that close adherence to healthy dietary recommendations significantly reduce the incidence of obesity and type 2 diabetes, especially among people at increased risk. However, large inter-individual variability exists in response to dietary interventions. To inform more effective obesity and type 2 diabetes prevention strategies, it is crucial to better understand the biological, environmental, and social factors that influence how people interact and respond to specific foods. In a recent large-scale genome-wide association study, our research team has identified 96 genomic regions associated with overall variation in dietary intake. This study provided evidence that inherited molecular differences are likely to impact on food intake (i.e., preference for certain foods) and metabolic homeostasis (i.e., glucose regulation). Connecting knowledge about human genetic variants with information from circulating metabolites can be particularly useful in understanding the mechanisms by which some people experience a detrimental response to specific foods. The specific objective of the PREMIER study is to carry out an interventional dietary study to measure the response of blood glucose and other biomarkers to a standardized meal, and evaluate the extent to which food choices differ among individuals with distinct genetic susceptibility.

Official Title
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PREMIER: PREvention of Metabolic Illness Through prEcision nutRition

Conditions
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Food Preferences, Obesity, Type 2 Diabetes, Metabolic Syndrome, Diet Habit, Nutritional and Metabolic Disease

Intervention / Treatment
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* Other: Dietary intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female. 21-65 years of age. Body mass index (BMI) between 18.5 and 30.0 kg/m2. Healthy (free of diagnosed diseases listed in the exclusion criteria). Willing to comply with the study intervention. Able to provide informed consent Exclusion Criteria: Refuse or are unable to give informed consent to participate in the study. Have type I or type II diabetes mellitus or are taking medications for type II diabetes mellitus. Those not on medications but having a capillary glucose level of >126 mg/dL based on fingertip glucose measurements will be excluded. Are obese (BMI>30.0kg/m2) or underweight (BMI<18.5kg/m2). Have had a heart attack (myocardial infarction) or stroke Have had cancer in the last 3 years, excluding skin cancer. Have an ongoing inflammatory disease i.e. Rheumatoid arthritis, systemic lupus erythematosus, polymyalgia and other connective tissue diseases. History of cirrhosis and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 3 times the upper limit of normal (ULN). Are currently suffering from acute clinically diagnosed depression. Currently taking or intending to take during the study duration any medication known to affect glycemic parameters, such as glucocorticoids or fluoroquinolones. Are unable to fast from 9pm the night before the clinic visit until 9am on the clinic day Are pregnant or breastfeeding. Are participating in another clinical study. Are vegan, suffering from an eating disorder or unwilling to eat foods that are part of the study.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: This is a recall-by-genotype study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Genotype of interest group<br>Individuals with desired genetic susceptibility will receive a standardized and an election meal in a full-day clinic visit. | Other: Dietary intervention<br>* To investigate whether individuals with divergent genetic susceptibility have different food preferences and have differential post-prandial glycemic and metabolomics responses to a standardized or an election meal.<br>|
| Placebo Comparator: Control<br>Individuals without genotype of interest (i.e., carrying the opposite genotype) will receive a standardized and an election meal in a full-day clinic visit. | Other: Dietary intervention<br>* To investigate whether individuals with divergent genetic susceptibility have different food preferences and have differential post-prandial glycemic and metabolomics responses to a standardized or an election meal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose | Measurement of blood glucose at regular intervals. | Day 1 | 
| High-fat meal preference | Number of participants with preference for a high-fat meal. | Day 1 | 
| Hunger perception before and after test meals consumption using visual analogue scales | Record of hunger perception before and after test meals using visual analogue scales. Participants will provide ratings raging from 0 to 100 based on six questions commonly used in visual analogue scales including: How hungry do you feel? (0=not at all hungry / 100=as hungry as I've ever felt); How full do you feel? (100=not at all full / 0=as full as I have ever felt); How strong is your desire to eat? (0=very weak / 100=very strong); How much do you think you could eat now? (0=nothing at all / 100=a large amount); Urge to eat (0=no urge to eat / 100=strong, want to eat now, waiting is very uncomfortable); Preoccupation with thoughts of food (0=no thoughts of food / 100=very preoccupied difficult to concentrate on other things). The minimum and maximum values range from 0 to 100, with higher numbers indicating higher hunger perception. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolomics by mass spectrometry analysis | Investigators will perform metabolomic profiling of plasma samples at regular intervals by using both targeted and untargeted approaches on an existing platform that measures  10000 metabolites (both polar and non-polar); they will compare their relative concentrations by genotype at selected loci before and after the interventions. | Day 1 | 
| Incretin levels by immunoassay kits | Measurement of blood Glucagon-Like Peptide-1 (GLP-1) and Gastric Inhibitory Polypeptide (GIP) concentrations at regular intervals | Day 1 | 
| Appetite satiety hormones levels by immunoassay kits | Measurement of blood Ghrelin, Leptin, Peptide YY (PYY), and Cholecystokinin (CCK) at regular intervals. | Day 1 |