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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
22
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.
Massacusetts General Hospital
Boston, Massachusetts, United States
Glucose at Times 30min, 60min, 120min, 180min
Measurement of blood glucose at regular intervals.
Time frame: Day 1
High-fat Meal Preference
Number of participants with preference for a high-fat meal.
Time frame: Day 1
Metabolomics by Mass Spectrometry Analysis (Reported as Fold Change in Metabolites From Baseline)
Investigators will perform metabolomic profiling of plasma samples at regular intervals by using both targeted and untargeted approaches on an existing platform that measures \~10,000 metabolites (both polar and non-polar); they will compare their relative concentrations (fold change) by genotype at selected loci before and after the interventions. Metabolomics will be performed using LC-MS techniques in the Clish Laboratory of the Broad Institute of MIT and Harvard (Cambridge, MA). Fold-change in metabolite values (from 0-\>120, 0-\>240, and 240-\>360 minutes) will be statistically analyzed to identify distinct patterns of metabolite change in response to mixed meals by genotype. Examples of metabolomic fold-change readouts are provided below, by genotype - limited examples are provided as fold-change reporting for \~10,000 metabolites, identified and unidentified, at 3 time points would be impracticable.
Time frame: Day 1
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