Diet Habit, Food Preferences, Metabolic Syndrome, Nutritional and Metabolic Disease, Obesity, Type 2 Diabetes
Conditions
Brief summary
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.
Interventions
OTHERDietary intervention
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.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NORCH (Nutrition Obesity Research Center at Harvard)
Boston Area Diabetes Endocrinology Research Center
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
This is a recall-by-genotype study
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucose at Times 30min, 60min, 120min, 180min | Day 1 | Measurement of blood glucose at regular intervals. |
| High-fat Meal Preference | Day 1 | Number of participants with preference for a high-fat meal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Metabolomics by Mass Spectrometry Analysis (Reported as Fold Change in Metabolites From Baseline) | Day 1 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Previously Proposed Outcomes: Hunger Perception, Incretin Levels by Immunoassay Kit, Satiety Hormones | baseline, 120min, 240min, 360min | Although these outcomes were initially proposed/intended, insufficient funds were available to collect or analyze these measures, and they were not ultimately collected. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Genotype of Interest Group Individuals with desired genetic susceptibility will receive a standardized and an election meal in a full-day clinic visit.
Dietary intervention: 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. | 12 |
| Control 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.
Dietary intervention: 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. | 10 |
| Total | 22 |
Baseline characteristics
| Characteristic | Genotype of Interest Group | Total | Control |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 4 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 18 Participants | 7 Participants |
| Age, Continuous | 55.2 years STANDARD_DEVIATION 8.9 | 56.2 years STANDARD_DEVIATION 8.5 | 57.5 years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 21 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Glucose at time 0 | 81.9 mg/dL STANDARD_DEVIATION 11.7 | 83.6 mg/dL STANDARD_DEVIATION 10.2 | 85.6 mg/dL STANDARD_DEVIATION 8.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 12 Participants | 20 Participants | 8 Participants |
| Region of Enrollment United States | 12 participants | 22 participants | 10 participants |
| Sex: Female, Male Female | 7 Participants | 14 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 10 |
| other Total, other adverse events | 0 / 12 | 0 / 10 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 |
Outcome results
Primary
Glucose at Times 30min, 60min, 120min, 180min
Measurement of blood glucose at regular intervals.
Time frame: Day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotype of Interest Group | Glucose at Times 30min, 60min, 120min, 180min | 120min | 84.1 mg/dL | Standard Deviation 22.5 |
| Genotype of Interest Group | Glucose at Times 30min, 60min, 120min, 180min | 180min | 80.8 mg/dL | Standard Deviation 12.5 |
| Genotype of Interest Group | Glucose at Times 30min, 60min, 120min, 180min | 30min | 112.9 mg/dL | Standard Deviation 19.3 |
| Genotype of Interest Group | Glucose at Times 30min, 60min, 120min, 180min | 60min | 94.5 mg/dL | Standard Deviation 24.1 |
| Control | Glucose at Times 30min, 60min, 120min, 180min | 60min | 118.4 mg/dL | Standard Deviation 34.3 |
| Control | Glucose at Times 30min, 60min, 120min, 180min | 120min | 94.1 mg/dL | Standard Deviation 10.9 |
| Control | Glucose at Times 30min, 60min, 120min, 180min | 30min | 119.8 mg/dL | Standard Deviation 15.6 |
| Control | Glucose at Times 30min, 60min, 120min, 180min | 180min | 81.9 mg/dL | Standard Deviation 9.4 |
Primary
High-fat Meal Preference
Number of participants with preference for a high-fat meal.
Time frame: Day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Genotype of Interest Group | High-fat Meal Preference | 8 Participants |
| Control | High-fat Meal Preference | 3 Participants |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Genotype of Interest Group | Metabolomics by Mass Spectrometry Analysis (Reported as Fold Change in Metabolites From Baseline) | taurodeoxycholic acid at 120 minutes | 10.4 fold-change from baseline | Standard Deviation 8.8 |
| Genotype of Interest Group | Metabolomics by Mass Spectrometry Analysis (Reported as Fold Change in Metabolites From Baseline) | glycochenodeoxycholic acid at 120 minutes | 6.7 fold-change from baseline | Standard Deviation 5.3 |
| Control | Metabolomics by Mass Spectrometry Analysis (Reported as Fold Change in Metabolites From Baseline) | taurodeoxycholic acid at 120 minutes | 4.2 fold-change from baseline | Standard Deviation 4 |
| Control | Metabolomics by Mass Spectrometry Analysis (Reported as Fold Change in Metabolites From Baseline) | glycochenodeoxycholic acid at 120 minutes | 3.9 fold-change from baseline | Standard Deviation 4.5 |
Other Pre-specified
Previously Proposed Outcomes: Hunger Perception, Incretin Levels by Immunoassay Kit, Satiety Hormones
Although these outcomes were initially proposed/intended, insufficient funds were available to collect or analyze these measures, and they were not ultimately collected.
Time frame: baseline, 120min, 240min, 360min
Population: Although these outcomes were initially proposed/intended, insufficient funds were available to collect or analyze these measures, and they were not ultimately collected.