PREMIER: PREvention of Metabolic Illness Through prEcision nutRition (PREMIER)

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 Overview

• Status: Completed
• Conditions: Obesity; Metabolic Syndrome; Type 2 Diabetes; Food Preferences; Diet Habit; Nutritional and Metabolic Disease
• Intervention / Treatment: Other: Dietary intervention

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massacusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Genotype of interest group; Individuals with desired genetic susceptibility will receive a standardized and an election meal in a full-day clinic visit.	Other: 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.
Placebo Comparator: 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.	Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-fat Meal Preference	Number of participants with preference for a high-fat meal.	Day 1
Glucose at Times 30min, 60min, 120min, 180min	Measurement of blood glucose at regular intervals.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline, 120min, 240min, 360min

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); NORCH (Nutrition Obesity Research Center at Harvard); Boston Area Diabetes Endocrinology Research Center

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2021
• Primary Completion (Actual): September 19, 2024
• Study Completion (Actual): September 19, 2024

Study Registration Dates

• First Submitted: October 18, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 22, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Metabolic Diseases
• Other Study ID Numbers: 2019P002638; P30DK040561 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Our research team will provide a personalized report containing individual's glycemic responses and potentially other biomarker responses to meals consumed by the end of the study.
• IPD Sharing Time Frame: 6-12 months after finishing the study intervention
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No