The TCF7L2 Gene: Dietary Prevention of T2DM

NCT03458494 | Terminated

• 1 other identifier: TCF7L2_2965
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Nutrients and chemicals in food are able to regulate expression of genetic elements. Gene-nutrient interaction in response specific diets can increase an individual's risk, shifting the individual from health toward the development of chronic disease. The Transcription Factor 7 Like 2 (TCF7L2) gene may either put individuals at risk for or protect from Type 2 diabetes mellitus in the presence of certain foods. The main purpose of this four-week study is to examine diet-induced gene-nutrient interaction, with a focus on glucose, insulin, inflammation (CRP) and the plasma metabolome in individuals who have either the CC or the TT form of the rs7903146 single nucleotide polymorphism (SNP) (C/T) within the TCF7L2 gene. The (2) one-week study diets, one Mediterranean diet (MedDiet) based and the other low-fat based will be separated by a (1) week return to a regular habitual diet.

Conditions

Type2 Diabetes; Glucose, High Blood

Keywords

type 2 diabetes; glucose; insulin; CRP; Metabolomics; gene-diet interaction; TCF7L2

Outcome Measures

Primary Outcomes (1)

• Glucose

  Plasma glucose levels (mg/dl) will be measured in the fasting state during each one of the intervention phases (the Mediterranean and low-fat diets) in participants with the TT and CC genotypes at the TCF7L2 rs7903146 SNP

  1 week per intervention arm

Secondary Outcomes (6)

• Insulin

  1 week per intervention arm

• Metabolomics

  1 week per intervention arm

• Very low density lipoproteins (VLDL)

  1 week per intervention arm

• Low-density lipoproteins (LDL)

  1 week per intervention arm

• High-density lipoproteins (HDL)

  1 week per intervention arm

Study Arms (2)

Mediterranean Diet

EXPERIMENTAL

during one week participants will receive food products common in the diet of Mediterranean populations

Other: Mediterranean Diet

Low-fat diet

EXPERIMENTAL

during one week participants will receive food products low in fat content

Other: Low-fat diet

Interventions

Mediterranean Diet OTHER

Participants will receive meals traditionally consumed in Mediterranean countries

Mediterranean Diet

Low-fat diet OTHER

Participants will receive meals with a low content of total fat.

Low-fat diet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women.
• years or older.
• Women who are not pregnant.
• A BMI ranging between 27 and 34

You may not qualify if:

• Unexplained elevation in serum transaminases (i.e. \>1.5 times the upper limit of normal) or with evidence of active liver disease, including primary biliary cirrhosis or pre-existing gallbladder disease.
• Severe renal dysfunction (serum creatinine \>2.0mg/dL).
• Excessive alcohol consumption (\>2 drinks/day).
• Preexisting CVD.
• Stable exertional angina pectoris requiring sublingual nitroglycerin within the prior 3 months.
• Uncontrolled T2D (fasting glucose \>126 mg/dl) or other significant endocrine disease.
• Uncontrolled hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \>100 mmHg).
• History of pancreatitis within 1 yr. prior to screening.
• Subjects on lipid-lowering or diabetes medications.
• Smoking.
• Pregnancy.
• Body mass index (BMI) below 27 or greater than 34 kg/m2
• Participants will also be excluded for drug abuse, extreme dietary habits, multiple food allergies, extreme levels of physical or athletic activity, or by changes in body weight \>20 lbs. during the last 6 months.
• Inability to follow any of the experimental diets or to perform the sampling required for this study.
• Thyroid diseases.

Sponsors & Collaborators

• Tufts University: lead
• Allen Foundation Inc.: collaborator

Study Sites (1)

JM-USDA Human Nutrition Research Center on Aging at Tufts University

Boston, Massachusetts, 02111, United States

Location

Related Publications (2)

• Corella D, Carrasco P, Sorli JV, Estruch R, Rico-Sanz J, Martinez-Gonzalez MA, Salas-Salvado J, Covas MI, Coltell O, Aros F, Lapetra J, Serra-Majem L, Ruiz-Gutierrez V, Warnberg J, Fiol M, Pinto X, Ortega-Azorin C, Munoz MA, Martinez JA, Gomez-Gracia E, Gonzalez JI, Ros E, Ordovas JM. Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population. Diabetes Care. 2013 Nov;36(11):3803-11. doi: 10.2337/dc13-0955. Epub 2013 Aug 13.

  PMID: 23942586 BACKGROUND

• Lai CQ, Gervis JE, Parnell LD, Lichtenstein AH, Ordovas JM. Changes in triglyceride-rich lipoprotein particle profiles in response to one-week on a low fat or Mediterranean diet by TCF7L2 rs7903146 genotype: a randomized crossover dietary intervention trial. Genes Nutr. 2025 Mar 6;20(1):4. doi: 10.1186/s12263-025-00763-y.

  PMID: 40050721 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

Diet, Mediterranean; Diet, Fat-Restricted

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Diet, Plant-Based; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Jose M Ordovas, PHD

  Tufts University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist, Lab Director JM-USDA-HNRCA

Model Details: randomized crossover dietary intervention

Study Record Dates

• First Submitted: February 24, 2018
• First Posted: March 8, 2018
• Study Start: February 15, 2018
• Primary Completion: April 30, 2020
• Study Completion: April 30, 2020
• Last Updated: September 4, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)