The Genetic Effects of rs7903146 and Dietary Intake on Type 2 Diabetes Mellitus Risk in a Healthy Population

The Association Between TCF7L2 rs7903146, Diet and Type 2 Diabetes Mellitus Risk

This study investigates the association of genetic effects of rs7903146 and dietary intake on type 2 Diabetes Mellitus (T2DM) risk in a healthy population. T2DM risk was assessed through glycated haemoglobin (HbA1c) concentration in 73 subjects. Dietary intake was assessed using a validated food frequency questionnaire (FFQ).

Study Overview

• Status: Completed
• Conditions: Health Behavior; Diet Habit; Genetic Predisposition; Blood Glucose, High

Detailed Description

Type 2 diabetes mellitus (T2DM) is a global epidemic linked to 1.6 million deaths in 2016. Diet, lifestyle and environment contribute significantly to T2DM-risk. Genome-wide association studies identify the transcription factor 7-like 2 (TCF7L2) rs7903146 (C/T) gene as one of the most important associated with T2DM-risk. The T-allele is associated with a two-fold increase in relative risk of T2DM across different populations. However, most studies associating genetic effects of dietary intake on rs7903146 and T2DM-risk utilised volatile instantaneous measures of glucose(5) and focussed on individual macronutrients. Understanding the association of rs7903146 and overall macronutrient intake using a stable blood homeostasis marker may provide a fuller insight into T2DM-risk.

The study included data for all variables (participant characteristics: sex (female/male), age (years), height (cm), weight (kg), body mass index (BMI) (kg/m2), body fat percentage (%), fat mass (kg), lean mass (kg), waist/hip (ratio), dietary intake, HbA1c (mmol/mol and %) and physical activity (hours/week). All data was collected at St Mary's University between April to July 2019. Participants was genotyped and allocated into two groups: major allele (C) homozygote versus minor allele (T) homozygote plus heterozygote. T2DM-risk was assessed through their value of HbA1c and participants were classified as follows: normal (<42mmol/mol/ <6.0%), pre-diabetic (42 to 47 mmol/mol/ 6.0% to 6.4%), diabetes (48mmol/mol /6.5% or over).

• Study Type: Observational
• Enrollment (Actual): 73

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, TW1 4SX
    • St Marys University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Male-female age between 18 to 64.9 years old

Description

Inclusion criteria: Eligibility criteria required healthy adults free from metabolic condition and free from medication affecting glycated haemoglobin levels.

Exclusion criteria: Individuals with HbA1c levels ≥48 mmol/mol or ≥6.5% were excluded due to a classification as T2DM (WHO, 2011).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA	salivary (1-ml) DNA for genotype TCF7L2 gene (rs7903146 SNP)	3 months
Hba1c	capillary blood collected (via the ears or fingers) using a Microvette CB Lithium Heparin tube (SARSTEDT AG & C0., Nümbrecht, Germany)	3 months
Diet intake	Dietary intake estimated using The European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk (food frequency questionnaire)	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	Body weight in kg measured by bioelectrical impedance analysis using a 0.5kg clothing offset	3 months
Waist	Waist measurement was taken midway between iliac crest and lowest rib	3 months
Hip	Hip circumference was measured over the greater trochanters at their widest point (nearest 0.1cm)	3 months
Height	Subject height was recorded to the nearest 0.1-cm via stadiometer	3 months
Physical activity	Assessed through Physical Activity Readiness Questionnaire (PAR-Q)	3 months
Fat mass	Measured in kg and percentage (%) measured by bioelectrical impedance analysis	3 months
Lean mass	Measured in kg and percentage (%) measured by bioelectrical impedance analysis	3 months

Collaborators and Investigators

• Sponsor: St Mary's University College

Publications and helpful links

General Publications

• Podboi ICR, Stephenson S, Pilic L, Graham CA, King A, Mavrommatis Y. Dietary Intake and TCF7L2 rs7903146 T Allele Are Associated with Elevated Blood Glucose Levels in Healthy Individuals. Lifestyle Genom. 2021;14(4):117-123. doi: 10.1159/000518523. Epub 2021 Aug 12.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2019
• Primary Completion (Actual): September 20, 2019
• Study Completion (Actual): October 2, 2019

Study Registration Dates

• First Submitted: June 19, 2020
• First Submitted That Met QC Criteria: June 23, 2020
• First Posted (Actual): June 25, 2020

Study Record Updates

• Last Update Posted (Actual): June 25, 2020
• Last Update Submitted That Met QC Criteria: June 23, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Disease Attributes; Diabetes Mellitus; Diabetes Mellitus, Type 2; Disease Susceptibility; Genetic Predisposition to Disease
• Other Study ID Numbers: SMEC_2018-19_034

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No