Sweet Sensing in Type 2 Diabetes

Identifying the Mechanisms of Gut-brain Axis to Sweet Sensing in Patients With Type 2 Diabetes Using Neuroimaging Techniques

Diabetes is a global challenge and the number of people affected by diabetes is expected to rise to 5.5 million by 2030, of which 90% are type 2 diabetes (T2D). Habitual high consumption of sugars is an important risk factor in the development, and progression, of type 2 diabetes (T2D). Several studies have now shown that individuals with T2D have reduced lingual sweet taste sensation and this in turns increases their sugar intake to achieve the same hedonic reward values compared to the healthy population. This subsequently will lead to development of diabetes or worsening of the blood sugar control.

Phase 1 of our study aims to identify the alterations in oral sweet taste sensitivity in individuals with type 2 diabetes and assess whether this is linked to sweet preference and habitual sugar consumption. In phase 2, we will use functional magnetic resonance imaging (MRI), a powerful technique used widely for diagnosing disease and investigating physiological and pathological process, to investigate whether diabetes or prediabetes status modulates activation of taste and reward-related brain responses to lingual sweet taste stimulation. Phase 3 will be investigating the reward-related brain responses to gut taste stimulation using functional MRI.

These new data will reveal the central mechanisms of sweet sensing in different status of diabetes and this will help develop novel treatment targets to improve metabolic and vascular outcomes in individuals with prediabetes or T2D.

Study Overview

• Status: Enrolling by invitation
• Conditions: Type 2 Diabetes; Prediabetes

• Study Type: Observational
• Enrollment (Estimated): 505

Contacts and Locations

Study Locations

• United Kingdom
  • East Midlands
    • Nottingham, East Midlands, United Kingdom, NG7 2QE
      • University of Nottingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

We will be inviting potential participants from primary care team and also healthy volunteer from the university campus or to the public by displaying poster around the campus and health facilities.

Description

Inclusion Criteria:

• General Eligibility Criteria

  • For T2D: Confirmed Type 2 Diabetes Mellitus (HbA1c>48 mmol/mol (6.5%) and managed by the anti-diabetic drug metformin alone diagnosed within the last 10 years
  • For Prediabetes: HbA1c 42-48 mmol/mol and no less than 3 years since diagnosis
  • Non-diabetes who had HbA1c screened at their GP in the last 12 months: HbA1c≤42mmol/mol

Phase 1

Inclusion criteria:

Adults aged between 18 -60 years with type 2 diabetes or healthy individuals who had HbA1c checked within the last 12 months. Healthy volunteers who did not have HbA1c screened at their GP will be offered an opportunistic screening blood test.

Phase 2 and 3:

Inclusion criteria:

right-handed adults between 18- 60 years with type 2 diabetes, pre-diabetes and healthy individuals who had HbA1c checked within the last 12 months. Healthy volunteers who did not have HbA1c screened at their GP will be offered an opportunistic screening blood test.

Exclusion Criteria:

• Phase 1 exclusion criteria

  1. Current pregnancy or breastfeeding
  2. Current treatment with insulin or any other diabetic medications apart from metformin
  3. History of neurological, gastrointestinal injury or disease
  4. Any medication that is known to alter taste perception
  5. Smokers

Phase 2 and 3 exclusion criteria

1. individuals with Neurological or gastrointestinal disorders (IBD/ IBS)
2. those who have contraindications to MRI including metal implants
3. those who are unable to lie flat
4. smokers
5. those who have taken part in research projects within the last 3 months (projects involving administering a drug, invasive procedure i.e. venepuncture >50 ml, endoscopy, or exposure to ionising radiation)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Type 2 diabetes group; Inclusion criteria right or left handed age between 18-60 years HbA1c >48 mmol/mol duration of diabetes less than 10 years only for those who are treated with metformin excluding those with neurological disorder, gastrointestinal disorders, current pregnancy or breast feeding, on medications which can alter taste perception, current smokers, allergy to sugar, those who has contraindication to MRI, those who cannot lie flat, those who have taken part in research projects within the last 3 months
Prediabetes group; Inclusion criteria right handed individuals age between 18-60 years HbA1c between 42-48 mmol/mol, diagnosis of pre-diabetes not less than 3 years only for those who are treated with metformin excluding those with neurological disorder, gastrointestinal disorders, current pregnancy or breast feeding, on medications which can alter taste perception, current smokers, allergy to sugar, those who has contraindication to MRI, those who cannot lie flat, those who have taken part in research projects within the last 3 months
Healthy group; Inclusion criteria right or left handed individuals age between 18-60 years HbA1c </=42 mmol/mol only for those who are treated with metformin excluding those with neurological disorder, gastrointestinal disorders, current pregnancy or breast feeding, on medications which can alter taste perception, current smokers, allergy to sugar, those who has contraindication to MRI, those who cannot lie flat, those who have taken part in research projects within the last 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the sensitivity and preference of lingual sweet taste in individuals with T2D, and those without T2D to evaluate how this is impacted by habitual sugar consumption.	December 2024 to December 2026
To compare brain responses to lingual sweet sensing in individuals with prediabetes and T2D, and those without prediabetes or T2D, and their association with habitual sugar consumption.	from Dec 2024 to Dec 2026

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine how brain responses to intestinal sweet sening predict the rate of intestinal glucose absorption.	Feb 2025 to Dec 2026

Collaborators and Investigators

• Sponsor: University of Nottingham
• Investigators: Principal Investigator: Sally Eldeghaidy, BSc, MSc, PhD, University of Nottingham

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 27, 2025
• First Submitted That Met QC Criteria: January 27, 2025
• First Posted (Actual): February 3, 2025

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 4, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Type 2 diabetes; taste receptors; pre diabetes; sweet sensitivity; sweet preference; sugar craving
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus
• Other Study ID Numbers: 24008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are not planning to share individual participant data but will publish in scientific papers and conferences with the overall results.

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