Investigating Plasma Biomarker Molecules Associated With the Progression of Prediabetes to Overt Type 2 Diabetes

Type2 Diabetes Mellitus Clinical Trial

Official title:

Biomarkers Identification for the Progression From Pre-diabetes to T2D

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04851223
• Other study ID #: LSC 20/ 311
• Secondary ID: 245301
• Status: Recruiting
• Start date: March 22, 2021
• Est. completion date: September 22, 2023

Study information

• Verified date: May 2022
• Source: University of Roehampton
• Contact: Richard W Mackenzie
• Phone: +447985749102
• Email: richard.mackenzie[@]roehampton.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

There are an estimate 7 million people in the United Kingdom living with pre-diabetes. The increasing number of new cases of pre-diabetes presents a global health concern due to funding implications.

The progression from pre-diabetes to overt type 2 diabetes is often characterised by a reduction in insulin secretion (or β-cell dysfunction). Whilst inflammation may contribute to β-cell dysfunction, a complete picture is still lacking. The proposed research will help develop a more complete understanding of the molecules that may trigger β-cell failure, a process that often connects pre-diabetes to overt diabetes.

The aims of this project are;

1. Run large-scale proteomics and metabolomics analysis in pre-diabetic individuals to determine possible biomarker molecules.

2. Use measures and / or classifications of insulin resistance and diabetes (i.e. β-cell function and Disposition Index) to establish whether particular metabolic and / or proteomic signatures (aim 1) are associated with the development of pre-diabetes.

3. To determine if the possible metabolite or protein profile changes are associated with the progression or regression of pre-diabetes from baseline (0 month) to the end of the National Diabetes Prevention Programme (NDPP) (9 month).

Description:

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterised by elevated blood sugar. This represents a worldwide concern due to the secondary complications associated with type 2 diabetes, which are considered an important cause of early death; particularly, given the predicted increase. The cost associated with the treatment and the complications associated with diabetes reaches £10 billion every year and it is expected to increase. From approximately 425 million (2017) it is projected that 629 million adults will be living with diabetes by 2045. Therefore, this matter requires effective interventions aimed at improving blood sugar control, reducing the burden on the economy while improving the quality of life among T2DMs.

Insulin, a hormone that is allowing the body to use or store sugar derived from food, is manufactured by the β-cells in the pancreas. The progression from pre-diabetes to overt type 2 diabetes is typically diagnosed at the point of β-cell failure. Several factors are known to contribute to β-cell dysfunction such as: obesity (especially abdominal obesity), high blood pressure and elevated fats in the blood. Around 80% of the people who have been diagnosed with T2DM are either obese or overweight and they have been observed to have increased levels of fatty acids in the blood following a meal, which can induce insulin resistance. High levels of fatty acids have also been associated with an increased production of pro-inflammatory cytokines, which are small proteins that have an effect on organs or other cells, contributing to chronic inflammation. High levels of chronic inflammation increase the chances of developing metabolic disorders such as T2DM. However, a complete picture of this process is still lacking.

The proposed study will help develop a more complete understanding of the molecules that may trigger β-cell failure.

The identification of these molecules that are implicated in β-cell failure, can lead to the development of targeted interventions for those at risk of developing type 2 diabetes and potentially preventing habitual hyperglycaemia and type 2 diabetes.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: September 22, 2023
• Est. primary completion date: June 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Pre-diabetic individuals between 18 and 65 years of age

Pre-diabetes criteria:

• Glycated hemoglobin (HbA1c) values between 42 - 47 mmol/mol

• Fasting plasma glucose levels between 6.1 - 6.9 mmol/L

• Blood pressure <140 mmHg systolic/ <90 mmHg diastolic

Exclusion Criteria:

• Individuals suffering from any complications (i.e. nerve or kidney disorders, damage of the retina, vascular diseases, strokes, persistent high blood pressure, cardiovascular disease,haemophilia), those with anaemia, blood borne diseases, those who are pregnant or in the postpartum period (within 3 months after delivery), have high blood pressure >140 mmHg systolic/ >90 mmHg diastolic, current smokers, individuals requiring strong anticoagulant medication, such as warfarin (the anticoagulant effect of non-steroidal anti-inflammatory drugs is too small to pose a hazard), insulin or other medications affecting the typical levels of blood glucose are unfortunately unable to take part in this study. Individuals must not be involved in any other study which involves the sampling of blood and must not have donated blood in the last 12 weeks (for males) or 16 weeks (for females). A health questionnaire will be carried out to confirm your eligibility for the study.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Intolerance
• Pre Diabetes
• Prediabetic State
• Type2 Diabetes Mellitus

Locations

Country	Name	City	State
United Kingdom	University of Roehampton	London

Sponsors (1)

Lead Sponsor	Collaborator
University of Roehampton

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA. 2003 Jan 1;289(1):76-9. — View Citation

Reaven GM, Hollenbeck C, Jeng CY, Wu MS, Chen YD. Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM. Diabetes. 1988 Aug;37(8):1020-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body weight Measurements	Weight in kilograms	Changes from baseline to 6 and 9 months
Primary	Body mass Index measurements	kg/m^2	Changes from baseline to 6 and 9 months
Primary	Changes in insulin and glucose	Effect of insulin and glucose levels expressed in mg/dl	Changes from baseline to 6 and 9 months
Primary	Changes in BCAA and its derivatives	metabolites levels via mass spectrometry analysis	Changes from baseline to 6 and 9 months

External Links

•   Diabetes UK. (2014). Cost of diabetes report
•   International Diabetes Federation. (2017). IDF diabetes atlas. 8th edn