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

NCT ID: NCT04851223

Last Updated: 2022-05-18

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 130 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-03-22
• Study Completion Date: 2023-09-22

Brief 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).

Detailed 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.

Conditions

Type2 Diabetes Mellitus; Pre Diabetes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Pre Diabetics

No interventions assigned to this group

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Roehampton

OTHER

Sponsor Role: lead

Responsible Party

Richard Mackenzie

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Roehampton

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Richard W Mackenzie

Role: CONTACT

richard.mackenzie@roehampton.ac.uk

+447985749102

Facility Contacts

Richard Mackenzie, Dr.

Role: primary

Richard.Mackenzie@roehampton.ac.uk

07985749102

References

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. doi: 10.1001/jama.289.1.76.

Reference Type: BACKGROUND

PMID: 12503980 (View on PubMed)

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. doi: 10.2337/diab.37.8.1020.

Reference Type: BACKGROUND

PMID: 3292322 (View on PubMed)

Other Identifiers

245301

Identifier Type: OTHER

Identifier Source: secondary_id

LSC 20/ 311

Identifier Type: -

Identifier Source: org_study_id