PhD Study : Off Target Benefits of GLP-1 therapy in type 2 Diabetes

Summary

Diabetes is characterized by hyperglycaemia with Type 2 diabetes (T2D) accounting for 90% of all cases (~450M cases globally). Obesity and a lack of exercise increase a person’s risk of T2D. Hyperglycaemia in T2D creates several complications for patients, including risk of heart disease, depression and memory loss. This study will focus on a class of drugs called GLP-1 analogues that are currently used to bring hyperglycaemia under control in T2D. However, early evidence shows that GLP-1 analogues reduce the risk of heart disease and improve depression and memory. A clinical trial assessing the efficacy of liraglutide (a GLP-1 analogue) in early Alzheimer’s disease (AD) is ongoing; however, patients with T2D are excluded.

AIM: To evaluate anti-depressant, anxiolytic, cognitive and cardiovascular outcomes in patients with T2D treated with GLP-1 analogues, as part of their routine clinical care, compared to those treated with other T2D drugs.

EXPERIMENTAL PLAN: Participants receiving GLP-1 therapy as part of their routine clinical care who have a diagnosis of T2D alone and those with both T2D and (AD)/Mild Cognitive Impairment (MCI) will be compared with control groups treated with other T2D drugs, and apparently healthy controls. All participants will be recruited from the WHSTC. Ethical approval and research governance is in place for this study and the recruitment process has been established in on-going studies. This approach will provide an indication of the efficacy of GLP-1 therapy on cognitive outcomes in patients with T2D and MCI/AD.

In brief, the proposed programme of work will address the following objectives:

Objective 1: Compare Beck Depression inventory scores between those on GLP-1 analogues, other T2D drugs, and apparently healthy controls.

Objective 2: Compare Beck anxiety inventory scores in patients on GLP-1 analogues, other T2D drugs, and healthy controls.

Objective 3: Compare Standardised Mini Mental State Exam (SMMSE) scores and Quick Mild Cognitive Impairment screen (qMCI) scores in patients on GLP-1 analogues, other T2D drugs, and apparently healthy controls.

Objective 4: Compare cardiovascular comorbidity in patients on GLP-1 analogues, other T2D drugs, and apparently healthy controls.

Objective 5: Compare Beck depression and anxiety inventories, SMMSE and qMCI in prospective participants at baseline, and 6 months after initiation of therapy to assess changes in scores attributable to GLP-1 analogue therapy. This research will determine whether the cardioprotective benefits of GLP-1 analogue therapy, suggested in clinical trial populations, are realized in the general T2D population. It will also assess if anti-depressant, anti-anxiety and neuroprotective effects of GLP-1 result in significantly improved scores in standardized assessments in a general T2D population. GLP-1 analogues are expensive compared to other T2D drugs and are not normally prescribed to people with newly diagnosed T2D, but as a fourth-line therapy. If the findings of this study indicate GLP-1 analogues reduce heart disease, depression and memory loss in the general T2D population this may promote their use earlier in T2D progression. Prevention of complications would offset the cost of these drugs. This study will provide important information that will inform clinical decision making in T2D treatment.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Sound understanding of subject area as evidenced by a comprehensive research proposal
• A comprehensive and articulate personal statement

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Masters at 65%
• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Research project completion within taught Masters degree or MRES
• Sound understanding of subject area as evidenced by a comprehensive research proposal
• Work experience relevant to the proposed project
• Publications - peer-reviewed
• Experience of presentation of research findings
• A comprehensive and articulate personal statement

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living