PhD Study : The Diabetic Lung: Impact of Diabetes and Obesity on Lung Health (IDOL study)

Summary

Background:

Type 2 Diabetes (T2D) is a complex metabolic disorder, driven by obesity and elevated blood glucose concentrations (hyperglycaemia). Secondary complications, including vascular disturbances, account for most morbidity and mortality associated with T2D. The lung is not usually considered an end target organ for damage in diabetes. However, increasing evidence suggests that diabetes is detrimental to lung health. People with T2D have reduced pulmonary function even after controlling for known risk factors such as smoking and age [1]. T2D increases the risk of developing inflammatory lung diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD), but not lung cancers [2]. Both asthma and COPD share a common aetiology with T2D in the form of obesity, which increases the risk of developing asthma and COPD by 2 and 2.3-fold respectively [3]. The T2D-lung disase association is established both clinically and epidemiologically [4]. However, the underlying mechanisms behind this association are not well understood. It has been proposed that the hyperinflammatory state associated with obesity [5] and the potential damage caused by hyperglycaemia to the respiratory vasculature have roles to play [6].

This study therefore aims to determine whether obesity and/or hylerglycaemia drives the reductions in lung function observed in those with T2D.

Objectives and study design:

(1)To conduct a systematic review to identify trends in lung health in those with T2D and in obese, non-diabetic populations. This objective will examine the presence of restrictive and obstructive respiratory phenotypes in these groups and will determine the known relationships between glycaemic control, obesity, and lung function.

(2)To compare the transcriptomic profiles of airway epithelial cells grown under normal and high glucose conditions. Quantitiative PCR experiments will identify novel markers associated with hyperglycaemia in the airways.

(3)To interrogate data from in-house cohorts and the UK Biobank to identify prognostic biomarkers for the development of lung disease. Analysis will determine the incidence of comorbid T2D/lung diseases in these populations and compare the clinical, proteomic and genomic profiles of people with T2D alone, versus those with T2D and a lung condition.

References:

1.Kinney GL, Black-ShinnJL, Wan ES. Et al. (2019) Diabetes Care 37 (2) 389-395; DOI: 10.2337/dc13-1435

2.Khafaie MA, Salvi SS, Yajnik CS. et al. (2019) Multidiscip Respir Med 14, 22. https://doi.org/10.1186/s40248-019-0184-5

3.Kim SH, Sutherland ER, Gelfand EW. (2014) Allergy Asthma Immunol Res. 2014;6(3):189-195. doi:10.4168/aair.2014.6.3.189

4.Khateeb J, Fuchs E, Khamaisi M. (2019) Rev Diabet Stud. 15:1-15. doi:10.1900/RDS.2019.15.1

5.Mancuso P. (2010) Obesity and lung inflammation. J Appl Physiol 108(3):722-8. doi: 10.1152/japplphysiol.00781.2009.

6.Kolahian S, Leiss V, Nürnberg B. (2019) Rev Endocr Metab Disord. 20(3):303-319. doi:10.1007/s11154-019-09516-w

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.

Funding and eligibility