Assessing human carotid body, cardiovascular and respiratory function in diabetic patients with and without obstructive sleep apnoea

Patients with diabetes have impaired cardiovascular and respiratory responses to multiple stimuli including a fall in blood oxygen (hypoxia), a rise in blood carbon dioxide (hypercapnia) and a decrease in blood glucose (hypoglycaemia). Diabetic patients also have reduced exercise tolerance. The mechanisms accounting for these dysfunctional reflex responses remain unresolved. The carotid body is an important sensory organ that continuously monitors the blood perfusing the brain. It is stimulated by hypoxia, hypercapnia, hypoglycaemia and exercise, and is important in activating protective cardiovascular and respiratory reflexes under these circumstances. We hypothesise that a pathological change in carotid body function in diabetic patients contributes to impaired cardiovascular and respiratory reflex control, thereby increasing vulnerability to hypoxia, hypercapnia and hypoglycaemia, as well as reducing the ability to exercise. Obstructive sleep apnoea is also very common in diabetic patients and this may further impair carotid body and cardiovascular-respiratory function.

In this PhD Studentship we will measure human carotid body and cardiovascular-respiratory function in diabetic patients with and without obstructive sleep apnoea and make comparisons against healthy controls. Training will be provided to measure ECG, minute ventilation (spirometry), arterial blood pressure, O2 saturation, blood gases, as well as performing biomarker analysis. We will compare cardiovascular-respiratory reflex responses to acute hypoxia, hypercapnia, hypoglycaemia and exercise between the different groups. This will enable us to identify if carotid body dysfunction in diabetic patients causes impaired cardiovascular-respiratory reflex control, and if this is exacerbated by obstructive sleep apnoea.

Applicants should have a strong background in one of the following: biomedical sciences, human physiology, cardiovascular physiology or respiratory physiology. They should have a commitment to biomedical science or physiology research and hold, or realistically expect to obtain, at least an Upper Second-Class Honors Degree in biomedical sciences or a physiology related subject.

How to apply
Informal enquiries should be directed to Dr Andrew Holmes ([email protected]), Dr Joesph Welch ([email protected]) or Dr Andrew Coney ([email protected]), who will form the supervisory team.

To be considered for this studentship, please send the following documents to Dr Andrew Holmes ([email protected])

• A detailed CV, including your nationality and country of birth;

• Names and addresses of two referees;

• A covering letter highlighting your research experience/capabilities;

• Copies of your degree certificates with transcripts;

• Evidence of your proficiency in the English language, if applicable.

References:
Holmes AP, Swiderska A, Nathanael D, Aldossary HS, Ray CJ, Coney AM, Kumar P. (2022). Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing? Frontiers in Physiology 13:908617.

Holmes AP and Kumar P (2023). Low sugar and the drive to breathe: Is insulin another adequate stimulus for the carotid body. Experimental Physiology 108(2): 167-168

Holmes AP, Ray CJ, Thompson EL, Alshehri Z, Coney AM, Kumar P (2019). Adrenaline activation of the carotid body: Key to CO2 and pH homeostasis in hypoglycaemia and potential pathological implications in cardiovascular disease. Respiratory Physiology and Neurobiology 265: 92-99

Thompson EL, Ray CJ, Holmes AP, Pye R, Wyatt CN, Coney AM & Kumar P (2016). Adrenaline release evokes hyperpnoea and an increase in ventilatory CO2 sensitivity during hypoglycaemia: a role for the carotid body. The Journal of Physiology 594(15):4439-52.