Title: The impact of obstructive sleep apnoea treatment on microvascular complications in patients with type 2 diabetes: A feasibility study
Funder: Department of Health and Social Care

Abstract: Background:Obstructive sleep apnoea (OSA) is very common in patients with type 2 diabetes (T2D) (40-86% prevalence). I have found that OSA is independently associated with diabetic microvascular complications (retinopathy, nephropathy and neuropathy). I have also found that patients with T2D and OSA had a greater decline in renal function (measured by estimated glomerular filtration rate (eGFR)) compared to those with T2D alone over 2.5 years follow-up period and the progression to advanced retinopathy was greater in the OSA group over 5 years follow-up. The impact of OSA on eGFR decline and the development of advanced retinopathy was independent of confounders. Hence, it is possible that OSA results in the development and progression of diabetes-related microvascular complications. Diabetes-related microvascular complications have significant impact on patients morbidity and mortality. Despite improvements in metabloic control, these complications remain very common. Hence, there is need for new therapeutic options. My findings suggest that OSA could be a novel treatment target for these complications. My overall hypothesis is that treatment of OSA in patients with T2D can slow eGFR decline. Aims:My aim is to perform a feasibility study of conducting a randomised controlled trial (RCT) to determine the impact of treatment of OSA on the progression of diabetic nephropathy (as measured by eGFR) in patients with T2D. If the feasibility study is successful, I intend to apply for a Health Technology Assessment grant to fund a full scale RCT assessing the impact of OSA treatment on renal function in patients with OSA and T2D. The primary aims of this study are assessing willingness of participants to be randomised; assessing willingness of clinicians to recruit participants and recruitment rates; assessing the follow-up rates and adherence/compliance rates; providing data to inform the sample size for the main trial. Plan of investigation:Adults with T2D will be recruited from the out-patient diabetes clinics of 4 hospitals. Patients with known OSA, any respiratory disorder or end-stage renal disease will be excluded. Following consent and collection of baseline data, patients will undergo a home-based sleep study using a portable multichannel device to clarify the participants OSA status. Patients who have OSA and excessive daytime sleepiness (EDS) will be referred to the NHS for routine care. Patients with OSA but no EDS will be randomised to treatment (continuous positive airway pressure [CPAP] in the moderate-severe OSA group, mandibular repositioning device [MRD] in the mild OSA group) or no treatment for 2 years. Criteria for success of the feasibility study: Recruiting the proposed sample size within the planned time frames Conducting the study in accordance with the proposed time frames in regard to interpreting the sleep studies, initiating patients on treatment. Achieving a follow-up rate 80% for patients randomized to active treatment or no treatment.Achieving a CPAP usage 4 hours/night in 80% patients randomized to CPAP treatment. Generating mean and standard deviation regarding the predicted response to the planned intervention to allow sample size calculations for the future RCT Data collected:Patients will be characterised extensively including their OSA status and microvascular complications. This is in addition to quality of life and other demographic, clinical and biochemical data. Potential benefits to patients and the NHS:The results of this feasibility study will allow me to conduct a full-scale RCT assessing a potentially new treatment for diabetes microvascular complications. This could have a major impact on the way how we manage patients with T2D and microvascular complications. A beneficial effect on the rate of eGFR decline and/or other microvascular complications will have significant impact on health care resources and on the burden of T2D for many patients.

Lay abstract: Background:Obstructive sleep apnoea (OSA) (a common disorder in which patients stop breathing intermittently during sleep) is associated with microvascular complications (kidney, eye and nerve disease) progression in patients with diabetes. Objectives:To assess the feasibility of conducting a trial examining the impact of OSA treatment on microvascular complications. A feasibility study is needed to assess adherence to treatment allocation and willingness of patients to be randomised Design: Participants will be examined for OSA and if appropriate will be allocated to either active treatment or no treatment. Outcomes: The results will inform us whether conducting a larger trial is feasible.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: CARDIOVASCULAR;METABOLIC AND ENDOCRINE;RESPIRATORY