Sleep Disorders in Patients with Type 2 Diabetes

Abstract

Introduction Type 2 diabetes (T2D) is a growing global health challenge. Diabetes-related microvascular complications like retinopathy, nephropathy, and neuropathy contribute significantly to morbidity, mortality, and healthcare costs. Despite the significant efforts to manage glycaemic and metabolic control, the prevalence of these complications is rising. Gaining a deeper understanding of their underlying causes and exploring alternative preventive strategies are crucial in reducing the health and economic burden of T2D. Sleep disorders are highly prevalent among patients with T2D. The interrelationship between obstructive sleep apnoea (OSA), T2D, and microvascular complications is well established, with obesity recognised as a major risk factor. However, the impact of OSA treatment -continuous positive airway pressure (CPAP) - still needs to be investigated. Furthermore, the relationship between sleep disorders, including sleep duration and sleep quality, and T2D needs to be examined. Fragility fractures are also common among individuals with T2D, highlighting the need to explore whether OSA contributes to an increased risk of such fractures. Aims In this thesis, I aimed to assess the following: Aim 1: The impact of OSA treatment on microvascular complications in patients with T2D. Aim 2: The longitudinal relationship between sleep duration and obesity in patients with T2D. Aim 3: The relationship between sleep quality and microvascular complications in patients with T2D. Aim 4: The relationship between OSA and the risk of fragility fractures in patients with T2D. Methods To examine the first 3 aims, I used data collected from the SLEEP T2D study. SLEEP T2D is an observational cohort study with an embedded feasibility RCT in a subgroup of patients. The feasibility RCT is an open-label multicentre trial in which patients with OSA were randomised to CPAP vs No CPAP. For aim 4, I conducted a retrospective study in patients with T2D using data from the Clinical Practice Research Datalink (CPRD) Aurum, a real-world primary care database. Results For Aim 1: 83 participants fulfilled the eligibility criteria for the RCT and were followed up for 2 years. I found that OSA treatment had a favourable impact on diabetic peripheral neuropathy (DPN). It also had a favourable impact on the estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), and quality of life. For Aim 2: 204 participants were included in the analysis and followed up for two years. Short sleep duration was defined as (≤ 6 sleep duration per night). The prevalence of short sleep duration was 54.9%. I found that short sleep duration was significantly associated with obesity, as measured by body mass index (BMI) and waist circumference. Additionally, I discovered that baseline short sleep duration was linked to weight gain in patients with T2D (P = 0.04). For Aim 3: 194 participants were included in this analysis. The prevalence of poor sleep quality was 75.8% (poor sleep quality was defined as PSQI > 5). The study did not show an association between sleep quality and diabetes-related microvascular complications, except for pain and adiposity measures in patients with T2D. For Aim 4: A total of 83,919 patients with T2D were included in cohort 1: 19,795 patients with OSA and 64,124 without OSA. 88,119 patients with T2D were included in cohort 2: 21,769 patients with OSA and 66,350 without OSA. OSA was associated with an increased risk of fragility fractures in patients with T2D compared to those with T2D but without OSA. This association persisted regardless of whether OSA was diagnosed before or after the diagnosis of T2D and remained significant even after adjusting for potential confounders. Conclusion Among patients with T2D, being randomized to CPAP showed a favourable association with improvements in diabetic peripheral neuropathy, diabetic nephropathy, and quality of life compared to those without CPAP. Furthermore, short sleep duration was associated with obesity and increased risk of weight gain in patients with T2D. Poor sleep quality was also significantly associated with obesity and pain in patients with T2D. Additionally, patients with both T2D and OSA had a significantly higher risk of fragility fractures compared to those with T2D but without OSA, regardless of whether OSA was diagnosed, proceeded or followed the diagnosis of T2D.