The cumulative impact of type 2 diabetes and obstructive sleep apnoea on cardiovascular, liver, diabetes-related and cancer outcomes

David R Riley; Alex Henney; Matthew Anson; Gema Hernadez; Sizheng S Zhao; Uazman Alam; John P H Wilding; Sonya Craig; Daniel J Cuthbertson

doi:10.1111/dom.16059

The cumulative impact of type 2 diabetes and obstructive sleep apnoea on cardiovascular, liver, diabetes-related and cancer outcomes

Diabetes Obes Metab. 2024 Nov 11. doi: 10.1111/dom.16059. Online ahead of print.

Authors

David R Riley^{1

2

3}, Alex Henney^{1

2

3}, Matthew Anson^{1

2

3}, Gema Hernadez⁴, Sizheng S Zhao⁵, Uazman Alam^{1

2

3}, John P H Wilding^{1

2

3}, Sonya Craig⁶, Daniel J Cuthbertson^{1

2

3}

Affiliations

¹ Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK.
² Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University NHS Foundation Trust, Liverpool, UK.
³ Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK.
⁴ TriNetX LLC, Cambridge, Massachusetts, USA.
⁵ Centre for Musculoskeletal Research at University of Manchester, Manchester, UK.
⁶ Liverpool Sleep & Ventilation Unit, Aintree University Hospitals NHS Foundation Trust, Liverpool, UK.

PMID: 39529454
DOI: 10.1111/dom.16059

Abstract

Aim: A bidirectional relationship exists between obstructive sleep apnoea (OSA) and type 2 diabetes (T2D). We aimed to examine the cumulative impact of having both OSA and T2D on patient outcomes, relative to having either condition alone.

Materials and methods: Using TriNetX, a global federated research network (n = 128 million), we undertook two retrospective cohort studies, using time-to-event analysis. Analysis 1 compared OSA with T2D versus OSA alone; analysis 2 compared T2D with OSA versus T2D alone. Propensity score matching using greedy nearest neighbour (calliper 0.1) balanced the cohorts (1:1) for significant covariates. Primary outcomes were cardiovascular, liver, diabetes-related (microvascular) and cancer events over 1-5 years.

Results: Analysis 1 (n = 179 688): A codiagnosis of T2D/OSA significantly increased risk of all-cause mortality (hazard ratio [HR] 1.52; confidence interval [CI]: 1.48, 1.57), dementia (HR 1.19; CI: 1.12, 1.26), liver (HR 2.20; CI: 1.77, 2.73), pancreatic (HR 1.62; CI: 1.35, 1.93), colon, renal and endometrial cancers; all cardiovascular, microvascular and liver related outcomes versus OSA alone over 1-5 5 years following OSA diagnosis. Analysis 2 (n = 240 094): A codiagnosis of OSA/T2D significantly increased the risk of peripheral (HR 1.39; CI: 1.36, 1.43) and autonomic (HR 1.63; CI: 1.51, 1.75) neuropathy; retinopathy (HR 1.13; CI: 1.09, 1.18), CKD (HR 1.21; CI: 1.18, 1.23); all cardiovascular and liver outcomes; all-cause mortality and several obesity related cancers versus T2D alone.

Conclusions: T2D significantly potentiates risk of cardiovascular, malignancy and liver-related outcomes in individuals with OSA. OSA, in individuals with T2D, significantly potentiates risk of cardiovascular disease, malignancy, death and several microvascular complications (retinopathy, CKD, peripheral/autonomic neuropathy).

Keywords: cardiovascular disease; dementia; malignancy; microvascular complications; obstructive sleep apnoea; type 2 diabetes.