Microvascular complications in patients with type 2 diabetes: the impact of ethnicity, sleep and oxidative stress

Tahrani, Abd Al Magid (2013). Microvascular complications in patients with type 2 diabetes: the impact of ethnicity, sleep and oxidative stress. University of Birmingham. Ph.D.

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Abstract

Background: Diabetes-related Microvascular complications are associated with significant morbidity, mortality and economic burden. Effective treatments for microvascular complications, apart from improved metabolic and blood pressure control, are lacking. Hence, improved understanding of the pathogenesis of these complications is needed to develop new treatments. Obstructive sleep apnoea (OSA) is very common in type 2 diabetes (T2DM) and has been shown to stimulate the same harmful pathways as hyperglycaemia, particularly those that are involved in the pathogenesis of microvascular complications. Hence, it is plausible that OSA is associated with microvascular complications in patients withT2DM. Aims: To explore the interrelationships between OSA and microvascular complications in patients with T2DM and the possible mechanisms behind such relationship. Methods: A cross-sectional study of South Asians and White Europeans with T2DM were randomly recruited from the outpatients of two secondary care diabetes clinics in the UK. Patients were extensively characterised including assessments for OSA and microvascular complications. Results: Patients (n=234) were included in the analysis. OSA prevalence was 64.5%. OSA patients had worse metabolic profile than those without OSA. The prevalence of all microvascular complications (except cardiac autonomic neuropathy) was higher in patients with OSA compared to patients without. After adjustment for a wide range of confounders, OSA remained independently associated with microvascular complications. OSA and hypoxaemia severity correlated with the severity of complications. Based on blood samples and skin biopsies collected during the study, patients with OSA had increased oxidative and nitrosative stress and impaired microvascular regulation compared with patients without OSA. Furthermore, ethnic differences in OSA accounted for some of the ethnic differences in microvascular complications. Conclusion: I have identified a novel association between OSA and microvascular complications in patients with T2DM, with increased nitrosative stress and oxidative stress and impaired microvascular regulation as possible mechanisms. Further prospective observational and interventional studies are needed to assess the impact of OSA and its treatment on the development and progression of microvascular complications.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):