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Obstructive Sleep Apnoea (OSA) Predicts Microvascular Complications in Type 2 Diabetes

Obstructive Sleep Apnoea (OSA) Predicts Microvascular Complications in Type 2 Diabetes. Martin J Stevens MD, FRCP, Professor of Medicine University of Birmingham, UK. Objectives. To understand the prevalence of OSA in diabetes

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Obstructive Sleep Apnoea (OSA) Predicts Microvascular Complications in Type 2 Diabetes

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  1. Obstructive Sleep Apnoea (OSA) Predicts Microvascular Complications in Type 2 Diabetes Martin J Stevens MD, FRCP, Professor of Medicine University of Birmingham, UK

  2. Objectives • To understand the prevalence of OSA in diabetes • To describe the mechanisms whereby OSA may exacerbate diabetes complications • To understand the association of OSA with the microvascular complications of diabetes

  3. Prevalence of diabetes macrovascularand microvascular complications ‡ † * Macrovascular Microvascular *In NHANES, “chronic kidney disease" refers to people with microalbuminuria (albumin:creatinine ratio >30 µg/mg). †In the NHANES analysis, "foot problems" includes foot/toe amputations, foot lesions, and numbness in the feet. ‡"Eye damage" includes a positive response by NHANES participants to the question, "Have you been told diabetes has affected your eyes/had retinopathy?" Retinopathy is damage to the eye's retina. In NHANES, people without diagnosed diabetes were not asked this question, therefore, prevalence information for nondiabetics is not available. American Association of Clinical Endocrinologists. State of Diabetes Complications in America Report. Available at: http://www.aace.com/newsroom/press/2007/images/DiabetesComplicationsReport_FINAL.pdf. Accessed April 18, 2007 14 NA.

  4. Multiple metabolic pathways may contribute to diabetic microvascular complications UKCYM01503b February 2013 Adapted from: Boulton AJM, et al. Diabetes Care. 2004; 27:1548–1586 and Vinik A, et al. Nat Clin Pract Endocrinol Metab. 2006; 2(5):269-281.

  5. OSA: Background • Obstructive sleep apnea is a common medical disorder that affects at least 4% of men and 2% of women. • It is characterized by instability of the upperairway during sleep, which results in markedly reduced (hypopnea)or absent (apnea) airflow. • Apnea/hypopnea episodes are usually accompanied with cyclical oxygen desaturations and cyclical changes in blood pressure and heart rate. • OSA and type 2 diabetes (T2DM) share common risk factors such as age and obesity

  6. Methods • Subjects were recruited randomly from the diabetes out-patient clinics of a tertiary centre in the UK • DPN was diagnosed using the Michigan Neuropathy Screening Instrument (MNSI). Retinopathy was graded using retinal photography. Nephropathy was assessed using eGFR and urine albumin/creatinine ratios • OSA was assessed by an unattended home-based portable multi-channel respiratory device (Alice PDX, Philips Respironics, USA) • An apnea-hypopnea index (AHI) ≥ 5 events/hour was the cut off to diagnose OSA. AHI ≥ 15 considered to be consistent with moderate to severe OSA

  7. OSA prevalence Tahrani et al Am. J. Resp. Crit. Care Med. 2012 186:434-41

  8. An example of a sleep study from a patient with type 2 diabetes and OSA. The top row shows air flow followed by thoracic and abdominal movements followed by oxygen saturations. Red areas represent apnoeas, pink areas represent hypopneas and green areas represent oxygen desaturations

  9. Diabetes microvascular complications • Neuropathy • Nephropathy • Retinopathy

  10. Diabetes microvascular complications • Neuropathy • Nephropathy • Retinopathy

  11. Infection of the Chronic Charcot Foot

  12. Skin (intraepidermal) nerve fibres are reduced in diabetes Diabetes Non Diabetic Tahrani A, Stevens MJ et al. Diabetes Care 2012; 35:1913-8

  13. Prevalence of DPN in relation to OSA status Tahrani et al Am. J. Resp. Crit. Care Med. 2012 186:434-41

  14. The autonomic nervous system regulates many different tissues

  15. N-13 Ammonia Blood Flow Distal Short Axis Proximal Short Axis Vertical Long Axis Horizontal Long Axis C-11 HED Advanced cardiac sympathetic dysinnervation in diabetes FLOW C-11 HED Stevens et al Circulation 1999

  16. OSA is associated with CAN

  17. Effect of OSA on skin structure Non-diabetic Diabetes: No OSA Diabetes: Mild OSA Diabetes: Severe OSA

  18. Diabetes microvascular complications • Neuropathy • Nephropathy • Retinopathy

  19. Approximately 40% of patients with type 2 diabetes show signs of CKD1 CKD prevalence was greater among people with diabetes than among those without diabetes (40.2% versus 15.4%)† * Normal kidney function, no sign of kidney damage ** Albuminuria – kidney damage Adapted from 1. Koro CE, et al. Clin Ther. 2009;31:2608–2617 and 2. Saydah S, et al. JAMA. 2007;297(16):1767.

  20. OSA and diabetic nephropathy prevalence • Overall OSA prevalence: 64.3% (144/224) • 38.4% (86/224) mild • 25.9% (58/224) moderate to severe • Nephropathy prevalence: 40.2% (90/224) • Albuminuria 33.0% (74/224) • eGFR (ml/min/1.73 m2) ≥ 90: 45.5% (102/224) 60-89: 37.9% (85/224) 30-59: 15.2% (32/224) 15 -29:1.3% (3/224) < 15: 0% (0/224)

  21. OSA and diabetic nephropathy: Cross-sectional univariable analysis Tahrani A et al, Diabetes Care 2013; 36:3718-25

  22. OSA and diabetic nephropathy: Cross-sectional multivariable analysis Adjusted for gender, ethnicity, age, diabetes duration, BMI, mean arterial pressure, HbA1c, triglycerides, treatment with insulin, GLP-1 analogues, anti-hypertensives, total cholesterol, HDL, lipid lowering treatment, anti-platelets, oral anti diabetes agents, alcohol (units per week), smoking (current or ex smoking vs. none). Tahrani A et al, Diabetes Care 2013; 36:3718-25

  23. Diabetic nephropathy: natural history

  24. OSA and eGFR: Longitudinal analysis

  25. OSA and eGFR: Longitudinal analysis

  26. Impact of CPAP on eGFR decline (eGFR < 90) Tahrani A et al, Diabetes Care 2013; 36:3718-25

  27. Diabetes microvascular complications • Neuropathy • Nephropathy • Retinopathy

  28. A C B Diabetic Retinopathy Hall R, et al. Diabetes mellitus. In: A Colour Atlas of Endocrinology. 2nd ed. 1990:chap 7.

  29. The relationship between OSA status and sight threatening diabetic retinopathy, retinopathy and maculopathy

  30. Summary: OSA is associated with microvascular complications in patients with T2DM • Tahrani AA et al AM J RespirCrit Care Med 2012 • Tahrani AA et al Diabetes Care 2013 • Tahrani AA et al Eur J Ophthalmol 2013

  31. OSA/ Intermittent Hypoxia Hyperglycaemia ROS/ RNS ET - 1 PAI - 1 PKC AGE Hexosamine Polyol VEGF pathway pathway pathway pathway TGF - B NF - KB NO HTN Vascular complications The postulated mechanisms linking OSA and microvascular complications • HTN: hypertension; ROS: reactive oxygen species; RNS: reactive nitrogen species PKC: protein kinase C; AGE: advance glycation end-products.

  32. Obstructive sleep apnoea predicts microvascular complications in type 2 diabetes Thank you!

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