obstructive sleep apnoea (osa) predicts microvascular complications in type 2 diabetes
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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 - PowerPoint PPT PresentationTRANSCRIPT
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
• To describe the mechanisms whereby OSA may exacerbate diabetes complications
• To understand the association of OSA with the microvascular complications of diabetes
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27.8
22.9
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1.8 1.7 2.1 1.1 1.8
6.1
10
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Heart attack Chest pain Coronaryheart
disease
Congestiveheart failure
Stroke Chronickidneydisease
Footproblems
Eye damage
Perc
enta
ge w
ith c
ompl
icat
ions
Diagnosed diabetesNormal blood sugar levels
Prevalence of diabetes macrovascular and microvascular complications
Macrovascular Microvascular
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.
*†
‡
*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.
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.
Multiple metabolic pathways may contribute to diabetic microvascular complications
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 upper airway
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
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
OSA prevalence
Tahrani et al Am. J. Resp. Crit. Care Med. 2012 186:434-41
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
Diabetes microvascular complications
• Neuropathy• Nephropathy• Retinopathy
Diabetes microvascular complications
• Neuropathy• Nephropathy• Retinopathy
Infection of the Chronic Charcot Foot
Skin (intraepidermal) nerve fibres are reduced in diabetes
Non Diabetic Diabetes
Tahrani A, Stevens MJ et al. Diabetes Care 2012; 35:1913-8
Prevalence of DPN in relation to OSA status
Tahrani et al Am. J. Resp. Crit. Care Med. 2012 186:434-41
The autonomic nervous system regulates many different tissues
Advanced cardiac sympathetic dysinnervation in diabetes
C-11 HEDFLOW
C-11 HED
DistalShort Axis
ProximalShort Axis
VerticalLong Axis
HorizontalLong Axis
N-13 Ammonia Blood Flow
Stevens et al Circulation 1999
OSA is associated with CAN
OSA+ OSA- P value
Cardiac autonomic neuropathy (Spectral analysis, >= 3 abnormalities
69.9% 54.3% 0.034
Effect of OSA on skin structure
Diabetes: Mild OSA Diabetes: Severe OSA
Diabetes: No OSA Non-diabetic
Diabetes microvascular complications
• Neuropathy• Nephropathy• Retinopathy
Approximately 40% of patients with type 2 diabetes show signs of CKD1
* Normal kidney function, no sign of kidney damage** Albuminuria – kidney damage
CKD prevalence was greater among people with diabetes than among those without diabetes (40.2% versus 15.4%)†
CKD Stage eGFR (mL/min)
No CKD ≥ 90*
1 ≥ 90**
2 60–89
3 30–59
4 15–29
5 < 15 or dialysis
Adapted from 1. Koro CE, et al. Clin Ther. 2009;31:2608–2617 and 2. Saydah S, et al. JAMA. 2007;297(16):1767.
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)
OSA and diabetic nephropathy: Cross-sectional univariable analysis
Total Cohort OSA- (n=80) OSA+ (n=144) P
Diabetic nephropathy 19 (23.8%) 71 (49.3%) < 0.001
Albuminuria 16 (20.0%) 58 (40.3%) 0.002
Macroalbuminuria 4 (5.0%) 19 (13.2%) 0.05
Serum creatinine (µmol/l ) 74.4 (23.4) 90.9 (36.8) <0.001
Estimated GFR (ml/min/1.73 m2) 92.9 (25.1) 82.2 (27.6) 0.005
Estimated GFR < 60 ml/min/1.73 m2 5 (6.3%) 32 (22.2%) 0.002
Tahrani A et al, Diabetes Care 2013; 36:3718-25
OSA and diabetic nephropathy: Cross-sectional multivariable analysis
Model R2 OR 95% CI P valueUnadjusted 0.09 3.12 1.70-5.75 p<0.001
Adjusted 0.46 2.64 1.13-6.16 p=0.02
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
Diabetic nephropathy: natural history
OSA and eGFR: Longitudinal analysis
OSA and eGFR: Longitudinal analysis
Impact of CPAP on eGFR decline (eGFR < 90)
Tahrani A et al, Diabetes Care 2013; 36:3718-25
Diabetes microvascular complications
• Neuropathy• Nephropathy• Retinopathy
A
CB
Diabetic Retinopathy
Hall R, et al. Diabetes mellitus. In: A Colour Atlas of Endocrinology. 2nd ed. 1990:chap 7.
The relationship between OSA status and sight threatening diabetic retinopathy, retinopathy and maculopathy
Total cohort OSA- (n=74) OSA+ (n=125) P value
Sight threatening diabetic retinopathy
21.6% (16) 48.8% (61) <0.001
None 40.5% (30) 29.6% (37) 0.006
Background 54.1% (40) 46.4% (58) <0.01
Pre-proliferative 1.4% (1) 14.4% (18) <0.001
Proliferative 4.1% (3) 9.6% (12) <0.01
Maculopathy 17.6% (13) 44.0% (55) <0.001
Summary: OSA is associated with microvascular complications
in patients with T2DM
Unadjusted OR (95%CI) Adjusted OR (95%CI)
Sight threatening retinopathy
3.5 (1.8-6.6) 3.7 (1.6-8.9)
Neuropathy 4.09 (2.28–7.35) 2.77 (1.36–5.62)
Nephropathy 3.12 (1.70-5.75) 2.64 (1.13-6.16)
Tahrani AA et al AM J Respir Crit Care Med 2012Tahrani AA et al Diabetes Care 2013Tahrani AA et al Eur J Ophthalmol 2013
The postulated mechanisms linking OSA and microvascular complications
HyperglycaemiaOSA/ Intermittent
Hypoxia ROS/ RNS
Polyolpathway
Hexosaminepathway
AGE pathway
PKCpathway
HTN
ET-1PAI-1VEGFTGF-BNF-KB
NO
Vascular complications
HTN: hypertension; ROS: reactive oxygen species; RNS: reactive nitrogen species PKC: protein kinase C; AGE: advance glycation end-products.
Obstructive sleep apnoea predicts microvascular complications in type 2 diabetes
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