MD Conference Express ATS 2013 - (Page 14)
CLINICAL TRIAL HIGHLIGHTS
Data Link Obstructive Sleep Apnea
and Type 2 Diabetes
Written by Wayne Kuznar
Official
Peer-Reviewed
Highlights From
14
July 2013
Evidence supports an interaction between obstructive sleep apnea (OSA) and type 2 diabetes
mellitus (T2DM). OSA is highly prevalent in persons with T2DM, with some estimates of the
prevalence of moderate to severe OSA (defined as an apnea-hypopnia index [AHI] ≥5) as high as
61% [Einhorn D et al. Endocr Pract 2007], but the direction of causality is not yet clear.
Patrick Lévy, MD, PhD, University Joseph Fourier, Grenoble, France, gave an overview of the
relationship between OSA and T2DM. In a consecutive series of 60 patients with T2DM, 77% had
an AHI≥5, and adjusted HbA1C levels increased with increasing severity of OSA [Aronsohn RS et al.
Am J Respir Crit Care Med 2010].
Data also suggest that OSA is independently associated with altered glucose metabolism
to promote the development of T2DM. Adjusted odds ratios for the incidence of diabetes in
moderate to severe OSA compared with no OSA range from 1.43 to 13.45 [Pamidi S, Tasali E.
Front Neurol 2012].
Young lean men with OSA had reduced insulin sensitivity and higher total insulin secretion
than controls despite similar glucose levels after an oral glucose tolerance test [Pamidi S et al.
Diabetes Care 2012]. Increasing severity of AHI was independently associated with impaired
glucose metabolism in a multicentric cohort of 1599 subjects without T2DM [Priou P et al.
Diabetes Care 2012].
Sleep fragmentation and intermittent hypoxia can lead to insulin resistance and pancreatic
b-cell dysfunction through sympathetic activation, alterations in the HPA axis (ie, increase in
levels of cortisol), oxidative stress, activation of inflammatory pathways that promote the release of
interleukin-6 and tumor necrosis factor-a, and adverse changes in adipokine profiles including a
reduction in adiponectin.
Intermittent hypoxia causes reduced muscle glucose utilization in the soleus muscle in lean
mice [Iiyori N et al. Am J Respir Crit Care Med 2007] and increased b-cell proliferation and cell
death presumably due to oxidative stress [Xu J et al. Free Radic Biol Med 2009]. An increase in
free fatty acid uptake by the liver induced by intermittent hypoxia may upregulate transcriptional
pathways of lipid biosynthesis through HIF-1, leading to liver insulin resistance and nonalcoholic
steatohepatitis conceivably through accelerated adipose tissue lipolysis [Mirrakhimov AE, Polotsky
VY. Front Neurol 2012].
In morbidly obese people, chronic intermittent hypoxia is an independent predictor for nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis, and fibroinflammation [Aron-Wisnewsky J
et al. J Hepatol 2012]. Chronic intermittent hypoxia was found to have differential metabolic effects
in lean and obese mice, inducing NAFLD, oxidative stress, and inflammation in only the obese mice
[Drager LF et al. Obesity 2011].
In uncontrolled studies, it has been initially evidenced that long-term continuous positive
airway pressure (CPAP) reduced HbA1C levels in diabetic individuals with sleep-disordered
breathing [Babu AR et al. Arch Intern Med 2005]. Also, a rapid improvement in insulin sensitivity in
patients with OSA obtained after initiation of CPAP may reflect a reduction in sympathetic activity
[Harsch IA et al. Am J Respir Crit Care Med 2004]. The effect was smaller in obese patients, which
suggests that in obese patients, insulin sensitivity is determined more by obesity than OSA.
Anthropometric variables (weight, body mass index, subcutaneous fat, visceral fat) improved
significantly in a group of OSA patients who underwent 3 months of CPAP compared with sham CPAP
[Sharma SK et al. N Engl J Med 2011]. This may explain the overall improvement in the metabolic
profile in this study where the study group was highly selected (ie, untreated moderately obese
subjects presenting with dysmetabolism). So far, this paper provided the most impressive results but
most randomized controlled trials did not confirm this metabolic improvement during OSA treatment
[Weinstock TG et al. Sleep 2012; Sivam S et al. Eur Respir J 2012; Hoyos CM et al. Thorax 2012]. Pepin et
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Table of Contents for the Digital Edition of MD Conference Express ATS 2013
MD Conference Express ATS 2013
Contents
Prevention and Early Treatment of Acute Lung Injury
Nocturnal Noninvasive Ventilation Improves Outcomes in Multiple Disorders
Hospital Readmissions: Challenges and Opportunities
EBUS-TBNA: Accurate and Safe for Detecting Sarcoidosis
Data Link Obstructive Sleep Apnea and Type 2 Diabetes
Statin Use Improves Respiratory-Related Mortality in Patients With COPD
Addition of Spironolactone to Ambrisentan May Be a Novel Treatment Strategy to Improve Outcome in Patients With PAH
Haloperidol Does Not Prevent Delirium in Ventilated ICU Patients
Beraprost Plus Sildenafil Effective in Pulmonary Arterial Hypertension
Dupilumab Is Safe and Effective for Controlling Asthma Attacks
Once-Daily QVA149 Improves Breathlessness in COPD Patients
CPAP in CVD and OSA Does Not Significantly Improve Cardiovascular Biomarkers
CPAP Reduces BP in Patients With Resistant Hypertension and Obstructive Sleep Apnea
Effects of Obesity on COPD
Pulmonary Embolism
Ventilator-Associated Pneumonia
Lung Cancer Screening
Idiopathic Pulmonary Fibrosis
Non-Small-Cell Lung Cancer
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