e60 Diabetes Care Volume 37, March 2014

RESPONSE TO COMMENT ON GRIMALDI ET AL. Association of Obstructive Sleep Apnea in Babak Mokhlesi,1,2 Daniela Grimaldi,1,2 and Rapid Eye Movement Sleep With Reduced Eve Van Cauter1,3 Glycemic Control in Type 2 Diabetes: Therapeutic Implications. Diabetes Care 2014;37:355–363 Diabetes Care 2014;37:e60–e61 | DOI: 10.2337/dc13-2662

We are grateful to Drs. Scarlata and Suboptimal CPAP adherence is common anecdotal experience that some of their Antonelli-Incalzi (1) for their interest in and is indeed a likely reason for the patients start using CPAP in the middle our recent publication in Diabetes negative findings of the only of the night after an awakening. They Care (2). We respectfully have to randomized controlled trial of CPAP in incorrectly quote the official statement disagree with their statement that our type 2 diabetic patients with OSA (3). of the American Thoracic Society on study focused on “how rapid eye We also agree with Scarlata and CPAP adherence tracking systems as a movement (REM) sleep deprivation Antonelli-Incalzi that in some instances reference to support this anecdotal due to obstructive sleep apnea [OSA] CPAP may not effectively treat OSA evidence (5). Currently, we are not affects glycemic control in type 2 despite adequate adherence. This may aware of published empirical data diabetes.” Indeed, our study was a be due to an inadequate pressure documenting the proportion of OSA cross-sectional analysis and did not setting, excessive mask leak, ventilatory patients who start the night on CPAP include an experimental paradigm of instability, and/or emergence of central and then discontinue it after a few REM sleep deprivation. In fact, the apneas due to CPAP. However, as hours of treatment as compared median duration of REM sleep in our reported by Mulgrew et al. (4), most of with those who initiate CPAP in the cohort was 20.3% of the total sleep the residual respiratory events observed middle of the night after an timedwell within the normal range during a full-night polysomnogram on awakening. For what it is worth, our (Supplementary Table 1 in ref. 2). The effective CPAP settings are hypopneas own anecdotal experience suggests primary aim of our study was to and central apneas that occur that the vast majority of patients with estimate the impact of OSA in REM predominantly during non-REM sleep. OSA start the night on CPAP and then sleep and in non-REM sleep on glycemic Our study demonstrated that in contrast remove it after a few hours. This to respiratory events in REM sleep, events control (as assessed by HbA1c)in constructive comment by Scarlata and during non-REM sleep (i.e., apneas, patients with type 2 diabetes. In Antonelli-Incalzi (1) illuminates the need hypopneas, microarousals, and oxygen addition, we simulated the impact of for a quantitative study of the modalities desaturations) are not associated with different durations of nocturnal CPAP of CPAP use under real-life conditions and glycemic control in patients with type 2 therapy on HbA1c and observed that for intervention studies comparing diabetes. Therefore, simulations that longerdurationsofCPAPusetreat more cognitive and cardiometabolic outcomes would take into account residual events apneas and hypopneas during REM following early versus late use of CPAP occurring mostly in non-REM sleep would sleep and lead to better glycemic during the night. control. We explicitly specified that our most likely lead to conclusions similar to COMMENTS AND RESPONSES those reached in our analysis.

– simulations were based on the assumption of “optimally titrated CPAP Our model was constructed on the ” Funding. B.M. has received funding from the use. Scarlata and Antonelli-Incalzi assumption that CPAP is initiated at the National Institutes of Health (NIH). E.V.C. has eLETTERS point out that this assumption may not beginning of the sleep period. Scarlata received investigator-initiated grants from NIH be met under real-life conditions. and Antonelli-Incalzi share their and ResMed Foundation.

1Department of Medicine, Sleep, Metabolism and Health Center, University of Chicago, Chicago, IL 2Department of Medicine, Section of Pulmonary and Critical Care, Sleep Disorders Center, University of Chicago, Chicago, IL 3Department of Medicine, Section of Endocrinology, Diabetes and Metabolism University of Chicago, Chicago, IL Corresponding author: Babak Mokhlesi, [email protected]. © 2014 by the American Diabetes Association. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. care.diabetesjournals.org Mokhlesi, Grimaldi, and Van Cauter e61

Duality of Interest. B.M. has served as a Care 2014;37:355–363 (Letter). Diabetes 4. Mulgrew AT, Lawati NA, Ayas NT, et al. consultant to Philips/Respironics and is involved Care 2014;37:e59. DOI: 10.2337/dc13-2429 Residual sleep apnea on polysomnography in a study sponsored by Philips/Respironics. 2. Grimaldi D, Beccuti G, Touma C, Van Cauter after 3 months of CPAP therapy: clinical E.V.C. has received investigator-initiated grants E, Mokhlesi B. Association of obstructive implications, predictors and patterns. Sleep from the Philips/Respironics. No other potential Med 2010;11:119–125 conflicts of interest relevant to this article were sleep apnea in rapid eye movement sleep reported. with reduced glycemic control in type 2 5. Schwab RJ, Badr SM, EpsteinL J, et al.; ATS diabetes: therapeutic implications. Diabetes Subcommittee on CPAP Adherence Tracking References Care 2014;37:355–363 Systems. An official American Thoracic 1. Scarlata S, Antonelli-Incalzi R. Comment on 3. West SD, Nicoll DJ, Wallace TM, Matthews Society statement: continuous positive Grimaldi et al. Association of obstructive DR, Stradling JR. Effect of CPAP on insulin airway pressure adherence tracking systems. sleep apnea in rapid eye movement sleep resistance and HbA1c in men with The optimal monitoring strategies and with reduced glycemic control in type 2 obstructive sleep apnoea and type 2 outcome measures in adults. Am J Respir Crit diabetes: therapeutic implications. Diabetes diabetes. Thorax 2007;62:969–974 Care Med 2013;188:613–620