Response to Comment on Grimaldi et al. Association of Obstructive Sleep Apnea in Rapid Eye Movement Sleep With Reduced Glycemic Control in Type 2 Diabetes: Therapeutic Implications. Diabetes Care 2014;37:355–363

We are grateful to Drs. Scarlata and Antonelli-Incalzi (1) for their interest in our recent publication in Diabetes Care (2). We respectfully have to disagree with their statement that our study focused on “how rapid eye movement (REM) sleep deprivation due to obstructive sleep apnea [OSA] affects glycemic control in type 2 diabetes.” Indeed, our study was a cross-sectional analysis and did not include an experimental paradigm of REM sleep deprivation. In fact, the median duration of REM sleep in our cohort was 20.3% of the total sleep timedwell within the normal range (Supplementary Table 1 in ref. 2). The primary aim of our study was to estimate the impact of OSA in REM sleep and in non-REM sleep on glycemic control (as assessed by HbA1c) in patients with type 2 diabetes. In addition, we simulated the impact of different durations of nocturnal CPAP therapy on HbA1c and observed that longer durations of CPAP use treat more apneas and hypopneas during REM sleep and lead to better glycemic control. We explicitly specified that our simulations were based on the assumption of “optimally titrated CPAP use.” Scarlata and Antonelli-Incalzi point out that this assumption may not be met under real-life conditions. Suboptimal CPAP adherence is common and is indeed a likely reason for the negative findings of the only randomized controlled trial of CPAP in type 2 diabetic patients with OSA (3). We also agree with Scarlata and Antonelli-Incalzi that in some instances CPAP may not effectively treat OSA despite adequate adherence. This may be due to an inadequate pressure setting, excessive mask leak, ventilatory instability, and/or emergence of central apneas due to CPAP. However, as reported by Mulgrew et al. (4), most of the residual respiratory events observed during a full-night polysomnogram on effective CPAP settings are hypopneas and central apneas that occur predominantly during non-REM sleep. Our study demonstrated that in contrast to respiratory events inREMsleep, events during non-REM sleep (i.e., apneas, hypopneas, microarousals, and oxygen desaturations) are not associated with glycemic control in patients with type 2 diabetes. Therefore, simulations that would take into account residual events occurringmostly in non-REM sleep would most likely lead to conclusions similar to those reached in our analysis.