Insulin Resistance, Hyperglycemia, and Risk of Developing Obstructive Sleep Apnea in Men and Women in the United States

<b>Rationale:</b> Recent prospective studies suggest diabetes as a risk factor for the development of obstructive sleep apnea (OSA). However, the extent to which diabetes-related traits, such as hyperglycemia and insulin resistance, are related to OSA risk remains uncertain. <b>Objectives:</b> To examine the risk of developing OSA according to baseline concentrations of fasting insulin and hemoglobin A1c (HbA1c). <b>Methods:</b> Participants from four prospective U.S. cohorts were included: NHS (Nurses' Health Study; 2002-2012), NHSII (Nurses' Health Study II; 1995-2013), HPFS (Health Professionals Follow-up Study; 1996-2012), and MESA (Multi-Ethnic Study of Atherosclerosis; 2000-2012). OSA was assessed by self-reported clinical diagnosis in NHS/NHSII/HPFS and at-home polysomnography in MESA (defined as Apnea-Hypopnea Index ⩾30). <b>Results:</b> Of 9,283 participants with fasting insulin data, 790 (8.5%) developed OSA over 10 to 18 years of follow-up. After adjusting for sociodemographic, lifestyle, and comorbidity factors, the odds ratio for incident OSA comparing the extreme quintiles of fasting insulin was 3.59 (95% confidence interval, 2.67-4.82; <i>P</i>-trend < 0.0001). Of 6,342 participants with HbA1c data, 715 (11.3%) developed OSA. The comparable odds ratio for HbA1c was 2.21 (95% confidence interval, 1.69-2.89; <i>P</i>-trend < 0.0001). Additional adjustment for body mass index and waist circumference attenuated the associations for fasting insulin (<i>P</i>-trend = 0.005) and HbA1c (<i>P</i>-trend = 0.03). In the fully adjusted model simultaneously including both biomarkers, only fasting insulin but not HbA1c was associated with OSA risk. <b>Conclusions:</b> Independent of obesity, insulin resistance may play a more important role than hyperglycemia in the pathogenesis of OSA. Given the limitation of using self-reported diagnosis to exclude baseline prevalent OSA cases, additional studies are needed to further establish the temporal relationship and assess whether improving insulin resistance may reduce OSA risk.