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

Abstract Rationale 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. Objectives To examine the risk of developing OSA according to baseline concentrations of fasting insulin and hemoglobin A1c (HbA1c). Methods 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). Results 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; P-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; P-trend < 0.0001). Additional adjustment for body mass index and waist circumference attenuated the associations for fasting insulin (P-trend = 0.005) and HbA1c (P-trend = 0.03). In the fully adjusted model simultaneously including both biomarkers, only fasting insulin but not HbA1c was associated with OSA risk. Conclusions 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.