Original ArticleObstructive sleep apnea and incident type 2 diabetes
Introduction
Given the morbidity and mortality associated with type 2 diabetes mellitus [1], the identification of potentially modifiable risk factors for diabetes remains a clinical and public health priority. Obstructive sleep apnea (OSA) is a common condition with approximately 13% of adult men and 6% of adult women having moderate to severe undiagnosed OSA [2]. Evidence collected over the last two decades from clinical and community-based studies suggests that OSA is associated with insulin resistance, glucose intolerance, and type 2 diabetes independent of the confounding effects of obesity [3], [4]. Moreover, data from murine models [5] and experimental human studies [6] have also shown that exposure to intermittent hypoxia and sleep fragmentation can lead to alterations in insulin sensitivity and glucose disposal. Thus, observational [7], [8], [9], [10], [11] and experimental data [12], [13] are convergent and implicate OSA as an independent risk factor for development of diabetes. Unfortunately, interventional data examining the effects of OSA treatment on metabolic outcomes such as insulin sensitivity, glucose tolerance, and glycosylated hemoglobin have been equivocal [12], [13], and thus have raised significant doubt regarding the role of OSA in the pathogenesis of type 2 diabetes. Thus, recommendations regarding case-identification for OSA in those at risk for metabolic dysfunction need to be tempered by the lack of a strong empirical base. Part of the challenge in interpreting the available interventional data on the effects of OSA treatment on metabolic parameters is due to the wide range of methodological limitations in the available studies [7]. Relatively limited sample sizes, poor adherence with treatment, and duration of treatment are some of the many pitfalls in the treatment-related data available to date. There is also a dearth of longitudinal data on whether untreated OSA in those free of diabetes increases the predisposition for developingdiabetes [14], [15]. Longitudinal evidence to support temporality of the association between OSA and diabetes, and whether the association is independent of obesity, is lacking. Availability of such evidence would motivate case-identification and early intervention for OSA to mitigate some of the risk for developing diabetes. The longitudinal studies that have examined the impact of OSA on incident diabetes have either been based on clinical samples [10], [11] or have not included full montage polysomnography [9], [11]. Therefore, using data from a subset of Atherosclerosis Risk in Communities Study (ARIC) participants who took part in the Sleep Heart Health Study (SHHS), the current study sought to determine whether OSA is associated with incident diabetes, independent of known confounding factors such as obesity.
Section snippets
Study population
In 1987–1989, using population-based probability sampling, the ARIC study enrolled 15,792 adults (aged 45–64 years) from four US communities [16]. A total of four follow-up visits have taken place (1990–1992, 1993–1995, 1996–1998, and 2011–2013) since the initial visit. During the fourth ARIC visit (1996–1998), which constitutes baseline for the present study, a subset of 1920 ARIC participants from the study sites of Washington County, MD and suburban Minneapolis, MN were recruited into the
Results
The 1453 participants in the final analytic sample were 53.5% female, on average 62.5 years old, and had a mean BMI of 28.3 kg/m2. Over a median of 12.8 years (max = 13.7 years) of follow-up, 285 incident diabetes cases occurred, yielding a crude total diabetes incidence of 17.6 per 1000 person-years. Of the sample, 5.7% had severe OSA, 12.9% had moderate OSA, 28.8% had mild OSA, and 52.6% were without OSA (Table 1). Those with severe OSA were more likely to be older, male, current or former
Discussion
Severe OSA, as assessed by in-home polysomnography, was associated with a 71% increased risk of incident type 2 diabetes, independent of potential diabetes risk factors including BMI and waist circumference, in this community-based sample. The current study provides strong evidence for a longitudinal association between OSA and incident diabetes. The association persisted even after the analyses were restricted to obese individuals, providing further credence to the idea that OSA increases the
Conclusion
In a community-based longitudinal study, objectively measured severe OSA was associated with greater risk of incident diabetes. Notably, the association was independent of BMI and waist circumference, and persisted even when the sample was restricted to obese participants. These findings complement the existing evidence suggesting a causal relationship between severe OSA and risk of diabetes, and support recommendations from the International Diabetes Federation that health professionals
Funding
This study was supported by the National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), and the cooperative agreements U01HL53934 (University of Minnesota) and U01HL64360 (Johns Hopkins University). P.L. was supported by the National Heart, Lung and Blood Institute (R21 HL121412), E.S. by the National Institute of Diabetes and Digestive and
Conflict of interest
This was not an industry supported study. All authors have no relevant conflict of interest to disclose.
The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2016.05.009.
Acknowledgments
The authors thank the staff and participants of the SHHS-ARIC study for their important contributions.
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