Obstructive Sleep Apnea and Incident Diabetes. A Historical Cohort Study

Kendzerska, Tetyana; Gershon, Andrea S.; Hawker, Gillian; Tomlinson, George; Leung, Richard

doi:10.1164/rccm.201312-2209oc

Cited by 234 publications

(176 citation statements)

References 52 publications

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“…Individuals with OSA are at increased risk for cardiovascular disease, diabetes, and other disorders that carry significant morbidity and premature mortality, underscoring the need to better understand the etiology of this disorder and to identify targets for novel interventions (1)(2)(3). Although there is strong evidence supporting the importance of familial, and specifically genetic factors in influencing OSA susceptibility (4), its genetic basis is not well understood.…”

mentioning

confidence: 99%

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans

Cade

Chen

Stilp

et al. 2016

Am J Respir Crit Care Med

120

102

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Rationale: Obstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability.Objectives: To define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts.Methods: Genome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, MultiEthnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration.Measurements and Main Results: Two novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 3 10 28 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 3 10 28 for respiratory event duration) and seven additional loci were identified with suggestive significance (P , 5 3 10 27 ). Secondary sex-stratified analyses also identified one significant and several suggestive associations. Multiple loci overlapped genes with biologic plausibility.Conclusions: These are the first genome-level significant findings reported for obstructive sleep apnea-related physiologic traits in any population. These findings identify novel associations in inflammatory, hypoxia signaling, and sleep pathways.

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mentioning

confidence: 99%

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans

Cade

Chen

Stilp

et al. 2016

Am J Respir Crit Care Med

120

102

View full text Add to dashboard Cite

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“…Observational studies have also demonstrated that OSA is an independent risk factor for prediabetes and incident diabetes (10)(11)(12)(13). Both animal and human models of intermittent hypoxia and sleep fragmentation acutely mimicking OSA show evidence of insulin resistance and glucose intolerance (14)(15)(16)(17).…”

mentioning

confidence: 99%

Eight Hours of Nightly Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Improves Glucose Metabolism in Patients with Prediabetes. A Randomized Controlled Trial

Pamidi

Wroblewski²,

Stępień

et al. 2015

Am J Respir Crit Care Med

160

117

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Rationale: Although obstructive sleep apnea (OSA) is associated with impaired glucose tolerance and diabetes, it remains unclear whether OSA treatment with continuous positive airway pressure (CPAP) has metabolic benefits.Objectives: To determine the effect of 8-hour nightly CPAP treatment on glucose metabolism in individuals with prediabetes and OSA.Methods: In a randomized controlled parallel group study, 39 participants were randomly assigned to receive either 8-hour nightly CPAP (n = 26) or oral placebo (n = 13). Sleep was polysomnographically recorded in the laboratory on each night. CPAP adherence was ensured by continuous supervision. Participants continued their daily routine activities outside the laboratory. Glucose metabolism was assessed at baseline and after 2 weeks of assigned treatment using both the oral and intravenous glucose tolerance tests. The primary outcome was the overall glucose response as quantified by the area under the curve for glucose during 2-hour oral glucose tolerance testing. Secondary outcomes included fasting and 2-hour glucose and insulin, the area under the curves for insulin and insulin secretion, norepinephrine, insulin sensitivity, acute insulin response to glucose, and 24-hour blood pressure.

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“…4,8 There is signifi cant heterogeneity across seven published longitudinal studies 4,[9][10][11][12][13][14][15] of OSA-related diabetes risk in terms of sample sizes, numbers of incident cases, followup periods, and referral bias associated with selected samples. In the Wisconsin cohort, no independent association of ; Peter G. Catcheside, PhD 2,4 ; Robert J. Adams, MBBS, MD 1 1 moderate-severe OSA with incident diabetes was observed, 9 and other studies have demonstrated only modest associations.…”

mentioning

confidence: 99%

“…In the Wisconsin cohort, no independent association of ; Peter G. Catcheside, PhD 2,4 ; Robert J. Adams, MBBS, MD 1 1 moderate-severe OSA with incident diabetes was observed, 9 and other studies have demonstrated only modest associations. [10][11][12][13][14][15] Consequently, a recent systematic review found "little published evidence of a longitudinal association between OSA and diabetes." 8 The importance of polysomnography (PSG) indices other than the apnea-hypopnea index (AHI), such as hypoxia, for incident diabetes is unclear.…”

mentioning

confidence: 99%

Nocturnal Hypoxemia and Severe Obstructive Sleep Apnea are Associated with Incident Type 2 Diabetes in a Population Cohort of Men

Appleton

Vakulin

McEvoy

et al. 2015

Journal of Clinical Sleep Medicine

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BRIEF SUMMARYCurrent Knowledge/Study Rationale: The generalizability of fi ndings from the few studies that identify OSA as a risk factor for the development of diabetes may be limited by small samples, few incident cases, and possible referral bias that may apply to clinical samples. The importance of other polysomnographic measures (e.g., oxygen desaturation) and sleepiness in the development of diabetes is also unclear. Study Impact: The current study has identifi ed that severe undiagnosed OSA and nocturnal intermittent hypoxemia were independently associated with the development of diabetes in a large population cohort of middle-aged and older men. Given the scale of the problem of undiagnosed OSA, improved management is required to ensure that a patient presenting with one condition is screened and treated for the other with a strategy that does not rely on the presence of excessive daytime sleepiness. Study Objectives:Studies examining the longitudinal association of untreated obstructive sleep apnea (OSA) with diabetes in population samples are limited. This study therefore examined the relationship between previously undiagnosed OSA with incident type 2 diabetes in communitydwelling men aged ≥ 40 y. Methods: The Men Androgen Infl ammation Lifestyle Environment and Stress (MAILES) Study is a longitudinal population-based cohort in Adelaide, South Australia. Clinic assessments at baseline and follow-up identifi ed diabetes (self-reported doctor diagnosed, fasting plasma glucose ≥ 7.0 mmol/L, glycated hemoglobin ≥ 6.5% or diabetes medication use) and included anthropometry. At cohort follow-up (2010-2012), n = 837 underwent full in-home unattended polysomnography (PSG, Embletta X100, Broomfi eld, CO). Results: Of 736 men free of diabetes at baseline, incident diabetes occurred in 66 (9.0%) over a mean follow-up time of 56 mo (standard deviation = 5, range: 48-74 mo). Incident diabetes was associated with current oxygen desaturation index (3%) ≥ 16 events/h (odds ratio [OR]: 1.85 [1.06-3.21]), and severe OSA [OR: 2.6 (1.1-6.1)], in adjusted models including age, percentage total body fat, and weight gain (> 5 cm waist circumference). An age-adjusted association of incident diabetes with percentage of total sleep time with oxygen saturation < 90% did not persist after adjustment for percentage of body fat. No modifi cation of these relationships by excessive daytime sleepiness was observed. Conclusions: Severe undiagnosed OSA and nocturnal hypoxemia were independently associated with the development of diabetes. A reduction in the burden of undiagnosed OSA and undiagnosed diabetes is likely to occur if patients presenting with one disorder are assessed for the other. Keywords: cohort study, epidemiology, men, nocturnal hypoxemia, obstructive sleep apnea, polysomnography, type 2 diabetes Citation: Appleton SL, Vakulin A, McEvoy RD, Wittert GA, Martin SA, Grant JF, Taylor AW, Antic NA, Catcheside PG, Adams RJ. Nocturnal hypoxemia and severe obstructive sleep apnea are associated with incident type 2 diabetes i...

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Obstructive Sleep Apnea and Incident Diabetes. A Historical Cohort Study

Abstract: Among people with OSA, and controlling for multiple confounders, initial OSA severity and its physiologic consequences predicted subsequent risk for incident diabetes.

Cited by 234 publications

References 52 publications

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans

Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans

Eight Hours of Nightly Continuous Positive Airway Pressure Treatment of Obstructive Sleep Apnea Improves Glucose Metabolism in Patients with Prediabetes. A Randomized Controlled Trial

Nocturnal Hypoxemia and Severe Obstructive Sleep Apnea are Associated with Incident Type 2 Diabetes in a Population Cohort of Men

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