Obstructive sleep apnea is a predictor of abnormal glucose metabolism in chronically sleep deprived obese adults

Giovanni Cizza, Paolo Piaggi, Eliane A Lucassen, Lilian de Jonge, Mary Walter, Megan S Mattingly, Heather Kalish, Gyorgy Csako, Kristina I Rother, Sleep Extension Study Group, Giovanni Cizza, Paolo Piaggi, Eliane A Lucassen, Lilian de Jonge, Mary Walter, Megan S Mattingly, Heather Kalish, Gyorgy Csako, Kristina I Rother, Sleep Extension Study Group

Abstract

Context: Sleep abnormalities, including obstructive sleep apnea (OSA), have been associated with insulin resistance.

Objective: To determine the relationship between sleep, including OSA, and glucose parameters in a prospectively assembled cohort of chronically sleep-deprived obese subjects.

Design: Cross-sectional evaluation of a prospective cohort study.

Setting: Tertiary Referral Research Clinical Center.

Main outcome measures: Sleep duration and quality assessed by actigraphy, sleep diaries and questionnaires, OSA determined by a portable device; glucose metabolism assessed by oral glucose tolerance test (oGTT), and HbA1c concentrations in 96 obese individuals reporting sleeping less than 6.5 h on a regular basis.

Results: Sixty % of subjects had an abnormal respiratory disturbance index (RDI≥5) and 44% of these subjects had abnormal oGTT results. Severity of OSA as assessed by RDI score was associated with fasting glucose (R = 0.325, p = 0.001) and fasting insulin levels (ρ = 0.217, p = 0.033). Subjects with moderate to severe OSA (RDI>15) had higher glucose concentrations at 120 min than those without OSA (RDI<5) (p = 0.017). Subjects with OSA also had significantly higher concentrations of plasma ACTH (p = 0.009). Several pro-inflammatory cytokines were higher in subjects with OSA (p<0.050). CRP levels were elevated in this sample, suggesting increased cardiovascular risk.

Conclusions: OSA is associated with impaired glucose metabolism in obese, sleep deprived individuals. Since sleep apnea is common and frequently undiagnosed, health care providers should be aware of its occurrence and associated risks.

Trial registration: This study was conducted under the NIDDK protocol 06-DK-0036 and is listed in ClinicalTrials.gov NCT00261898.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Oral glucose tolerance test.
Figure 1. Oral glucose tolerance test.
Glucose (Panel A) and insulin (Panel B) concentrations during 120-min OGTT in patients with a sleep apnea diagnosis (RDI ≥5, white circles, N = 58) and without a sleep apnea diagnosis (RDI

Figure 2. Fasting glucose concentration increases with…

Figure 2. Fasting glucose concentration increases with sleep apnea severity as quantified by the RDI…

Figure 2. Fasting glucose concentration increases with sleep apnea severity as quantified by the RDI score.
Fasting glucose concentrations rose progressively from subjects without sleep apnea (84.9±6.7 mg/dL; mean±SD) to those with mild (90.4±12.9 mg/dL), moderate (92.5±8.9 mg/dL), and severe (93.9±17.9 mg/dL) sleep apnea (test for trend: p = 0.025). Data are presented as mean with 95% CI.

Figure 3. Relationship between RDI and fasting…

Figure 3. Relationship between RDI and fasting glucose (Panel A), fasting insulin (Panel B), HOMA…

Figure 3. Relationship between RDI and fasting glucose (Panel A), fasting insulin (Panel B), HOMA index (Panel C), and 120-min glucose (Panel D).
RDI is reported on a safe-logarithmic scale, namely, LOG10(1+ RDI).
Figure 2. Fasting glucose concentration increases with…
Figure 2. Fasting glucose concentration increases with sleep apnea severity as quantified by the RDI score.
Fasting glucose concentrations rose progressively from subjects without sleep apnea (84.9±6.7 mg/dL; mean±SD) to those with mild (90.4±12.9 mg/dL), moderate (92.5±8.9 mg/dL), and severe (93.9±17.9 mg/dL) sleep apnea (test for trend: p = 0.025). Data are presented as mean with 95% CI.
Figure 3. Relationship between RDI and fasting…
Figure 3. Relationship between RDI and fasting glucose (Panel A), fasting insulin (Panel B), HOMA index (Panel C), and 120-min glucose (Panel D).
RDI is reported on a safe-logarithmic scale, namely, LOG10(1+ RDI).

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