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. 2020 Nov;158(5):2155-2164.
doi: 10.1016/j.chest.2020.05.600. Epub 2020 Jun 18.

Sleep-Disordered Breathing and Free Fatty Acid Metabolism

Darko Stefanovski  1 , Ray C Boston  1 , Naresh M Punjabi  2
Affiliations

Sleep-Disordered Breathing and Free Fatty Acid Metabolism

Darko Stefanovski et al. Chest. 2020 Nov.

Abstract

Background: Sleep-disordered breathing (SDB) is independently associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. However, data on whether SDB alters the metabolism of free fatty acids (FFAs) are lacking.

Research question: The primary objective of the current study was to characterize alterations in FFA metabolism across the spectrum of SDB severity.

Study design and methods: The study sample included 118 participants with and without SDB who underwent full-montage polysomnography, the frequently sampled IV glucose tolerance test (FSIGTT), and body composition measurements including determination of percent body fat. Parameters of lipolysis suppression, time to FFA nadir, and FFA rebound after an IV glucose challenge were derived using a mathematical model. Multivariable regression analyses were used to characterize the independent associations between SDB severity and parameters of FFA metabolism.

Results: SDB severity, as assessed by the apnea-hypopnea index, was associated with adipocyte insulin resistance, a decrease in the glucose- and insulin-mediated suppression of lipolysis, a longer duration to reach a nadir in FFA levels during the FSIGTT, and a sluggish rebound in FFA levels after suppression. Severity of SDB-related hypoxemia was independently associated with adipocyte insulin resistance and the time to reach the FFA nadir during the FSIGTT. Finally, a higher percentage of stage N3 sleep was positively associated with greater suppression of lipolysis and a faster rebound in the FFA levels during the FSIGTT.

Interpretation: Independent of adiposity, SDB is associated with impairments in FFA metabolism, which may contribute to the development of glucose intolerance and type 2 diabetes in SDB.

Keywords: fat metabolism; free fatty acids; sleep apnea; sleep-disordered breathing.

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Figures

Figure 1
Figure 1
Glucose (A) and free fatty acid (B) profiles from the frequently sampled IV glucose tolerance test for quartiles of the apnea-hypopnea index. AHI = apnea-hypopnea index; FFA = free fatty acid.
Figure 2
Figure 2
Adjusted values (mean and 95% CIs) of adipo-IR for quartiles of the AHI. adipo-IR = adipose tissue insulin resistance index. See Figure 1 legend for expansion of other abbreviation.
Figure 3
Figure 3
Adjusted values (mean and 95% CIs) of lipolysis suppression rate (A), FFA rebound slope (B), time to FFA nadir (C), and nadir FFA levels (D). See Figure 1 legend for expansion of abbreviations.
Figure 4
Figure 4
Adjusted values (mean and 95% CIs) of adipo-IR (A) and time to FFA (B) nadir for tertiles of oxygen desaturation. See Figure 1 and 2 legends for expansion of abbreviations.
Figure 5
Figure 5
Adjusted values (mean and 95% CIs) of lipolysis suppression rate (A) and FFA rebound slope (B) for tertiles of slow wave (N3) sleep percentage. See Figure 1 legend for expansion of abbreviation.
Figure 6
Figure 6
Possible mechanisms linking sleep-disordered breathing and the development of type 2 diabetes.
See this image and copyright information in PMC

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