Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism

Maria Pallayova, Kimberley E. Steele, Thomas H. Magnuson, Michael A. Schweitzer, Nathan R. Hill, Shannon Bevans-Fonti, Alan R. Schwartz

Research output: Contribution to journalArticle

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Abstract

Background: Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA) and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM) and impaired glucose metabolism (IGM).Methods: Forty-five severely obese adults (36 women) without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS) and pancreatic beta-cell function (HOMA-B).Results: Both increases in apnea-hypopnea index (AHI) and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (P = 0.003). In subjects with NGM (n = 30), OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS) independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-α (r=-0.76; P = 0.001) in women with NGM and with IL-6 (rho=-0.55; P = 0.035) in women with IGM (n = 15) matched individually for age, adiposity, and AHI.Conclusions: OSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-α and IL-6 have been discerned in our study to suggest that sleep apnea and particularly nocturnal oxyhemoglobin desaturations are associated with chronic metabolic fluxes and specific cytokine stressors that reflect links between sleep apnea and glucose metabolism. The study may help illuminate potential mechanisms for glucose dysregulation in OSA, and resolve some controversy over the associations of OSA with TNF-α and IL-6 in previous studies.

Original languageEnglish
Article number83
JournalCardiovascular Diabetology
Volume9
DOIs
Publication statusPublished - 1 Dec 2010
Externally publishedYes

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Sleep Apnea Syndromes
Obstructive Sleep Apnea
Homeostasis
Biomarkers
Glucose
Insulin Resistance
Prediabetic State
Interleukin-6
Oxyhemoglobins
Adiposity
Insulin-Secreting Cells
Apnea
Cytokines
Polysomnography
Hematologic Tests
Comorbidity
Fasting
Insulin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism. / Pallayova, Maria; Steele, Kimberley E.; Magnuson, Thomas H.; Schweitzer, Michael A.; Hill, Nathan R.; Bevans-Fonti, Shannon; Schwartz, Alan R.

In: Cardiovascular Diabetology, Vol. 9, 83, 01.12.2010.

Research output: Contribution to journalArticle

Pallayova, Maria ; Steele, Kimberley E. ; Magnuson, Thomas H. ; Schweitzer, Michael A. ; Hill, Nathan R. ; Bevans-Fonti, Shannon ; Schwartz, Alan R. / Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism. In: Cardiovascular Diabetology. 2010 ; Vol. 9.
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AU - Steele, Kimberley E.

AU - Magnuson, Thomas H.

AU - Schweitzer, Michael A.

AU - Hill, Nathan R.

AU - Bevans-Fonti, Shannon

AU - Schwartz, Alan R.

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N2 - Background: Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA) and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM) and impaired glucose metabolism (IGM).Methods: Forty-five severely obese adults (36 women) without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS) and pancreatic beta-cell function (HOMA-B).Results: Both increases in apnea-hypopnea index (AHI) and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (P = 0.003). In subjects with NGM (n = 30), OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS) independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-α (r=-0.76; P = 0.001) in women with NGM and with IL-6 (rho=-0.55; P = 0.035) in women with IGM (n = 15) matched individually for age, adiposity, and AHI.Conclusions: OSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-α and IL-6 have been discerned in our study to suggest that sleep apnea and particularly nocturnal oxyhemoglobin desaturations are associated with chronic metabolic fluxes and specific cytokine stressors that reflect links between sleep apnea and glucose metabolism. The study may help illuminate potential mechanisms for glucose dysregulation in OSA, and resolve some controversy over the associations of OSA with TNF-α and IL-6 in previous studies.

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