TY - JOUR
T1 - Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism
AU - Pallayova, Maria
AU - Steele, Kimberley E.
AU - Magnuson, Thomas H.
AU - Schweitzer, Michael A.
AU - Hill, Nathan R.
AU - Bevans-Fonti, Shannon
AU - Schwartz, Alan R.
N1 - Funding Information:
We would like to acknowledge Philip L. Smith, MD, Vsevolod Y. Polotsky, MD, PhD, and Naresh M. Punjabi, MD, PhD for their helpful review and suggestions on this paper. Grant Support Supported by NIH HL50381 and NCRR UL1 RR 025005. Maria Pallayova is the recipient of a European Respiratory Society Fellowship Number LTRF 15-2008. Parts of this study were presented at the International Conference of the American Thoracic Society ATS 2010, May 14-19, 2010 in New Orleans, LA, USA.
Funding Information:
Competing interests MP received grant support (November 10, 2008 - November 9, 2009) from the European Respiratory Society, and was supported through a NIH grant (November 10, 2009 - June 30, 2010). KES, THM, MAS, NRH, and SBF declare that they have no competing interest. ARS received grant support (July 1, 2005 - present) from the NIH. ARS is a scientific advisor for Apnex Medical, Cardiac Concepts and Sova Pharmaceutical, and has stock of less than 1000 USD in Sova Pharmaceutical.
PY - 2010/12/1
Y1 - 2010/12/1
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.
AB - 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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U2 - 10.1186/1475-2840-9-83
DO - 10.1186/1475-2840-9-83
M3 - Article
C2 - 21122092
AN - SCOPUS:78649513781
SN - 1475-2840
VL - 9
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
M1 - 83
ER -