Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolismReportar como inadecuado

Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cardiovascular Diabetology

, 9:83

First Online: 01 December 2010Received: 22 October 2010Accepted: 01 December 2010


BackgroundNotwithstanding 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.

MethodsForty-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.

ResultsBoth 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.

ConclusionsOSA 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.

Abbreviation listAHI apnea-hypopnea index

BMI body mass index

CRP C-reactive protein

CV coefficient of variation

ELISA enzyme-linked immunosorbent assay

HOMA homeostasis model assessment

HOMA-B HOMA estimate of steady state beta-cell function

HOMA-IR HOMA estimate of steady state insulin resistance

HOMA-IS HOMA estimate of steady state insulin sensitivity

IGM impaired glucose metabolism

IQR interquartile range

IL-1ß interleukin-1ß

IL-6 interleukin-6

IL-8 interleukin-8

LowSaO 2 mean low oxyhemoglobin saturation during sleep

MeanSaO 2 mean oxyhemoglobin saturation during sleep

MinSaO 2 minimum oxyhemoglobin saturation during sleep

NGM normal glucose metabolism

NREM non-rapid eye movement

ODI number of oxyhemoglobin desaturation events ≥ 4% per hour of sleep

OSA obstructive sleep apnea

PSG polysomnography

r Pearson product-moment correlation coefficient

REM rapid eye movement

rho Spearman-s rank correlation coefficient

TNF-α tumor necrosis factor-alpha

sTNFαR1 soluble tumor necrosis factor-alpha receptor 1

sTNFαR2 soluble tumor necrosis factor-alpha receptor 2

WASO wake after sleep onset

ΔSaO 2 degree of oxyhemoglobin desaturation associated with each disordered breathing Event.

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2840-9-83 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Maria Pallayova - Kimberley E Steele - Thomas H Magnuson - Michael A Schweitzer - Nathan R Hill - Shannon Bevans-Fonti -


Documentos relacionados