title: Glucose tolerance and cardiovascular risk biomarkers in non-diabetic non-obese obstructive sleep apnea patients: Effects of long-term continuous positive airway pressure.
abstract: BACKGROUND
  Insulin resistance, glucose dyshomeostasis and oxidative stress are associated to the cardiovascular consequences of obstructive sleep apnea (OSA). The effects of a long-term continuous positive airway pressure (LT-CPAP) treatment on such mechanisms still remain conflicting.
  
  
  OBJECTIVE
  To investigate the effect of LT-CPAP on glucose tolerance, insulin sensitivity, oxidative stress and cardiovascular biomarkers in non-obese non-diabetic OSA patients.
  
  
  METHODS
  Twenty-eight apneic, otherwise healthy, men suffering from OSA (mean age = 48.9 ± 9.4 years; apnea-hypopnea index = 41.1 ± 16.1 events/h; BMI = 26.6 ± 2.8 kg/m(2); fasting glucose = 4.98 ± 0.37 mmol/L) were evaluated before and after LT-CPAP by an oral glucose tolerance test (OGTT), measuring plasma glucose, insulin and proinsulin. Glycated hemoglobin, homeostasis model assessment resistance insulin, blood lipids, oxidative stress, homocysteine and NT-pro-brain natriuretic peptide (NT-proBNP) were also measured.
  
  
  RESULTS
  LT-CPAP treatment lasted 13.9 ± 6.5 months. At baseline, the time spent at SaO2<90%, minimal and mean SaO2 were associated with insulin area under the curve during OGTT (r = 0.448, P = 0.011; r = -0.382; P = 0.047 and r = -0.424; P = 0.028, respectively) and most other glucose/insulin homeostasis biomarkers, as well as with homocysteine (r = 0.531, P = 0.006; r = -0.487; P = 0.011 and r = -0.409; P = 0.034, respectively). LT-CPAP had no effect on all the OGTT-related measurements, but increased plasma total antioxidant status (+7.74%; P = 0.035) in a duration-dependent manner (r = 0.607; P < 0.001), and decreased both homocysteine (-15.2%; P = 0.002) and NT-proBNP levels (-39.3%; P = 0.002).
  
  
  CONCLUSIONS
  In non-obese non-diabetic OSA patients, nocturnal oxygen desaturation is strongly associated to insulin resistance. LT-CPAP does not improve glucose homeostasis nor insulin sensitivity but has a favorable effect on antioxidant capacity and cardiovascular risk biomarkers.
authors: HP2 Laboratory, Inserm U1042, Grenoble Alpes University, Grenoble, France; Department of Biochemistry Toxicology and Pharmacology, Biology & Pathology Institute, Grenoble University Hospital, Grenoble, France. Electronic address: dmonneret2@gmail.com.
authors: D
authors: D
authors: Monneret
authors: HP2 Laboratory, Inserm U1042, Grenoble Alpes University, Grenoble, France; Sleep, Exercise and Physiology Laboratory, EFCR, Grenoble University Hospital, Grenoble, France.
authors: R
authors: R
authors: Tamisier
authors: Department of Biochemistry Toxicology and Pharmacology, Biology & Pathology Institute, Grenoble University Hospital, Grenoble, France.
authors: V
authors: V
authors: Ducros
authors: HP2 Laboratory, Inserm U1042, Grenoble Alpes University, Grenoble, France; Department of Biochemistry Toxicology and Pharmacology, Biology & Pathology Institute, Grenoble University Hospital, Grenoble, France.
authors: P
authors: P
authors: Faure
authors: Department of Endocrinology, Pole DIGIDUNE, Grenoble University Hospital, Grenoble, France.
authors: S
authors: S
authors: Halimi
authors: Department of Cardiology, Grenoble University Hospital, Grenoble, France.
authors: J P
authors: JP
authors: Baguet
authors: HP2 Laboratory, Inserm U1042, Grenoble Alpes University, Grenoble, France; Sleep, Exercise and Physiology Laboratory, EFCR, Grenoble University Hospital, Grenoble, France.
authors: P
authors: P
authors: Lévy
authors: HP2 Laboratory, Inserm U1042, Grenoble Alpes University, Grenoble, France; Sleep, Exercise and Physiology Laboratory, EFCR, Grenoble University Hospital, Grenoble, France.
authors: J L
authors: JL
authors: Pépin
authors: HP2 Laboratory, Inserm U1042, Grenoble Alpes University, Grenoble, France; Department of Endocrinology, Pole DIGIDUNE, Grenoble University Hospital, Grenoble, France.
authors: A L
authors: AL
authors: Borel
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000378:metabolism*; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D045422:Continuous Positive Airway Pressure; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000378:metabolism; D017286:Polysomnography; D011384:Proinsulin / Q000378:metabolism; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D006710:Homocysteine; D007328:Insulin; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments; D011384:Proinsulin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human; C109794:pro-brain natriuretic peptide (1-76)
keywords: Biomarkers; Cardiovascular risk; Glucose tolerance; Long-term CPAP; Obstructive sleep apnea; Oxidative stress