Metabolomic profile associated with obstructive sleep apnoea severity in obese pregnant women with gestational diabetes mellitus: A pilot study.

Obstructive sleep apnoea (OSA) is prevalent in obese women with gestational diabetes mellitus (GDM). The present pilot study explored associations between OSA severity and metabolites in women with GDM. A total of 81 obese women with diet-controlled GDM had OSA assessment (median gestational age [GA] 29 weeks). The metabolic profile was assayed from fasting serum samples via liquid chromatography-mass spectrometry (LC-MS) using an untargeted approach. Metabolites were extracted and subjected to an Agilent 1,290 UPLC coupled to an Agilent 6,545 quadrupole time-of-flight (Q-TOF) MS. Data were acquired using electrospray ionisation in positive and negative ion modes. The raw LC-MS data were processed using the OpenMS toolkit to detect and quantify features, and these features were annotated using the Human Metabolite Database. The feature data were compared with OSA status, apnea-hypopnea index (AHI), body mass index (BMI) and GA using "limma" in R. Correlation analyses of the continuous covariates were performed using Kendall's Tau test. The p values were adjusted for multiple testing using the Benjamini-Hochberg false discovery rate correction. A total of 42 women (51.8%) had OSA, with a median AHI of 9.1 events/hr. There were no significant differences in metabolomics profiles between those with and without OSA. However, differential analyses modelling in GA and BMI found 12 features that significantly associated with the AHI. These features could be annotated to oestradiols, lysophospholipids, and fatty acids, with higher levels related to higher AHI. Metabolites including oestradiols and phospholipids may be involved in pathogenesis of OSA in pregnant women with GDM. A targeted approach may help elucidate our understanding of their role in OSA in this population.

Continuous Positive Airway Pressure Therapy in Gestational Diabetes With Obstructive Sleep Apnea: A Randomized Controlled Trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with gestational diabetes mellitus (GDM). This study assessed the effects of continuous positive airway pressure (CPAP) in obese pregnant females with GDM and OSA. METHODS: A randomized controlled trial was conducted (April 2014 - June 2016). Obese females at 24 to 34 weeks gestation and with diet-controlled GDM were screened for OSA. Those with OSA were randomly assigned to receive 2 weeks nightly CPAP or be part of a waitlist control group. After 2 weeks, all patients were offered CPAP. The primary outcome was glucose metabolism, obtained from an oral meal tolerance test (MTT) at baseline and 2 weeks. Pregnancy outcomes were collected. RESULTS: Eighteen patients were randomized to CPAP and 18 to control groups. There were no significant changes between groups in fasting glucose, glucose response to MTT, and insulin sensitivity or secretion after 2 weeks. Those adherent to CPAP had significantly improved insulin secretion (P = .016) compared to the control group. When a counterfactual instrumental variable approach was applied to deal with nonadherence, the CPAP group had significantly improved insulin secretion (P = .002) and insulin sensitivity (P = .015). Lower rates of preterm delivery (P = .002), unplanned cesarean section (P = .005), and neonatal intensive care unit admissions (P < .001) were observed among those who used CPAP longer than 2 weeks. CONCLUSIONS: Two weeks of CPAP in females with GDM and OSA did not result in improved glucose levels, but insulin secretion improved in those adherent to CPAP. Continued CPAP use was possibly associated with improved pregnancy outcomes. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Obstructive Sleep Apnea and Gestational Diabetes: Incidence and Effects of Continuous Positive Airway Pressure Treatment on Glucose Metabolism; Identifier: NCT02108197; URL: https://clinicaltrials.gov/ct2/show/NCT02108197.

Obstructive sleep apnea and diet-controlled gestational diabetes.

BACKGROUND: Obstructive sleep apnea (OSA) was shown to be associated with gestational diabetes mellitus (GDM). However, prevalence of OSA in GDM women, its relationship to metabolic control, and predictive factors have not been studied. MATERIAL AND METHODS: Eighty-two obese pregnant women with diet-controlled GDM between 24 and 34 weeks of gestation participated. The Berlin questionnaire was used to assess OSA symptoms. OSA was diagnosed using an overnight monitor. Fasting glucose and hemoglobin A1c (HbA1c) were obtained. Those with OSA underwent meal tolerance test (MTT) to assess their metabolic parameters. Classification tree analysis was used to develop a screening tool for OSA. RESULTS: At a median gestational age of 29 weeks, OSA was diagnosed in 52.4% of the women, with a median apnea hypopnea index of 9.4 (interquartile range 6.4, 12.4). More severe OSA was significantly correlated with higher fasting glucose but not HbA1c. For those with OSA, sleep parameters related to oxygen desaturation significantly correlated with higher fasting insulin resistance and more severe ß-cell dysfunction, as evaluated by MTT. A screening tool involving two variables, neck circumference and Berlin Questionnaire score, was developed. The sensitivity and specificity were 86% and 51%, respectively. The overall accuracy was 70%. CONCLUSION: OSA is prevalent in obese pregnant women with diet-controlled GDM in the late second to early third trimester. OSA severity, especially the degree of oxygen desaturation, correlated with fasting glucose, insulin resistance, and ß-cell function. A simple screening tool involving the Berlin Questionnaire and neck circumference can aid in predicting OSA in this patient group.