TABLE 2 - uploaded by Johan Verbraecken
Content may be subject to copyright.
![] Type 2 Diabetes Mellitus, Diabetic Medication Usage, and Mean HbA1c by OSA Severity](profile/Johan-Verbraecken/publication/262382298/figure/tbl2/AS:601804920348672@1520492882018/Type-2-Diabetes-Mellitus-Diabetic-Medication-Usage-and-Mean-HbA1c-by-OSA-Severity.png)
Source publication
![TABLE 1 ] Patient Characteristics Stratifi ed by OSA Severity](profile/Johan-Verbraecken/publication/262382298/figure/tbl1/AS:601804916133936@1520492881995/Patient-Characteristics-Stratifi-ed-by-OSA-Severity_Q320.jpg)
![TABLE 2 ] Type 2 Diabetes Mellitus, Diabetic Medication Usage, and Mean...](profile/Johan-Verbraecken/publication/262382298/figure/tbl2/AS:601804920348672@1520492882018/Type-2-Diabetes-Mellitus-Diabetic-Medication-Usage-and-Mean-HbA1c-by-OSA-Severity_Q320.jpg)
![TABLE 3 ] Crude and Adjusted ORs of Prevalent Diabetes Mellitus...](profile/Johan-Verbraecken/publication/262382298/figure/tbl3/AS:601804920340480@1520492882039/Crude-and-Adjusted-ORs-of-Prevalent-Diabetes-Mellitus-Stratifi-ed-by-OSA-Severity_Q320.jpg)
![TABLE 4 ] Crude and Adjusted ORs of Prevalent Diabetes Mellitus By...](profile/Johan-Verbraecken/publication/262382298/figure/tbl4/AS:601804920352770@1520492882065/Crude-and-Adjusted-ORs-of-Prevalent-Diabetes-Mellitus-By-Subgroup-Stratifi-ed-by-OSA_Q320.jpg)
Background:
OSA is associated with an increased risk of cardiovascular morbidity. A driver of this is metabolic dysfunction and in particular type 2 diabetes mellitus (T2DM). Prior studies identifying a link between OSA and T2DM have excluded subjects with undiagnosed T2DM, and there is a lack of population-level data on the interaction between OS...
Contexts in source publication
Context 1
... of T2DM increased significantly as OSA severity increased. Of the overall cohort, 17.2% was dia- betic, increasing from 6.6% in subjects without OSA to 28.9% in those with severe OSA, with a similar pattern seen in diabetic medication usage and mean HbA1c levels ( Table 2 ). Refl ecting this, in comparison with sub- jects with no sleep-disordered breathing, those with mild, moderate, and severe disease had unadjusted OR of 2.33 (95% CI, 1.85-2.93), ...
Citations
... The direct impact of OSA on CVD has been related to the intimate bidirectional association between OSA and metabolic syndrome, insulin resistance (IR), obesity, and type 2 diabetes mellitus (T2DM), all mechanisms involved in CVD development and progression [5][6][7][8][9][10][11][12][13]. For instance, it has been suggested that OSA induces IR and alters glucose homeostasis which subsequently increases the risk of T2DM. ...
Background
Obstructive sleep apnea (OSA) has a bidirectional association with metabolic syndrome, and insulin resistance (IR). The triglyceride-glucose (TyG) index could be a simply calculated marker of IR in OSA. However, its clinical application appears still limited. Hence, this systematic review and meta-analysis aimed to respond to this question by analyzing all the existing studies showing an association between OSA and the TyG index.
Methods
Four online databases, including PubMed, Scopus, the Web of Science, and Embase were searched for studies evaluating the TyG index in OSA. After screening and data extraction, a random-effect meta-analysis was performed to compare the TyG index in OSA patients vs. healthy controls by calculating standardized mean difference (SMD) and 95% confidence interval (CI) and pooling the area under the curves (AUCs) for diagnosis of OSA based on this index.
Results
Ten studies involving 16,726 individuals were included in the current systematic review. Meta-analysis indicated that there was a significantly higher TyG index in patients with OSA, compared with the healthy controls (SMD 0.856, 95% CI 0.579 to 1.132, P < 0.001). Also, TyG had a diagnostic ability for OSA representing a pooled AUC of 0.681 (95% CI 0.627 to 0.735). However, based on the two studies’ findings, no difference between different severities of OSA was observed. Finally, our data showed that the TyG index is a good potential predictor of adverse outcomes in these patients.
Conclusion
Our study revealed that the TyG index is an easy-to-measure marker of IR for assessing OSA, both in diagnosis and prognosis. Our study supports its implementation in routine practice to help clinicians in decision-making and patient stratification.
... Recent epidemiological surveys indicate that 14-49% of adults have clinically significant OSA in Europe and the United States [3]. Obesity, type 2 diabetes, and metabolic disease are the stronger risk factors of OSA [4,5]. OSA prevalence is high and is rising worldwide, which may be due to the growing prevalence of obesity and overweight [6]. ...
... The prevalence of OSA is increasing worldwide due to the continuously growing of overweight and obese individuals [4,5]. Patients with OSA have a higher risk of developing cardiovascular diseases, heart failure, strokes, and cancer [24]. ...
Objective:
Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear.
Methods:
Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFβ expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial-mesenchymal transition (EMT) in vivo.
Results:
OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFβ signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression.
Conclusions:
IH promotes lung cancer progression by upregulating TGFβ signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.
... Specifically, in females with MS-SDB, sUA ≥ 5 mg/dL increased the risk of developing DM. In Asian women with OSA, the frequency of DM is reported to be lower compared to populations predominantly consisting of Western obese (mean BMI 31 kg/m 2 ) males with MS-SDB (10% vs. 21%) [37][38][39]. In our cohort, the average BMI of females with MS-SDB was 26 kg/m 2 . ...
Sleep-disordered breathing (SDB) is often accompanied by noncommunicable diseases (NCDs), including gout. However, the association between serum uric acid (sUA) levels and NCDs is complicated in patients with SDB. We aimed to clarify this issue utilizing large-scale epidemiological data. This community-based study included 9850 inhabitants. SDB and its severity were assessed by a 3% oxygen desaturation index (3% ODI) corrected for sleep duration using wrist actigraphy. The associations between sUA and moderate to severe SDB (MS-SDB) and sUA and NCDs in patients with MS-SDB were analyzed. A total of 7895 subjects were eligible. In females, the prevalence of MS-SDB increased according to an elevation in sUA levels even after adjusting for confounders, and sUA ≥ 5 mg/dL was the threshold. These were not found in males. There was a positive interaction between sUA ≥ 5 mg/dL and female sex for MS-SDB. In females with MS-SDB, the prevalence of diabetes mellitus (DM) increased according to an elevation in sUA levels, and those with sUA ≥ 5 mg/dL showed a higher prevalence of DM than their counterparts. There is a clear correlation between sUA levels and the severity of SDB, and elevated sUA poses a risk for DM in females with MS-SDB.
... Increasing research suggests that OSA is an independent risk indicator for type 2 diabetes [15] . The European Sleep Apnea Database (ESADA) [16] is one of several crosssectional cohort studies showing an independent association with type 2 diabetes and insulin resistance, and a pooled estimate of the proportional risk for diabetes to nine original studies was 1.69 (95% CI 1.45-1.80) [15] . ...
... The current findings showed that RE burden was an independent predictor of type 2 diabetes in OSA, over and above the risk associated with intermittent hypoxia. This is a new finding because previous epidemiological studies in general populations 10,31 and clinical cohorts 32 have only reported a direct linear relationship between hypoxic load and prevalent or incident diabetes (as reviewed by Kent et al. 2015 14 ). However, an association with type 2 diabetes has been found even for mild OSA with limited oxygen desaturation. ...
Aim:
To determine the association between total sleep time (TST) spent in increased respiratory effort (RE) and the prevalence of type 2 diabetes in a large cohort of individuals with suspected obstructive sleep apnoea (OSA) referred for in-laboratory polysomnography (PSG).
Materials and methods:
We conducted a retrospective cross-sectional study using the clinical data of 1128 patients. Non-invasive measurements of RE were derived from the sleep mandibular jaw movements (MJM) bio-signal. An explainable machine-learning model was built to predict prevalent type 2 diabetes from clinical data, standard PSG indices, and MJM-derived parameters (including the proportion of TST spent with increased respiratory effort [REMOV [%TST]).
Results:
Original data were randomly assigned to training (n = 853) and validation (n = 275) subsets. The classification model based on 18 input features including REMOV showed good performance for predicting prevalent type 2 diabetes (sensitivity = 0.81, specificity = 0.89). Post hoc interpretation using the Shapley additive explanation method found that a high value of REMOV was the most important risk factor associated with type 2 diabetes after traditional clinical variables (age, sex, body mass index), and ahead of standard PSG metrics including the apnoea-hypopnea and oxygen desaturation indices.
Conclusions:
These findings show for the first time that the proportion of sleep time spent in increased RE (assessed through MJM measurements) is an important predictor of the association with type 2 diabetes in individuals with OSA.
... No major difference, however, was noted among AHI or hypoxic markers as predictors of HbA1c levels . A similar trend for higher values of HbA1c in severe OSA was found in diabetic subjects (Kent, Grote, Ryan et al., 2014). The prevalence of type 2 diabetes increased with OSA severity, independent of obesity (Kent, Grote, Ryan et al., 2014). ...
... A similar trend for higher values of HbA1c in severe OSA was found in diabetic subjects (Kent, Grote, Ryan et al., 2014). The prevalence of type 2 diabetes increased with OSA severity, independent of obesity (Kent, Grote, Ryan et al., 2014). ...
Obstructive sleep apnoea (OSA) is a common disease in the general population, and is associated with increased cardiovascular risk and several comorbidities. Obesity favours upper airway collapsibility, but other pathophysiological traits have been identified, i.e. upper airway muscle activity, modulation of the respiratory drive, and the arousal threshold. OSA causes chronic intermittent hypoxia, inflammatory activation and autonomic imbalance with diurnal and nocturnal sympathetic hyperactivity. Disentangling so many components to investigate the pathogenesis of OSA's consequences is very hard clinically. However, albeit imperfect, clinical medicine constitutes a major source of inspiration for basic research, and a mutual exchange of information is essential between clinicians and physiologists to improve our understanding of disease states. OSA is no exception, and this narrative review will summarize the results of clinical studies performed over the years by the European Sleep Apnoea Database (ESADA) Study Group, to explore the variables linked to markers of intermittent hypoxia as opposed to the traditional assessment of OSA severity based on the frequency of respiratory events during sleep (the Apnoea Hypopnoea Index). The results of the clinical studies indicate that intermittent hypoxia variables are associated with several comorbidities, although evidence of a cause–effect relationship is still missing in many cases. It is also possible that adaptive rather than maladaptive responses could be evoked by intermittent hypoxia. The intensity, duration and frequency of intermittent hypoxia episodes causing adaptive rather than maladaptive responses, and their clinical implications, deserve further investigation. image
... Meanwhile, sleep disorders accelerate the development of T2DM by worsening the metabolic control, which forms into a vicious spiral (Barone and Menna-Barreto, 2011). Researchers have found that poor sleep quality (Martyn-Nemeth et al., 2018), insufficient or excessive sleep duration, changes of sleep structure (Koren et al., 2011), decreasing sleep efficiency (Hur et al., 2020), increasing OSA severity (Kent et al., 2014), etc. are associated with poor diabetic control. Also, sleep disorders are strongly related to ANS function of T2DM patients (Jordan et al., 2014). ...
... Due to the complex interaction among sleep, diabetic control and ANS function that sleep have a significant effect on both ANS and metabolic function, especially glycemic control of T2DM patients (Koren et al., 2011;Jordan et al., 2014;Kent et al., 2014;Martyn-Nemeth et al., 2018;Hur et al., 2020), partial correlation analysis was required to manifest the association between non-linear HRV metrics in sleep stages and glycemic control indicators clearly. With the nullification of sleep quality metrics, most of the correlations retained, which supported the significant correlations acquired by simple correlation analysis. ...
Introduction: Autonomic nervous system (ANS) plays an important role in the exchange of metabolic information between organs and regulation on peripheral metabolism with obvious circadian rhythm in a healthy state. Sleep, a vital brain phenomenon, significantly affects both ANS and metabolic function.
Objectives: This study investigated the relationships among sleep, ANS and metabolic function in type 2 diabetes mellitus (T2DM), to support the evaluation of ANS function through heart rate variability (HRV) metrics, and the determination of the correlated underlying autonomic pathways, and help optimize the early prevention, post-diagnosis and management of T2DM and its complications.
Materials and methods: A total of 64 volunteered inpatients with T2DM took part in this study. 24-h electrocardiogram (ECG), clinical indicators of metabolic function, sleep quality and sleep staging results of T2DM patients were monitored.
Results: The associations between sleep quality, 24-h/awake/sleep/sleep staging HRV and clinical indicators of metabolic function were analyzed. Significant correlations were found between sleep quality and metabolic function (|r| = 0.386 ± 0.062, p < 0.05); HRV derived ANS function showed strengthened correlations with metabolic function during sleep period (|r| = 0.474 ± 0.100, p < 0.05); HRV metrics during sleep stages coupled more tightly with clinical indicators of metabolic function [in unstable sleep: |r| = 0.453 ± 0.095, p < 0.05; in stable sleep: |r| = 0.463 ± 0.100, p < 0.05; in rapid eye movement (REM) sleep: |r| = 0.453 ± 0.082, p < 0.05], and showed significant associations with glycemic control in non-linear analysis [fasting blood glucose within 24 h of admission (admission FBG), |r| = 0.420 ± 0.064, p < 0.05; glycated hemoglobin (HbA1c), |r| = 0.417 ± 0.016, p < 0.05].
Conclusions: HRV metrics during sleep period play more distinct role than during awake period in investigating ANS dysfunction and metabolism in T2DM patients, and sleep rhythm based HRV analysis should perform better in ANS and metabolic function assessment, especially for glycemic control in non-linear analysis among T2DM patients.
... Furthermore, OSA could aggravate the evolution of diabetes, since it has an adverse effect on glycemic control (3,4), a key contributing factor in the development of vascular complications. ...
Rationale:
Obstructive sleep apnea (OSA) is associated with impaired glycemic control and a higher risk of vascular complications, such as diabetic kidney disease (DKD). However, the effect of apnea-hypopneas suppression on DKD progression is unclear.
Objectives:
To assess the effect of continuous positive airway pressure (CPAP) on urinary albumin-to-creatinine ratio (UACR) in patients with DKD and OSA.
Methods:
In a 52-weeks, multicentric, open-label, parallel, and randomized clinical trial, 185 patients with OSA and DKD were randomized to CPAP and usual care (n=93) or usual care alone (n=92).
Measurements and main results:
UACR, estimated glomerular filtration rate (eGFR), serum levels of creatinine and glycated hemoglobin, insulin resistance, lipid levels, sleepiness and quality of life. 52-week change in UACR from baseline did not differ significantly between the CPAP group and the usual-care group. However, in per-protocol analyses, which included 125 participants who met prespecified criteria for adherence, CPAP treatment was associated with a great reduction in UACR (mean difference, -10.56% [95% confidence interval {CI}, -19.06 to -2.06]; p=0.015). CPAP effect on UACR was higher in non-sleepy patients with more severe OSA, worse renal function and more recent diagnosis of DKD. CPAP treatment also improved glycemic control and insulin resistance, as well as sleepiness and health-related quality of life.
Conclusions:
In patients with OSA and DKD, the prescription of CPAP did not result in a statistically significant reduction in the albuminuria. However, good adherence to CPAP treatment in addition to usual care may result in long-term albuminuria reduction compared to usual care alone. Clinical trial registration available at www.
Clinicaltrials:
gov, ID: NCT02816762.
... In 137 patients with diagnosed T2DM and preDM with extreme obesity (BMI > 40 kg/m 2 ), the ORs for associated OSA were 3.18 (95% CI; 1.00, 10.07) and 4.17 (CI; 1.09, 15.88), respectively, after adjustment for age, obesity, and insulin levels [82]. The European Sleep Apnoea Cohort Study demonstrated that for all levels of obesity, the presence of OSA increased the risk of T2DM and was associated with worse glycaemic control [83]. Moreover, a metanalysis of 25 studies covering 154,948 OSA patients showed an association between OSA and increased risk of impaired fasting glucose and T2DM development [84]. ...
Obstructive sleep apnoea (OSA) and type 2 DM mellitus (T2DM) share obesity as a major risk factor. Furthermore, these conditions share overlapping mechanisms including inflammation, activation of the autonomic nervous system, and hypoxia-linked endocrinopathy. Hence, the pathogenesis of the two conditions may be more closely related than previously recognised. This raises the question of whether treatment of OSA might assist resolution of obesity and/or T2DM. Here, we present a narrative review of the literature to identify clinical and scientific data on the relationship between obstructive sleep apnoea and T2DM control. We found there is a paucity of adequately powered well-controlled clinical trials to directly test for a causal association. While routine screening of all T2DM patients with polysomnography cannot currently be justified, given the high prevalence of sleep disordered breathing in the overweight/obese population, all T2DM patients should at a minimum have a clinical assessment of potential obstructive sleep apnoea risk as part of their routine clinical care. In particular, screening questionnaires can be used to identify T2DM subjects at higher risk of OSA for consideration of formal polysomnography studies. Due to morbid obesity being a common feature in both T2DM and OSA, polysomnography should be considered as a screening tool in such high-risk individuals.
... In addition, moderate-to-severe OSA is significantly associated with cardiovascular and metabolic diseases, such as systemic arterial hypertension, coronary artery disease, heart failure, and stroke. All these factors could lead to substantial morbidity and mortality [37,38]. As a result, early identification and treatment of patients with moderate-to-severe OSA are important. ...
Obstructive sleep apnoea (OSA) is characterised by repetitive episodes of upper airway collapse and breathing cessation during sleep. Empty nose syndrome (ENS) is a surgically iatrogenic phenomenon of paradoxical nasal obstruction despite an objectively patent nasal airway. This study aimed to investigate sleep quality and the presence of OSA in ENS patients. Forty-eight ENS patients underwent full-night polysomnography. Total nasal resistance (TNR) was determined using anterior rhinomanometry. Symptoms and quality of life were evaluated by the empty nose syndrome 6-item questionnaire (ENS6Q), Sino-Nasal Outcome Test-22 (SNOT-22), and Epworth Sleepiness Scale questionnaires (ESS). Fourteen, twelve, and fourteen patients had mild, moderate, and severe OSA, respectively. The apnoea–hypopnoea index (AHI) and the lowest SpO2 were 23.8 ± 22.4/h and 85.9 ± 11.1%, respectively. N1, N2, N3 and rapid-eye-movement sleep comprised 30.2 ± 16.9%, 47.3 ± 15.5%, 2.1 ± 5.4%, and 20.0 ± 8.1% of the total sleep time. Body mass index, neck circumference, serum total immunoglobulin E, and ENS6Q score were significantly associated with AHI in the regression analysis. The ENS6Q scores correlated positively with AHI, arousal index, and ESS score, but negatively with TNR. ENS patients showed a high OSA prevalence and significant sleep impairment. The extent of OSA was associated with obesity levels and ENS symptom severity. The ENS6Q scores correlated negatively with nasal resistance, and positively with arousal frequency and daytime sleepiness. The recognition of individuals experiencing marked OSA and provision of appropriate intervention is critical to preventing long-term morbidity and mortality, and improving therapeutic outcomes in ENS patients.
