Journal of Obesity & Metabolic Syndrome

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December, 2023 | Vol.32 No.4

J Obes Metab Syndr 2023; 32(4): 338-345

Published online December 30, 2023 https://doi.org/10.7570/jomes23030

Copyright © Korean Society for the Study of Obesity.

Smoking Disturbs the Beneficial Effects of Continuous Positive Airway Pressure Therapy on Leptin Level in Obstructive Sleep Apnea

Merve Aktan Suzgun1,* , Vasfiye Kabeloglu2, Gülcin Benbir Senel1, Derya Karadeniz1

1Neurology Department, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul; 2Department of Neurology, Bakirkoy Mazhar Osman Research and Training Hospital, Istanbul, Turkey

Correspondence to:
Merve Aktan Suzgun
https://orcid.org/0000-0002-0332-8453
Neurology Department, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
Tel: +90-538-714-7101
Fax: +90-212-632-0027
E-mail: merve.aktansuzgun@iuc.edu.tr

Received: March 23, 2023; Reviewed : July 31, 2023; Accepted: October 11, 2023

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: This study aimed to determine how smoking alters the effect of positive airway pressure (PAP) therapy on metabolic syndrome in obstructive sleep apnea (OSA).
Methods: In this clinical trial, morphometric measures, metabolic syndrome parameters, and apnea-hypopnea index (AHI) in OSA patients were recorded and compared between active smokers and non-smokers. The mean change in metabolic syndrome parameters measured before and after 3 months of PAP therapy was determined. The study included 72 males and 43 females.
Results: Morphometric values and mean AHI did not differ between active smokers and non-smokers. When the percentage of unchanged, increased, or decreased metabolic parameters measured before and after treatment was analyzed, leptin level tended to increase in active smokers with OSA after PAP therapy compared with non-smokers (P=0.034, adjusted for confounders).
Conclusion: Serum leptin level was stable or decreased in non-smokers, while 40% of active smokers had increased leptin level. Therefore, smoking plays a predisposing role in leptin resistance despite PAP therapy in OSA patients.

Keywords: Obstructive sleep apnea, Continuous positive airway pressure, Leptin, Metabolic syndrome, Smoking

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by obstruction of the upper airway during sleep, leading to fragmentation of sleep and intermittent hypoxia with episodes of apnea or hypopnea and increased respiratory effort.1 OSA is associated with several comorbidities, including cardiovascular,2 neurological,3-5 and endocrinological6 disorders. Metabolic syndrome, characterized by central obesity, decreased plasma high-density lipoprotein, elevated blood pressure, and increased fasting plasma glucose and plasma triglyceride (TG),7-9 is more common and severe in patients with OSA.10,11 The appropriate and effective treatment of OSA using positive airway pressure (PAP) therapy results in improvement of many metabolic syndrome parameters, confirming the strong association between OSA and metabolic syndrome.12-15 Atik et al.14 showed that 3 months of PAP treatment significantly decreased total cholesterol, low-density lipoprotein (LDL) cholesterol, and glycosylated hemoglobin (HbA1c) levels in OSA patients. In agreement with these findings, Dorkova et al.15 showed that PAP therapy reduced total cholesterol and homeostatic model assessment of insulin resistance (HOMA-IR) in addition to systolic and diastolic blood pressure. On the other hand, limitations related to control of pre-existing comorbid diseases or concomitant risk factors are debatable in the cohorts of these studies.16

Smoking is an important relevant concomitant risk factor for both OSA and metabolic syndrome. Smoking increases the risk of metabolic syndrome and related systemic complications up to 2.5 to 3-fold.17 Smoking also exacerbates OSA by causing chronic inflammation and neuromuscular dysfunction in the upper airways18 and decreases PAP adherence possibly because of the more frequent side effects associated with the upper airway.19 To the best of our knowledge, the effect of active smoking on the baseline parameters of metabolic syndrome after PAP treatment in patients with OSA has not yet been reported. In the present study, we hypothesized that active smokers with OSA would benefit less from PAP treatment compared with non-smoker patients with OSA in terms of favorable metabolic changes. Therefore, the effects of active smoking on the parameters of metabolic syndrome in OSA patients treated with PAP therapy were investigated.

Patient selection

This was a prospectively designed study to analyze the clinical, laboratory, and polysomnography (PSG) data of patients admitted to our Sleep and Disorders Unit with symptoms/signs of sleep-disordered breathing. One-night PSG was recorded and scored according to the latest version of the “Manual for scoring sleep and related events” by the American Academy of Sleep Medicine,20 and the diagnosis of OSA was based on the latest version of the International Classification of Sleep Disorders (ICSD-3).21 All patients >18 years of age with an apnea-hypopnea index (AHI) ≥15 per hour, who agreed to participate and provided written informed consent, were consecutively included in the study. Exclusion criteria were previous or current use of PAP therapy; pregnancy; malignancy, type 1 diabetes mellitus, chronic obstructive pulmonary disease, cardiovascular disease, dementia, or psychiatric disorder; insulin therapy, anti-diabetic, anti-hypertensive, or anti-hyperlipidemic treatment; and alcohol and/or substance use/abuse. The local ethics committee approved the study (approval number: 83045809/8252). A detailed informed consent form was obtained from all study participants.

Clinical evaluation

All patients meeting inclusion and exclusion criteria were clinically examined, and the smoking status of the patients was recorded as active smoker or non-smoker. Active smoking was defined as inhaling mainstream smoke, including occasional use in social events. Patients who had never smoked were accepted as non-smokers. Subjects exposed to secondhand smoking, defined as passive environmental tobacco smoke exposure and individuals who had quit smoking, were excluded. Electronic cigarette users were also excluded from the study because the effects and dosages could not be reliably quantified. Demographic and anthropometric data of the patients including age, gender, body mass index (BMI), as well as neck, waist, and hip circumferences were also recorded.

Biochemical tests

Fasting blood samples were obtained from all participants in the morning following PSG recording, and the following parameters were studied:

(1) Plasma glucose (using the hexokinase method)

(2) HbA1c (using high-pressure liquid chromatography)

(3) Serum insulin (using the electrochemiluminescence immunoassay [ECLIA] method)

(4) Oral glucose tolerance test (OGTT) to measure plasma glucose levels at the first and second hours following 75 g of oral glucose administered after 10 hours of fasting

(5) Plasma TG and LDL (using an enzymatic method in an automatic analyzer)

(6) Serum leptin (using the enzyme-linked immunosorbent assay [ELISA] method)

(7) HOMA-IR index [fasting plasma glucose (mmol/L)×fasting serum insulin level (mIU/L)/22].

Follow-up evaluations

All participants were enrolled for manual PAP titration in the sleep laboratory, and the therapeutic measures were adjusted using the recent international guidelines.22 All patients were strictly advised to comply to PAP therapy, and a follow-up examination was planned for three months after initiation of therapy. All patients were advised to continue their habitual living conditions without major changes during the study period.

At the follow-up examination, compliance with therapy was evaluated based on the output of the PAP machine. Patients who used PAP therapy effectively (for at least five nights in a week and for at least 4 hours per night corresponding to approximately 70% of nights per week) were accepted as compliant participants based on the definition by the Centers for Medicare and Medicaid Services.19 Patients who did not continue with PAP therapy for 3 months or subjects who used PAP therapy ineffectively were non-compliant and were excluded from the study (Fig. 1). Clinical examination, anthropometric measures, and biochemical tests were all repeated for the compliant participants. A change in parameter was accepted as stable when it remained within the limits of ±1 standard deviation (SD) and as increased or decreased when the change was more than ±1 SD.

Statistical analysis

Data were analyzed using SPSS version 15.0 (SPSS Inc.) software. Nominal parameters were compared using the chi-square test, and non-parametric continuous parameters were compared using the Mann-Whitney U-test. Subgroup analyses to compare pre- and post-treatment values were performed using the Wilcoxon test (due to non-parametric distribution of the parameters). The Mantel-Haenszel test was performed to adjust the confounders in the chi-square test. Adjustment for multiple comparisons in the Mann-Whitney U-test were measured using one-way analysis of variance (ANOVA) and post hoc least significant difference tests. Spearman correlation test was performed in the analysis of relationships between biochemical parameters. Patients with OSA were subgrouped as obese (BMI >30 kg/m2) or non-obese (BMI <30 kg/m2) and subjected to Spearman correlation analysis to evaluate the relationship among parameters of metabolic syndrome in both active smokers and non-smokers. A P<0.05 was considered statistically significant.

The present study included 115 patients (72 males, 62.6%); 53.3% (n=61) were active smokers, and the smoking percentage was similar between male and female patients with OSA (52.4% vs. 55.6%, P=0.596). The mean age of the study population was 53.4±14.3 years, and active smokers were significantly younger than non-smokers (P=0.034) (Table 1). The mean BMI was 31.5±4.6 kg/m2, mean neck circumference 41.4±4.1 cm, mean waist circumference 110±13.4 cm, and mean hip circumference 112.6±8.4 cm. Anthropometric measurements did not significantly differ between active smokers and non-smokers (Table 1).

In PSG recordings, the mean AHI was lower in active smokers than in non-smokers; however, the difference was not significant (32.8±20.1/hour vs. 47.2±25.6/hour, P=0.169). The ratio of severe OSA in non-smokers was significantly higher than in active smokers (P=0.049) (Table 1). All other PSG parameters were similar between the active smoker and non-smoker patients (data not shown).

At the follow-up examination after three months of PAP therapy, neither clinical nor anthropometric parameters showed significant changes (data not shown). In biochemical parameters, changes in plasma TG and LDL levels, fasting plasma glucose, OGTT at hour 1 and 2, HOMA-IR index, blood HbA1c level, and serum insulin and leptin levels did not show significant difference in active smoker and non-smoker OSA patients (Table 2).

Conversely, in analysis of stable, decreased, or increased parameters (Table 3), serum leptin level was decreased in 78.6% of non-smoker OSA patients after 3 months of treatment and decreased in only 46.7% of active smoker OSA patients despite effective treatment (P=0.029). This significant difference was confirmed after adjusting for confounding factors, including gender, age, and weight, using the Mantel-Haenszel test (P=0.034). Furthermore, leptin level was increased in 40% of active smoker OSA patients but not in any of the non-smoker OSA patients. Leptin levels before and after PAP therapy in active smoker and non-smoker patients with OSA are shown in Fig. 2. Spearman correlation analyses showed that elevated leptin level in active smokers positively correlated with TG and HOMA-IR, both in pre- (P=0.374 and P=0.367, respectively) and post-treatment (P=0.252 and P=0.232, respectively) measurements, although they were not significantly different. In subgroup analyses, leptin level in obese (BMI ≥30 kg/m2) active smoker OSA patients positively correlated with HOMA-IR at follow-up examination after PAP treatment but also without significance (P=0.062).

The main and original finding of the present study was that active smoking in OSA results in elevated leptin level despite effective PAP therapy, even after adjusting for important confounders. OSA is associated with increased serum leptin level,23,24 and treatment of OSA with PAP therapy results in reduction of serum leptin level.25,26 In a meta-analysis of 11 studies with 413 participants by Chen et al.27, PAP treatment significantly reduce serum leptin level without concomitant weight loss, starting from the 3rd day of the treatment and lasting for 3 months and beyond. Similarly, in the present study, a significant decrease in leptin level was observed in non-smoker OSA patients after months of effective PAP therapy, without any significant changes in body weight or BMI. However, in active smokers, the effect of PAP treatment was blunted, and leptin level further increased.

Smoking impairs insulin signaling via intramuscular lipid accumulation due to lipodystrophy in adipose tissues,28 which explains the lack of benefit from insulin-sensitizing effects following weight loss in smokers. Smoking was suggested as a predictor of increased serum leptin level independent of gender, BMI, or AHI in OSA patients.29 Although PAP treatment was shown to effectively reduce serum leptin level,25-27,30 contradictory data were also reported in the literature. In one study, serum leptin and adiponectin levels were not significantly changed in OSA patients with coronary artery disease after PAP treatment.31 Furthermore, an increase in plasma leptin level in parallel with an increase in waist circumference was observed after 12 months regardless of PAP treatment, and lifestyle modifications were suggested. Therefore, confounding factors, such as smoking, should be considered when evaluating the effects of PAP treatment on metabolic parameters.

Leptin plays an important role in energy balance and lipid storage, and increased levels are associated with obesity and insulin resistance.32,33 In the present study, HOMA-IR was increased as leptin level increased; although this positive correlation was not significant, it was more pronounced in obese patients. Conversely, a positive and significant correlation between leptin and insulin resistance (HOMA-IR) was observed after adjusting for age, sex, smoking, BMI, and TG level.32 In addition to obesity, direct effects of leptin on the hypothalamus were proposed as an underlying pathophysiologic mechanism of metabolic consequences.34 Elevated serum leptin level was shown to play an important role in many hormonal, metabolic, thrombotic, and inflammatory processes, leading to further systemic complications.35-38 Therefore, elevated leptin level could potentially lead to secondary adverse effects during OSA, which is also an important contributor to increased leptin level. This bidirectional relationship between OSA and leptin emphasizes the importance of an effective OSA treatment using PAP therapy as well as rational therapeutic approaches including lifestyle changes and habitual modifications such as body weight loss and smoking cessation.

The main limitations of our study were the small number of participants and short follow-up duration. Long-term data from a larger cohort would provide additional information regarding the multifactorial and complex relationship between OSA and leptin in terms of confounding factors such as smoking and the effects of PAP treatment. In addition, a dose-response relationship between smoking and OSA was reported in the literature,39 and total smoking exposure and smoking intensity should be measured as important confounding factors in future studies. Furthermore, because leptin is a hormone secreted by adipose tissue, adjusting leptin level based on body fat mass would provide a better estimation of the relationship between smoking and metabolic syndrome components before and after PAP therapy. The lack of data on body fat mass as well as dietary intake that may also affect serum leptin level is another important limitation of the present study. These emerging questions require further research for more comprehensive understanding.

In conclusion, the results of the present study showed that serum leptin level was stable or decreased in non-smokers with OSA after PAP therapy and increased in 40% of active smokers. Because high serum leptin level is closely associated with leptin resistance characterized by increased central leptin expression and decreased leptin receptors, smoking may play a predisposing role in leptin resistance in patients with OSA despite PAP therapy. To better understand leptin resistance in smoker and non-smoker subjects with OSA, further biomarker studies are needed on the metabolic consequences of leptin resistance in active smoker and non-smoker patients with OSA.

This study was funded by Istanbul University Scientific Research Projects Department (Project number: 31684).

Study concept and design: GBS; acquisition of data: MAS, VK, and GBS; analysis and interpretation of data: MAS, VK, and DK; drafting of the manuscript: MAS; critical revision of the manuscript: GBS and DK; statistical analysis: MAS and VK; obtained funding: VK and DK; administrative, technical, or material support: MAS, VK, and GBS; and study supervision: DK.

Fig. 1. Flow diagram for inclusion and exclusion criteria of the study. PAP, positive airway pressure.
Fig. 2. Box-plot representation of the mean serum leptin levels in active smoker and non-smoker patients with obstructive sleep apnea before and after positive airway pressure (PAP) treatment.

Clinical parameters of the study groups on initial evaluation

Variable Active smokers (n = 61) Non-smokers (n = 54) P
Age (yr) 49.5 ± 8.2 (32.0–63.0) 56.4 ± 9.9 (38.0–71.0) 0.034*
BMI (kg/m2) 30.9 ± 4.5 (25.0–40.1) 33.2 ± 5.8 (27.1–44.0) 0.448
Weight (kg) 92.7 ± 16.2 (68.0–134.0) 96.6 ± 20.0 (70.0–132.0) 0.728
Neck circumference (cm) 41.7 ± 3.8 (35.0–47.2) 42.6 ± 4.6 (35.0–52.0) 0.822
Waist circumference (cm) 107.5 ± 11.6 (87.0–133.0) 115.9 ± 16.2 (89.0–142.0) 0.166
Hip circumference (cm) 111.4 ± 9.7 (99.0–129.0) 115.3 ± 8.4 (103.0–131.0) 0.294
AHI (/hr) 32.8 ± 20.1 (5.0–76.0) 47.2 ± 25.6 (8.0–80.0) 0.169
OSA subtypes 0.049*
Mild (AHI 5–14/hr) 9 (14.8) 5 (9.2)
Moderate (AHI 15–29/hr) 26 (42.6) 5 (9.2)
Severe (AHI ≥ 30/hr) 26 (42.6) 44 (81.6)

Values are presented as mean± standard deviation (range) or number (%).

*Statistically significant.

BMI, body mass index; AHI, apnea-hypopnea index; OSA, obstructive sleep apnea.

Changes in biochemical parameters in active smoker and non-smoker obstructive sleep apnea patients before and after PAP therapy

Biochemical parameter Active smokers Non-smokers P *
Before PAP therapy After PAP therapy Before PAP therapy After PAP therapy
Triglyceride (mg/dL) 187.7 ± 94.2 187.2 ± 110.5 148.0 ± 61.2 136.0 ± 52.5 0.585
P 0.985 0.390
ΔTriglyceride (%) 106.3 ± 42.8 (37.8–204.2) 98.2 ± 34.3 (34.5–170.5)
LDL (mg/dL) 145.6 ± 39.2 135.4 ± 35.0 127.6 ± 30.8 128.2 ± 27.9 0.480
P 0.231 0.915
ΔLDL (%) 94.9 ± 18.6 (50.8–138.2) 103.0 ± 22.4 (84.0–174.2)
Fasting plasma glucose (mg/dL) 112.9 ± 53.2 106.6 ± 32.2 105.5 ± 14.1 104.7 ± 14.0 0.180
P 0.349 0.745
ΔFasting plasma glucose (%) 98.0 ± 14.9 (70.9–137.8) 99.6 ± 9.4 (86.0–122.2)
1st-hour OGTT (mg/dL) 165.6 ± 44.4 165.1 ± 53.0 185.0 ± 30.0 183.8 ± 38.5 0.157
P 0.371 0.330
Δ1st-hour OGTT (%) 94.6 ± 18.5 (64.2–116) 96.4 ± 12.9 (75.4–116.5)
2nd-hour OGTT (mg/dL) 116.4 ± 56.1 117.2 ± 30.0 145.8 ± 33.3 136.6 ± 37.8 0.119
P 0.760 0.153
Δ2nd-hour OGTT (%) 108.1 ± 33.5 (68.0–185.9) 93.8 ± 15.3 (75.7–116.8)
HOMA index 6.7 ± 8.0 5.8 ± 4.8 6.2 ± 3.6 6.6 ± 6.6 0.536
P 0.580 0.696
ΔHOMA index (%) 117.1 ± 62.6 (32.7–258.5) 99.8 ± 45.3 (48.3–210.2)
HbA1c (mmol/mol) 5.7 ± 0.4 5.6 ± 0.5 6.0 ± 0.4 5.7 ± 0.4 0.068
P 0.393 0.055
ΔHbA1c (%) 98.5 ± 4.5 (92.5–106.5) 94.8 ± 2.5 (90.9–100)
Serum insulin level (IU/mL) 22.4 ± 18.6 19.0 ± 13.0 24.2 ± 13.4 26.0 ± 23.6 0.225
P 0.517 0.631
ΔSerum insulin level (%) 108.5 ± 57.7 (15.3–253.5) 100.0 ± 40.1 (51.4–184.2)
Serum leptin level (ng/mL) 12.9 ± 10.0 11.5 ± 6.3 17.4 ± 9.4 13.3 ± 6.6 0.197
P 0.372 0.052
ΔSerum leptin level (%) 101.8 ± 42.4 (51.2–185.7) 79.8 ± 16.0 (53.9–106.1)
Body weight (kg) 92.7 ± 16.2 90.6 ± 16.6 96.6 ± 19.8 94.6 ± 17.6 0.868
P 0.179 0.123
ΔBody weight (%) 97.7 ± 6.6 (75.6–104.7) 98.4 ± 4.0 (90.4–104.8)
BMI (kg/m2) 30.9 ± 4.5 28.4 ± 8.2 33.2 ± 5.8 32.6 ± 4.8 0.832
P 0.202 0.132
ΔBMI (%) 97.7 ± 6.7 (75.1–104.5) 98.4 ± 4.3 (90.4–105.0)
Neck circumference (cm) 41.7 ± 3.8 41.6 ± 4.2 42.6 ± 4.6 41.8 ± 4.1 0.330
P 0.736 0.091
ΔNeck circumference (%) 100.0 ± 3.0 (92.1–106.1) 98.4 ± 3.0 (91.4–102.4)

Values are presented as mean± standard deviation (range). Adjustments for the multiple comparisons including age were made by using the one-way analysis of variance (ANOVA) and post hoc least significant difference test. Δ Refers to the levels of change before and after PAP therapy given in percentages (%).

*P-values given for the changes in parameters between patients with active smoking and non-smokers; P-values given for the changes in parameters before and after PAP therapy in patients with active smoking and non-smokers.

PAP, positive airway pressure; LDL, low-density lipoprotein; OGTT, oral glucose tolerance test; HOMA, homeostatic model assessment; HbA1c, glycosylated hemoglobin; IU, international unit; BMI, body mass index.

Changes in biochemical parameters (in percentages) based on the difference between initial (pre-treatment) and second (post-treatment) measurements as stable, decreased, or increased in active smoker and non-smoker patients with OSA

Biochemical parameter Active smokers Non-smokers P
Stable Decreased Increased Stable Decreased Increased
ΔTriglyceride (mg/dL) 12.5 50.0 37.5 28.6 42.9 28.6 0.542
ΔLDL (mg/dL) 31.3 43.8 25.0 21.4 50.0 28.6 0.832
ΔFasting plasma glucose (mg/dL) 25.0 37.5 37.5 57.1 35.7 7.1 0.087
Δ1st-hour OGTT (mg/dL) 0 46.2 53.8 9.1 54.5 36.4 0.435
Δ2nd-hour OGTT (mg/dL) 14.3 42.9 42.9 0 69.2 30.8 0.227
ΔHOMA index 43.8 18.8 37.5 28.6 42.9 28.6 0.351
ΔHbA1c (mmol/mol) 56.3 21.9 21.9 81.8 18.2 0 0.178
ΔSerum insulin level (IU/mL) 18.8 43.8 37.4 21.4 42.9 35.7 0.983
ΔSerum leptin level (ng/mL) 13.3 46.7 40.0 21.4 78.6 0 0.029*

Δ Refers to the levels of change.

*Statistically significant.

LDL, low-density lipoprotein; OGTT, oral glucose tolerance test; HOMA, homeostatic model assessment; HbA1c, glycosylated hemoglobin; IU, international unit.

  1. Park JG, Ramar K, Olson EJ. Updates on definition, consequences, and management of obstructive sleep apnea. Mayo Clin Proc 2011;86:549-54.
    Pubmed KoreaMed CrossRef
  2. Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005;365:1046-53.
    Pubmed CrossRef
  3. Redline S, Yenokyan G, Gottlieb DJ, Shahar E, O'Connor GT, Resnick HE, et al. Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study. Am J Respir Crit Care Med 2010;182:269-77.
    Pubmed KoreaMed CrossRef
  4. Andrade AG, Bubu OM, Varga AW, Osorio RS. The relationship between obstructive sleep apnea and Alzheimer's disease. J Alzheimers Dis 2018;64(s1):S255-70.
    Pubmed KoreaMed CrossRef
  5. Manni R, Terzaghi M, Arbasino C, Sartori I, Galimberti CA, Tartara A. Obstructive sleep apnea in a clinical series of adult epilepsy patients: frequency and features of the comorbidity. Epilepsia 2003;44:836-40.
    Pubmed CrossRef
  6. Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE, et al. Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol 2004;160:521-30.
    Pubmed CrossRef
  7. Bonsignore MR, Esquinas C, Barceló A, Sanchez-de-la-Torre M, Paternó A, Duran-Cantolla J, et al. Metabolic syndrome, insulin resistance and sleepiness in real-life obstructive sleep apnoea. Eur Respir J 2012;39:1136-43.
    Pubmed CrossRef
  8. Castaneda A, Jauregui-Maldonado E, Ratnani I, Varon J, Surani S. Correlation between metabolic syndrome and sleep apnea. World J Diabetes 2018;9:66-71.
    Pubmed KoreaMed CrossRef
  9. Framnes SN, Arble DM. The bidirectional relationship between obstructive sleep apnea and metabolic disease. Front Endocrinol (Lausanne) 2018;9:440.
    Pubmed KoreaMed CrossRef
  10. Parish JM, Adam T, Facchiano L. Relationship of metabolic syndrome and obstructive sleep apnea. J Clin Sleep Med 2007;3:467-72.
    Pubmed KoreaMed CrossRef
  11. Kim DH, Kim B, Han K, Kim SW. The relationship between metabolic syndrome and obstructive sleep apnea syndrome: a nationwide population-based study. Sci Rep 2021;11:8751.
    Pubmed KoreaMed CrossRef
  12. Hudgel DW, Patel SR, Ahasic AM, Bartlett SJ, Bessesen DH, Coaker MA, et al. The role of weight management in the treatment of adult obstructive sleep apnea: an official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2018;198:e70-87.
    Pubmed CrossRef
  13. Kabeloğlu V, Senel GB, Karadeniz D. Positive airway pressure normalizes glucose metabolism in obstructive sleep apnea independent of diabetes and obesity. Ideggyogy Sz 2020;73:417-25.
    Pubmed CrossRef
  14. Atik ND, Taşbakan S, Başoğlu OK. Effect of short term use of PAP treatment on metabolic parameters in patients with obstructive sleep apnea. Eur Respir J 2020;56(suppl 64):2154.
    CrossRef
  15. Dorkova Z, Petrasova D, Molcanyiova A, Popovnakova M, Tkacova R. Effects of continuous positive airway pressure on cardiovascular risk profile in patients with severe obstructive sleep apnea and metabolic syndrome. Chest 2008;134:686-92.
    Pubmed CrossRef
  16. Yim Yeh S, Rahangdale S, Malhotra A. Metabolic syndrome, obstructive sleep apnea, and continuous positive airway pressure: a weighty issue. Chest 2008;134:675-6.
    Pubmed KoreaMed CrossRef
  17. Kim SW, Kim HJ, Min K, Lee H, Lee SH, Kim S, et al. The relationship between smoking cigarettes and metabolic syndrome: a cross-sectional study with non-single residents of Seoul under 40 years old. PLoS One 2021;16:e0256257.
    Pubmed KoreaMed CrossRef
  18. Hsu WY, Chiu NY, Chang CC, Chang TG, Lane HY. The association between cigarette smoking and obstructive sleep apnea. Tob Induc Dis 2019;17:27.
    Pubmed KoreaMed CrossRef
  19. Mehrtash M, Bakker JP, Ayas N. Predictors of continuous positive airway pressure adherence in patients with obstructive sleep apnea. Lung 2019;197:115-21.
    Pubmed CrossRef
  20. Berry R, Quan S, Abreu A. The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications, version 2.6. American Academy of Sleep Medicine; 2020.
  21. American Academy of Sleep Medicine. International classification of sleep disorders. 3rd ed. American Academy of Sleep Medicine; 2014.
  22. Kushida CA, Chediak A, Berry RB, Brown LK, Gozal D, Iber C, et al. Clinical guidelines for the manual titration of positive airway pressure in patients with obstructive sleep apnea. J Clin Sleep Med 2008;4:157-71.
    Pubmed CrossRef
  23. Drummond M, Winck JC, Guimarães JT, Santos AC, Almeida J, Marques JA. Autoadjusting-CPAP effect on serum leptin concentrations in obstructive sleep apnoea patients. BMC Pulm Med 2008;8:21.
    Pubmed KoreaMed CrossRef
  24. Schäfer H, Pauleit D, Sudhop T, Gouni-Berthold I, Ewig S, Berthold HK. Body fat distribution, serum leptin, and cardiovascular risk factors in men with obstructive sleep apnea. Chest 2002;122:829-39.
    Pubmed CrossRef
  25. Sanner BM, Kollhosser P, Buechner N, Zidek W, Tepel M. Influence of treatment on leptin levels in patients with obstructive sleep apnoea. Eur Respir J 2004;23:601-4.
    Pubmed CrossRef
  26. Li AM, Ng C, Ng SK, Chan MM, So HK, Chan I, et al. Adipokines in children with obstructive sleep apnea and the effects of treatment. Chest 2010;137:529-35.
    Pubmed CrossRef
  27. Chen X, Niu X, Xiao Y, Dong J, Lu M, Kong W. Effect of continuous positive airway pressure on leptin levels in patients with obstructive sleep apnea: a meta-analysis. Otolaryngol Head Neck Surg 2015;152:610-8.
    Pubmed CrossRef
  28. Khan A, Fouda S, Mahzari A, Chan SM, Zhou X, Ratnam C, et al. Cigarette smoking blocks the benefit from reduced weight gain for insulin action by shifting lipids deposition to muscle. Clin Sci (Lond) 2020;134:1659-73.
    Pubmed CrossRef
  29. Hirotsu C, Albuquerque RG, Nogueira H, Hachul H, Bittencourt L, Tufik S, et al. The relationship between sleep apnea, metabolic dysfunction and inflammation: the gender influence. Brain Behav Immun 2017;59:211-8.
    Pubmed CrossRef
  30. Sánchez-de-la-Torre M, Mediano O, Barceló A, Piérola J, de la Peña M, Esquinas C, et al. The influence of obesity and obstructive sleep apnea on metabolic hormones. Sleep Breath 2012;16:649-56.
    Pubmed CrossRef
  31. Balcan B, Thunström E, Yucel-Lindberg T, Lindberg K, Ay P, Peker Y. Impact of CPAP treatment on leptin and adiponectin in adults with coronary artery disease and nonsleepy obstructive sleep apnoea in the RICCADSA trial. Sleep Med 2020;67:7-14.
    Pubmed CrossRef
  32. Shih YL, Huang TC, Shih CC, Chen JY. Relationship between leptin and insulin resistance among community-dwelling middle-aged and elderly populations in Taiwan. J Clin Med 2022;11:5357.
    Pubmed KoreaMed CrossRef
  33. Osegbe I, Okpara H, Azinge E. Relationship between serum leptin and insulin resistance among obese Nigerian women. Ann Afr Med 2016;15:14-9.
    Pubmed KoreaMed CrossRef
  34. Gruzdeva O, Borodkina D, Uchasova E, Dyleva Y, Barbarash O. Leptin resistance: underlying mechanisms and diagnosis. Diabetes Metab Syndr Obes 2019;12:191-8.
    Pubmed KoreaMed CrossRef
  35. Li WC, Hsiao KY, Chen IC, Chang YC, Wang SH, Wu KH. Serum leptin is associated with cardiometabolic risk and predicts metabolic syndrome in Taiwanese adults. Cardiovasc Diabetol 2011;10:36.
    Pubmed KoreaMed CrossRef
  36. Tsai JP. The association of serum leptin levels with metabolic diseases. Ci Ji Yi Xue Za Zhi 2017;29:192-6.
    Pubmed KoreaMed CrossRef
  37. Zamboni M, Zoico E, Fantin F, Panourgia MP, Di Francesco V, Tosoni P, et al. Relation between leptin and the metabolic syndrome in elderly women. J Gerontol A Biol Sci Med Sci 2004;59:396-400.
    Pubmed CrossRef
  38. Pérez-Pérez A, Sánchez-Jiménez F, Vilariño-García T, Sánchez-Margalet V. Role of leptin in inflammation and vice versa. Int J Mol Sci 2020;21:5887.
    Pubmed KoreaMed CrossRef
  39. Zeng X, Ren Y, Wu K, Yang Q, Zhang S, Wang D, et al. Association between smoking behavior and obstructive sleep apnea: a systematic review and meta-analysis. Nicotine Tob Res 2023;25:364-71.
    Pubmed KoreaMed CrossRef