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46. Kawahara S, Akashiba T, Akahoshi T, Takasji H.Nasal CPAP improves the quality of life and
lessens the depressive symptoms in patients with obstructive sleep apnea syndrome. Intern
Med. 2005;44:422–7.
47. Means MK, Lichstein KL, Edinger JD, Taylor DJ, Durrence HH, Husain AM, etal. Changes in
depressive symptoms after continuous positive airway pressure treatment for obstructive sleep
apnea. Sleep Breath. 2003;7:31–42.
48. Lee IS, Bardwell W, Ancoli-Israel S, etal. Effect of three weeks of continuous positive airway
pressure treatment on mood in patients with obstructive sleep apnoea: a randomized placebocontrolled study. Sleep Med. 2012;13:161–6.
49. Martinez-Garcia MA, Chiner E, Hernandez L, etal. Obstructive sleep apnoea in the elderly:
role of continuous positive airway pressure treatment. Eur Respir J. 2015;46:142–51.
50. Engdahl Sawyer AM, Gooneratne NS, Marcus CL, Ofer D, Richards KC, Weaver TE.A systematic review of CPAP adherence across age groups: clinical and empiric insights for developing CPAP adherence interventions. Sleep Med Rev. 2011;15:343.
51. Amiri H, Zamani N, Hassanian-Moghaddam H, Shadnia S.Cardiotoxicity of tricyclic antidepressant treated by 2650 mEq sodium bicarbonate: a case report. JRSM Cardiovasc Dis.
2016;5:2048004016682178.
52. Cooke MJ, Waring WS. Citalopram and cardiac toxicity. Eur J Clin Pharmacol.
2013;69(4):755–60.
53. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S.The occurrence of sleep-disordered
breathing among middle-aged adults. N Engl J Med. 1993;328:1230–5.
54. Edlund MJ, McNamara ME, Millman RP.Sleep apnea and panic attacks. Compr Psychiatry.
1991;32(2):130–2.
55. Takaesu Y, Inoue Y, Komadad Y, Kagimura T, Iimori M.Effects of nasal continuous positive
airway pressure on panic disorder comorbid with obstructive sleep apnea syndrome. Sleep
Med. 2012;13:156–60.
56. El-Solh A, Ayyar L, Akinnusi M, Sachin R, Akinnusi O.Positive airway pressure adherence in
veterans with posttraumatic stress disorder. Sleep. 2010;33:1495–500.
57. Chen CM, Kuo CY, Wu MN, Hung JY, Hsu CY, Tsai MJ.Increased risk of major depressive
disorder in sleep apnea patients in Taiwan. Sci Rep. 2021;11(1):765. https://doi.org/10.1038/
s41598- 020- 80759- 3.
58. Waterman L, Stahl ST, Buysse DJ, Lenze EJ, Blumberger D, etal. Self-reported obstructive sleep apnea is associated with nonresponse to antidepressant pharmacotherapy in late-life
depression. Depress Anxiety. 2016;33(12):1107–13.
G. J. Teran et al.
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25
CamiloSilvaFroján, JuanaKarinaZapataCárdenas,
SaioaEcheverríaAndueza, andPatriciaAndradaÁlvarez
25.1 Obesity
The relationship between obesity and OSA is well-known and has been the subject
of multiple studies for years. Obesity is one of the main components contributing to
OSA. The incidence of OSA in obese patients is signicantly higher than in the
general population. Thus, OSA is present in 40% of patients with obesity, and 70%
of patients with OSA are obese [1]. In addition, a 10% weight gain is associated
with a sixfold increase in the risk of development of sleep apnea [2].
Obesity is a complex disease associated with a large number of comorbidities.
About 13% of the world’s adult population were obese in 2016, and the worldwide
prevalence of obesity nearly tripled between 1975 and 2016 [3]. As the prevalence
of obesity has increased, so have the many associated comorbidities, including OSA.
Obesity is dened as an excessive increase in body fat. There is also an excess of
body fat in overweight, although less than in obesity. Even though the dening
characteristic of the disease is excess body fat, the clinical diagnosis of overweight
and obesity is usually made with the body mass index (BMI). As dened by the
C. S. Froján (*)
Department of Endocrinology and Nutrition, Clínica Universidad de Navarra,
Pamplona, Spain
Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
(CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain
Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA),
Pamplona, Spain
e-mail: csilvafr@unav.es
J. K. Z. Cárdenas · S. E. Andueza · P. A. Álvarez
Department of Endocrinology and Nutrition, Clínica Universidad de Navarra,
Pamplona, Spain
e-mail: jzapatac@unav.es; secheverriaa@unav.es; pandrada@unav.es
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
P. M. Baptista et al. (eds.), Obstructive Sleep Apnea,
https://doi.org/10.1007/978-3-031-35225-6_25
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C. S. Froján et al.
World Health Organization BMI is the patient’s weight in kilograms divided by the
square of his height in meters (kg/m2). Overweight is dened by a BMI greater than
or equal to 25kg/m2, and obesity is diagnosed with a BMI greater than or equal to
30kg/m2 (see Table25.1) [4]. It is a simple formula, easy to obtain only by knowing
the weight and height of a subject. Still, does not entirely t the denition of obesity
since an individual’s excess weight is not always due to fat mass. For example, a
subject with a lot of muscle mass may have excess weight but not necessarily fat
mass. Thus, the estimation of the absolute amount of fat—adiposity—that a patient
has can be done with the so-called body composition methods, of which there are
several types. The most common body composition assessments are Bioelectrical
Impedance Analysis (BIA), Skinfold Test, Air Displacement Plethysmography
(BodPod®), and DEXA Scan. Using these methods, we can obtain the percentage of
body fat concerning the total weight of a specic individual. For example, a man is
considered overweight with a body fat percentage between 20 and 24.9% and obese
when it is equal to or greater than 25%. In women, these fat percentages to dene
overweight and obesity are 30–34.9% and ≥35%, respectively, because women have
a higher fat percentage than men. In this way, using air displacement plethysmography, it has been described that up to 30% of women with normal BMI have a percentage of body fat compatible with obesity. In men, this n ding occurs in 25% of
subjects with normal weight [5].
But not only is adiposity essential in the development of obesity comorbidities.
The distribution of body fat also plays an important role. The central deposition of
fat (android, perivisceral; characteristic of males), as opposed to the gluteal-femoral
(gynoid, subcutaneous; characteristic of females), is associated with a higher risk of
comorbidities, mainly cardiometabolic. Differences have been found between both
forms of fat storage concerning the size and number of adipocytes, their innervations, vascularization, and their metabolic and secretory activity (adipokines),
which may explain their different cardiometabolic risk prole [6]. There are various
methods and indices to assess the type of fat deposit in an individual. The most used
are the waist circumference, waist/height ratio, the waist to hip ratio, or the measurement of abdominal fat using radiological methods such as computed tomography scan (CT scan) or magnetic resonance imaging (MRI).
Table 25.1 WHO
classication of weight status
Weight status Body mass index (BMI, kg/m2)
Underweight <18.5
Normal range 18.5–24.9
Overweight 25.0–29.9
Obese
Obese class I 30–34.9
Obese class II 35–39.9
Obese class III
BMI=weight (kg)/height2 (m2)
≥30
≥40
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25.1.1 Obesity andthePathophysiology ofOSA
The pathophysiology of OSA is complex and involves several factors, such as airway anatomy or neuromuscular function (Fig.25.1). Obesity occupies a very relevant place in the pathophysiology of OSA due to several factors. Firstly, a pharyngeal
fat deposit would cause a decrease in the luminal diameter, facilitating the collapse
of the airway during sleep. In addition, the pharyngeal cross-sectional area may be
smaller because of reduced functional residual capacity (lower lung volume), a
common n ding in patients with obesity and a large abdomen [7]. Thus, OSA has
been related to neck circumference since it is a marker of adiposity in that area [8,
9], waist circumference, and other indices of central obesity [10]. Another relevant
factor is decreased upper airway muscle protective strength or altered muscle structure secondary to fatty inltration [11]. In short, obesity is related to greater upper
airway collapsibility that predisposes to OSA, which improves signicantly with
weight loss [7].
Adipokines or adipocytokines are peptides and proteins secreted mainly by adipocytes and play diverse roles in body homeostasis. Adipose tissue has emerged as
a metabolically active tissue implicated in many processes, such as metabolism,
inammation, and cardiovascular diseases. Current evidence suggests that adipokines (leptin, adiponectin, chemerin, etc.) may play a role in the complex relationship between OSA and metabolic disorders [12].
Fig. 25.1 Pathophysiology interaction between obesity and OSA
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C. S. Froján et al.
25.1.2 OSA andWeight Gain
OSA is one of the most common sleep disturbances that can severely compromise
sleep quality in affected individuals. There is evidence that insufcient sleep may
promote metabolic, hormonal, and behavioral changes that lead to weight gain [13],
which could help perpetuate the vicious circle of obesity-OSA.
Daytime fatigue and sleepiness secondary to inadequate sleep quality contributes
to asthenia, sedentary lifestyle, and less physical exercise, which causes a decrease
in energy expenditure and facilitates weight gain. In addition, an inverse relationship exists between physical activity levels and OSA severity [14].
OSA severity is associated with unhealthy dietary preferences contributing to
obesity and greater cardiometabolic risk [14].
Several peptides and hormones play a role in the complex appetite/satiety regulating system. Leptin is a signicant adipokine secreted mainly by the adipocytes of
the white adipose tissue and is positively correlated with fat mass. It has a fundamental role in regulating energy balance by reducing energy intake (anorexigenic
effect) and increasing energy expenditure. Leptin acts at the hypothalamus, decreasing appetite, and is elevated in obese patients (hyperleptinemia) due to excess fat
mass. However, leptin resistance has been described in these individuals, which,
despite presenting high levels of it, appetite does not decrease [15].
An increasing amount of evidence suggests that long-term exposure to chronic
intermittent hypoxia, as occurs in OSA, may contribute to leptin resistance, negatively affecting food intake control [16]. In some studies, CPAP treatment decreased
leptin, but this effect was not observed in others [17].
Ghrelin is a peptide secreted from the oxyntic glands in the gastric fundus.
Among other actions, ghrelin stimulates the appetite (orexigenic effect), and thus its
plasma levels increase during fasting and decrease during the postprandial period.
There is some evidence for an increase in the level of ghrelin in patients with OSA,
which could be related to intermittent hypoxia and sleep fragmentation. In some
studies, CPAP treatment contributed to decreased ghrelin, but others did not observe
this effect [17].
OSA increases the resting metabolic rate, the main component of energy expenditure. This nding is paradoxical since this phenomenon should favor weight loss
or maintenance. It has been suggested that the impact on the energy balance produced by the increase in resting metabolic rate would be counteracted by a surge in
caloric intake [18].
25.1.3 OSA andWeight Loss
Obesity treatment focuses on achieving a healthy diet and physical activity habits
that promotes weight loss. On this basis, pharmacological or surgical treatments can
be added. As a matter of fact, due to their close association, one of the main goals of
patients with OSA and obesity is weight loss, for it can reduce fatty deposits in the
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neck and tongue [19] as well as abdominal fat [20], improving airow during sleep.
Lifestyle-induced weight loss studies in patients with OSA have demonstrated that
at least 5–10% loss of the initial body weight can improve the severity of the syndrome [21], even in patients with moderate or severe OSA [22]. Obese patients
should be encouraged to lose weight to improve OSA, and counseling regarding diet
modication and exercise with a weight management team (dietitian, endocrinologist, psychologist, etc.) may be benecial [23].
In recent years, the pharmacological treatment of obesity has experienced signicant progress thanks to the inclusion of glucagon-like peptide-1 (GLP-1) receptor agonists. The Sleep Apnea Scale study demonstrated a reduction in weight
(−5.7% of initial weight) and improvement in the apnea–hypopnea index (AHI)
(−12 events h−1) with Liraglutide [24]. The most novel Semaglutide improves
Liraglutide results in weight loss, so a more signicant effect for improving AHI
occurs, although this aspect is currently under study [25]. Pharmacological treatment of obesity is indicated in patients with any degree of obesity and even in those
with overweight and associated comorbidities.
Bariatric surgery has developed remarkably in the last two decades as an effective and safe intervention for obesity management. For instance, on average, it can
generate more weight loss in obese patients (≈30% of initial weight) compared to
conservative treatment. Although many surgical techniques have been implemented,
the two most used today are the sleeve gastrectomy and Roux-en-Y gastric bypass.
OSA is a common comorbidity in bariatric patients, with an estimated incidence of
35–96%. A recent meta-analysis conrmed a signicant decrease in AHI after bariatric surgery (−25.1h−1) [26]. In addition, the patients who improved their weight
after the intervention and those who previously presented a greater severity of OSA
experienced a higher decline in AHI [27]. Furthermore, the American Academy of
Sleep Medicine recommends discussing referral to a bariatric surgeon to adults with
OSA and obesity (BMI ≥35kg/m2) who are intolerant or unaccepting of positive
airway pressure (PAP) as part of a patient-oriented discussion of alternative treatment options [28]. Also, other organizations, such as the National Heart, Lung, and
Blood Institute, recommend bariatric surgery for individuals with BMI ≥35kg/m2
and OSA, regardless of PAP adherence.
Finally, although CPAP treatment can improve various aspects of weight gain,
studies are inconclusive on its benet for weight loss [29]. Some of them even relate
it to weight gain [30], highlighting the complexity of obesity pathophysiology.
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25.2 Diabetes
Type 2 diabetes is associated with an increased risk of developing OSA.Patients
with type 2 diabetes have an increased adjusted incidence rate ratio (1.48) of OSA
than those without [31]. Several factors could explain this association. Diabetic
autonomic neuropathy, which can affect the control of breathing at different levels,
has been related to a higher incidence of OSA [32]. AHI disturbances have also
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been independently associated with higher odds of diabetic microvascular complications (nephropathy, retinopathy, and peripheral neuropathy) [33]. The high prevalence of OSA in type 1 diabetes patients suggests a pathophysiological role of
hyperglycemia and chronic micro and macrovascular complications [34].
In another aspect, it has been described how the intermittent hypoxia that appears
in OSA can worsen insulin resistance through, among other factors, activation of the
sympathetic nervous system, disturbances of oxidative stress, or systemic inammation [35]. However, in the various studies carried out to date, PAP therapy has
failed to improve glycemic control in type 2 diabetes patients [36], although sleep
apnea treatment improves this group’s blood pressure and quality of life. In this
sense, the American Diabetes Association (ADA) clinical guidelines recommend
checking patients with diabetes for the presence of symptoms suggestive of obstructive sleep apnea (e.g., excessive daytime sleepiness, snoring, or witnessed apnea)
and considering OSA screening in this group [37].
C. S. Froján et al.
25.3 Metabolic Syndrome andLipids
Metabolic syndrome is a term applied to the coexistence in the same individual of
abdominal overweight/obesity, dyslipidemia, type 2 diabetes, and high blood pressure. This combination of factors increases cardiovascular risk. Although there are
different diagnostic criteria for metabolic syndrome, it is estimated that up to a third
of the adult population may present with it.
Obstructive sleep apnea has been associated with metabolic syndrome or its core
components. The pathophysiological mechanisms previously described in the relationship between obesity, diabetes, and OSA are also linked to metabolic syndrome.
Thus, the benecial effects of CPAP on glucose metabolism and insulin resistance
in patients with OSA are not constant in all the studies carried out [38]. However,
arterial hypertension is associated with OSA, and several studies have demonstrated
that PAP therapy signicantly reduces blood pressure and improves cardiovascular
risk and metabolic syndrome [39]. Dyslipidemia is another essential component of
metabolic syndrome, typically manifested by hypertriglyceridemia and low HDLcholesterol (atherogenic dyslipidemia). The association between the presence of
OSA and atherogenic dyslipidemia is inconsistent and is inuenced by possible
confounders such as obesity, diabetes, or insulin resistance. Still, data from the
European Sleep Apnea Database Cohort (ESADA) showed that OSA severity was
independently associated with cholesterol and triglyceride concentrations [40].
Furthermore, OSA was positively associated with serum triglyceride levels in
men with a normal waist circumference [41]. Several mechanisms can mediate this
relationship, including chronic intermittent hypoxia, sympathetic activation, or
sleep fragmentation. Although studies on the possible benet of CPAP treatment on
the lipid prole are inconsistent, a recent meta-analysis showed that CPAP treatment decreases total cholesterol at a small magnitude but has no effect on other
dyslipidemia markers in OSA [42].
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25.4 Other Endocrinological Diseases (Fig.25.2)
25.4.1 Acromegaly
Acromegaly is a low-prevalence disease resulting from growth hormone (GH)
excess, usually in the context of a GH-producing pituitary tumor. It is associated
with a phenotype characterized by an increase in the size of the acral parts of the
body (hands and feet) and several changes in facial features (prognathism, and
enlargement of the forehead, lips and nose). OSA prevalence is 69% in patients with
acromegaly [43]. By the time the diagnosis of acromegaly is made, which is usually
late and with evident morphological alterations since it is a slowly evolving disease,
has an inuence on the development of OSA.Consequently, the presence of pharyngeal/tongue thickening, increased collagen production, or tissue edema contributes
to narrowing the upper airway, facilitating OSA [44].
25.4.2 Hypothyroidism
Hypothyroidism is a common endocrine disorder involving the failure of the thyroid
gland to produce thyroid hormone. Overt hypothyroidism has an estimated OSA
prevalence between 25 and 50% [45]. Subclinical hypothyroidism is a common
disorder diagnosed when peripheral thyroid hormone levels (free thyroxine or T4)
are within normal reference laboratory range. Still, serum thyroid-stimulating hormone (TSH) levels are mildly elevated. In a moderate or severe OSA population,
16.4% of patients had some thyroid disorder, and 8% were newly diagnosed with
Fig. 25.2 Endocrine diseases and pathophysiology of OSA
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subclinical hypothyroidism [46]. The presence of tissue edema, macroglossia, or
goiter may explain this higher prevalence, but other mechanisms have been suggested, such as alterations in ventilatory drive and respiratory muscle function.
Levothyroxine replacement therapy improves symptoms of OSA and sleep efciency for some patients with overt hypothyroidism. Therefore, it can be deduced
that hypothyroidism- ism contributes to OSA, but not a determining one. Another
study showed no difference in the frequency and severity of OSA among euthyroid
patients and those with either treated or untreated subclinical hypothyroidism [47].
C. S. Froján et al.
25.4.3 Cushing’s Syndrome
Cushing’s syndrome results from prolonged exposure to exogenous or endogenous
glucocorticoids. The most common cause is iatrogenic Cushing’s syndrome due to the
exogenous administration of glucocorticoids with therapeutic intent. It is associated
with the appearance of a typical phenotype characterized by obesity with a central
accumulation of fat and muscle atrophy. It also presents multiple metabolic manifestations such as type 2 diabetes, high blood pressure, or dyslipidemia. This characteristic
phenotype explains the increased prevalence of OSA detected in patients with the
syndrome through an accumulation of fat in the cervical area and more signicant
muscle weakness. In one study, the prevalence of OSA was higher (50% vs. 23%) in
patients with Cushing’s syndrome compared with control subjects [48].
25.4.4 Primary Hyperaldosteronism
Primary hyperaldosteronism is caused by excess aldosterone secretion by one or
both adrenal glands, leading to sodium retention, intravascular volume expansion,
and arterial hypertension. It is frequently associated with hypokalemia, although it
is not an essential nding for diagnosis. OSA prevalence in patients with primary
hyperaldosteronism is high, 45.8–67.6%. Treatment for hyperaldosteronism, either
surgical (adrenalectomy) or pharmacological (spironolactone or amiloride), can signicantly improve the AHI. A higher prevalence of primary hyperaldosteronism has
also been described in patients with OSA (34%). Several studies have demonstrated
higher aldosterone levels in patients with OSA; this excess, as seen in hyperaldosteronism; may exacerbate its severity. The overnight uid shifting into the neck and
consequent pharyngeal edema can also contribute to upper airway obstruction and
OSA [49].
25.4.5 Male Hypogonadism
Male hypogonadism is a clinical syndrome characterized by a decit in the testosterone production by the testis. It can be of primary (testis) or central (hypothalamic–pituitary) origin. Symptoms depend on the age of onset, but in adults, it is
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439
characterized by erectile dysfunction, decreased libido, gynecomastia, muscle
weakness, or low bone mineral density, among others. A worsening of sexual function has been described in men with OSA, which could be related to a decrease in
testosterone levels. However, this relationship is complex and poorly understood
[50]. On the other hand, testosterone treatment in hypogonadal men could be associated with a greater tendency to uid retention and edema, which can worsen
OSA. Moreover, testosterone treatment can increase the hematocrit. In addition, the
Endocrine Society recommends against testosterone replacement therapy in hypogonadal men with elevated hematocrit or untreated severe obstructive sleep
apnea [51].
Take-Home Message
• There is a relationship between OSA and obesity, diabetes, or metabolic
syndrome.
• The central deposition of fat (android, perivisceral; characteristic of males), as
opposed to the gluteal-femoral (gynoid, subcutaneous; characteristic of females),
is associated with a higher risk of comorbidities, mainly cardiometabolic.
• Other classical endocrine disorders such as Acromegaly, Hypothyroidism,
Cushing’s syndrome, primary hyperaldosteronism, and male hypogonadism
show a high incidence of OSA.
• The pathophysiological mechanisms involved in these associations are diverse
and, in some cases, poorly understood.
• Although benecial in many aspects, treatment of OSA with positive airway
pressure (PAP) does not always show improvement.
References
1. Punjabi NM, Sorkin JD, Katzel LI, Goldberg AP, Schwartz AR, Smith PL.Sleep-disordered
breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care
Med. 2002;165:677–82.
2. Peppard PE, Young T, Palta M, Dempsey J, Skatrud J.Longitudinal study of moderate weight
change and sleep-disordered breathing. JAMA. 2000;284(23):3015–21.
3. World Health Organization. https://www.who.int/news- room/fact- sheets/detail/o.
4. World Health Organization. Obesity: preventing and managing the global epidemic. Report of
a WHO consultation on obesity. World Health Organization Technical Report Series, vol. 894.
Geneva: World Health Organization; 1998.
5. Gó Mez-Ambrosi J, Silva C, Galofré JC, Escalada J, Santos S, Millán D, etal. Body mass
index classication misses subjects with increased cardiometabolic risk factors related to elevated adiposity. Int J Obes. 2012;36:286–94.
6. Rodriguez A, Catalan V, Gomez-Ambrosi J, Fruhbeck G.Visceral and subcutaneous adiposity:
are both potential therapeutic targets for tackling the metabolic syndrome? Curr Pharm Des.
2007;13(21):2169–75.
7. Pillar G, Shehadeh N. Abdominal fat and sleep apnea. Diabetes Care.
2008;31(Supplement_2):S303–9.
8. Kim SE, Park BS, Park SH, Shin KJ, Ha SY, Park J, etal. Predictors for presence and severity of obstructive sleep apnea in snoring patients: signicance of neck circumference. J Sleep
Med. 2015;12(2):34–8.
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