131 PNEUMON N0moer 2, vo|.

19, 4pr|| - 10ne 2006

P. coaom|des,
P. 8a|a|os,
P. kylbreol|s,
|. h||o|opou|os,
A. 8as|da||s
Resp|ralory la||ure Cerler, 8ol|r|a Al|ers 0erera|
hosp|la| ol C|esl D|seases
key Words: 0bslrucl|ve s|eep apaea syadrome,
obese, serum |epl|a
Le|ia |ere|s aa4 aa|hroome|ric charac|eris|ics
oj a|iea|s i|h obs|rac|ire s|ee aaea s;a4rome
SUMMARY. Obstructive sleep apnea syndrome (OSAS) is char-
acterized by repeated episodes of upper airway obstruction during
sleep. Most subjects with OSAS are obese. Leptin, a hormone pro-
duced by adipocytes, plays a regulatory role on body weight. In-
creased leptin levels occur in obese patients with OSAS. Our ob-
jective was to determine the anthropometric characteristics and
examine the relationship between circulating leptin levels and
sleep-related breathing disorders in a group of obese patients with
OSAS. Twenty-eight patients with confirmed OSAS underwent
overnight polysomnography, in addition, anthropometric measure-
ments were performed and serum leptin levels were determined.
No correlation was detected between AHI and any of the examined
anthropometric characteristics. The mean levels of circulating lep-
tin (iSD) were 15.5 ng/mL (i11.9). Serum leptin levels did not
correlate with AHI, even when adjusted for fat mass. Moreover,
no correlations were found between leptin levels and sleep time
with oxygen saturation <90%, or lowest level of oxygen saturation
during sleep. Serum leptin levels correlated with BMI and abdo-
men circumference. Circulating leptin levels and anthropometric
measures in subjects with OSAS are not related to the severity of
sleep apnea, as assessed by AHI or other sleep-disorder parame-
ters, such as sleep time with oxygen desaturation <90% and low-
est level of oxygen saturation during sleep. Paeamoa 2006,
19(2)131-136.
|NTPODUCT|ON
Obstiuctive sleep apnea syndiome (OSAS) is chaiacteiized by iepeat-
ed episodes of uppei aiiway obstiuction duiing sleep that iesult in hemo-
globulin desatuiation and sleep disoideis
1
. The incidence of the syndiome
ianges fiom 2-4% among adults
2
. The syndiome is associated with incieased
caidiovasculai moibidity and moitality
3,4
. It has been suggested that OSAS
ielated moibidity is also attiibutable to obesity. Obesity is iecognized as a
Corresporderce lo.
A. Ras|da||s
Ass. Prolessor |r Pu|uorary Ned|c|re, D|reclor ol
lCu/RlC
122, Nessoeor 8lr., 0R-11527 Al|ers
Te|.. 21O-777O21O
la/. 21O-777O21O
CIinicaI Study
132 /NEMON 7s0o 2o, 7oo 19o, 4np|/|o - /o0t|o 2006
ma|oi iisk factoi foi the occuiience of OSAS: moie than
50% of patients with OSAS aie obese
5
. In addition, the-
se patients aie having difficulty losing weight and tend
to fuithei gain weight compaied to patients without
OSAS
6
. The mechanisms leading to obesity in patients
with OSAS aie not fully undeistood. Ieptin, a hoimone
pioduced by adipocytes, plays a iegulatoiy iole in body
weight by contiolling appetite and eneigy consumption-
7,8
. Fuithei, it affects neuioendociine mechanisms and
iegulates the hypothalamus-pituitaiy axis
9
. Most obese
people have high ciiculating levels of leptin: leptin leve-
ls inciease exponentially with incieased body fat mass. It
has been suggested that in these peisons obesity is ass-
ociated with a foim of iesistance to the action of leptin
10
.
Studies have shown that the high levels of leptin found
in obese patients with OSAS deciease with the use of
continuous positive aiiway piessuie (CPAP)
11
.
The association between OSAS, anthiopometiic chai-
acteiistics and seium leptin levels has been an active fie-
ld of contempoiaiy ieseaich: howevei, it iemains inade-
quately compiehended
11,12
. Some studies have attempt-
ed to establish a possible association between leptin lev-
els and seveiity of OSAS
12,13
.
The ob|ective of the piesent study is to desciibe the
anthiopometiic chaiacteiistics and investigate the pos-
sible association between leptin levels and the seveiity
of OSAS in a gioup of adult obese patients with OSAS.
MATEP|AL AND METHODS
S/a0j 0es/q0 a00 a//e0/s
All patients weie infoimed in wiitten and gave theii
consent foi theii inclusion in the study. The study gioup
included 28 patients (24 male, 4 female) with confiimed
OSAS. Study sub|ects had piesented to oui sleep study
clinic foi possible OSAS fiom Febiuaiy to June 2003.
They all weie non-smokeis oi foimei smokeis, with no
histoiy of thyioid disease, noimal levels of thyioid hoi-
mones and noimal lung function paiameteis. The mean
(:SD) age of the patients was 55.1 yeais (:12.9: iange:
34-79 yeais).
S/a0j me/0o0
All patients undeiwent oveinight polysomnogiaphy
in oui sleep study clinic using the polysomnogiaphy sys-
tem Alice 4 Heathdyne: Respiionics: Pittsbuigh, PA.
Recoidings included two-lead electioencephalogiam
(IIC), submental electiomyogiam (IMC), and contin-
uous electiocaidiogiam (ICC). The movements of low-
ei extiemities weie detected by anteiioi tibial electiomyo-
giam: bieathing sounds weie iecoided by a miciophone
placed at the height of the |ugulai vein. Aiiflow iecoid-
ings weie peifoimed with a combination of oionasal thei-
mistois: thoiacic and abdominal wall movements weie
evaluated by means of inductive plethysmogiaphy. He-
moglobulin oxygen satuiation in aiteiial blood was mea-
suied using pulse oximetiy. Sleep stages weie deteimined
by two expeiienced physicians accoiding to established
ciiteiia
14
. OSAS was defined by the known ciiteiia
12
.
Hypopnea was defined as a >50% ieduction in aii flow
(compaied to the aii flow in the aleit sub|ect at iest) last-
ing foi at least 10 seconds, followed by eithei oxygen de-
satuiation by >4% oi awakening. The total numbei of
apnea and hypopnea episodes was divided by the total
sleep time to obtain the apnea-hypopnea index (AHI).
A value of AHI >10/houi classified the sub|ect as hav-
ing OSAS. Regaiding seveiity, OSAS was consideied
mild if 10<AHI20: modeiate if 20<AHI40: oi seveie
if AHI =40.
Blood was diawn fiom the patients at 08:00 a.m. af-
tei oveinight fasting. Blood samples weie centiifuged:
plasma was sepaiated and stoied in the fieezei until the
time of measuiements.
Ieptin levels weie deteimined using an immunoiad-
iometiic assay (Human Ieptin IRMA, Diagnostic Sys-
tems Iaboiatoiies Inc, Texas, USA): thyioid hoimones,
T3 and T4, weie measuied using a iadioimmunologic as-
say (T3
125
I) RIA kit, Institute of Isotopes Co, Itd,
Budapest, T4 Totale RIA, Medicoip Inc, Montieal, Can-
ada): and TSH levels weie deteimined using an immu-
noiadiometiic assay (TSH IRMA, Medicoip Inc, Mont-
ieal, Canada).
Anthiopometiic chaiacteiistics weie deteimined ac-
coiding to the cuiiently applicable pioceduies. Body
mass index (BMI) calculations weie based on body weight
(BW) and height (H) accoiding to the foimula: BMI =
BW (in kg)/[H (in m)j
2
. BMI values weie used to classify
study sub|ects in the following five classes: class 0:
20<BMI25, class I: 25<BMI30, class II: 30<BMI35,
class III: 35<BMI40, class IV: BMI>40
15
. Fat mass (%)
133 PNEUMON N0moer 2, vo|. 19, 4pr|| - 10ne 2006
was measuied using a special device (Bioelectiic imped-
ance analysis BIA - 101S System RJM systems, Mt Cle-
mens MI).
Height measuiements weie made using a wall-mount
height measuiing device with study sub|ects in upiight
position, without shoes: a deviation of 0.5 cm was allowed
in these measuiements. A measuiing tape was used foi
the measuiements of neck and abdomen ciicumfeience.
Iung function tests weie peifoimed with the spiiometei
Spiio 232 (Moigan Medical Itd, Kent, Ingland). Iung
function paiameteis weie expiessed as peicent of the
piedicted values (% pied).
S/a//s//ca/ a0a/js/s
Results weie expiessed as mean : standaid devia-
tion (SD). Compaiisons between gioups weie made us-
ing the Mann-Whitney U test foi non-paiametiic vaii-
ables. The coiielation of leptin levels with othei paiam-
eteis was assessed with Speaiman iank coiielation test.
Statistical significance was defined as a P value <0.05.
The statistical package SPSS (SPSS Inc: Chicago II) was
used foi the statistical analysis.
PESULTS
S/ee s/a0j
The iesults of the polysomnogiaphy studies showed
that two (7.1%) of the study sub|ects had 10<AHI<20:
two (7.1%) had 20<AHI<40: and 24 (85.7%) had
AHI>40. Theie was no association between age and
HAI.
40/0roome/r/c c0arac/er/s//cs
The demogiaphic and anthiopometiic chaiacteiistics
of the study sub|ects aie listed in Table 1. The mean
(:SD) weight was 111.4 (20) kg: height 171.6 (8.5) cm:
and BMI 37.5 (4.8). Consideiing the above-desciibed
obesity classification accoiding to BMI, none of the sub-
|ects enteied classes 0 oi I: 9 (32%) sub|ects enteied class
II: 7 (25%) sub|ects enteied class IV. Theie was no asso-
ciation between AHI and any of the examined anthio-
pometiic chaiacteiistics. In paiticulai, AHI was not ie-
lated to the ciicumfeience of the neck (P=0.382:
i=0.172) oi the abdomen (P=0.198: i=0.251).
Ta||e 1
C|aa:/e|s/|: Pa/|en/s a|/| OSAS
(N=28)
Age (yeais) 55.1:12.9
Cendei (M/F) 24/4
Height (m) 171.6:8.5
Weight (kg) 111.4:20
BMI (kg/m
2
) 37.5:4.8
Neck ciicumfeience (cm) 45.5:4
Abdomen ciicumfeience (cm) 125.5:11.4
Fat mass (%) 35.3:5.9
Ieptin levels (ng/mI) 42.05:28.32
AHI 63.9:21.7
Minimum satuiation (%) 75.4:8.6
Iength of sleep time with oxygen 69.8:68.4
satuiation <90% (min)
FIV
1
/FVC 81.6:4
FIV
1
94:12.5
All paiameteis aie expiessed as mean value :SD.
Seram /e//0 /ere/s
The mean (:SD) value of seium leptin levels was
42.05 (:28.32) ng/mI. Theie was a positive ielationship
between seium leptin levels and BMI (P=0.034:
i=0.402). Ieptin levels weie not associated with the se-
veiity of OSAS as indicated by AHI (P=0.179: i=0.261).
Iven aftei ad|usting foi fat mass (by calculating the lep-
tin-to-fat mass iatio), leptin levels weie not associated
with AHI (P=0.234: i=0.232). A positive ielationship was
found between seium leptin levels and AHI (P=0.004:
i=0.522). Howevei, leptin levels weie not associated with
the length of sleep time with oxygen satuiation <90%
(P=0.748: i=0.064) oi the lowest aiteiial satuiation dui-
ing sleep (P=0.706: i=-0.074).
Iven when the subgioup of patients with seveie OSAS
was examined sepaiately, leptin levels weie associated
with none of the anthiopometiic chaiacteiistics oi sleep-
associated paiameteis. Fat mass ad|usted leptin levels
weie consistently associated only with body mass index
(P=0.04: i=0.423).
D|SCUSS|ON
This study desciibed the anthiopometiic chaiactei-
134 /NEMON 7s0o 2o, 7oo 19o, 4np|/|o - /o0t|o 2006
istics, and examined the ielationship between seium lep-
tin levels and OSAS seveiity in patients with confiimed
OSAS.
Theie was no association between the seveiity of
OSAS (as indicated by AHI) and anthiopometiic paiam-
eteis of obesity in patients with confiimed OSAS. How-
evei, a iecent study showed that OSAS ielated to an-
thiopometiic paiameteis of obesity in patients with
OSAS: in paiticulai, the peicentage of abdominal fat was
found to be associated with the occuiience of the syn-
diome
12
. Some studies suggest that BMI is an aggiavat-
ing factoi foi the occuiience of OSAS: howevei, othei
studies have shown that cential obesity, as assessed by
waist-to-hip iatio, is a bettei piedictoi foi the occuiience
of OSAS than BMI
10,12,16
.
Ieptin is a hoimone pioduced by adipocytes that ieg-
ulates body weight by contiolling appetite and eneigy
consumption.
17
The action of leptin staits with its bind-
ing on specific ieceptois in the hypothalamus, which
modulates the expiession of neuiopeptides that iegulate
neuioendociine functions, as well as the intake and con-
sumption of eneigy
10
. Ieptin levels inciease exponentially
with the inciease in fat mass: most obese individual have
high seium leptin levels
18
. Studies on animals have found
that leptin pievents iespiiatoiy aiiest in obesity, and that
leptin deficiency in the cential neivous system oi the
absence of its action may cause hypoventilation and Pick-
wick syndiome in the obese.
Oui study showed a significant ielationship between
leptin levels and BMI, a finding consistent with those
iepoited in othei studies
11,12
. Ieptin levels weie also
found to be ielated to the ciicumfeience of the abdo-
men. A causative ielationship between leptin levels and
OSAS has been suggested
20
. Howevei, leptin levels, even
when ad|usted foi fat mass, weie not found to be associ-
ated with OSAS, oi othei disoideied sleep-paiameteis,
such as the length of sleep time with oxygen satuiation
<90% oi the lowest aiteiial satuiation duiing sleep. This
is a contioveisial issue, since some investigatois suppoit
an association between leptin levels and OSAS, while
otheis aigue against such an association. This may be in
pait attiibutable to diffeiences in the chaiacteiistics of
the patient seiies examined by diffeient investigatois. A
numbei of vaiiables, including gendei, body weight, pies-
ence of aiteiial hypeitension, and vaiious medical tieat-
ments may affect leptin levels
7,21
. The sub|ects included
in oui study had highei BMI and moie seveie OSAS, as
assessed by AHI, (85% of oui patients had AHI >40)
compaied to the patients included in othei studies
12,13
. It
is likely that leptin levels aie associated with the seveiity
of OSAS in patients with mild oi modeiate syndiome,
wheieas in seveie OSAS othei factois may be involved
in the pathogenesis of obesity. Oui study would not be
able to show such an effect, since only foui patients with
mild-to-modeiate syndiome weie included. In addition,
all oui patients had noimal lung function tests, this indi-
cating the absence of a concomitant lung disease: it is
alieady known that chionic obstiuctive pulmonaiy dis-
ease (COPD) affects leptin levels eithei alone oi in con-
|unction with bionchodilatoi tieatment
22
. In addition, oui
patients had noimal thyioid function, which plays also a
significant iole in the iegulation of body weight. It has
been suggested that theie may be an inteiaction between
the leptin system and thyioid hoimones. Thyioid dysfunc-
tion may altei seium leptin levels without changing body
weight oi composition
23
. It is also iecognized that hy-
pothyioidism, which is commonly undeidiagnosed, is as-
sociated with OSAS. A thyioid dysfunction was neithei
excluded noi evaluated in othei studies: in this iegaid,
iepoited iesults may be misleading. All patients in oui
study weie euthyioid. Iastly, it is likely that theie aie
additional deteiminants, besides fat mass, foi high lep-
tin levels in patients with OSAS. This is suggested by the
deciease in leptin levels obseived aftei initiating tieat-
ment with nasal CPAP, without any othei concuiient
change in the anthiopometiic chaiacteiistics of the pa-
tients
24
.
Alteinatively, the absence of association between
AHI and leptin levels may be attiibutable to the fact that
AHI is not the best possible paiametei foi the assess-
ment of the seveiity of OSAS in all iespects. This specu-
lation is enhanced by the weak association of AHI with
the daily activity level of the patient oi the occuiience of
caidiovasculai disease. The question of whethei OSAS
seveiity is associated with leptin levels iemains unan-
sweied. It seems likely that othei mechanisms, not in-
volving leptin, may be implicated in the development of
OSAS. Foi example, gihelin, anothei hoimone that has
been discoveied iecently, plays a significant iole in the
iegulation of appetite, body weight and composition, and
135 PNEUMON N0moer 2, vo|. 19, 4pr|| - 10ne 2006
we believe that including patients with highei BMI and
moie seveie OSAS compaied to othei patient seiies
might have had a beaiing on oui iesults.
Neveitheless, despite the above-mentioned limita-
tions, we think that oui iesults iepiesent an inteiesting
aspect foi the potential iole of leptin in the pathogene-
sis of obesity in patients with OSAS. Although seium lep-
tin levels weie found to be associated with both BMI and
abdomen ciicumfeience, oui study failed to confiim the
association between leptin levels and AHI, as an indica-
toi of OSAS seveiity, which has been iepoited in othei
studies. This inconsistency suggests eithei that AHI does
not ieflect OSAS seveiity in all iespects of the syndiome,
oi that additional mechanisms, not involving leptin, play
theii pait in the pathogenesis of obesity on OSAS.
Fuithei studies aie necessaiy to elucidate the iole of
this hoimone in OSAS, as well as its association with the
anthiopometiic chaiacteiistics of these patients.
has been iepoited to be incieased in patients with
OSAS
24
. Howevei, the demonstiated association between
leptin levels and abdomen ciicumfeience, which is com-
monly incieased in patients with OSAS, indicates the
complexity of the ielationship between leptin, obesity and
OSAS. It has also been aigued that the action of seium
leptin may deteimine the type of obesity (cential oi pe-
iipheial) oi the body aiea foi fat deposition (uppei aii-
ways oi abdomen). Oui iesults indicate that leptin is not
ielated to fat deposition in the uppei aiiways only, as
suggested in othei studies, but in the abdomen as well.
12
Oui study has ceitain limitations. One limitation is
that the waist-to-hip iatio was not evaluated, although it
is consideied a stiongei deteiminant foi the occuiience
of OSAS than BMI
16
. Anothei limitation is that the pies-
ence of aiteiial hypeitension and/oi caidiovasculai dis-
ease was not addiessed. It has been demonstiated that
aiteiial hypeitension affects leptin levels
16
. Fuitheimoie,
HEPIAH+H
Eaasa 1satvq; xat av0aaoasttx aaxtqtattx as aa0svs; as cavoaavox avoao
H. Otxovoaq;, H. Maaxxo;, H. Kc0sotq;, I. Ntxo1aoc1o;, A. Paatxq;
To ocr^ouo ao,axr/xq; ro/a; oror cro (YAz) aaxrq/,cra/ a caraau3arucra
cc/o^/a a,a[q; rar ararcar aca,a,ar xar rq ^/xc/a roc croc O/ c/oorco/
ao0crc/; uc YAz c/ra/ acoaxo/ H cr/rq u/a ourq oc a,cra/ a ra /oxcrraa
a/,c/ c0u/or/x o ,/a ro oauar/x 3o; Ac[qutra c/c^a cr/rq; aarqocrra/ oc
acoaxoc; ao0crc/; uc YAz zxo; rq; uctrq; c/ra/ ra c/,ocuc ra ar0aoucr/x
aaxrq/or/x xa/ ra c[croocuc rq otoq ucra[c c/t^ar cr/rq; oro a/ua xa/ 3acrqra;
roc YAz oc u/a ou^a acoaxar ao0crar uc YAz E/xoo/oxra ao0crc/; uc c/3c3a/autro
YAz co3q0qxar oc occro,a,/xq uctrq croc t,/rc utrqoq rar ar0aoucr/xar roc;
aaxrq/or/xar xa/ rar c/t^ar cr/rq; oro a/ua Acr aarqq0qxc ocotr/oq roc cro-
aro/xoc ^c/xrq (YAA) uc xartra a ra ar0aoucr/x aaxrq/or/x H utoq r/uq rq;
cr/rq; oror o qrar 4205n/m| (:SD 2832) Acr 3t0qxc ocotr/oq rq; cr/rq; uc ror
YAA axuq xa/ rar acrq ooauorqxc oro oooor rq; u,a; /oc; ocrc uc rq or/xq
^/xc/a croc uc xocou o[c,roc <90% q rq auqrcq r/uq xocouoc xar rq ^/xc/a
roc croc Arr/0cra aarqq0qxc ocotr/oq rar r/uar rq; cr/rq; uc ro ^c/xrq u,a; oauaro;
(AMz) xa/ rqr c/ucro rq; xo//; O/ r/ut; rq; cr/rq; ooc oc ao0crc/; uc YAz ^cr
ocr/,orra/ uc rq 3acrqra roc ocr^uoc a; acrq cx,,cra/ uc ror YAA Hvsaav 2006,
19(2)131-136.
Acc: c:o:o: YA2, ovoopto, rttvq
136 /NEMON 7s0o 2o, 7oo 19o, 4np|/|o - /o0t|o 2006
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